Astragalus (Huang Qi) – promising recent research

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The dried root of the northern and eastern Asian plant Astragalus membranaceous var mongholicus, (Astragalus membranaceus, or Astragalus) has a long history of use as a medicine. It is a common ingredient of many traditional Chinese medicine (TCM) formulations, and used for a diverse range of therapeutic purposes. Western medical herbalists mostly use Astragalus as an immunomodulator for immune conditions, and conditions such as chronic fatigue.

Interest is growing in the potential clinical applications of this plant for several chronic conditions commonly experienced by humans, and we have seen more clinical trials taking place over the past few years, mostly in China. Several of these published in the past two years, have provided some encouraging results.

Cancer related fatigue

Astragalus extracts and astragaloside IV, a key active phytochemical, have shown many relevant pharmacological effects of relevance to the management of several different types of cancer. These implicate a potential ability to improve the response rate to certain chemotherapy drugs(1,2), and also to improve symptoms of tiredness and fatigue, which are highly debilitating and often appear or worsen during treatment with chemotherapy or radiotherapy. When severe, a pause or cessation in chemotherapy treatment may then be needed, which can sometimes compromise efficacy.

In China, Astragalus or its polysaccharide extracts, have long been used as part of the management of cancer, and cancer-related fatigue, generally as an adjunctive treatment alongside conventional medicine(3,4).

A recent phase 2 randomised clinical trial (RCT) in which 66 Taiwanese patients with stage 2 or 3 breast cancer took Astragalus polysaccharides or placebo as an adjuvant to the first four cycles of anthracycline-based chemotherapy, reported several benefits. While mean changes in fatigue intensity were similar in both groups, premenopausal women experienced less chemotherapy-induced fatigue and insomnia than those given placebo(5). A similar reduction in cancer-related fatigue was seen in another small recent retrospective cohort study which evaluated outcomes in women taking Astragalus polysaccharides during chemotherapy for various forms of gynaecological cancers(6).

A 2025 review of eight clinical trials summarised evidence supportive of the efficacy of Astragalus in patients with cancer-related fatigue and to improve their quality of life, although due to the small number of studies and different cancer types involved, called for further well designed trials to further validate such use (7).

Treatment of post-Covid chronic fatigue

Astragalus has long been held in high regard by practitioners as a treatment or tonic to support those with post-viral or chronic fatigue syndromes. With fatigue being a prominent feature of post-Covid condition (long Covid), and this having a large burden both on the individual and on health systems, interventions to reduce the extent of fatigue experienced, are of great interest.

A small prospective observational study recently reported alleviation of fatigue in patients with long Covid, for a combination of Astragalus with another well known Asian medicinal plant, Dan Shen (Salvia miltiorrhiza)(8). Significant improvements in fatigue levels as well as brain fog were reported after four weeks treatment with 30% ethanolic extracts of the roots of these two plants, using validated rating scales. While only fifty long Covid patients took part in this study, and larger studies are needed, these results are encouraging.

Diabetes and kidney disease

Astragalus is one of the most commonly used Chinese medicinal plants for the management of diabetes mellitus, particularly type 2 diabetes(9).

Astragalus or its polysaccharide fraction appear to help improve symptoms in some diabetics by addressing insulin resistance, modulating the immune system, protecting pancreatic islet cells, and modulating the intestinal microbiome. Potential benefits also in managing diabetic complications, including diabetic retinopathy and nephropathy, have also been reported(10).

A recent meta-analysis of 48 RCT’s involving 3,759 patients which compared Astragalus-based traditional medicine formulations with western medicines, reported higher rates of total efficacy for those who received the Astragalus-based traditional treatment, or this combined with western medicines, than western medicine treatment alone for the treatment of diabetic peripheral neuropathy(11).

Another systematic review and meta-analysis published last year, found improved outcomes for patients with stage 3 diabetic nephropathy, who took Astragalus alongside renin-angiotensin-aldosterone system (RAAS) blockers(12). The 32 studies and 2,462 patients included in the clinical trials reviewed, found the combination treatment to be safe and to further lower fasting plasma glucose and 24 hour urinary protein levels, compared to RAAS treatment alone.

Several other clinical studies have reported protection against declining renal function in early stage chronic kidney disease, when Chinese formulations containing Astragalus as a key ingredient, are taken alone or in conjunction with conventional medicines(13-15).

A recent systematic review of RCT’s of plant-based foods and medicinal plants in chronic kidney disease and dialysis patients, found Astragalus to be one of the most promising medicinal plants, but recommended further studies are carried out(16).

A recent study with a rat model of hyperuricaemic nephropathy identified Astragalus-induced modulation of the gut microbiota and short chain fatty acid profiles, and influences on the gut-kidney axis, as possible mechanisms of its benefits to the kidney(17).

Prostate problems

A mixture of Astragalus and Angelica gigas (Korean angelica) or placebo was given to 85 men with symptoms of benign prostatic hypertrophy (BPM), in a 12 week preclinical trial in Korea(18).  The herbal treatment was associated with improvement in bladder emptying and the International Prostate Symptom Scores (OIPPS), as well as International Index of Erectile Function (IIEF)(18).

Potential benefits of Astragalus polysaccharides in the management of prostate cancer, have been further revealed by in vitro studies recently. Various favourable effects were seen on the immune systems response to prostate cancer cells, and inhibition of cancer cell migration, although high concentrations of the extract were used(19).

Several other studies provide evidence of the potential usefulness of this phytomedicine in prostate cancer treatment(20-22), and further clinical studies into its effects on prostate health are now underway.

Anti-aging properties?

Extracts of Astragalus have antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic, antihyperglycemic, hepatoprotective, cardioprotective and neuroprotective effects. These effects collectively suggest an ability to protect against various age-related pathologies(23, 24).

Such applications have been given further support, by results of a recent French study involving forty healthy volunteers aged between 40 and 70 years. This investigated the influences of a six month course of a dietary supplement containing Astragalus, on the average length of telomeres(25).   Telomeres are ribonucleoproteins that form a protective buffer at the ends of chromosomes, and help to maintain genomic integrity during the cell cycle. With aging they decline in length, and average telomere size, which is measured in peripheral blood leukocytes, is used as a marker of biological age and chronic stress exposure. Telomere shortening in peripheral blood leukocytes is also an established risk factor for cardiovascular disease, diabetes and cancer.

At the end of the six month study, the median telomere length was found to be significantly longer in subjects who had taken the Astragalus based supplement, than in those who took placebo capsules. No significant adverse events were reported. These findings suggest potential benefits in promoting general health, extending life expectancy and supporting healthy aging(25).

Benefits are also associated with the use of Astragalus or its incorporation into farming systems or environments. Applications in animal husbandry include its usefulness as a stock feed to promote weight gain(26), or as an additive to dairy cows during the postpartum period. A recent study found giving Astragalus as a feed additives to dairy cows after calving to have positive effects on wound recovery and immune function, and to shorten the breeding interval(27). Potential applications for Astragalus polysaccharides in alleviating the inflammation of bovine mammmary fibrosis, a consequence of chronic mastitis in dairy cows, have also been recently reported(28).

Enhanced immunity to bacterial pathogens such as Aeromonas hydrophila has been observed when Astragalus was used as a functional feed supplement in several finfish and shellfish aquaculture settings(29, 30). These could also be of interest to the growing Aotearoa New Zealand Aquaculture industry.

Summary

These are just some of the more than 2,000 scientific papers on Astragalus species which have been published during the past two years, which in itself is a reflection of the importance and promise of this plant family, for both human and animal health applications. With chronic conditions such as diabetes, kidney disease, cancer or postviral-related fatigue placing an increasing burden on the health of so many, further well designed clinical studies including different population groups, are called for.

References:

  1. Zhang J, Wu C, Gao L, Du G, Qin X. Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects. Adv Pharmacol. 2020;87:89-112.
  2. Cheng M, Hu J, Zhao Y, Jiang J, Qi R, Chen S, Li Y, Zheng H, Liu R, Guo Q, Zhang X, Qin Y, Hua B. Efficacy and Safety of Astragalus-Containing Traditional Chinese Medicine Combined With Platinum-Based Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis. Front Oncol. 2021 Aug 4;11:632168.
  3. Tang Z, Tian X. Astragalus membranaceus: A Traditional Chinese Medicine with Multifaceted Impacts on Breast Cancer Treatment. Biomolecules. 2024 Oct 21;14(10):1339.
  4. Lu Q, Jiang J, Wang X, Wang R, Han X. Advancements in the Research of Astragalus membranaceus for the Treatment of Colorectal Cancer. Am J Chin Med. 2025;53(1):119-146.
  5. Shen WC, Chen SC, Wang CH, Hung CM et al, Astragalus polysaccharides improve adjuvant chemotherapy-induced fatigue for patients with early breast cancer. Sci Rep. 2024 Oct 28;14(1):25690. 
  6. Chang CC, Lee YL, Yin CH, Chang CC, Lin YH. Efficacy of astragalus polysaccharides (PG2) in alleviating chemotherapy-induced fatigue in gynecologic cancer: a retrospective cohort study. Discov Oncol. 2025 Jul 12;16(1):1322. 
  7. Sheng X, Yang L, Huang B, Lin G, Wang Y, Wu X, Lin R. Efficacy of Astragalus Membranaceus (Huang Qi) for Cancer-Related Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Studies. Integr Cancer Ther. 2025 Jan-Dec;24:15347354241313344. 
  8. Joung JY, Lee JS, Choi Y, Kim YJ et al, Evaluating myelophil, a 30% ethanol extract of Astragalus membranaceus and Salvia miltiorrhiza, for alleviating fatigue in long COVID: a real-world observational study. Front Pharmacol. 2024 Jun 20;15:1394810. 
  9. Hong KF, Liu PY, Zhang W, Gui DK, Xu YH. The Efficacy and Safety of Astragalus as an Adjuvant Treatment for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Integr Complement Med. 2024 Jan;30(1):11-24. 
  10. Liu S, Wang L, Zhang Z, Leng Y, Yang Y, Fu X, Xie H, Gao H, Xie C. The potential of astragalus polysaccharide for treating diabetes and its action mechanism. Front Pharmacol. 2024 Apr 10;15:1339406
  11. Jing P, Hongzheng H, Zhenqi WU, Meijuan Z, Zuojing LI, Gang C. Long-term efficacy and safety of Huangqi-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials. J Tradit Chin Med. 2024 Apr;44(2):229-242. 
  12. Lin YQ, Yu F, Chen HJ, Deng YR et al, Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis. Ren Fail. 2024 Dec;46(2):2359033
  13. Dong F, Cheng J, Lin S, Hu Z, Chen G, He L. The clinical research on serum cystatin-C alteration on stage II chronic kidney disease with gubenquduyishen decoction treatment. J Ethnopharmacol. 2010 Oct 5;131(3):581-4. 
  14. Wang YJ, He LQ, Sun W, Lu Y et al,. Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial. J Ethnopharmacol. 2012 Feb 15;139(3):757-64.
  15. Lin MY, Chiu YW, Chang JS, Lin HL et al, Association of prescribed Chinese herbal medicine use with risk of end-stage renal disease in patients with chronic kidney disease. Kidney Int. 2015 Dec;88(6):1365-1373. 
  16. Josa E, Barril G, Ruperto M. Potential Effects of Bioactive Compounds of Plant-Based Foods and Medicinal Plants in Chronic Kidney Disease and Dialysis: A Systematic Review. Nutrients. 2024 Dec 14;16(24):4321.
  17. Qu T, Zhang N, Cai J, Li C, Zhang Y, Xu X, Zhang S, Lv W, Liang T. Integrated bioinformatics and multi-omics reveal Astragalus extract’s gut-kidney axis mechanism in hyperuricemic nephropathy via purine metabolism. Phytomedicine. 2025 Oct;146:157121.
  18. Lee JH, Yoon D, Park GD, Kim KS et al, SHPro® (mixture of Angelica gigas and Astragalus membranaceus) in men with lower urinary tract symptoms: A randomized, double-blind, placebo-controlled clinical trial. Investig Clin Urol. 2025 Nov;66(6):539-550
  19. Wu CY, Yang YH, Lin YS, Shu LH, Liu HT, Lu CK, Wu YH, Wu YH. The effect and mechanism of astragalus polysaccharides on T cells and macrophages in inhibiting prostate cancer. Biomed J. 2025 Feb;48(1):100741. 
  20. Guo S, Ma B, Jiang X, Li X, Jia Y. Astragalus Polysaccharides Inhibits Tumorigenesis and Lipid Metabolism Through miR-138-5p/SIRT1/SREBP1 Pathway in Prostate Cancer. Front Pharmacol. 2020 May 5;11:598. 
  21. You X, Wu Y, Li Q, Sheng W, Zhou Q, Fu W. Astragalus-Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy. Front Pharmacol. 2022 Jun 29;13:895696.
  22. Kim SY, Park JE, Lee HJ, Sim DY et al,. Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers. Int J Mol Sci. 2024 Feb 28;25(5):2799
  23. Liu P, Zhao H, Luo Y. Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic. Aging Dis. 2017 Dec 1;8(6):868-886. 
  24. Tian J, Huo R, Wang Y, Wang J, Fang F, Fang C. Astragalus Polysaccharide Alleviates Cognitive Decline in D-Galactose-Induced Aging. Biol Pharm Bull. 2025;48(5):523-536.
  25. de Jaeger C, Kruiskamp S, Voronska E, Lamberti C et al,. A Natural Astragalus-Based Nutritional Supplement Lengthens Telomeres in a Middle-Aged Population: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2024 Sep 3;16(17):2963
  26. Wei H, Ding L, Wang X, Yan Q et al, Astragalus root extract improved average daily gain, immunity, antioxidant status and ruminal microbiota of early weaned yak calves. J Sci Food Agric. 2021 Jan 15;101(1):82-90. 
  27. Huang Y, Yan Q, Jiang M, Guo S, Li H, Lin M, Zhan K, Zhao G, Duan J. Astragalus membranaceus Additive Improves Serum Biochemical Parameters and Reproductive Performance in Postpartum Dairy Cows. Front Vet Sci. 2022 Jul 11;9:952137
  28. Zhang J, Liu K, Yang T, Duan H, Xiao L, Zhang Q, Zhang Y, Dong W, Zhao X. Mechanism of Astragalus Polysaccharide in Alleviating Bovine Mammary Fibrosis Through ROS/NLRP3 Inhibition and EMT Regulation. Antioxidants (Basel). 2025 Apr 23;14(5):503.
  29. Abdel-Latif HMR, Ahmed HA, Shukry M, Chaklader MR, Saleh RM, Khallaf MA. Astragalus membranaceus Extract (AME) Enhances Growth, Digestive Enzymes, Antioxidant Capacity, and Immunity of Pangasianodon hypophthalmus Juveniles. Fishes. 2022; 7(6):319.
  30. Yin G, Ardó L, Thompson KD, Adams A, Jeney Z, Jeney G. Chinese herbs (Astragalus radix and Ganoderma lucidum) enhance immune response of carp, Cyprinus carpio, and protection against Aeromonas hydrophila. Fish Shellfish Immunol. 2009 Jan;26(1):140-5.

Baical Skullcap – useful for anxiety, neurological & mood disorders

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Baical Skullcap

The root of Scutellaria baicalensis (known as Baical skullcap or Huangqin) is an important plant medicine in China, Russia, Mongolia, Korea and Japan.  It is a prominent constituent of many Traditional Chinese Medicine formulations, including those used for allergic diseases, respiratory tract infections, pneumonia, colitis, hepatitis, dementia, Parkinson’s disease and cancer (1).

Scutellaria baicalensis is botanically related to Scutellaria lateriflora (commonly known as Skullcap or American Skullcap). This skullcap species is better known in western herbal medicine, particularly for its anxiolytic and sedative properties(2). 

Over 50 compounds have been isolated and identified from Baical skullcap, including flavonoids, terpenoids, volatile oils and polysaccharides. Most research implicates various flavonoids including baicalein (5,6,7-trihydroxyflavone) and its metabolite baicalin and wogonin, as being key active phytochemicals(3). 

Neurological effects

Neuroprotective effects have been reported for Baical skullcap as well as baicalin, baicalein and wogonin in a range of animal models and in vitro systems(4-6). These include protection against damage to dopamine neurons in the striatum, hippocampus and substantia nigra, suggesting a potential role in Parkinson’s disease(7, 8). Alleviation of both abnormal motor behavioural and depression-like behavior in rodent models of Parkinson’s disease, has also been reported for baicalein(9, 10).

Mitigation of brain injury in the acute stage of ischaemic stroke, and a lessening of subsequent motor dysfunction and cognitive impairment, has been reported following Baical skullcap administration in several rodent studies (5, 11-14). Improved cognition in aged rats, vascular dementia and in animal models of Alzheimer’s disease, are other reported outcomes following administration of concentrated flavonoid extracts made from this plant (15, 16). These include those also extracted from its stem and leaf, as per my herbblurb article posted in April, on additional uses for the aerial parts of Baical skullcap(17). Antioxidant, anti-inflammatory, mitochondrial protective and gut microbiome modulatory effects, seem to be contributory to these various neuroprotective actions(5, 13, 18-20). 

These are impressive findings. The potential applications of Baical skullcap as part of the clinical management of ischaemic stroke in humans, a leading cause of mortality and disability, are of great interest, and clinical studies are warranted.

Effects in anxiety and depression

Anxiolytic effects have been shown in animal studies for Baical skullcap and some of its flavonoid constituents(21-23). Baicalein, baicalin and wogonin are positive modulators of the benzodiazepine binding site of GABAA receptors, the same sites of action of benzodiazepine drugs such as diazepam, a possible mechanism of action in anxiety disorders(21, 24-26). Unfortunately however, human studies involving its use as a single herb rather than as part of a formulation, are lacking.

Behavioural studies have also revealed a potential for Baical skullcap to alleviate prenatal stress-induced anxiety and depression-like behaviours in the offspring of mice. Mechanisms of action were related at least partially through protecting placental barrier function, reversing an overactive hypothalamic-pituitary-adrenal (HPA) axis, and reducing neurodevelopmental dysfunction(27).

I recently presented on antidepressant herbs apart from St Johns Wort, to a practitioner audience, something I’ve done several times in the past, and which I regard as a very important subject(28). Depression is a very common human illness, and as in many countries, antidepressant prescribing rates in Aotearoa New Zealand have been increasing in recent decades.  Given that as with individual drug treatments, only 60-65% of patients respond to the well researched St John’s Wort, there exists a need to research and increase our knowledge on additional herbal interventions that may be helpful as part of the management of mood disorders.  

Baical skullcap is also an ingredient in many traditional Chinese medicine formulae used to treat a range of nervous system conditions, including depression(29).  It is also sometimes combined with another widely used Chinese medicinal plant, Bupleurum (Bupleurum chinense) in these formulations(30). Favourable effects have also been shown for its root and flavonoids in animal models of depression(19), although this in itself doesn’t necessarily indicate antidepressant properties in humans.

While much less researched than its Asian cousin, Scutellaria lateriflora has also been reported to have a mood enhancing effect after two weeks treatment, in a British crossover study involving 43 healthy participants(31).

Recent clinical trial

A six week placebo-controlled clinical trial involving 180 participants with mild to moderate depression who took Baical skullcap with or without saffron, recently took place in Belgium(32).

This trial selected participants aged between 18 and 75 presenting with a depressive episode according to the DSM-5 definition, experiencing mild to moderate depressive symptoms using the Beck Depression Inventory, and having had a depressive episode within the last two years. Those with other mental health conditions or those taking any psychotropic treatment, were excluded.

Four treatment arms were used. The first group (n=42) took an extract of Baical skullcap alone, the second (n=43) a Saffron extract alone, the third (n=48) a combination of these two phytomedicines, and the fourth (n=47) a placebo capsule daily, for 42 days. The Saffron used was standardised for its content of crocins and safranal, and the Baical skullcap was standardised for baicalin.

Participants were assessed prior to commencing treatment, then after three and six weeks of treatment, and at two weeks following the end of treatment. Primary outcomes were the standardized depression scale measured using the Beck Depression Inventory and Hamilton Depression score. Subjects also completed other questionnaires assessing positive and negative affects, anxiety levels, quality of life, and wellbeing levels.

Improvements occured in both mood and sleep in all four groups, particularly between the 21 day and 42 day treatment period. While differences between groups in terms of the depression measurements weren’t statistically significant, anxiety levels were decreased with all three treatment but not the placebo group. Scores for Emotional Assessment, a self-rated scale describing feelings and emotions, were also improved but maintained at 56 days only for the Baical skullcap and combined Baical skullcap and Saffron treated groups. Minimal adverse effects were reported across all treatment groups. 

While this study failed to reveal evidence of an antidepressant effect for Baical skullcap, Saffron also failed to achieve this to statistical significance, despite several trials having reported such effects for it already (33). Methodological issues such as low participant numbers and/or the dosages used being too low, may have been contributory. The study did however, produce data suggesting an anti anxiety or anxiolytic effect, and overall improvement in self rated feelings and emotions. Given the link  between chronic and poorly controlled anxiety and a predisposition to depression, further studies with larger numbers and using different dosages are recommended.

This is one of the first well designed clinical trials published in an English language journal implicating an anxiolytic and possible antidepressant effect for Baical skullcap.

References:

  1. Zhao T, Tang H, Xie L, Zheng Y, Ma Z, Sun Q, Li X. Scutellaria baicalensis Georgi. (Lamiaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol. 2019 Sep;71(9):1353-1369. 
  2. Shen J, Li P, Liu S, Liu Q, Li Y, Sun Y, He C, Xiao P. Traditional uses, ten-years research progress on phytochemistry and pharmacology, and clinical studies of the genus Scutellaria. J Ethnopharmacol. 2021 Jan 30;265:113198. 
  3. Wang ZL, Wang S, Kuang Y, Hu ZM, Qiao X, Ye M. A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol. 2018 Dec;56(1):465-484.
  4. Si L, An Y, Zhou J, Lai Y. Neuroprotective effects of baicalin and baicalein on the central nervous system and the underlying mechanisms. Heliyon. 2024 Dec 10;11(1):e41002. 
  5. Seo HW, Ha TY, Ko G, Jang A, Choi JW, Lee DH, Chang KA. Scutellaria baicalensis Attenuated Neurological Impairment by Regulating Programmed Cell Death Pathway in Ischemic Stroke Mice. Cells. 2023 Aug 23;12(17):2133.
  6. Huynh DL, Ngau TH, Nguyen NH, Tran GB, Nguyen CT. Potential therapeutic and pharmacological effects of Wogonin: an updated review. Mol Biol Rep. 2020 Dec;47(12):9779-9789. 
  7. Lee HJ, Noh YH, Lee DY, Kim YS, Kim KY, Chung YH, Lee WB, Kim SS. Baicalein attenuates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. Eur J Cell Biol. 2005 Nov;84(11):897-905
  8. Zhao WZ, Wang HT, Huang HJ, Lo YL, Lin AM. Neuroprotective Effects of Baicalein on Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain. Mol Neurobiol. 2018 Jan;55(1):130-137.
  9. Gao L, Li C, Yang RY, Lian WW, Fang JS, Pang XC, Qin XM, Liu AL, Du GH. Ameliorative effects of baicalein in MPTP-induced mouse model of Parkinson’s disease: A microarray study. Pharmacol Biochem Behav. 2015 Jun;133:155-63. 
  10. Zhao X, Kong D, Zhou Q, Wei G, Song J, Liang Y, Du G. Baicalein alleviates depression-like behavior in rotenone- induced Parkinson’s disease model in mice through activating the BDNF/TrkB/CREB pathway. Biomed Pharmacother. 2021 Aug;140:111556.
  11. Li M, Meng Z, Yu S, Li J, Wang Y, Yang W, Wu H. Baicalein ameliorates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via regulating GPX4/ACSL4/ACSL3 axis. Chem Biol Interact. 2022 Oct 1;366:110137. 
  12. Shang Y, Cheng J, Qi J, Miao H. Scutellaria flavonoid reduced memory dysfunction and neuronal injury caused by permanent global ischemia in rats. Pharmacol Biochem Behav. 2005 Sep;82(1):67-73. 
  13. Liang W, Huang X, Chen W. The Effects of Baicalin and Baicalein on Cerebral Ischemia: A Review. Aging Dis. 2017 Dec 1;8(6):850-867.
  14. Zhao S, Kong W, Zhang S, Chen M, Zheng X, Kong X. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia-reperfusion injury. Neural Regen Res. 2013 Dec 5;8(34):3183-92.
  15. Song HR, Cheng JJ, Miao H, Shang YZ. Scutellaria flavonoid supplementation reverses ageing-related cognitive impairment and neuronal changes in aged rats. Brain Inj. 2009 Feb;23(2):146-53.
  16. Ma S, Xu CC, Dong YC, Li CX, Shang YZ. Scutellaria Baicalensis Georgi Stem and Leaf Flavonoids Ameliorate the Learning and Memory Impairment in Rats Induced by Okadaic Acid. Comb Chem High Throughput Screen. 2025;28(2):263-277.
  17. Rasmussen PL, Baical Skullcap – additional uses for aerial parts. www.herbblurb.com April 7, 2025.
  18. Im AR, Kim YH, Uddin MR, Lee HW, Chae SW, Kim YH, Jung WS, Kang BJ, Mun CS, Lee MY. Scutellaria baicalensis Extracts and Flavonoids Protect Rat L6 Cells from Antimycin A-Induced Mitochondrial Dysfunction. Evid Based Complement Alternat Med. 2012;2012:517965.
  19. Wang C, Gao MQ. Research Progress on the Antidepressant Effects of Baicalin and Its Aglycone Baicalein: A Systematic Review of the Biological Mechanisms. Neurochem Res. 2024 Jan;49(1):14-28.
  20. He P, Qiao R, Liu C, Zhang W, Li H, He F. Neuroprotective Mechanisms of Baicalin in Ischemia Stroke. ACS Chem Neurosci. 2025 Jun 4;16(11):1978-1995. 
  21. Hui KM, Huen MS, Wang HY, Zheng H, Sigel E, Baur R, Ren H, Li ZW, Wong JT, Xue H. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem Pharmacol. 2002 Nov 1;64(9):1415-24. 
  22. de Carvalho RS, Duarte FS, de Lima TC. Involvement of GABAergic non-benzodiazepine sites in the anxiolytic-like and sedative effects of the flavonoid baicalein in mice. Behav Brain Res. 2011 Aug 1;221(1):75-82. 
  23. Warlick H 4th, Leon L, Patel R, Filoramo S, Knipe R, Joubran E, Levy A, Nguyen H, Rey J. Application of gabapentinoids and novel compounds for the treatment of benzodiazepine dependence: the glutamatergic model. Mol Biol Rep. 2023 Feb;50(2):1765-1784. 
  24. Liao JF, Wang HH, Chen MC, Chen CC, Chen CF. Benzodiazepine binding site-interactive flavones from Scutellaria baicalensis root. Planta Med. 1998 Aug;64(6):571-2.
  25. Wang H, Hui KM, Chen Y, Xu S, Wong JT, Xue H. Structure-activity relationships of flavonoids, isolated from Scutellaria baicalensis, binding to benzodiazepine site of GABA(A) receptor complex. Planta Med. 2002 Dec;68(12):1059-62. 
  26. Wang F, Xu Z, Ren L, Tsang SY, Xue H. GABA A receptor subtype selectivity underlying selective anxiolytic effect of baicalin. Neuropharmacology. 2008 Dec;55(7):1231-7.
  27. Li L, Zhang W, Sun C, Chai Z, Wang K, Zhou Q, Wang X. Scutellariae radix Ameliorates Prenatal Stress-Induced Anxiety-Like and Depression-Like Behavior in the Offspring via Reversing HPA Axis Hyperfunction and Ameliorating Neurodevelopmental Dysfunction. Dev Neurosci 2024 Dec 19:1-19.
  28. Rasmussen PL, Herbs other than St Johns Wort that can be useful in treating Depression. NZ Association of Medical Herbalists, NZAMH, Conference, Christchurch, New Zealand, 6-7 September 2025.  www.nzamh.org.nz/assets/ Conference-brochure-2025-final.pdf.
  29. Ma Y, Zhou X, Zhang F, Huang C, Yang H, Chen W, Tao X. The effect of scutellaria baicalensis and its active ingredients on major depressive disorder: a systematic review and meta-analysis of literature in pre-clinical research. Front Pharmacol. 2024 Mar 20;15:1313871. 
  30. Bing Y, Li Z, Liu L, Wang D, Liu K, Li J, Li S, Qu Z, Zou X. Preliminary exploration of the antidepressant mechanism of Bupleurum scorzonerifolium-Scutellaria baicalensis and its core SSa-Baicalin combination. J Ethnopharmacol. 2025 Sep 25;353(Pt B):120426.
  31. Brock C, Whitehouse J, Tewfik I, Towell T. American Skullcap (Scutellaria lateriflora): a randomised, double-blind placebo-controlled crossover study of its effects on mood in healthy volunteers. Phytother Res. 2014 May;28(5):692-8. 
  32. Dormal V. Nutrients. 2025 Feb 26;17(5):809.Wang C, Neurochem Res. 2024 Jan;49(1):14-28. doi: 10.1007/s11064-023-04026-3
  33. Chauhan S, Tiwari A, Verma A, Padhan PK, Verma S, Gupta PC. Exploring the Potential of Saffron as a Therapeutic Agent in Depression Treatment: A Comparative Review. Yale J Biol Med. 2024 Sep 30;97(3):365-381.

Baical Skullcap – additional uses for aerial parts

On By philrasmIn Antibiotic Resistance, antimicrobial, Herbal Medicine, UncategorizedLeave a comment

Baical Skullcap

Scutellaria baicalensis (known as Baical skullcap or Huangqin) is an important plant medicine in China, Russia, Mongolia, Korea and Japan.  It is a prominent constituent in a large number of Traditional Chinese Medicine formulations used to treat numerous disease conditions. These include allergic diseases, respiratory tract infections, pneumonia, colitis, hepatitis, dementia, Parkinson’s disease and cancer.

Scutellaria baicalensis is botanically related to Scutellaria lateriflora (commonly known as Skullcap or American Skullcap in western Herbal Medicine), best known for its anxiolytic and sedative properties.  However, the root of Baical skullcap is the plant part traditionally used, whereas for American Skullcap it is the aerial parts (leaves and stems).

Over 50 compounds have been isolated and identified from Baical skullcap, including flavonoids, terpenoids, volatile oils and polysaccharides. Flavonoids including baicalein and its metabolite baicalin and wogonin, are key active phytochemicals.  These occur in highest levels within the root, and virtually all research on this impressive plant has involved use of root-derived preparations.

Research on aerial parts

While not well known, other parts of Baical skullcap, are also sometimes used for therapeutic purposes.

Improved cognition in vascular dementia and in animal models of Alzheimer’s disease, and prevention of cerebral ischaemia reperfusion injury, have previously been reported in rats following administration of concentrated flavonoid extracts made from stems and leaves of Scutellaria baicalensis (1-5). While required dosages were large, favourable results using these animal models for common age-related conditions are encouraging. They also highlight potential applications in both veterinary and human medicine, for parts of the plant normally regarded as waste products from root farming operations. These have a different phytochemistry to the root, with the flavonoid scutellarin being predominant.

Poultry industry applications

The poultry industry is a huge global operation, but as it has grown and poultry farms become larger, challenges in relation to animal health and husbandry have also increased.

Most chicken farms around the world still rely heavily on regular use of antibiotics for disease prevention and control, and sometimes also to promote growth. However, such widespread use can lead to deposition of antibiotic residues in the soil and waterways, and the promotion of microbial mutations and antibiotic resistance. These are serious consequences for the environment, animal and human health(6).  Since 2006, the European Union has banned the use of antibiotics as growth promoters in farm animals. Their use in Australia and New Zealand, is also now limited to sick animals only.

Bacterial and viral infections nevertheless remain challenging for poultry farmers, and can lead to substantial losses in laying hens or in those farmed for meat.  Despite improvements in housing and management practices in recent years, infections such as salmonella or bird flu remain a constant threat.

A recent study by Chinese researchers, has now found the normally discarded tops of Baical skullcap to offer promise in helping farmers to manage respiratory tract pathogens in poultry.

Recent research

The study, conducted by agricultural researchers and veterinarians in Beijing, investigated the effects of an ethanolic extract of the stems and leaves of Scutellaria baicalensis, on respiratory symptoms in diseased laying hens.

Three groups of 60 diseased laying hens were randomly selected. One group was given a diet supplemented with dried Baical skullcap stem and leaf powder, another with a hydroethanolic extract of the stem and leaf, and one the usual diet only, for a period of 12 days.

After the 12 day supplementation period, hens given the Baical skullcap extract had a marked improvement in respiratory tract symptoms such as coughing, a runny nose and labored breathing. Subsequent biopsies revealed a significant improvement in lung tissue lesions and inflammation. Baical skullcap supplementation was also associated with a significant upward trend in the egg production rate starting 3 days after supplementation commenced, as well as improvements in egg quality(7).

Previous work

Earlier work in Europe found a combination of turmeric and baical skullcap given as a feed additive to chickens decreased gut inflammation and improved the health of chickens with the pathogen Salmonella enteritidis(8). Salmonella is a serious pathogen in chickens which can affect both meat and egg production and quality.

Another recent Chinese study found a combination of baical skullcap with flowers of Lonicera japonica (Japanese honeysuckle, a noxious weed in Aotearoa New Zealand)(9), to mitigate the negative effects of Clostridia perfringens infection in chickens. This is another gastrointestinal pathogen causing reduced growth and mortality in poultry, also normally treated with antibiotics. Mechanisms of action were related to improvement in intestinal barrier function, leading to a positive influence on the growth performance of challenged birds(10).

Economic and environmental benefits

Potential applications to develop animal feed products containing readily available and cheap or free plant materials to manage chicken diseases naturally rather than through agrichemicals, are made apparent by this recent research.

While above ground parts of medicinal plants where the root is harvested are usually returned to the land in the form of mulch or as some form of compost, an ability to utilize these also to produce valuable medicines, is preferential.

The area of commercial cultivation of Baical skullcap in China alone is currently more than four times that of all Aotearoa New Zealand apple and pear orchards combined. This in itself speaks to the market potential of farming for the highly medicinal root.  With additional poultry industry applications being revealed for plant parts generally regarded as a waste byproduct, the case for increased research to further develop a sustainable and profitable scaled up medicinal plant cultivation industry here, continues to strengthen.

Refs:

  1. Cao Y, Liang L, Xu J, Wu J, Yan Y, Lin P, Chen Q, Zheng F, Wang Q, Ren Q, Gou Z, Du Y. The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats. Acta Biochim Biophys Sin (Shanghai). 2016 May;48(5):437-46.
  2. Zhao S, Kong W, Zhang S, Chen M, Zheng X, Kong X. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia-reperfusion injury. Neural Regen Res. 2013 Dec 5;8(34):3183-92. doi: 10.3969/j.issn.1673-5374.2013.34.002.
  3. Zhang H, Liu QQ, Ding SK, Li H, Shang YZ. Flavonoids From Stems and Leaves of Scutellaria Baicalensis Georgi Improve Composited Aβ-Induced Alzheimer’s Disease Model Rats’ Memory and Neuroplasticity Disorders. Comb Chem High Throughput Screen. 2023;26(8):1519-1532. 
  4. Ma S, Xu CC, Dong YC, Li CX, Shang YZ. Scutellaria Baicalensis Georgi Stem and Leaf Flavonoids Ameliorate the Learning and Memory Impairment in Rats Induced by Okadaic Acid. Comb Chem High Throughput Screen. 2025;28(2):263-277
  5. Wang X, Xie Y, Bayoude A, Zhang B, Yu B. Discovering the Q-marker of scutellaria baicalensis against viral pneumonia integrated chemical profile identification, pharmacokinetic, metabolomics and network pharmacology. J Ethnopharmacol. 2025 Jan 31;340:119232.
  6. Rasmussen PL, ‘Antibiotics and their effects on Plants. www.herbblurb.com July 27, 2017.
  7. Wang X, Wu S, Guo N, Yu F, Xu X, Wang X, Yu X, Liu X, Dong H. Scutellaria baicalensis stem and leaf combat chicken-derived respiratory bacterial infection. Microb Pathog. 2025 May;202:107439. 
  8. Varmuzova K, Matulova ME, Gerzova L, Cejkova D, Gardan-Salmon D, Panhéleux M, Robert F, Sisak F, Havlickova H, Rychlik I. Curcuma and Scutellaria plant extracts protect chickens against inflammation and Salmonella Enteritidis infection. Poult Sci. 2015 Sep;94(9):2049-58.
  9. Rasmussen PL, ‘Honeysuckle and other useful weeds surrounding us. www.herbblurb.com January 24, 2019.
  10. Li S, Zhang K, Bai S, Wang J, Zeng Q, Peng H, Lv H, Mu Y, Xuan Y, Li S, Ding X. Extract of Scutellaria baicalensis and Lonicerae flos improves growth performance, antioxidant capacity, and intestinal barrier of yellow-feather broiler chickens against Clostridium perfringens. Poult Sci. 2024 Jul;103(7):103718.

Medicine Security in Unsettled Times

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Medicinal plants in history

Health workforce shortages. Lengthening waiting lists. Hospital cost over-runs. Type 2 Diabetes, the hidden epidemic. Pandemic viruses.  Antibiotic resistance. Aging populations. Increasing meth use. There’s certainly more than a few nightmares for health policy analysts and decision makers to grapple with, when determining how to best allocate government health spending.

Apart from needing food and shelter, being able to resist the many life-threatening and injurious events and diseases that living on Planet Earth entails, has always been essential for our survival as a species. Thus in addition to having food security (access to sufficient healthy and nutritious food), the adequate supply of affordable and efficacious medicines, is a fundamental requirement to ensure good health and survival of human populations.

Humans have traditionally relied largely upon plants and fungi for medicines, and history shows they have served us well. However, despite the development of chemical drugs occurring only just over a hundred years ago, we often fail to acknowledge how the supply chain of medicinal plants, has greatly influenced the course of human history to date.

During the second world war, Cinchona officinalis (Peruvian bark) for instance, from which the valuable antimalarial drug quinine derives, was sourced almost exclusively from Java in Indonesia. However, after the Japanese invasion in 1942 and the capture by Nazis of processing facilities in the Netherlands, allied forces experienced a critical shortage of antimalarial drugs, which subsequently limited their operations in the southwest Pacific. Concerted efforts were therefore made to establish Cinchona cultivation in other locations, and new plantations in south America were developed(1).

Trade in black pepper, cinnamon and many other spices from India, China and south east Asia to Europe, were key contributors to the accumulation of wealth in early ancient cities such as Constantinople, Alexandria, Damascus and Venice.  Europeans fought the Crusades in large part to maintain a portal to the valuable spice trade. The Opium Wars between China, Britain and France in the mid 19th century, arose from China’s attempts to suppress the large European controlled trade of opium to China at that time.

These and many other examples, are reminders about how plants with powerful pharmacological properties have been important to humans. And how our access to them through either trade barriers and/or insufficient local production, can become seriously restricted.

Pandemic lessons

A key realisation that emerged early during the Covid-19 pandemic, was that despite years of well-funded research and development, drugs don’t provide all the answers when treating or preventing disease. A vaccine was developed and distribution commenced in near record time, but this still took many months and had many limitations. Distribution was delayed particularly to poorer countries, and a large percentage of the world’s population resorted as they always have done, to traditional plant medicines instead.

The pandemic also exposed the failure and cluster risks of modern global medicine supply chains. As levels of demand surged, enormous pressures were placed on already stretched supply chains, and widespread supply bottlenecks appeared.  During the Covid-19 lockdown in February 2022, pharmacy and supermarket shelves in Aotearoa NZ were virtually cleared of analgesics as people stockpiled. China’s zero-Covid policy during the pandemic prompted the closures of its many production facilities. India, which obtains most of its active pharmaceutical ingredients (API’s) from China, feared an imminent shortage of these critical raw materials, and thus promptly halted its exports of many medicinal products.  

Since the pandemic, shortages have occurred in supplies of widely used drugs such as the antidepressant fluoxetine, oestradiol patches used for menopause, and paracetamol. Similar shortfalls have happened in many other countries. The forthcoming withdrawal of the U.S. from the World Health Organisation, also doesn’t bode well for future international collaboration or worldwide medicine security.

Antibiotic resistance, is another ticking timebomb already responsible for over a million deaths a year globally, and placing a growing burden on health budgets. Rates of antimicrobial resistance are increasing in Aotearoa New Zealand and globally, including to last-line carbapenem antibiotics usually reserved for severe infections(2). It is a serious problem directly related to their overusage. Resistance to commonly used disinfectants and sanitizing agents, is also of increasing concern(3-5). Reducing their usage through increased utilization of plant derived medicines to help control infection, is a highly recommendable and evidence-based strategy.

Medicine shortfalls

Economic pressures, subsidisation policies and looser regulatory provisions in low-wage countries, have led to vital parts of medicine manufacturing being relocated to Asian countries over the past couple of decades. Historically also, global supplies of medicinal plants have largely derived from countries with low labour costs.

Most of the world’s pharmaceutical production, and around 30% of the production of plants for medicines, now takes place in China and India.  The high concentration of drug manufacturing steps in a small number of sites, often concentrated in the same geographical area, makes a supply chain vulnerable(6). Modern supply chain concepts such as just-in-time delivery, mean fewer reserves are maintained throughout the value chain.

The rapidly increasing frequency of so-called extreme weather events, reduced biodiversity, global warming and climate change, will also cause further threats to trade and supply chain security. These and other human factors are having increasingly serious impacts not only on food production and supplies, but also on the health and habitats of medicinal plants, and our ability to access them.

Geopolitical events, including wars or the introduction of trade tariffs, can also impact suddenly and significantly on our ability to access medicines which are manufactured or sourced from far away. With an increasingly unsettled international situation and tensions currently in a number of areas of the world, supply chain risks and strategies to mitigate these, should be high on a government’s agenda.

Medicine supplies – a government priority

Governments around the world have been considering and implementing additional measures to better secure medicine supply for their populations in the future. For a multitude of reasons, the inclusion of phytomedicines and their raw materials in these programmes, is essential.

Much was learned about the phytochemistry and potential medicinal properties of plants native to Aotearoa New Zealand during world war 2, when the government funded research in anticipation of a Japanese naval blockade limiting our imported medicine supply chain.

Cuba shifted to a more traditional and plant medicine based healthcare system following the introduction of a U.S. embargo in 1961. It now has some of the best health outcomes in the world, and its population’s average life expectancy is the same as that in the U.S. This has been achieved through an emphasis on prevention and education, universal coverage and access to treatment, within a highly proactive and well resourced primary healthcare system. Cuba’s spending per capita on health, is only a fraction of that allocated in the U.S., and less than half that spent in Aotearoa New Zealand (7).

Need for a Natural Health Agency

Healthy plant based foods and efficacious phytomedicines are powerful tools when building resilience to geopolitical or natural events which disrupt medicine supplies, and contribute greatly to better medicine security.

Aotearoa New Zealand is one of the best food and beverage producing countries in the world, with an ability to grow a wide range of foods and medicinal plants. From blueberries to kiwifruit, green tea to ginkgo, ginseng to saffron, numerous plants seem to have special characteristics and world leading levels of active phytochemicals, when grown here.

This capability together with a hard working and adaptable farming community, smart scientists and an innovative culture, provides the key criteria needed to further establish and promote a robust and export driven natural health product industry here. This could become a major contributor to our economy, as a sustainable, value added and profitable industry well aligned with our intrinsic and unique strengths as a country, and employ and retain both highly skilled and less skilled workforces. A scaled up commercial medicinal plant cultivation and processing industry would also help to mitigate risks from being over dependent on dairy and meat exports, and enable more self-sufficiency and medicine security, at the same time.

A New Zealand Space Agency was established in 2016, to be the lead government agency for space policy, regulation and sector development. This supports the ventures of companies such as Rocket Lab and Elon Musk’s SpaceX, and a NZ Space and Advanced Aviation Strategy 2024 to 2030 sets out the steps being taken to catalyse the sector’s growth.

In its current efforts to improve economic and wellbeing outcomes for Aotearoa New Zealand, it would be refreshing to see the government also implement the establishment of a Natural Health Agency. This could develop much needed new regulations for the sector, facilitate more research and development to support its growth, and improve patient access to evidence-based plant medicine treatments within primary health care. Expenditure on imported drug medicines would be reduced, and rural communities and our environment benefit through establishing new medicinal plant crops and related processing ventures.  

The natural health products sector is a complex but highly promising one for Aotearoa New Zealand, and a strategic, well integrated and coordinated bipartisan programme resourced over several years and insulated from our three year election cycles, would be an excellent use of limited government funds, in these changing times.

And it should lead to more resilience and medicine security, when the next pandemic or serious geopolitical event pulls the carpet out from our currently largely imported medicine supply chain.

References:

  1. Shanks GD. Historical Review: Problematic Malaria Prophylaxis with Quinine. Am J Trop Med Hyg. 2016 Aug 3;95(2):269-72. doi: 10.4269/ajtmh.16-0138.
  2. Ministry of Health , Manatū Hauora. Growing risk of antimicrobial resistance infection in New Zealand, 18 Nov 2024. https://www.health.govt.nz/news/growing-risk-of-antimicrobial-resistance-infection-in-new-zealand#:~:text=’Resistant%20strains%20of%20bacteria%20and
  3. Van den Poel B, Saegeman V, Schuermans A. Increasing usage of chlorhexidine in health care settings: blessing or curse? A narrative review of the risk of chlorhexidine resistance and the implications for infection prevention and control. Eur J Clin Microbiol Infect Dis. 2022 Mar;41(3):349-362.
  4. Kampf G. Acquired resistance to chlorhexidine – is it time to establish an ‘antiseptic stewardship’ initiative? J Hosp Infect. 2016 Nov;94(3):213-227. 
  5. Fernandes ÂR, Rodrigues AG, Cobrado L. Effect of prolonged exposure to disinfectants in the antimicrobial resistance profile of relevant micro-organisms: a systematic review. J Hosp Infect. 2024 Sep;151:45-59. 
  6. OECD Health Policy Studies. Securing Medical Supply Chains in a Post-Pandemic World. OECD Health Policy Studies, OECD Publishing, Paris. ISSN 2024-319X (online)
  7. M, Sarvestani MA. A Review on the Approach to Herbal Medicine in Cuban Healthcare System. Hispanic Health Care International. 2024;0(0). doi:10.1177/15404153241291747
  8. https://herbblurb.com/2019/06/21/why-new-zealand-grown-herbs-are-best/

Cinchona seedlings growing in Washington DC, USA, in November 1943 taken from Mindanao in the Philippines to re-establish quinine production in the Americas.

US Army Photograph, now in the public domain.

An introduced botanical paradise seen on holiday in Aotearoa New Zealand

On By philrasmIn Uncategorized1 Comment

Achillea millefolium (Yarrow) was the first familiar medicinal plant to proudly show itself to me on the 1st day of a recent six day campervan trip from Christchurch to the west coast of Te Waipounamu (the South Island), of Aotearoa New Zealand. Growing and flowering prolifically along the roadside and beyond as we ventured inland towards Arthurs Pass, I wished I could have stayed another night in the campsite, and had the chance to harvest a decent batch.

Yarrow is a great plant to have nearby. So also apparently thought the Greek warrior Achilles, who is said to have applied its leaves and flowers topically to the sword and arrow wounds of his soldiers after battle, to close and heal their wounds. It is widely utilized in the traditional medicine of cultures from Europe to Asia to north America for numerous health conditions. They include spasmodic digestive and gynaecological complaints, and as a febrifuge and antimicrobial for fevers and infections(1). Relief from period pain was reported after drinking three cups of yarrow tea daily on days one to three of the menstrual cycle, in a clinical trial with 91 students aged 19-23(2).

Eschscholztia californica was a pretty poppy that called out with its bright yellow and orange flowers, in many roadside and dry gravelly patches throughout our journey. Related botanically to its opium-producing cousin, also seen in a couple of places thanks to the early Chinese goldminers of central Otago, Californian poppy is now a popular remedy for anxiety, insomnia and mild pain. My application of it however, has mainly been in patients withdrawing from substance dependency(3).

The amount of St John’s Wort (Hypericum perforatum) thriving in numerous locations in the Hawea, Wanaka and Queenstown districts and in other areas throughout our journey, was quite eye opening. I first wildcrafted and grew Hypericum as a student in the UK, and have dispensed it extensively within herbal formulations over the past 30 years.  A powerful antidepressant, antimicrobial and anti-inflammatory, with a multitude of applications both topically and internally.   

Mullein (Verbascum thapsus) was another one, appearing unexpectantly upon rounding many corners on sloping, dry hillbanks, with its distinctive upright stems poking towards the sky. As an invasive plant in many pastures and fields of rural New Zealand, with a rich content of polysaccharide hydrocolloids and other expectorant and anti-inflammatory phytochemicals, its long historical use as a lung tonic and for the management of upper respiratory tract infections, warrants more attention. While it’s a lot of work to harvest and dry the large lightweight leaves, it makes a great cough formula ingredient. The flowers and roots, also have established medicinal properties(4).

And then the rosehips. Through Lindis Pass into the upper Waitaki Valley as well as at the start of Arthurs Pass, fields and fields of them, dominated many parts of the landscape. Rosehips (Rosa canina) are probably best known for their vitamin C content, and in the 1940’s, locals from Otago and Southland wildcrafted the hips and sold them to the Greggs factory in Dunedin to manufacture syrups and powder forms. Rosehips were similarly wildcrafted in Britain during World War Two, and its syrup given to children and troops to prevent scurvy. 

Several clinical trials have reported efficacy of rosehip powder or extracts for the symptomatic treatment of osteoarthritis(5-7). Inhibitory effects against both cyclo-oxygenase 1 and 2 (COX-1 and COX-2) enzymes may contribute to these benefits(8, 9 ). Other traditional indications are for kidney stones, UTI’s and digestive ailments, and its oil is a popular application for skin health. Rosehips have antioxidant, anti-inflammatory, anti-obesity, anti-cancer, hepatoprotective, nephroprotective, cardioprotective, anti-aging, anti H. pylori, neuroprotective and antinociceptive activities(10).

Finally, heading back into Canterbury, the presence of Elder trees (Sambucus nigra), made themselves known upon the landscape. I made many batches of wine using Elder berries or flowers I wildcrafted when living in the U.K. many years ago, although it is a less common albeit somewhat invasive species here and prefers the cooler south rather than north island.  

Elder flowers are a great decongestant, and its berries rich in antioxidant anthocyanins and other anti-inflammatory polyphenols and vitamin C (11). Global demand greatly outstripped supply during the Covid-19 pandemic, due to its alleged antiviral properties (12, 13).

Many other established or invasive medicinal plants were seen during our journey, though most of these didn’t cry out so much to me.  It was the ones that I don’t see as much in the north island where I live, that served to remind me of the enormous geographical and botanical diversity that is characteristic of the Aotearoa New Zealand landscape.

And of course the extent and variety of our own native species was absolutely awe-inspiring, as it has been every time I’ve travelled on the west coast. The dominance of rātā (Metrosideros robusta) with its beautiful red flowers blanketing out in so many locations from within the dominant native beech forests (Nothofagus spp), was truly stunning.

We live in a country where there are bountiful supplies of medicinal plants. From many perspectives including those based upon invasive plant and land management, biodiversity, sustainability, economics and ultimately health outcomes, we should use more of them.

References:

  1. Ali SI, Gopalakrishnan B, Venkatesalu V. Pharmacognosy, Phytochemistry and Pharmacological Properties of Achillea millefolium L.: A Review. Phytother Res. 2017 Aug;31(8):1140-116
  2. Jenabi E, Fereidoony B. Effect of Achillea Millefolium on Relief of Primary Dysmenorrhea: A Double-Blind Randomized Clinical Trial. J Pediatr Adolesc Gynecol. 2015 Oct;28(5):402-4.
  3. Rasmussen PL, A Role for Phytotherapy in the Treatment of Benzodiazepine and Opiate Drug Withdrawal; Part 2, Treatment Approaches to Opiate Withdrawal, and Conclusions. Eur J Herbal Med, 1997; 13-10.
  4. Gupta A, Atkinson AN, Pandey AK, Bishayee A. Health-promoting and disease-mitigating potential of Verbascum thapsus L. (common mullein): A review. Phytother Res. 2022 Apr;36(4):1507-1522. 
  5. Rasmussen PL, Rosehip for Osteoarthritis. Phytonews 24, February 2006; published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  6. Christensen R, Bartels EM, Altman RD, Astrup A, Bliddal H. Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?–a meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2008 Sep;16(9):965-72. 
  7. Gruenwald J, Uebelhack R, Moré MI. Rosa canina – Rose hip pharmacological ingredients and molecular mechanics counteracting osteoarthritis – A systematic review. Phytomedicine. 2019 Jul;60:152958. 
  8. Jäger AK, Eldeen IM, van Staden J. COX-1 and -2 activity of rose hip. Phytother Res. 2007 Dec;21(12):1251-2. 
  9. Rasmussen PL, Rosehip acts as a cyclo-oxygenase inhibitor. Phytonews 29, June 2008; published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  10. Ayati Z, Amiri MS, Ramezani M, Delshad E, Sahebkar A, Emami SA. Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip: A Review. Curr Pharm Des. 2018;24(35):4101-4124.
  11. Stępień AE, Trojniak J, Tabarkiewicz J. Health-Promoting Properties: Anti-Inflammatory and Anticancer Properties of Sambucus nigra L. Flowers and Fruits. Molecules. 2023 Aug 24;28(17):6235.
  12. Wieland LS, Piechotta V, Feinberg T, Ludeman E, Hutton B, Kanji S, Seely D, Garritty C. Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review. BMC Complement Med Ther. 2021 Apr 7;21(1):112.
  13. Boroduske A, Jekabsons K, Riekstina U, Muceniece R, Rostoks N, Nakurte I. Wild Sambucus nigra L. from north-east edge of the species range: A valuable germplasm with inhibitory capacity against SARS-CoV2 S-protein RBD and hACE2 binding in vitro. Ind Crops Prod. 2021 Jul;165:113438.  

Mānuka and other Honeys – exciting recent research

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Honey as a medicine

Honey has been prized both as a food and medicine since the earliest times.(1,2)  Traditional medicine practices from around the world have long valued its therapeutic properties, particularly as a remedy for burns, cataracts, ulcers and wound healing.

All honeys are rich in antioxidant, anti-inflammatory and antimicrobial flavonoids, phenolic acids and other bioactive compounds cleverly extracted and manufactured by bees. These contribute to honey’s anti-inflammatory, antibacterial, antiviral, immunomodulatory and anti-allergic activities.(3-5)

While applications for wound care have become quite well known, clinical trials have also reported beneficial effects of honey intake on cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, and coughs in children.(6,7)

Different types of honey are classified depending on the floral source and/or the geographical regions from which they derive.

Mānuka honey

Mānuka honey is honey made by bees using nectar from flowers of Leptospermum scoparium, a small native tree which grows abundantly throughout Aotearoa New Zealand. Mānuka is an important plant in rongoā Māori and for medical herbalists here, with its bark, foliage and seeds used to compound preparations for wounds, cuts, sores and skin diseases, colds, coughs and gastrointestinal conditions.(8,9) Its essential oil, also has multiple anti-inflammatory, antimicrobial and other bioactivities.(10)

Apart from being a rich source of glucose, fructose and flavonoids such as quercetin and chrysin found in other honeys, Mānuka honey contains unique chemical compounds such as methylglyoxal (MGO), dihydroxyacetone, leptosperin glyoxal, methyl syringate and leptosin.(11)

While once regarded as being inferior to other culinary honeys in terms of its taste profile, interest in the medicinal properties of Mānuka honey began to grow during the 1980’s. Its reputation as a health promoting food grew rapidly, a key catalyst being research in the early 1980’s which showed Mānuka honey to have potent antibacterial activities. 

Antimicrobial properties

These were reported against a wide range of different human pathogens, but antibacterial properties against Staphylococcus aureus and the gut pathogen Helicobacter pylori, attracted particular interest for Mānuka honey.(11-14) With stomach problems being a common human complaint, this research together with anecdotal reports of improvement in various gastrointestinal problems when taking Mānuka honey, lead to increasing demand.

Mānuka honey impregnated dressings have been developed and shown to be effective in wound care and infection management. Successful applications include for diabetic and venous leg ulcers(16-18) and hospital acquired pressure injuries in critically ill children.(19)  These dressings are now being increasingly used by wound care nurse practitioners in Aotearoa New Zealand.

On a global level, much research is ongoing into the antibacterial activities of Mānuka and other honeys.  Numerous scientific papers involving the potential infection control and antimicrobial activities of Mānuka honey have been published over the past year, with several encouraging findings.(20-26)

Research into the use of medical grade Mānuka honey as a post surgical wound application also continues in a number of countries outside of Aotearoa New Zealand, with encouraging findings.(28-30) Applications in oral surgery and dentistry, are also receiving increased attention.(31, 32)

Mānuka honey at low concentrations has been reported to kill multidrug-resistant and extensively drug-resistant clinical strains of Salmonella Typhi.(22)  Saudi Arabian researchers have also reported activity against carbapenem-resistant Enterobacterales.(21)  Medical researchers in Sweden, have found topical Mānuka honey to reduce the bacterial count of Staphylococcus aureus in a comparable way to an intramuscular antibiotic.(33)  They have also advocated potential applications for Mānuka honey as an immediate treatment for war wounds in the field of combat.

 A clinical trial to compare the use of a medical grade honey with the antifungal drug fluconazole for vaginal thrush is currently underway in the Netherlands, and the results will be interesting.(34)

Honey and Cancer

With rates of cancer increasing steadily as the global population increases and people live longer, research into interventions to help reduce the treatment burden has become more compelling. Interest in potential applications of honey in cancer therapy go back a long way. In fact there are now more than 800 papers and several reviews on honey and cancer in the scientific literature, many with encouraging findings.(35-42)

In vitro antiproliferative and apoptotic effects for honey have been reported against a large number of different cancer cell types. These include bladder cancer, colon, melanoma, breast, cervical, oral, prostate, hepatic and osteosarcoma cancer.  Several different honey types including Mānuka, thyme, gelam and acacia honeys, have shown such activities.(43-50) Relevant activities have also been reported in studies involving rat and mice models of different forms of cancer, including breast, colon, bladder and Ehrlich Ascite carcinoma.(46, 47, 51-54)

Mānuka Honey & cancer

Potential applications of Mānuka preparations in cancer patients, were first reported for a gargle using a mix of mānuka and kānuka essential oils diluted in water, bringing relief to mucositis of the oropharyngeal area as a result of radiation treatment for head and neck cancers.(55)

In vitro research by a number of different researchers has found anti-proliferative effects of Mānuka honey on breast, colorectal, breast and melanoma cell lines. Researchers from United Arab Emirates found that Mānuka honey had potent on all three cancer cell lines in a time- and dose-dependent manner, and was effective at concentrations as low as 0.6% (w/v).(53, 54)

They’ve also found improved survival rates of mice with melanoma when Mānuka honey was administered as an injection, alongside treatment with the chemotherapy drug paclitaxel.(53) Subject to future parenteral product development and human clinical studies, this study suggests exciting potential applications as an adjunct in cancer chemotherapy.  

Enhanced anti-tumour responses against colorectal cancer in mice have been shown following oral administration of Mānuka honey over a four week period.(56) These effects were correlated with immunomodulatory activities and changes in the gut microbiota.

In 2017, Malaysian researchers reported inhibitory effects on tumour development for Mānuka and Tualang honeys in a rat model of breast cancer.(57)  Recently American researchers have also revealed inhibitory effects on human breast cancer progression in preclinical models for Mānuka honey. Mānuka honey reduced the proliferation of MCF-7 breast cancer cells but not that of non-malignant human mammary epithelial cells. Antitumor activity was in a similar range to that exerted by treatment of MCF-7 cells with the oestrogenic antagonist tamoxifen, widely used in the management of breast cancer. (58)

An Italian team has undertaken a considerable amount of research into Mānuka honey’s potential preventive effects against colon cancer. They reported strong inhibitory effects on human colon cancer cells in a dose-dependent manner.(59)  Anti-metastatic impacts on colon cancer stem-like cells, a reduction in the ability of colorectal cancer cells to migrate, and downregulation of pro-angiogenic factors, were revealed as likely mechanisms of Mānuka honey’s activity.(60, 61, 62)

Possible protective effects against prostate cancer cell metastases, have been reported for New Zealand thyme, mānuka and honeydew honeys. Both their phenolic and sugar components, were shown to reduce the cellular adhesion abilities of cancer cells, in this in vitro study.(63)

With these types of cancers having a high risk of metastases, while clinical studies are needed, these anti-metastatic effects of Mānuka honey, offer much promise.

Mechanisms of action

Several potential mechanisms of action are evident for potential preventive effects of Mānuka honey against cancer development. Oxidative stress and increased levels of free radicals is involved in cancer formation, and Mānuka honey is rich in antioxidant phenolic acids and polyphenols with in vitro antiproliferative activity against several types of cancer.(41, 54)

A low immune status is well known to increase the risk of cancer development. Italian research showing an ability of Mānuka honey to modulate the immune system by inducing immunostimulatory and anti-inflammatory effects, could potentially help with chemoprevention.(64)  It’s antimicrobial actions may also be useful, given that chronic infections such as Epstein-Barr virus, human papilloma virus and Helicobacter pylori, are also associated with a higher risk of cancer development.

Possible Chemotherapy adjunct?

Recent research involving an international team of researchers, has provided evidence of sensitising effects of Mānuka honey to chemotherapy  against colon cancer cells.(62) Mānuka honey was associated with downregulation of pro-angiogenic factors, and enhanced the cytotoxicity of 5-fluorouracil. This and other studies by the Italian team suggest a potential of Mānuka honey as an adjunctive intervention to increase the efficacy of this and potentially other anticancer drugs against colon cancer cells.(59, 61, 62)

Protective effects of honey against cisplatin-induced renal toxicity, has been shown both in animals and in patients with cancer.(65)  A recent review found significant evidence for an ability of honey to mitigate toxicity from anticancer chemotherapy toxicity, with multiple mechanisms for this being evident. These included inhibition of oxidative stress and NF-κB-mediated inflammation, the dampening of caspase-dependent apoptosis cascades, and several other potential molecular mechanisms.(42)  

Oral mucositis

Oral mucositis (stomatitis) is a serious complication of cancer chemotherapy resulting in pain, an inability to eat or drink, and often weight loss. It occurs in a large proportion of paediatric patients being treated for cancer, and in patients undergoing treatment with radiotherapy or chemotherapy for head, neck and breast cancers, and is difficult to treat in clinical practice.

At least fifteen clinical trials have now taken place involving Mānuka and several other honey types from around the world as an oral application for oral mucositis, with most finding positive results.(66-69) These include a clinical trial using Mānuka honey in children with leukaemia suffering from chemotherapy-induced oral mucositis.(70)

Summary

Honey is a natural product used since ancient times for its nutritive and therapeutic value.  Despite this extensive history, and a huge body of laboratory data now implicating its usefulness for a large number of serious health conditions in humans, clinical applications have been limited until recently, by there being few human trials, and widespread variability in honey quality.

Research is increasingly providing compelling evidence for preventative as well as potential clinical applications of different types of Mānuka honey, in modern medicine. This research, mostly undertaken outside of Aotearoa New Zealand, suggests exciting therapeutic value particularly in the management of infectious disease and cancer, both highly prevalent and expensive conditions which have a high burden on patients and healthcare systems.

Aotearoa New Zealand was the first country in the world to successfully produce and commercialise grades of honey suitable to be prescribed and sold or dispensed for serious medical conditions. Several other countries are now developing or have already developed their own medical honeys, and are putting these through clinical trials for a range of conditions.

In order to retain and further build Aotearoa New Zealand’s international reputation as a country producing some unique health promoting honeys, significant investment and a world class regulatory environment is needed. Therapeutic claims should be legally possible for products which have achieved clinical trial validation and meet quality standards. Without this, further innovation and product development may be compromised, while other countries forge ahead with developments, in what is certain to continue to be a growing global industry.

Given the extent of the many promising preclinical findings into the potential of Mānuka and other honeys to improve outcomes in cancer patients, more controlled clinical studies are needed. They should involve further work on animal models of cancer, as well as pilot clinical studies using phytochemically characterised types of honey, as an adjunctive treatment in patients receiving chemotherapy or radiotherapy.(9)

While much of the Mānuka honey industry here has gone through difficult times in the aftermath of Covid-19 and challenges in export markets, new and ongoing research suggests there is much more to this treasured local natural product, than just its value as a food.

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ADHD and useful Phytomedicines

On By philrasmIn Anxiety, Mental Health, Plant Medicine, StressLeave a comment

Introduction

ADHD (Attention deficit hyperactivity disorder) is a chronic neuro-behavioural condition characterised by a persistent pattern of inattention, hyperactivity and impulsiveness. It can disrupt education and social development of children and teenagers, and have a huge impact on a person’s life, yet is often undiagnosed.

The DSM (Diagnostic and Statistical Manual of Mental Disorders) describes three subtypes of ADHD. These include: ADHD-Inattentive type (ADHD-I), ADHD-Hyperactive/impulsive (ADHD-H), and ADHD-Combined type (ADHD-C). The presentation can change over time though, and a diagnosis provided at one specific time may differ from that provided at another time in a person’s life.

While reported rates of ADHD are higher than in the past, this is likely to be at least partially due to better recognition of the condition. It is a common condition among young children, and an estimated 50% of these retain ADHD symptoms for the rest of their lives. Research suggests around 5-8 percent of the population has ADHD but only 1-2 percent are diagnosed.  Diagnosis rates have historically been higher in boys than in girls, although rates are now thought to be similar for both genders.

Diagnosis of ADHD can be difficult and there is no diagnostic biological marker. Symptoms should have been present and persistent for a minimum of six months prior to the age of 12, are maladaptive, and cannot be explained by other psychiatric or medical disorders. However, often symptoms may not meet the criteria for a formal diagnosis of ADHD, despite causing significant issues in learning, social and family relationships.  

Symptoms

Impairing levels of inattention, disorganisazion, and/or hyperactivity-impulsivity, are key features of ADHD.  These symptoms are excessive for the age or development level.

In a classroom setting, children with ADHD will often tune out or appear to daydream. They can talk a lot, interrupt others and are unable to wait for their turn. Such children are frequently called out in class or a group or become known as the ‘class clown’, or the subject of bullying. These behaviours can exacerbate difficulties in ‘fitting in’ with peer groups or societal expectations.

While not an anxiety disorder as such, a large proportion of children with ADHD have coexisting psychiatric disorders, including but not limited to depression, bipolar disorder, autism spectrum disorders, eating disorders, and anxiety disorders (1). Adults with ADHD also often have an anxiety or substance use disorder, which can mask ADHD symptoms, sometimes for many years(2). Those with ADHD are also more likely to do dangerous and impulsive things.

Aetiology

Several potentially aetiological factors have been identified. ADHD has a significant familial and genetic predisposition, although the extent of the latter is somewhat contentious. Approximately 30% of children with epilepsy have ADHD .

Environmental contributions such as early childhood exposure to toxic heavy metals (especially lead) or phthalates, have received increased attention in recent years(3-7). Air pollution has also been associated with neurodevelopmental disorders including ADHD(8).

Other studies have associated ADHD with a higher prevalence of smoking, alcohol consumption, and excessive screen time among adolescents(9-11). Dysfunctions have been reported with BDNF (Brain derived neurotrophic factor) metabolism, dopaminergic neurotransmission, and with neurochemical parthways within the prefrontal cortex(12, 13).

However, these associations are complex, and to what extent they are aetiological versus outcome manifestations in those with ADHD, remains debatable.

Increasing greenness exposure or ‘nature medicine’, is likely to help protect against ADHD and other mental health conditions. A large New Zealand study has reported that children who always lived in a rural area after 2 years of age, were significantly less likely to develop ADHD(14 ).  Similar findings were reported in a German study, with residential greenness being protective, but air pollution being a risk factor(15).

Dietary factors may be contributory in some cases. Inattention was negatively correlated with fruit and vegetable consumption and a healthy dietary pattern, in a large population-based Swedish study (16). Some evidence suggests Vitamin D deficiency may be relevant to the pathogenesis of ADHD and autism, and supplementation with this as well as zinc and magnesium, both important cofactors in dopamine metabolism, may be useful(17, 18).

Treatments

The use of stimulant medications and particularly methylphenidate, is the usual treatment for ADHD. Methylphenidate is structurally similar to amphetamines, inhibits the reuptake of dopamine and noradrenaline, and leads to symptom improvement in around seventy percent of patients.  

Dexamphetamine is also occasionally used, as is its prodrug lisdexamfetamine. The selective noradrenaline reuptake inhibitors atomoxetine and viloxazine, are sometimes prescribed. These and alpha-2 adrenergic agonists guanfacine and clonidine, which stimulate noradrenergic neurotransmission in the prefrontal cortex, are occasionally used when stimulants or these drugs are not suitable or tolerated.

Reduced appetite, sleeping difficulties, nausea and abdominal pain are the most common adverse events to stimulant medication. Rare but serious adverse events can include cardiac problems, weight loss, mood fluctuations and psychotic disorders. These can cause concern as treatment can continue from childhood into adolescence and beyond.

Official guidelines discourage the use of medication in children under the age of six, although these are sometimes prescribed by a specialist in severe cases. ‘Off-label’ use of medicines in this age group, is increasingly common. However, few studies have taken place involving the use of ADHD drugs in very young children, and safety and efficacy data is generally lacking. 

Treatment programmes should also include psychological interventions such as counselling or psychotherapy, with patients’ and parents’ preferences and need for such treatment, always considered(19).  It is also often beneficial to not only treat a child, teenager or adult with ADHD, but also offer phytotherapy or other treatment support to their parents, partners or other family members. Adjunctive phytomedicines and sometimes lifestyle and dietary changes, can be very helpful.

Of note is that there are several disparities  in treatment guidelines and the selection and sequencing of various medications  in different countries. Danish guidelines for instance, do not recommend methylphenidate, lisdexamfetamine or atomoxetine as first line treatment options, while German guidelines provide specific drug recommendations tailored to individual comorbidities (1). A greater emphasis on psychotherapy, school and parental support systems and a higher bar before methylphenidate medication is trialed, is applied in some jurisdictions, particularly those where health care expenditure per capita is higher.

Some Useful Phytomedicines

An individualised treatment protocol incorporating plant medicines can offer much to ADHD patients. They can also help children who are resistant to stimulant medications, or those who wish to not take these medicines, or to keep drug dosage needs as low as possible.

Treatment selection depends on the particular type of ADHD, its symptomatology, and of course individual patient needs and wishes.  Given the diverse presentation of ADHD, a range of phytomedicines should be considered. An individualised but ‘trial and error’ approach is recommended, but desirable actions can include neuroprotection, cognition enhancement, anxiolytic and stimulant properties. Any use of other medications or presence of other health conditions should be taken into account.  Addressing other co –existing mental or physical health issues, can in itself often produce significant benefits, and sometimes avoid the need for additional drug-based interventions.

Where restlessness or accompanying anxiety are part of the symptomatology, anxiolytic and relaxant phytomedicines can be useful.  They include Bacopa, Chamomile, Holy basil, Kava, Lavender, Lemon balm, Skullcap, Passionflower, Skullcap, Valerian, Withania and more(20).  Many of these (Ginkgo, Bacopa, Lemon Balm, Valerian, Withania) also have neuroprotective activities and when used appropriately, can help improve cognition and learning outcomes.

Leaves of the Indian plant Bacopa (Bacopa monniera) have been used for anxiolytic and memory enhancing purposes for centuries. As with Ginkgo and Lemon Balm, it is neuroprotective and may help with cognition and attention deficit disorders. It is frequently used in the management of ADHD and autism in children and teenagers.

A recent 14 week Australian clinical trial into Bacopa’s effects in boys with ADHD aged 6-14, found no significant behavioural improvement. However, improvements occurred in their sleep routine and in cognitive flexibility and interpersonal problems(21).  Reduced symptoms of restlessness and improvement in self control, were reported in a smaller open label study in children with ADHD(22).  It is safe in children, although as a liquid its bitter taste can be an issue, particularly as dosage needs tend to be quite high.

Ginkgo (Ginkgo biloba) can be helpful in ADHD or for cognitive deficits in children, and combines very well with other psychoactive phytomedicines such as St Johns wort and anxiolytics. It is also hepatoprotective, and can be helpful when concomitant drug medications which can cause liver or kidney damage, are being taken.

Lemon balm (Melissa officinalis) is another generally safe anxiolytic, and like chamomile is indicated particularly where gastrointestinal upsets or eating disorders are associated with feelings of anxiety(23).  It can also help with cognition in teenagers, though large doses are generally required.

The Chinese medicinal herb Rehmannia (Rehmannia glutinosa) was reported to reduce impulsive and spontaneous behaviour and ameliorate hippocampal neurodevelopmental abnormalities an a rat model of ADHD(24).

Passionflower (Passiflora incarnata), has been shown to help control anxiety in several studies involving adult patients(25) . A combination with St Johns wort and Valerian was reported to reduce nervous agitation in children aged between 6 and 12 years(26)  .  Potential benefits in ADHD and autism, have been reported(27, 28), although larger and better controlled clinical trials are needed.

Kava (Piper methysticum) also has a place in the management of ADHD in some children and adults. Its effectiveness in treating anxiety has been affirmed through several clinical trials and meta-analyses. It may also exhibit a mild antipsychotic effect and be helpful for children with OCD or autism.

Withania (Withania somnifera) is a useful allrounder when it comes to anxiety and stress-associated conditions. As with all adaptogens, it acts on multiple relevant sites of action, neurotransmitter and hormonal systems(29), and is often an effective component of the treatment of ADHD in both young and older people.

St Johns wort (Hypericum perforatum) is our best known clinically effective antidepressant, and I have used it successfully in many hundreds of patients, over the past thirty years. While beyond the scope of this article, concerns about its safety and interactions with other medications, are also often unjustified, this depending on the type of St Johns wort used, and its phytochemical profile(30).

ADHD is now recognised as a common neurodivergent condition, which if not well managed and treated can cause enormous emotional and mental suffering in children, teenagers, adults and their friends and families.

Summary

As with most chronic health conditions, early diagnosis and interventions which are natural and affordable and incorporate a selfcare approach, can produce huge benefits and avoid the need for more serious treatments later on.  While not denying the usefulness of drug medications such as methylphenidate and atomoxetine, it is concerning given the frequency at which these can cause adverse events, that they are being so widely prescribed and relied upon.

If the need for a long term drug prescription can be avoided or drug dosage requirements kept to a minimum through the concomitant use of more natural interventions, then this is a preferred approach. While there is a need for further and larger clinical trials involving phytomedicines in the treatment of ADHD, many medicinal plants exhibit pharmacological actions of benefit to those dealing with this condition, and treatment targeted for each person’s individual clinical presentation, can produce huge benefits.

References:

  1. Van Vyve L, Dierckx B, Lim CG, Danckaerts M, Koch BCP, Häge A, Banaschewski T. Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines. Eur J Pediatr. 2024 Mar;183(3):1047-1056. 
  2. Neurodivergence and substance use. Te Puna Whakaiti Pamamae Kai Whakapiri, New Zealand Drug Foundation, Sept 2024.https://drugfoundation.org.nz/articles/neurodivergence-and-substance-use
  3. Farmani R,. Exploring the link between toxic metal exposure and ADHD: a systematic review of lead and mercury. J Neurodev Disord. 2024;16(1):44. 
  4. Moore S, Paalanen L, Melymuk L, Katsonouri A, Kolossa-Gehring M, Tolonen H. The Association between ADHD and Environmental Chemicals-A Scoping Review. Int J Environ Res Public Health. 2022 Mar 1;19(5):2849.
  5. Oh J, Kim K, Kannan K, Parsons PJ, Mlodnicka A, Schmidt RJ, Schweitzer JB, Hertz-Picciotto I, Bennett DH. Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study. Environ Health. 2024 Mar 14;23(1):27. 
  6. Robinson DM, Edwards KL, Willoughby MT, Hamilton KR, Blair CB, Granger DA, Thomas EA. Increased risk of attention-deficit/hyperactivity disorder in adolescents with high salivary levels of copper, manganese, and zinc. Eur Child Adolesc Psychiatry. 2024 Sep;33(9):3091-3099
  7. Symeonides C, Aromataris E, Mulders Y, Dizon J, Stern C, Barker TH, Whitehorn A, Pollock D, Marin T, Dunlop S. An Umbrella Review of Meta-Analyses Evaluating Associations between Human Health and Exposure to Major Classes of Plastic-Associated Chemicals. Ann Glob Health. 2024 Aug 19;90(1):52.
  8. Compa M, Baumbach C, Kaczmarek-Majer K, Buczyłowska D, Gradys GO, Skotak K, Degórska A, Bratkowski J, Wierzba-Łukaszyk M, Mysak Y, Sitnik-Warchulska K, Lipowska M, Izydorczyk B, Grellier J, Asanowicz D, Markevych I, Szwed M. Air pollution and attention in Polish schoolchildren with and without ADHD. Sci Total Environ. 2023 Sep 20;892:164759.
  9. Meng Z, Ao B, Wang W, Niu T, Chen Y, Ma X, Huang Y. Relationships between screen time and childhood attention deficit hyperactivity disorder: a Mendelian randomization study. Front Psychiatry. 2024 Sep 23;15:1441191
  10. Namimi-Halevi C, Dor C, Dichtiar R, Bromberg M, Sinai T. Attention-deficit hyperactivity disorder is associated with risky and unhealthy behaviours among adolescents. Public Health. 2024 Sep 25;237:51-56.
  11. Thorell LB, Burén J, Ström Wiman J, Sandberg D, Nutley SB. Longitudinal associations between digital media use and ADHD symptoms in children and adolescents: a systematic literature review. Eur Child Adolesc Psychiatry. 2024 Aug;33(8):2503-2526.
  12. Ijomone OK et al. Dopaminergic Perturbation in the Aetiology of Neurodevelopmental Disorders. Mol Neurobiol. Published online August 7, 2024.
  13. Liu DY, Shen XM, Yuan FF, Guo OY, Zhong Y, Chen JG, Zhu LQ, Wu J. The Physiology of BDNF and Its Relationship with ADHD. Mol Neurobiol. 2015 Dec;52(3):1467-1476. 
  14. Donovan GH et al, Association between exposure to the natural environment, rurality, and attention-deficit hyperactivity disorder in children in New Zealand: a linkage study. The Lancet Planetary Health, 2019; 3 (5): e226-e234
  15. Markevych I, Tesch F, Datzmann T, Romanos M, Schmitt J,  Heinrich J. Outdoor air pollution, greenspace, and incidence of ADHD: a semi-individual study. Sci Total Environ, 2018; 642:1362-1368
  16. Li HH, Yue XJ, Wang CX, Feng JY, Wang B, Jia FY. Serum Levels of Vitamin A and Vitamin D and Their Association With Symptoms in Children With Attention Deficit Hyperactivity Disorder. Front Psychiatry. 2020 Nov 23;11:599958
  17. Hemamy M, Pahlavani N, Amanollahi A, Islam SMS, McVicar J, Askari G, Malekahmadi M. The effect of vitamin D and magnesium supplementation on the mental health status of attention-deficit hyperactive children: a randomized controlled trial. BMC Pediatr. 2021 Apr 17;21(1):178
  18. Lange KW, Lange KM, Nakamura Y, Reissmann A. Nutrition in the Management of ADHD: A Review of Recent Research. Curr Nutr Rep. 2023 Sep;12(3):383-394.
  19. Schatz NK, Fabiano GA, Cunningham CE, dosReis S, Waschbusch DA, Jerome S, Lupas K, Morris KL. Systematic Review of Patients’ and Parents’ Preferences for ADHD Treatment Options and Processes of Care. Patient. 2015 Dec;8(6):483-97.
  20. https://herbblurb.com/2017/02/03/why-herbs-should-be-the-first-choice-of-treatment-for-acute-anxiety/
  21. Kean JD, Downey LA, Sarris J, Kaufman J, Zangara A, Stough C. Effects of Bacopa monnieri (CDRI 08®) in a population of males exhibiting inattention and hyperactivity aged 6 to 14 years: A randomized, double-blind, placebo-controlled trial. Phytother Res. 2022;36(2):996-1012.
  22. Dave UP, Dingankar SR, Saxena VS, et al. An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in children. Adv Mind Body Med. 2014;28(2):10-15.
  23. https://herbblurb.com/2021/01/29/lemon-balm-a-true-tonic-for-stress/
  24. Sun R, Yuan H, Wang J, Zhu K, Xiong Y, Zheng Y, Ni X, Huang M. Rehmanniae Radix Preparata ameliorates behavioral deficits and hippocampal neurodevelopmental abnormalities in ADHD rat model. Front Neurosci. 2024 May 30;18:1402056.
  25. Janda K, Wojtkowska K, Jakubczyk K, Antoniewicz J, Skonieczna-Żydecka K. Passiflora incarnata in Neuropsychiatric Disorders-A Systematic Review. Nutrients. 2020;12(12):3894. 
  26. Trompetter I, Krick B, Weiss G. Herbal triplet in treatment of nervous agitation in children. Wien Med Wochenschr. 2013;163(3-4):52-57. 
  27. Amini F, Amini-Khoei H, Haratizadeh S, et al. Hydroalcoholic extract of Passiflora incarnata improves the autistic-like behavior and neuronal damage in a valproic acid-induced rat model of autism. J Tradit Complement Med. 2023;13(4):315-324.
  28. Golsorkhi H, Qorbani M, Sabbaghzadegan S, Dadmehr M. Herbal medicines in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD): An updated systematic review of clinical trials. Avicenna J Phytomed. 2023;13(4):338-353.
  29. https://herbblurb.com/2017/02/03/why-herbs-should-be-the-first-choice-of-treatment-for-acute-anxiety/
  30. Rasmussen PL, St Johns Wort – Safety in Clinical Practice. Phytomed Webinar, available from Phytomed Medicinal Herbs Ltd, Auckland, New Zealand, February 2015

Tairāwhiti; whakapapa and botanical inspirations

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Early years

I was born in Waipiro Bay, a beautiful, remote bay on the east coast north of Gisborne, the north island of Aotearoa New Zealand. Driving down the narrow, windy gravel road to get to it from Te Puia in later years, was something I remembered fondly when watching the film Mahana, directed by Lee Tamahori.

Dad was the Power Board engineer and like his dad was also raised in Gisborne and on the coast, grandad being a truck driver in the district in the 1920’s and 1930’s.  Posted to Tokomaru Bay in 1957, Dad’s job was liasing with the local communities, farmers and power board gangs to plan and install powerlines and bring electricity (what he called juice), to the coast north of Ruatorea. Mum raised me and my three brothers, grew most of our veges, cooked our kai, did (and still does) some incredible baking, made most of our clothes, and  engaged actively in community affairs. Toko was a small but intimate and vibrant settlement with its own picture theatre, quite a few shops and a wharf, and there was always lots happening, as some of the East Coast pages of the former Gisborne Photo News remind us of.

I return to Tokomaru Bay every year, and always buy a calender, produced by the Tokomaru Bay Heritage Trust as a fundraiser towards restoration of the old wharf. This month’s (March 2024) page has a photo (posted below) of my primary school class soon after I started school. Standing two to the left of her, I remember the pride us little kids felt, when our teacher was crowned Queen of Tokomaru Bay. Life was slower, relationships and communities were strong, and few locked their doors at night.

Like many in the community at the time, Dad loved tramping, and would go away on Search and Rescue trips or take my older brothers and sometimes me into the bush, or up the slopes of Mt Hikurangi. The hill behind our house in Toko, was a decent climb and high enough to be a mountain in many countries. It was also a rich hunting ground for the possoms my brothers trapped and skinned, then nailed the furs to the walls of our garage to cure, before selling them for pocket money.

Mānuka and kānuka were scattered throughout most of the hilly sheep farms at that time, native pioneer species then considered a nuisance by farmers but cut for firewood and an extra income, by motivated locals.

Many areas of te ngahere (the bush) nearby contained a diverse wealth of native trees at all stages of growth, including kahikatea, pukatea, rimu, puriri, totara, matai, tanekaha, karaka and kohekohe. Smaller plants such as koromiko, tutu, kawakawa and ferns were also endemic, and many coastal areas were protected from storms or erosion by native plants including our famous pohutakawa, the one in Te Araroa being the largest in the world.

However, te ngahere back then was only a tiny fraction of what it was when Captain Cook and co landed on Kaiti Beach. Waihirere Domain and Greys Bush near Gisborne are reminders of the pre-European bush landscape that once characterised the region. A weekend trip to Waihirere Domain for a swim and turns on the long slide, followed by a family walk in the mysterious bush, was paradise as a youngster.  It made absolute sense when I learnt that Māori regarded trees as being senior to humans, and respected them for their provision of shelter, food, clothing and medicines, and the connection they provided between humans and their sacred ancestors, Papatūānuku and Ranginui.

A rich growing region

Horticulture was and still is the main type of farming in the Gisborne district. Watties once had a lot of vegetables grown for their canning and freezing operation by the Gisborne wharf, which was the biggest employer in town for many years. Sweetcorn from Gisborne and the east coast is amongst the sweetest and tastiest in the country, and can be eaten five nights a week with butter and a little salt when in season, without taste bud fatigue.

Fruit such as apples, pears, persimmons, citrus and strawberries have also long been grown throughout the entire ‘Poverty Bay flats’, as the district was once misnamed by  Captain Cook. The bay is now the largest citrus growing area in Aotearoa, and a growing provider of avocados, feijoas and kiwifruit.

A German migrant named Fredrich Wohnsiedler, who moved out of town to Ormond after his butchers shop in town was trashed during the first world war, became the first commercial grape grower and winemaker in the district. Since then of course the industry has grown and flourished in the region. Gisborne chardonnay is amongst the best in the world, but unlike Marlborough sauvignon blanc, hasn’t had the same marketing dollars put behind it, to achieve such a global reputation.

LeaderBrand, one of the biggest vegetable and salad growers in the country, was conceived in and grew out of the Gisborne district. It has grown to become a major producer of fresh vegetables for families in Aotearoa, and markets around the world.

The Farmers market in Gisborne every Saturday, is a wealth of offerings of what is one of the richest foodbowls of Aotearoa, and a warm reflection of a close and committed community.

Recent tough times

However, the Tairāwhiti region has also had it hard over the years, due to a combination of adverse economic and climatic events. The demise in traditional animal-based forms of farming, factory closures, unemployment and urbanisation, have exacerbated longstanding cultural and socioeconomic inequities within the region as with many areas of our country, and lead to increasing poverty related problems. The Covid 19 pandemic put a temporary brake on tourism, and the impacts of Cyclones Bola in 1988, and the dual hits of Cyclones Hale and Gabrielle in 2023, were massive.

Health Research Council of New Zealand data has found the level of housing and health deprivation in the Tairāwhiti region is amongst the highest in the country. Māori, who make up 45% of the population, are particularly prone to negative health outcomes, due to a range of factors including poor access to some health services.

Cyclone Gabrielle was a devastating event, when normality took a nosedive for the entire region of around 50,000 people. Flooding, slips, road closures, total destruction of hillsides and homes, forestry waste being deposited on beaches and farmland, and the subsequent loss of jobs, took a huge toll. Climate change and the relatively young geology and soil types in the region contributed to the severity of these impacts, as did an over reliance on an exotic plantation forestry sector. Large scale plantings of Pinus radiata in areas and on hillsides prone to erosion, a monoculture model based upon a single species that can impact negatively on many native plants, was in retrospect a flawed policy decision.

Future opportunities

The Tairāwhiti region’s history as an efficient and rich producer of a diverse range of plant crops and processed foods and beverages, provides insight into future opportunities. However, the peaks and troughs in supply and demand that various industries have incurred over the years, due to climatic or global economic events, changing consumer trends or corporate priorities, are sobering and informative.

A powerful attribute of the region and its population is resilience, something that has got it through many natural disasters and climatic events, and economic shocks, over several generations.  Out of adversity comes opportunity, and out of struggle, comes renewed strength and resolve. These truths are particularly relevant to the Tairāwhiti region in March 2024. While mistakes have been made with how we humans have treated and tried to reap a living from the land and sea, lessons have also been learned, and many new opportunities revealed.

Several local companies continue to make headway, into providing meaningful jobs and livelihoods for people in the region through horticulture based activities.  Apart from Leaderbrand and many vineyards, Riversun is the leading national supplier of grafted grapevines, and a breeder and propagator of premium avocado rootstocks and a range of other plant materials for commercial horticulturalists around the country.  Rua Bioscience operates a plant discovery and breeding programme from a research and cultivation centre in Ruatorea, with a vision to create cannabis-derived medicines that change people’s lives

The wealth of benefits provided both to the land, air and waterways, as well as to humans and other animals from a landscape that is rich in a wide range of native plants, needs little further explanation or justification. The challenge now, is to apply the knowledge gained from past successes and mistakes, and allocate resource and mahi to return many unstable terrains to native forests, and to foster a greater biodiversity within the ecosystem. Identifying and leveraging existing and new ways to obtaining some form of commercial return in the process, will catalyse and incentivise these much needed changes in our approach to land care.

Several opportunities also exist for crop trials or land use diversification, for landowners and iwi within the region. I’ve learnt from my personal experience that plants such as calendula, echinacea and withania all love the east coast soils and climate. There are many, many more, where commercial scale operations involving non-native as well as native medicinal plants could become profitable, through a sustained and collaborative approach.

Te Taiao

In Māori culture, Te Taiao is the natural world that contains and surrounds us, and acknowledges the interconnection of people and nature. It is underpinned by three guiding principles: 

  • Our land, water, air and biological life must be able to thrive without over-use.
  • Any use is a privilege, not a right, and
  • If something is not healthy or well, we must fix it.

For Aotearoa New Zealand, many factors are emerging which are likely to lead to increasingly difficult challenges to the current format and operational models of our farming sector. We have become over-dependent on agrichemicals and farming animals, and need to invest more in new crop and companion crop research, and give greater respect to Te Taiao and the need to nurture our natural heritage.

With rapidly changing geopolitical and climatic landscapes, supply chain disruptions and an increasing need for healthcare to revert to more natural and selfcare based approaches, phytomedicines will make a greater contribution to our country’s future.

As I reflect on the Toko Bay March 2024 calender page, I feel very grateful to have been raised in this part of Aotearoa, and conditioned by such a culturally and naturally rich environment and community.  These reflections and experiences also reinforce my long held belief, that Tairāwhiti is one of the most suitable regions for establishment of an industry based upon medicinal plants, and that this would have enormous benefits for both its people and environment.

Rosemary – a herbal protector

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Introduction

Rosemary (Rosmarinus officinalis, now known as Salvia Rosmarinus) is a well known plant commonly found in gardens and parks around the world. Its strongly aromatic leaves and prolific flowers are a magnet to bees and other pollinating insects, and its traditional culinary applications are widely embraced.

Medicinal properties of rosemary are of course also substantial, and ancient texts extol many virtues.  In The Physicians of Myddfai, a compilation of medieval recipes written in the 13th century at Myddfai in south Wales, it says of rosemary: “by washing each morning with the decoction and allowing it to dry naturally, the aged will retain a youthful look as long as they live”.

These appealing claims reflect rosemary’s antioxidant actions and multiple influences on cellular degradation and aging processes, and indicate the likely presence of other benefits when taken internally on a regular basis. In fact research is increasingly revealing its protective effects against many negative influences on health.

Protection against environmental toxins

Rosemary’s rich content of triterpene and other phenolic acid constituents such as rosmarinic, olenolic and ursolic acids contribute to its antioxidant and many antimicrobial activities. These help protect meat(1, 2), dairy products(3), fish(4,5) and other foods against spoilage and vegetable oils against oxidation(6). Apart from being a flavour enricher, these are longstanding traditional uses.

Toxic compounds released or deposited within the soil, air or waterways by human activities are now being revealed by more and more science, as having harmful outcomes on living organisms and their environment.

Heavy metals such as cadmium and lead are amongst these, and are widely distributed in the environment as a result of mining and combustion emissions. Rosemary protects against liver damage due to both of these, and against kidney damage from lead exposure(7, 8). Addition of rosemary to fresh water reduces cadmium accumulation in the tissues of freshwater fish, and associated oxidative stress(9). Washing fish in a rosemary solution, has been reported to reduce lead content(10). Applications to remove lead from wastewater, have also been suggested(11).

Such protective actions against toxic environmental contaminants have recently been extended to a remediation ability for rosemary against accumulation of cadmium and lead in a busy urban environment.  Rosemary plants inoculated with a mycorrhizal fungus (Funneliformis mosseae) thrived in cadmium and lead contaminated soils, and mitigated urban traffic pollution in dense traffic conditions(12).

Carnosic acid, another polyphenolic compound found in rosemary, shows a dose-related protective effect against neurotoxicity induced by dieldrin, an organochlorine pesticide implicated in neurological conditions such as Parkinson’s disease(13).

Antispasmodic, anti-histaminic and anti-allergic actions on the respiratory tract, have recently been demonstrated for several rosemary constituents, including rosmarinic, carnosic and ursolic acids, rosmanol and carnosol(14). Airborne environmental pollutants are becoming increasingly linked with a diverse array of chronic health conditions in humans, and these actions are therefore relevant.

Given its many chemopreventive properties against harmful environmental toxins, it is hardly surprising that rosemary constituents such as rosmarinic and carnosic acids have demonstrated effective anti-proliferative properties against various cancers, and are the subject of research to develop new cancer treatments(15, 16). Potential synergistic effects with certain anti-cancer drugs, have also been suggested from in vitro and pre-clinical studies(17).

Reducing harm from lifestyle factors

Many diets and lifestyles in the 21st century are associated with conditions such as liver disorders, weight gain, cardiovascular disease and diabetes type 2. As such, plant-based interventions to help reduce some of the negative health impacts of a poor diet or sedentary lifestyle, and provide an element of prevention against these highly prevalent medical conditions, are of interest.

Many benefits were reported following administration of a rosemary extract to young rats feed a high fat western style diet(18). These included reduced liver fat, liver cholesterol and triglycerides and increased plasma levels of HDL cholesterol.  Rats fed high doses of rosemary extract also had increased fasting plasma concentrations of Glucagon-like peptide-1 (GLP-1), suggesting possible benefits in weight management and diabetes. Modulation of the gut microbiota composition also occured.

Amelioration of the neurotoxic effects of the food flavour enhancer monosodium glutamate, has been reported in animal studies(19).

The various pharmacological effects of rosemary and its key constituents, also  align well with a potential role in the management of metabolic syndrome, a constellation of complex coexisting cardiometabolic risk factors such as hyperglycemia, dyslipidemia, inflammation, abdominal obesity, vascular disorders and hypertension that raise the risk of diabetes mellitus and cardiovascular disease(20). Protection against nephropathy in diabetic rats, and enhancement of the nephroprotective effects of insulin, has been reported following supplementation with rosemary oil(21).

Many studies have now shown hepatoprotective effects for rosemary(22-24). A combination of rosemary with hawthorn protected against alcoholic liver disease, in a rat model(25).

Collectively, these studies suggest protective effects on several common conditions related to obesity, excess alcohol or poor diets.

Protecting male fertility

Declining human fertility is a growing concern in recent decades. While reasons for this are numerous, exposure to airborne pollutants and environmental toxins such as microplastics and nanoplastics and synthetic insecticides, are known contributory factors(26, 27).

Recent research showing that a forty five day pretreatment with rosemary leaf extract alleviated the damaging effects on the adrenal glands and testes following exposure to the synthetic pesticide cypermethrin, are promising. Restoration of spermatogenesis (sperm cell production) was also reported(28). Previous work found co-administration of rosemary with etoposide reduced the extent of testicular injury and DNA damage induced by this antineoplastic drug in male rats(29). These studies suggest a potential by rosemary to guard against infertility, as an outcome of chemotherapy or environmental toxin exposure.

References:

  1. Gavriil A, Zilelidou E, Papadopoulos AE, et al. Evaluation of antimicrobial activities of plant aqueous extracts against Salmonella Typhimurium and their application to improve safety of pork meat. Sci Rep. 2021;11(1):21971.
  2. Olivas-Méndez P, Chávez-Martínez A, Santellano-Estrada E, et al. Antioxidant and Antimicrobial Activity of Rosemary (Rosmarinus officinalis) and Garlic (Allium sativum) Essential Oils and Chipotle Pepper Oleoresin (Capsicum annum) on Beef Hamburgers. Foods. 2022;11(14):2018.
  3. Gad, A. and Sayd, A. (2015) Antioxidant Properties of Rosemary and Its Potential Uses as Natural Antioxidant in Dairy Products—A Review. Food and Nutrition Sciences, 6, 179-193.
  4. Aala J, Ahmadi M, Golestan L, Shahidi SA, Shariatifar N. Effect of multifactorial free and liposome-coated of bay laurel (Laurus nobilis) and rosemary (Salvia rosmarinus) extracts on the behavior of Listeria monocytogenes and Vibrio parahaemolyticus in silver carp (Hypophthalmichthys molitrix) stored at 4 °C. Environ Res. 2023;216(Pt 2):114478.
  5. Abd El-Fatah RA, Rozan MA, Ziena HM, et al. Improvement of Microbial Quality, Physicochemical Properties, Fatty Acids Profile, and Shelf Life of Basa (Pangasius bocourti) Fillets during Chilling Storage Using Pepsin, Rosemary Oil, and Citric Acid. Foods. 2023;12(22):4170.
  6. Song X, Sui X, Jiang L. Protection Function and Mechanism of Rosemary (Rosmarinus officinalis L.) Extract on the Thermal Oxidative Stability of Vegetable Oils. Foods. 2023;12(11):2177. 
  7. Mężyńska M, Brzóska MM. Review of polyphenol-rich products as potential protective and therapeutic factors against cadmium hepatotoxicity. J Appl Toxicol. 2019;39(1):117-145
  8. Mohamed WA, Abd-Elhakim YM, Farouk SM. Protective effects of ethanolic extract of rosemary against lead-induced hepato-renal damage in rabbits. Exp Toxicol Pathol. 2016;68(8):451-461.
  9. Al-Anazi MS, Virk P, Elobeid M, Siddiqui MI. Ameliorative effects of Rosmarinus officinalis leaf extract and Vitamin C on cadmium-induced oxidative stress in Nile tilapia Oreochromis niloticus. J Environ Biol. 2015;36(6):1401-1408.
  10. Salim A, Hassanin MA, Zohair A. A simple procedure for reducing lead content in fish. Food Chem Toxicol. 2003;41(4):595-597. doi:10.1016/s0278-6915(02)00259-4
  11. Zarrabi A, Ghasemi-Fasaei R. Preparation of green synthesized copper oxide nanoparticles for efficient removal of lead from wastewaters. Int J Phytoremediation. 2022;24(8):855-866.
  12. Alinejad Z, Abtahi SA, Jafarinia M, Yasrebi J. The impact of arbuscular mycorrhizal symbiosis, Funneliformis mosseae, on rosemary phytoremediation ability under urban traffic. Int J Phytoremediation. 2024;26(2):250-262.
  13. Park JA, Kim S, Lee SY, et al. Beneficial effects of carnosic acid on dieldrin-induced dopaminergic neuronal cell death. Neuroreport. 2008;19(13):1301-1304.Atef RM, Abdel Fattah IO, Mahmoud OM, Abdel-Rahman GM, Salem NA. Protective effects of Rosemary extract and/or Fluoxetine on Monosodium Glutamate-induced hippocampal neurotoxicity in rat. Rom J Morphol Embryol. 2021;62(1):169-177.
  14. Farhadi F, Baradaran Rahimi V, Mohamadi N, Askari VR. Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases. Biofactors. 2023;49(3):478-501.
  15. Sirajudeen F, Bou Malhab LJ, Bustanji Y, et al. Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives. Biomol Ther (Seoul). 2024;32(1):38-55.
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  25. Atef RM, Abdel Fattah IO, Mahmoud OM, Abdel-Rahman GM, Salem NA. Protective effects of Rosemary extract and/or Fluoxetine on Monosodium Glutamate-induced hippocampal neurotoxicity in rat. Rom J Morphol Embryol. 2021;62(1):169-177.
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Phytomedicines and Regulatory Challenges

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Access to plant (phyto) medicines to prevent or treat illnesses or health conditions both acute and chronic, is an ethical obligation. Many factors impact on this, including their costs and affordability, their quality and availability in efficacious dosage forms, and how they are regulated

Termed Complementary Medicines in Australia, Herbal Medicinal Products in Europe, Botanical Drugs in the U.S.A, and Natural Health Products (NHP’s) in Aotearoa New Zealand and Canada, the products themselves are all used in some way to support human and animal health. How the population of each country regards and uses them, and what checks and balances governments decide to put on their safety and accessibility, is influenced by relevant legislation.

Plant medicines are however, a complex and diverse group of products. In practice, many countries have more than one regulatory agency (generally that responsible for foods, plus that responsible for medicines), involved in overseeing their compliance to what is often a rather confusing legislative framework.

NHP Regulations In Aotearoa New Zealand

In Aotearoa New Zealand, successive governments have struggled for more than 25 years to develop suitable new legislation to replace the hopelessly outdated 1981 Medicines Act, and bring regulations of medicines and NHP’s into the 21st century(1).  

The Australia New Zealand Therapeutic Products Agency (ANZTPA) was an attempt initiated by the New Zealand and Australian governments in 1996 to develop a joint trans-Tasman scheme for regulating therapeutic products. Government officials and industry representatives worked for eleven years on the detail of this new agency until 2007, when the New Zealand government postponed further legislation.

The next attempt was the Natural Health and Supplementary Products (NHSP) Bill, on which the government worked from 2011 until dropping it at the end of 2017.

The Therapeutic Products Bill was the third attempt to regulate all medicines and medical devices as well as NHP’s, and was introduced by the current government in November 2022. In July of this year it passed its third reading in the House, and subsequently became the Therapeutic Products Act (2023). Regulations as provided for in the Act are now being developed, and need to be in place by September 2026(2).

Regulatory Challenges

The huge plethora and diversity of brands and product types, digital marketing, ongoing incorporation of new technologies and supply chain disruptions, are driving constant changes in the availability of products in the marketplace.

The important issue of sustainability of some medicinal plants used as raw materials, is largely left to companies themselves to commit to, and voluntarily opt into secondary regulatory agencies such as the Union for Ethical Biotrade, EcoCert, Rainforest Alliance, FairWild and B-Corp.

Many medicinal plants are also foods, and well known culinary foods and spices such as beetroot, garlic, ginger and turmeric are incorporated into capsule and tablet dosage forms. Whether something is in fact a food or ‘dietary supplement’, or is actually ‘medicinal’, is a 6 million dollar question which extracts different answers depending on who is asked.

Many companies in the industry have leveraged this situation to their advantage, and the terms ‘dietary supplement’ or ‘food supplement’ are widely used as descriptive terms when selling products. Most plant-based NHP’s are safe and fulfill a nutritive or functional dietary need when taken in small doses as a supplement to the diet. Food regulations, while having some obligations on manufacturers and sponsors, also tend to have a lower regulatory bar and thus cost, than those for medicines.

Language however, and the terminology used to describe something can greatly influence one’s perception. By referring to most NHP’s as supplements rather than as pharmacologically active medicines, their perceived ability in the eyes of many to produce tangible health improvements, is somewhat compromised. In many ways it fosters an impression that NHP’s are pawns, rather than knights or rooks, kings or queens. As such their status or ‘mana’ (a Māori word that signifies the presence or intrinsic influence or power of something), is lessened.

Personally, since training in medical herbalism after several years working as a pharmacist, I’ve always regarded well manufactured and properly used plant extracts as medicines. The name of the company I founded 25 years ago, and the title of this blog, extols this principle.

Taking the right approach is a minefield for regulators though, and it is impossible to please everyone. Many parameters require consideration when trying to distinguish between a food or dietary supplement and a medicine. They include the product potency, therapeutic claims made for it, the medical condition(s) or intended application, the presence or absence of a qualified practitioner’s oversight, and the manufacturing standards and pharmacovigilance systems in place.

In practice, a more tiered and evolved approach to classification of NHP’s, to include categories apart from dietary supplements and medicines alone, would have much merit.

While alcohol is alcohol regardless of the form it is presented in, low alcohol beer and gin are poles apart, in terms of their alcohol content. Their accessibility, packaging, effects on the user and thus safety, therefore also vary significantly. The same enormous diversity exists in strength, efficacy and safety of many NHP’s being produced and sold today.  Logically therefore, as with drug-based medicines, it is appropriate that certain products should only be able to be prescribed, by suitably trained and registered practitioners(3).

Appraising traditional preparations versus modern pharmaceutical manufacturing methods for their relative risks, and ensuring evidence is sufficient to support therapeutic claims, are other challenging areas. For this and other regulatory tasks, adequate knowledge and training in NHP’s is an important capability need for the regulator. A well resourced regulator in budgetary and human expertise terms, and one built upon principles of good science, public safety, consultation and accountability, is therefore essential.

Prevention better than a cure

A more preventative and self help approach to personal health is critical to reduce the dual burden on governments and future taxpayers of aging populations and increasing resource needs of mainstream healthcare systems. Evidence suggests a vast number of plants can either enhance our resistance to and reduce our risks of a wide range of illnesses, or reduce our dependence on drug and hospital treatments. However, to utilise them as prophylactic and safe selfcare interventions, research, education, and a regulatory environment that facilitates this, needs to continue.

Additionally though, there is in fact a growing recognition of the ability of plant derived medicines to provide efficacious treatments for a whole host of serious illnesses and diseases for which conventional medicine is struggling to make more headway.  

Treatment of serious conditions

The incorporation of medicinal plants into mainstream healthcare including for serious conditions such as sepsis, post-stroke and kidney failure, has been a part of Chinese medicine for a long time(4-6). Also in Japan, Germany and other countries, parenteral products are manufactured from plant extracts and licenced with regulatory authorities for the treatment of specific conditions.

Results from a recent clinical trial in China have put the potential role of phytotherapy for the treatment of sepsis into the spotlight, with a significant reduction in mortality being reported following administration of a polyherbal parenteral preparation(7).  Sepsis is a seriously dysregulated host response to infection, and more than 19 million cases of severe sepsis occur globally each year, leading to at least 5 million deaths(8).

The study was a multicentre, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites in China. It included 1817 randomized patients aged 18 to 75 years with sepsis present for less than 48 hours, nearly half of whom had septic shock. Patients received either an intravenous infusion of the herbal preparation at a dose of 100 mL or volume-matched saline placebo every twelve hours for five days, alongside usual hospital care in either an ICU or medical ward. The primary outcome was 28-day all-cause mortality.

Of the 1760 patients who completed the trial, the 28-day mortality rate was significantly lower in the treatment than in the control group. Within the herbal and conventionally treated group, 165 of 878 patients (18.8%) had died, whereas in the control group who received conventional treatment alone, 230 of 882 patients (26.1%) had died after 28 days. The incidence of adverse events was very similar in both groups(7, 9).

With plant extracts containing multiple phytochemicals including some which may impede absorption, achieving adequate bioavailability from their oral administration can sometimes be a challenge, just as it is for some drugs.  Parenteral dosage forms are often life-saving in modern medicine, as intravenous or intramuscular injections can achieve much higher plasma and tissue levels, and thus enable better, faster and a more protracted efficacy to be achieved.

However, as every pharmacist knows, parenteral medicines need to be manufactured using a high level of Good Manufacturing Practice (GMP) standards, far greater than those in place for dietary or food supplements, to avoid serious adverse events or treatment failure that may result in death.

Leveraging the potential of phytotherapy

Studies such as this one, highlight the potential contribution of medicinal plants to modern healthcare, as being a whole lot more than that of ‘dietary supplements’ alone.

It is encouraging to see that in some countries of the world, companies, clinicians, governments and regulators have for some time now been actively embracing and researching new potential applications for their traditional plant medicines, including their parenteral (injectable) use for serious or difficult to treat conditions.

Incorporating these and other medicinal plants into current treatment protocols for serious and expensive to treat conditions such as acute infections, sepsis, diabetes, cancer and mental unwellness, is an ambitious aspiration, but an essential one. Additionally for most of these applications, adequate regulatory oversight and adherence to medicine-manufacturing standards, will also be required.

The current New Zealand government has now passed legislation to replace our hopelessly outdated 1981 Medicines Act, which was no easy task. However, many challenges exist with preparation of the subsequent regulations. These include providing a regulatory model that continues to allow self-selected NHP’s both as a safe self-help intervention, but also recognizes and fosters greater research into their potential applications for the prophylaxis or treatment of more serious conditions, and extends the clinical reach of our many highly trained NHP practitioners.

References:

  1. Rasmussen PL, NZ Politicians continue to let the Natural Health Products Industry and Practitioners Down. www.herbblurb.com Jun 19, 2020.
  2. https://www.health.govt.nz/our-work/regulation-health-and-disability-system/therapeutic-products-regulatory-regime
  3. Rasmussen PL, Statutory regulation of medical herbalists and naturopaths: an essential step towards a more cost and outcome beneficial future healthcare system. www.herbblurb.com 26 April, 2019.
  4. Cheng C, Yu X. Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics. Int J Mol Sci. 2021;22(20):11078. 
  5. Zhang L, Yang L, Shergis J, et al. Chinese herbal medicine for diabetic kidney disease: a systematic review and meta-analysis of randomised placebo-controlled trials. BMJ Open. 2019;9(4):e025653.
  6. Wei M, Wang D, Kang D, et al. Overview of Cochrane reviews on Chinese herbal medicine for stroke. Integr Med Res. 2020;9(1):5-9.
  7. Liu S, Yao C, Xie J, et al. Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial. JAMA Intern Med. 2023;183(7):647-655.
  8. Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016;193(3):259-272
  9. Rasmussen PL, Chinese parenteral phytomedicine reduces mortality from sepsis. Pharmacy Today, October 2023. ISSN 1170-1927