VALERIAN – MORE THAN JUST A SLEEPING AID

Roots of the European and northern Asian herb Valerian (Valeriana officinalis), are well known for their relaxant and anxiolytic properties, and usefulness in the management of insomnia and mild anxiety. Clinical trials into its effects on insomnia and sleep problems including in menopausal women and patients withdrawing from benzodiazepine drugs, have generally reported favourable findings(1-4).

As with all medicinal plants, a single useful application is a far-fetched concept, and Valerian is no different in this. Apart from being pleasing to some cats in a similar way catnip is, another increasingly supported application for this well known herb, is to help support cognitive function.

Conventional sleeping tablets such as triazolam and zopiclone have detrimental effects on cognitive function(5,6), but comparative studies found valerian to show no such negative effects(1, 7). Next day hangover like symptoms and cognitive deficits are relatively frequent adverse events of all drug-based anti-anxiety or sedative agents, so this itself is a significant valerian advantage. However, evidence that valerian may additionally protect against cognitive decline or enhance cognitive functions in other settings, is of interest.

Early indications of cognitive enhancing effects of valerian particularly in the elderly, came from a Korean study in aged mice published in the journal Exp Gerontology(8). Following 3 weeks of valerian root administration (and valerenic acid), improvements occurred in several behavioural parameters indicative of improved cognitive functions, including exploration of new objects, escape latency, and swimming speeds. These effects were accompanied by enhancement in nerve cell differentiation and neuroblast differentiation, and reduced serum levels of corticosterone, in the valerian versus control treated mice. While an animal study, these findings suggest similar cognitive promoting effects in elderly humans.

Since then, at least two human clinical studies have measured changes in cognitive function following valerian administration. These include a study with 39 patients on haemodialysis whose cognitive status improved after taking valerian 60 minutes before bedtime for one month(9). The prevalence of cognitive disorders in kidney failure patients undergoing haemodialysis is twice as high as the general population, and these are often undiagnosed(10).  Neuroprotective properties, as reported for ethanolic extracts of valerian in animal studies, may be contributory to such benefits(11, 12).

Another study explored cognitive dysfunction in 61 patients aged between 30 and 70 years, scheduled for elective coronary artery bypass surgery(13). Patients received either valerian or placebo capsules twice daily for 8 weeks following surgery. Cognitive brain function was evaluated prior to surgery and at 10-day and 2-months following, using the Mini Mental State Examination (MMSE) test. In the valerian treated patient group the mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day, and then increased to 27.45 ± 1.36 at the 60th day. Conversely in the placebo group, scores reduced from 27.37 ± 1.87 in the preoperative period to 24 ± 1.91 at the 10th day, and rose only slightly to 24.83 ± 1.66 at the 60th day. With post-operative cognitive decline now recognised as a negative outcome in many patients undergoing this increasingly common surgical procedure(14), the finding that valerian may prevent this, has implications for coronary artery bypass as well as potentially other forms of surgery.

Valerian is also used traditionally for digestive or menstrual cramps, and for nervous headaches(15, 16). Prior to the development of early tranquilliser drugs such as barbiturates, or when these weren’t accessible, it was also a valued intervention in the management of some forms of pain.

Support for these historical applications has emerged recently from results of a clinical trial in Iran which investigated the effects of valerian on tension headaches. These present as dull pain, tightness, or pressure around the forehead or back of the head and neck, and are the most common type of headache.

The study included 88 participants with tension-type headache, randomly assigned to take valerian or placebo capsules twice daily after dinner for a month. After this one month treatment, valerian was associated with a significant reduction in the negative impacts of headaches on daily living and disability, and a reduction in the severity score, relative to the placebo group(17).

Finally, as anti-anxiety and sedative drugs can impart clinical improvement in some patients with depression, and potential antidepressant activity has been implicated for valerian in an animal model of depression associated with chronic stress(18, 19), beneficial applications in some patients with depression, are possible. Depression can also be accompanied by cognitive disturbances and a compromised memory. As such, herbs such as ginkgo and valerian for which benefits on associated cognitive function have been shown, may offer additional effects beyond those of antidepressant herbs and drugs, in the management of patients with depressive illness.

Refs:

  1. Dorn M. Forsch Komplementarmed Klass Naturheilkd. 2000 Apr;7(2):79-84
  2. Poyares DR et al, Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):539-45
  3. Ziegler G et al, Eur J Med Res. 2002 Nov 25;7(11):480-6.
  4. Taavoni S et al, Menopause. 2011 Sep;18(9):951-5.
  5. Gunja N. J Med Toxicol. 2013 Jun;9(2):163-71.
  6. Stranks EK et al, J Clin Exp Neuropsychol. 2014;36(7):691-700 
  7. Hallam KT et al, Hum Psychopharmacol. 2003 Dec;18(8):619-25.doi: 10.1002/hup.542.
  8. Nam SM et al, Exp Gerontol. 2013 Nov;48(11):1369-77.
  9. Samaei A et al, BMC Nephrol. 2018 Dec 27;19(1):379
  10. Erken E et al, Clin Nephrol. 2019 May;91(5):275-283
  11. Malva JO et al, Neurotox Res. 2004;6(2):131-40.
  12. De Oliviera DM et al, Neurochem Res. 2009 Feb;34(2):215-20.
  13. Hassani S et al, Psychopharmacology (Berl). 2015 Mar;232(5):843-50.
  14. Ngcobo NN et al, S Afr J Psychiatr. 2020 Jul 9;26:1470.
  15. Rudolf Fritz Weiss, Herbal Medicine, published by Volker Fintelmann 1998
  16. Barker J. The Medicinal Flora of Britain and Northwestern Europe. Winter Press, West Wickham, Kent, UK, 2001. ISBN 1 874581 630
  17. Azizi H et al, Avicenna J Phytomed. May-Jun 2020;10(3):297-304
  18. De Brito APA et al, Front Neurosci 2020; 14:759.
  19. Kandilarov IK et al, Folia Med (Plovdiv) 2018; 60(1):110-116.

Ligustrum lucidum – synergistic effects with other herbs and drugs in the management of cancer, bone marrow suppression, and depression?

I’ve written previously about the many medicinal properties of the dark red fruits of Ligustrum lucidum (Glossy Privet), the most invasive tree in New Zealand(1, 2). These include prophylactic effects against osteoporosis, beneficial effects on bone growth and strength, protection actions against liver toxins, and possible applications for one of our biggest and growing health burdens, diabetes mellitus.

During the March to June New Zealand Covid-19 Lockdown, I became more attentive to my local environment, and being a herbalist, plants featured prominently in this. Plants in our individual immediate environments can be useful as a source of food, recreation, exercise, de-stressing, and other survival related concerns, including as medicines.

It is however, a sad reflection on the current human disconnect from our local environment, that while this tree offers an evidence-based and readily available partial solution to common health problems experienced by thousands of New Zealanders, hardly anyone seems to know about this, or consider utilising this plant for something useful. Just as we viewed Mānuka many years ago, when it was cursed as an unwanted scrubweed by farmers, until its numerous medicinal properties became recognised again.

Ligustrum fruits are also used as an adjunct in cancer therapy(3). Inhibitory effects against benzopyrene and aflatoxin induced cancer(3, 4), potential applications in the treatment of liver(5) and brain(6) cancer, and enhanced sensitivity of human colorectal carcinoma cells to the chemotherapy drug doxorubicin(7), have been reported.

During chemotherapy treatment of cancer patients, a common and serious adverse event is myelosuppression, damage to the bone marrow resulting in decreased production of blood cells (haematopoiesis), and lowered immunity.

Ginseng (Panax ginseng) has been reported to ameliorate myelosuppression produced by the chemotherapy drug 5-flurouracil(8). Recent research now suggests that Ligustrum also may help with the clinical management of this condition, and that a combination of Ligustrum with Panax ginseng, even more so(9).

Mice who developed myelosuppression following administration of the chemotherapy drug cyclophosphamide, were given aqueous extracts of either Panax ginseng, Ligustrum lucidum, or a combination of these two herbs. Both ginseng and Ligustrum each individually increased levels and activity of several different haemotopoietic factors including peripheral blood cells, bone marrow cells and colony-forming unit-granulocyte macrophages, and upregulated cytokines involved in haematopoiesis. These protective effects against bone marrow suppression were even greater though, when a combination of Ginseng and Ligustrum was used.

Combining Ligustrum with Ginseng and using as an adjunctive treatment during chemotherapy treatment, may therefore help manage the negative effects on bone marrow thus enabling an optimal chemotherapy regimen to be implemented. Preventative effects against chemotherapy-induced myelosuppression have also been reported for a combination of Ligustrum with Eleutherococcus senticosus(10).

Other recent research on Ligustrum suggests it may also combine well with the highly regarded medicinal fungus Cordyceps(11). The Cordyceps genus are a type of fungi requiring an insect or insect larvae as host. Cordyceps has been used in TCM for over 300 years to treat a diverse range of conditions, including respiratory, kidney, liver and cardiovascular diseases, low libido, impotence, hyperlipidaemia, hyperglycaemia, fatigue, convalescence, and to promote energy(12).  Cordyceps is also gaining interest as a potential anti-cancer agent(13, 14), including as an inhibitor of metastases (secondary cancers), and as an adjunct during chemotherapy and radiotherapy(15, 16).

Unlike the closely related Cordyceps sinensis, a species restricted to a specific zone and insect host which has been overharvested in the wild and now endangered, Cordyceps militaris is cultivated on a range of host insects, and still contains significant levels of a key active compound cordycepin (3-deoxyadenosine). However, upon entering the body cordycepin is quickly metabolized into an inactive metabolite 3′-deoxyinosine, by the enzyme adenosine deaminase which is widely distributed in mammalian blood and tissues, thus limiting its activity when administered alone.

However, researchers in Shanghai have recently shown that oleanolic acid and ursolic acid, key triterpenoid constituents extracted from Ligustrum lucidum fruits, act as potent adenosine deaminase inhibitors. This suggests combining cordycepin or Cordyceps with Ligustrum, may be another useful combination in clinical practice(11).

Finally, potential applications of Ligustrum lucidum in the management of some types of depression, have recently been revealed(17).

Depression sometimes develops as a result of a head injury or in neurodegenerative disorders such as Parkinson’s disease or dementia, with central nervous system inflammation (neuroinflammation) being a common underlying factor. Recent clinical and preclinical evidence also suggests that this inflammation in nerve tissues may be a key factor involved in the onset of major depression(18).

Phenol glycosides from Ligustrum lucidum were evaluated for their effects on neuroinflammation and depressive-like behavior in mice. Mice received the Ligustrum derived extract for two weeks prior to treatment with lipopolysaccharide (LPS), which induced an inflammatory reaction. Ligustrum phenol glycoside pre-treatment ameliorated LPS-induced depressive-like behaviors, effects associated with reduced neuroinflammation of the hypothalamus, less activation of microglia (a type of brain cell) and inflammatory cytokine production, and improvement in vitamin D metabolism.

Like hundreds of other clever plants, Ligustrum lucidum has become so well colonised in New Zealand it is classed as a ‘noxious’ weed. The dark purple brown berries that appear in autumn make a wonderful healthy feast for our large bird population who excrete the seeds far and wide. And like lots of introduced plants endemic in our environment (weeds), it provides a readily accessible, free or cheap source of plant medicine with many potential benefits.

The above research on this plant is just some of that published this year to date. Perhaps assigning ‘shovel ready’ unemployed Kiwis to harvest the berries at the same time as culling numbers of this tree and undertaking further research towards processing these into natural medicines, might improve human and animal health, reduce medical care costs and prevent chronic debilitating illnesses. This would make sense in the Covid-19 plighted economy we are now living in.

 

Refs:

  1. Rasmussen PL, https://herbblurb.com/2016/03/10/ligustrum-lucidum-noxious-weed-or-useful-osteoporosis-treatment/
  2. Rasmussen PL, https://herbblurb.com/2019/01/24/honeysuckle-and-other-useful-weeds-surrounding-us/
  3. Wong BY et al, Mutat Res 1992; 279(3):209-216.
  4. Niikawa M et al, Mutat Res 1993; 319(1):1-9.
  5. Hu B et al, Oncol Rep 2014; 32(3):1037-1042.
  6. Jeong JC et al, Phytother Res 2011; 25(3):429-434.
  7. Zhang JF et al, Integr Cancer Ther 2011; 10(1):85-91.
  8. Raghavendran HRB et al, PLoS One. 2012;7(4):e33733.doi: 10.1371/journal.pone.0033733.
  9. Han J et al, J Ginseng Res. 2020 Mar;44(2):291-299.
  10. Wang C et al, Biomed Pharmacother 2019; 109:2062-2069.
  11. Guan H et al, Biomed Chromatogr. 2020 Mar;34(3):e4779
  12. Olatunju OJ et al, Fitoterapia 2018; 129; 293-316.
  13. Nakamura K et al, J Pharmacol Sci. 2015 Jan;127(1):53-6.
  14. Khan MA et al, Curr Med Chem.2020;27(6):983-996.
  15. Bi Y et al, Mol Pharm. 2018 Nov 5;15(11):4912-4925.doi:
  16. Ho SY et al, Int J Mol Sci. 2019 Oct 28;20(21):5366
  17. Feng R et al, Phytother Res. 2020 Jun 30.
  18. Troubat R et al, Eur J Neurosci 09 March 2020. 2020 Mar 9.doi: 10.1111/ejn.14720.

 

New Zealand Horseradish – a winter tonic for lungs and immunity and more

Aside from being a condiment to various foods, horseradish (Armoracia rusticana) root has been traditionally used for coughs and colds for centuries in Europe and parts of Asia. Making a syrup from the distinctively pungent large roots of this plant which grew vigorously at my allotments when I was a herbal student in the UK many years ago, was one of my first experiences with manufacturing a herbal cough medicine, and it is great to now have access to this wonderful herb, grown here in New Zealand.

The source of its pungency and warming aromatic properties, are phytochemicals known as glucosinolates (so-called ‘mustard oil glycosides’) which break down to release volatile and highly bioactive compounds known as isothiocyanates. These act as natural expectorants to encourage mucus elimination, as well as having warming and invigorating actions that can improve the body’s natural defences against unwanted bugs.

Horseradish and its isothiocyanates have been subject to a fair amount of research in recent years, findings from which provide further support for both its traditional as well as potential new applications.

Antimicrobial actions are prominent features of horseradish extracts. Significant antibacterial activity has been shown against a wide range of pathogenic microbes, including bacteria responsible for chest, skin, oral and urinary tract infections(1-6). Isothiocyanates derived from horseradish also exhibit a non-selective antimicrobial activity against several bacterial strains including resistant forms of Haemophilus influenza and E. coli, and yeasts such as Candida albicans(2, 4, 7).  The principle isothiocyanate allyl isothiocyanate has synergistic antifungal activity with the drug fluconazole against Candida biofilms(8).

Clinical studies using a combination of horseradish root with nasturtium herb have found it to have comparable efficacy to antibiotics in the treatment of acute sinusitis and acute bronchitis(1). A combination of horseradish with green tea and other herbs has also been reported to have greater efficacy than oseltamivir in preventing H3N2 avian influenza viral transmission(9), suggesting potential antiviral actions.

An excessive host inflammatory response in the lungs is increasingly linked to an unfavourable prognosis when highly pathogenic bacterial or viral infections take hold in the respiratory tract. As such, the anti-inflammatory properties of horseradish and its affinity for the lungs, are probably useful. Diverse anti-inflammatory effects including reduced nitric oxide, tumor necrosis factor-α and interleukin-6 release, and COX-2 expression, have been reported(10-14). Apart from being anti-inflammatory(15), allyl isothiocyanate induces the expression of multidrug resistance-associated protein 1 (MRP1), which plays a protective role against oxidative stress, lung inflammation and progression of chronic obstructive pulmonary disease (COPD)(16).

Other horseradish phytochemicals have also been associated with anti-inflammatory activities in human immune cells. These include inhibition of the cyclooxygenase (COX-2) enzyme, as well as lipoxygenase pathways (PGE2 synthesis and leukotriene LTB4 release)(10, 14). Anti-inflammatory and potential neuroprotective effects, have also been reported recently for hydantoin and thiohydantoin constituents of horseradish(17).

Like many medicinal plants, horseradish is a powerful antioxidant, and recent research suggests a link between its antimicrobial activities, and antioxidant properties(12). An Italian study found fumigation with allyl isothiocyanate to enhance the Vitamin C, polyphenol and flavonoid content of kiwifruit after 120 days of storage, thus improving its antioxidant and potential health benefits(18).

Protection against DNA damage and cell death from oxidative stress, and inhibition of the COX-1 enzyme may also contribute to the reputation of horseradish to protect against various cancers. Isothiocyanates such as allyl isothiocyanate derived from horseradish and other plants such as brasiccas and nasturtium have been increasingly investigated for their anticancer properties in recent years(10, 19, 20, 21). Horseradish flavonoid constituents such as kaempferol and quercetin also seem to help prevent cellular mutations that can lead to cancer(22).

The use of horseradish as a condiment to help digest rich food has been given a tick of approval by Serbian and Austrian research showing powerful spasmolytic (muscle relaxant) effects on the bowel for its isothiocyanates(4, 23). Potential benefits in the management of diabetes type 2 have also been implicated by recent reports that it is a strong inhibitor of the enzyme α-glucosidase, which breaks complex carbohydrates down to glucose(24).

New Zealand grown horseradish is an ideal herb to include in a winter immune tonic, as well as a regular tonic for those who through lifestyle or occupational exposure to various carcinogens, may be at risk of COPD or various cancers. Its affinity for lung conditions in particular, make it a valuable herb to enhance immunity and optimise lung health, during 2020.

References:

 

  1. Goos KH et al, Arzneimittelforschung 2006; 56(3):249-257.
  2. Conrad A et al. Drug research 2013; 63(2):65-68.
  3. Park HW et al, Biocontrol Sci 2013; 18(3):163-168.
  4. Dekic MS et al, Food Chem. 2017 Oct 1;232:329-339.
  5. Eichel V et al, BMC Complement Med Ther. 2020 May 24;20(1):156.
  6. Mickymaray S et al, Medicina (Kaunas) 2019 Jun 19;55(6):289
  7. Mutters MT et al, Fitoterapia. 2018 Sep;129:237-240.
  8. Raut JS et al, J Microbiol Biotechnol. 2017 Apr 28;27(4):685-693
  9. Oxford JS et al, Am J Ther. Sep-Oct 2007;14(5):462-8.
  10. Weil MJ et al, J Agric Food Chem. 2005 Mar 9;53(5):1440-4
  11. Marzocco S et al, Food Funct. 2015 Dec;6(12):3778-88
  12. Manuguerra S et al, Nat Prod Res. 2020 Jun;34(11):1567-1570
  13. Marzocco S et al, Food Funct. 2015 Dec;6(12):3778-88
  14. Herz C et al, Evid Based Complement Alternat Med 2017. 2017:1950692
  15. Subedi L et al, Int J Mol Sci. 2017 Jul 3;18(7):1423.
  16. Wang S et al, Oxid Med Cell Longev. 2015;2015:903782.
  17. Lee TH et al, J Nat Prod. 2019 Nov 22;82(11):3020-3024.
  18. Ugolini L et al, J Food Sci Technol. 2017 Mar;54(3):751-760
  19. Zhang Y et al, Mol Nutr Food Res. 2010 Jan;54(1):127-35.
  20. Gerhauser C. Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):405-10
  21. Novio S et al, Molecules. 2016 May 12;21(5):626.
  22. Gafricova M et al, Molecules 2014 Mar 14;19(3):3160-72.
  23. Donnerer J, Liebmann I. Pharmacology. 2017;99(1-2):79-83.
  24. Javaid A et al, Comb Chem High Throughput Screen. 2020 May 26 (epub ahead of print)

 

NZ POLITICIANS CONTINUE TO LET THE NATURAL HEALTH PRODUCTS INDUSTRY AND PRACTITIONERS DOWN

Almost all of New Zealand’s economy is based upon plants, and how prolifically they grow here. Even after much of the native bush was felled to make way for sheep, cows and pine trees, it’s the grass and plants that replaced this, that feed milk or meat producing animals. Agricultural products continue to make up a huge percentage of our exports and GDP contribution, even more so now that Covid-19 has seen plummeting earnings from industries such as tourism and foreign student education provision.

The success of NZ’s Food and Beverage industries derives not only from our reputation for producing high quality products, but also establishment of and maintenance of world class regulations. Nobody in Shanghai or Tokyo or New York wants to buy NZ organic milk from grass fed cows, unless they are sure that what they are paying a premium for, is exactly as stated on the label, and that it is safe. Regulations are there to make sure expected quality parameters are upheld, ensure safety, and in many industry sectors, help facilitate exports.

As with quality food and beverage products, herbal medicines are growing in popularity and global demand, and the current Covid 19 pandemic has reminded us that drugs are not always a solution to rely upon to save us from nature’s dominance over our plight.

Demand for various herbal medicines has long surpassed the point where demand exceeds supply. As with the global food supply chain, changing consumer preferences and climate change stressors, are also contributing to this supply shortfall.

As I’ve written previously, this provides huge opportunities for New Zealand. We have a rich diversity of natural resources, fertile soils, great farmers, and an enviable track record of research and development in biological and agricultural sciences, and pharmaceutical company development.

Why then have successive governments since the last Labour one, not taken the need to regulate and enable the absolutely huge growth potential of a local natural health product industry seriously?

The recent decision by the Ministry of Health to reclassify ‘Artemisia annua extract’ as a prescription only medicine, is symptomatic of these serious regulatory deficits for natural health products.

On 18 May the Ministry of Health issued a Gazette notice to reclassify ‘Artemisia annua extract’ as a Prescription-Only Medicine, following receipt by the New Zealand Pharmacovigilance Centre of 29 reports of hepatic adverse reactions occurring in patients taking two specific products purchased ‘over-the-counter’, and made in NZ from a supercritical CO2 extract of Artemisia annua in grapeseed oil.

What this effectively means, is that all Artemisia annua containing products in addition to those containing the particular extract involved in these adverse event reports, have now become ‘prescription only’. In other words, medical herbalists and naturopaths, most of whom have undertaken at least 3 years study to obtain a degree qualification in natural medicine, are no longer able to treat patients with traditional and GMP manufactured preparations of this herb. But somehow, doctors and other registered medical practitioners who have had no training at all in herbal or natural medicine, are suddenly deemed adequately qualified to prescribe ‘Artemisia annua extract’.

In fact no other regulator in the world has restricted access to all ‘Artemisia annua extracts’, because evidence implicating the herb Artemisia annua itself in liver adverse events, is basically zilch. There is a lack of adverse event reports involving Artemisia annua-containing products reported to pharmacovigilance agencies in other countries, and no previous association of Artemisia annua with liver adverse events exists in its extensive scientific literature.

Such a cluster of cases in New Zealand only, all apart from 1 relating to one particular product manufactured and sold direct to consumers as a ‘dietary supplement’, reeks of a product quality problem. The supercritical CO2 extract used, is also very different to more traditionally used forms of Artemisia annua. As is low alcohol beer from Schnapps.

 

Why then has the NZ regulator taken this course of action?

Lack of any definition of a ‘natural health product’ in any New Zealand legislation, should raise a large red flag, in terms of how ridiculously outdated our regulations for natural health products are. This is the case despite the NZ Natural Health Products Industry trying for more than 20 years to get successive governments to introduce regulations to replace the completely outdated 1981 Medicines Act, and inadequate Dietary Supplements Regulations.

In 2003, the NZ and Australian governments signed a treaty to establish a joint scheme for the regulation of Therapeutic Products (ANZTPA), which would have included regulations also for natural health products. These are known as and regulated as ‘complementary medicines’, by the Australian regulator, the TGA.

Government officials, industry representatives, academics and lawyers from both countries then spent 11 years consulting, developing and preparing these regulations for implementation, but opposition from the National, NZ First and Green Parties, and a Labour government majority of 1 at the time, lead to this legislation only passing its first reading in the house, and then being canned by the new National government in 2014.

National and the Greens then spent some years developing a new NZ-only draft Bill, the Natural Health and Supplementary Products Bill. This proposed a much lighter regulatory agency than ANZTPA, but as with ANZTPA, involved a large amount of work and consultation by government officials, industry representatives and academics, who evaluated and prepared a list of several thousand permitted ingredients able to be included in natural health products without any need to apply for a Medicines licence. However, National dragged their heels on this despite being in power for 3 terms of government and the Bill was never passed, even though it was supported by National, the Greens, Labour and NZ First, with only the ACT party opposing it.

Upon coming to power in 2017, the current Labour-NZ First coalition government removed the Natural Health Products Bill from the order paper while it was awaiting its third reading, soon after talks with its coalition partner NZ First.

Various communications and workshops with industry have since taken place, with the apparent objective of reinventing the wheel and finding out how to appropriately regulate natural health products and draft a new Bill, although no timeline for this has been provided. The recent extension of the ‘Dietary Supplement Regulations’ (under which most natural health products are currently ‘regulated’) to 2026, suggests that the government still has no sense of urgency about the need for a drastically different regulatory environment.

Meanwhile this regulatory void means committed New Zealand companies trying to build export markets for locally produced natural health products are struggling to assure customers in offshore markets of their product quality and safety parameters. To make it even harder for them, for several years we’ve had a situation where many products are being imported and sold into New Zealand with illegal label statements and therapeutic claims, but nothing is being done to stop these imported brands competing with more law abiding local companies.

Industry and Ministry of Health officials share some of the responsibility for this debacle, and it is time we stopped pretending that these products are all ‘dietary supplements’. Plant medicines are true medicines, and when good quality products are taken in optimal doses, they can be as effective as drugs for many health conditions. The Australian view of natural health products as ‘complementary medicines’, is much more appropriate, their regulatory system acknowledges their ability to sometimes have therapeutic effects, and also permits such claims to be made on their packaging, where scientific or traditional evidence exists. It also recognises that natural health practitioners after training at least 3 years to obtain degree level qualifications, have particular skills that enable them to use certain forms of herbal medicines that may not necessarily be appropriate or safe as ingredients in ‘over the counter’ products.

The dairy, beef, wine, kiwifruit and so many other vibrant export industries have all been established not only through being lucky enough to have perfect growing conditions here, but also a regulatory system in place that fulfils the needs of any premium quality and premium priced product, to be sold into offshore markets.

Natural health products are challenging to regulate appropriately, but isn’t everything? It’s time for elements of the industry to stop pretending all products are ‘dietary supplements’ rather than medicines, and for New Zealand politicians from all parties to stop messing around with the Natural Health Product Industry like a game of political football, before the next 3 year election cycle.

The long game as we reflect on the post-Covid world, has to seriously leverage New Zealand’s many unique strengths and quality attributes, to create a sustainable portfolio of industries which can boost export revenue, have high margins, look after the environment, and respect the principles of Kaitiakitanga. The local Natural Health Products industry tick all these boxes, but is now in urgent need of world class regulations to support its export lead growth.

 

 

Ginkgo – much more than a herb for cognition – part 2.

Ginkgo istock3Apart from possible benefits in the management of conditions such as dementia, stroke, diabetic neuropathies, macular degeneration and glaucoma, the cardioprotective and neuroprotective properties of ginkgo suggest potential applications in other situations in which there is exposure to various drugs or substances with a risk of adverse events.

Adjunct with neurotoxic drugs

Concomitant use of ginkgo may be useful when taking or exposed to other drugs or chemical toxins(1, 2). Animal studies have reported protective actions of ginkgo against ototoxicity (inner ear and auditory nerve damage) from the antibiotic drug gentamycin(3), kidney (nephro) toxicity, liver (hepato) toxicity and genotoxicity from the herbicide glyphosate(4), and nerve damage from the herbicide paraquat(1).

These studies suggest that patients being prescribed gentamycin or other aminoglycoside antibiotics which have a risk of causing hearing or kidney damage, or people regularly using or exposed to herbicides such as glyphosate or paraquat, may benefit from taking ginkgo at the same time.

 

Supporting liver function:

Ginkgo leaf is a very bitter herb, and some would say that it is therefore hardly surprising that it is a useful agent for liver conditions. In fact there are now numerous studies showing it has protective actions on the liver.

These hepatoprotective effects have been reported in rodent studies against a wide range of liver toxins. They include alcohol, paracetamol, rifampicin & other chemicals(5-11). Improvements have been shown to occur in several liver abnormalities including malondialdehyde levels, glutathione levels, superoxide dismutase, elevated liver enzymes (LFT’s), and histological damage.

Hepatoprotective effects similar to those of silymarin were reported in a 2011 study involving treatment of rats with silymarin or ginkgo for a week prior, or 4 weeks post administration of nitrosodiethylamine, a known liver carcinogen(12). Other rodent studies have revealed potential antitumour effects against liver cancer for ginkgo(13, 14).

These studies suggest ginkgo could be a useful adjunct to take during treatment with the common analgesic paracetamol, as well as other drugs sometimes associated with liver adverse events, such as azathioprine, isoniazid, statins, ketoconazole and nitrofurantoin.

 Ginkgo when given in larger than usual doses to rats, has protective actions against both acute and chronic alcohol-induced liver damage, effects associated with its antioxidant actions, and improvement in hepatic microcirculation(15-18). Those whose alcohol intake is excessive, may do well to consider taking ginkgo to help ameliorate some of its negative effects on the liver.

Adjunct with chemotherapy:

Adverse events to chemotherapy are common, and use of cytotoxic drugs such as doxorubicin and cisplatin can lead to infertility, kidney damage (nephrotoxicity) and damage to the heart (cardiotoxicity) in some cancer patients.

Pre-treatment or concomitant treatment with large doses of oral or intraperitoneal ginkgo in rats has been shown to help protect against chemotherapy-induced adverse effects on other organs. These include protection against cisplatin-induced peripheral neuropathy(19), protection against cisplatin and doxorubicin cardiotoxicity, and cisplatin nephrotoxicity and ototoxicity(20-25).

Other studies have reported protective effects for ginkgo against the damaging effects of doxorubicin & cisplatin on testicular function in male rats(26, 27), and against against oxidative and genotoxic damage in patients with differentiated thyroid cancer during 90 day radio-iodine treatment(28). These results suggest possible benefits of ginkgo if taken during chemotherapy or radiotherapy treatment, by patients wanting to have children in the future.

While few human clinical trials have investigated these promising findings from animal studies, a Chinese clinical trial has reported a lower incidence of ECG abnormalities and cardiotoxicity in 60 breast cancer patients being treated with doxorubicin, when ginkgo was prescribed concurrently(29). Adjunctive Ginkgo also slightly improved overall survival in a small trial involving 27 patients with advanced hepatocellular cancer, compared to previous sorafenib monotherapy(30).

Adjunct with antipsychotics:

The response of schizophrenia patients to antipsychotic drug medications is often less than ideal, and the frequency of adverse events to these associated with low levels of compliance. Findings from a Chinese clinical trial involving 12 weeks of ginkgo and haloperidol or placebo and haloperidol administration in a group 109 schizophrenia patients and previously treated with antipsychotic medications for at least 6 months, are therefore of interest(31).

At the end of the 12 week study, 57% of the ginkgo treated group were rated as responders, versus only 38% of the haloperidol only treatment group, which in itself is highly significant. Additionally however, a lower incidence of extrapyramidal side effects, a major problem with haloperidol and other older generation antipsychotic drugs, was also seen in the ginkgo-treated group(31, 32).

Improvement in some schizophrenia symptom scores was also reported in a subsequent study involving adjunctive ginkgo treatment in patients taking olanzapine, a newer generation antipsychotic drug(33).

Potential applications of ginkgo in the management of other psychiatric conditions including depression and ADHD, have also been suggested(34, 35), though further clinical studies are needed.

 

Dosage:

A concern is the use of relatively large doses in most animal studies, yet those used in human clinical studies are often much lower, and sometimes probably less than what they should have been. Also given that most neurodegenerative conditions such as dementia, diabetic neuropathies, glaucoma and macular degeneration are slow to develop but tend to be progressive, unless clinical trials involve large participant numbers and continue for a long period of time, their ability to statistically detect clinically significant outcomes , is limited.

Despite these challenges and the cost of long term clinical trials, given the hugely debilitating nature of all of these conditions, and their large burden on both patients and the health care system, further trials to validate promising findings from in vitro and animal studies, and determine optimal dosage and treatment protocols in humans are needed.

 

And finally:

New Zealand is an excellent country for growing ginkgo, and locally harvested ginkgo leaves have been shown to contain high levels of ginkgo flavone glycosides and terpene lactones.

While it is sometimes claimed that ginkgolic acid, a minor component of ginkgo leaves, is associated with allergic reactions, the evidence basis for this is unconvincing. In fact research is increasingly showing that this compound probably contributes to ginkgo’s cognitive benefits(36), and exhibits a wide range of other useful pharmacological properties. These include anti-diabetic(37), anti-fibrotic(38) and potential anticancer properties, including against pancreatic (39), liver, colon and gastric cancers (40-42).

 

References:

  1. Silva AM et al, Plants (Basel). 2019 Nov 29;8(12):556.
  2. Rasmussen PL, 2017. Ginseng, Ginkgo and Ginger – the 3 G’s, paper presented to NHAA International Conference on Herbal Medicine, Brisbane, Australia, 17-19 March 2017.
  3. Yang TH et al, J Nutr Biochem 2011; 22(9):886-894.
  4. Cavusoglu K et al, J Med Food 2011; 14(10):1263-1272.
  5. Shenoy KA et al, Indian J Physiol Pharmacol 2002 Apr;46(2):167-74
  6. Luo YJ et al, World J Gastroenterol 2004; 10(7):1037-1042.
  7. He SX et al, World J Gastroenterol 2006; 12(24):3924-8.
  8. Yuan G et al, Phytother Res 2007; 21(3):234-238.
  9. Naik SR et al, Liver Int. 2007 Apr;27(3):393-9.
  10. Yang L et al, Fitoterapia. 2011 Sep;82(6):834-40.
  11. Parimoo HA et al, Toxicon. 2014 Apr;81:1-12.
  12. El Mesallamy HO et al, Cancer Cell Int 2011; 11(1):38.
  13. Dias MC et al, Chem Biol Interact. 2008 May 9;173(1):32-42.
  14. Ahmed HH et al, Acta Biochim Pol. 2017;64(1):25-33.
  15. Yao P et al, Food Chem Toxicol 2007 Aug;45(8):1333-42.
  16. Yuan Q et al, J Ethnopharmacol 2017 Jan 4;195:1-9.
  17. Rasmussen PL, Protective effects of ginkgo against alcohol-induced liver damage Phytonews 27, 2007. June. Published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  18. Rasmussen PL, Ginkgo: beneficial effects in liver disease? Phytonews 19, 2004. Published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  19. Ozturk G et al, Toxicol Appl Pharmacol. 2004 Apr 1;196(1):169-75
  20. Naidu MUR et al, Indian J Exp Biol. 2002 Aug;40(8):894-900
  21. Gulec M et al, Toxicol Ind Health. 2006 Apr;22(3):125-30.
  22. Cakil B. et al, J Laryngol Otol. 2012 Nov;126(11):1097-101
  23. Song J et al, Evid Based Complement Alternat Med 2013; 2013:846126.
  24. Dias MA et al, Int Tinnitus J. 2015;19(2):12-9
  25. Esen E et al, J Int Adv Otol 2018 Apr;14(1):22-26.
  26. Yeh YC et al, Br J Pharmacol. 2009 Jan;156(1):48-61
  27. Amin A et al, J Biomed Biotechnol. 2012;2012:362049.
  28. Dardano A et al, Thyroid 2012; 22(3):318-324.
  29. Yi SY et al, Zhongguo Zhong Xi Yi Jie He Za Zhi 28(1):68-70, Jan 2008.
  30. Cai Z et al, Phytomedicine 2016; 23(12):1295-1300
  31. Zhang XY et al, J Clin Psychiatry 2001; 62(11):878-883.
  32. Chen X et al, Psychiatry Res 2015; 228(1):121-127.
  33. Atmaca M et al, Psychiatry Clin Neurosci 2005; 59(6):652- 656.
  34. Montes P et al, CNS Neurol Disord Drug Targets. 2015;14(1):132-49
  35. Shakibaei F et al, Complement Ther Clin Pract 2015; 21(2):61-67.
  36. Mango D et al, Front Pharmacol. 2016 Oct 26;7:401
  37. Yoon SY et al, Bioorg Chem 2018; Dec; 81:264-269
  38. Qiu F et al, Toxicol Appl Pharmacol 2018; 15:345:1-9
  39. Ma J et al, Oncotarget 2015 Aug 28;6(25):20993-1003
  40. Qiao L et al, Oncol Lett 2017; 14(5):5831-5838
  41. Li H et al, Oncol Rep. 2019 Jan;41(1):369-376.
  42. Liang JR et al, Biomed Pharmacother. 2020 May;125:109585

ginkgo photo

Ginkgo – much more than a herb for cognition (part 1).

Extracts made from leaves of the ginkgo tree (Ginkgo biloba) are a widely used herbal medicine, mostly due to a reputation to help support cognitive functions in both healthy young(1,2) and middle-aged(3,4) people. However, numerous other potential applications exist for the bitter leaves of this beautiful tree, which has actions as a strong antioxidant and microcirculatory enhancer(5).

Neuroprotective:

More than 400 of the 4000 papers on ginkgo published in the peer-reviewed scientific literature, relate to protective effects against nerve damage or degeneration, in in vitro and animal studies. These include reduced neurodegeneration and oedema in animal models of brain ischaemia(6-8), implicating potential applications of ginkgo to help prevent or reduce ischaemia-induced damage in stroke prone patients(9).

Clinical studies in humans show improved neurological and cognitive outcomes when ginkgo is taken in the immediate period following a stroke(10-12), without increasing the incidence of vascular events. The largest of these was a Chinese multicentre study where 450mg ginkgo extract was given daily together with 100mg aspirin for a 6 month period, in 348 post-stroke patients(11). While these results are promising, further trials involving greater patient numbers and longer treatment durations, are needed.

Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. Studies in animal models of Parkinsons disease have implicated beneficial actions of ginkgo or its constituents(13-18). These include a reduction in elevated oxidative stress markers and inflammatory cytokines, reduced locomotion impairment(13), clearance of the alpha-synuclein (α-syn) protein by ginkgolic acid(17), and regulation of brain copper levels(19).

Two small trials involving a daily dosage of 240mg extract have investigated ginkgo’s effects on patients with multiple sclerosis, but with mixed results(20, 21).

Potential applications exist also for ginkgo to help protect against neurodegenerative retinal diseases such as macular degeneration or glaucoma, and diabetes.

Glaucoma is primarily a condition of raised intraocular pressure, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. As vascular dysregulation, reduced microcirculation, oxidative stress and inflammation are contributory to its development, ginkgo has relevant pharmacological actions that may be useful(22-25).

Ginkgo pretreatment and early post-treatment has been shown to protect retinal ganglion cells from damage in a rat model of chronic glaucoma(26). Few clinical trials have taken place apart from a Korean trial involving 99 patients given ginkgo for 2 years, which reported improved visual function in some patients with normal tension glaucoma(27). Given the limited treatment options for this increasingly common condition, the use of ginkgo as an adjuvant or preventive therapy should be further explored(24).

Similar potential benefits would seem to exist for age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults over 50 years of age. Two trials involving a total of 119 people have reported some positive effects of ginkgo on vision in AMD patients, for doses of 160mg or 240mg per day taken over a 6 month period(28). A Russian trial involving 240mg ginkgo extract together with lutein, zeaxanthin, vitamins C, E, A and B2, rutin, zinc, selenium and bilberry in diabetic patients with initial stages of diabetic retinopathy or combined diabetic retinopathy and AMD, also found evidence of both preventive and treatment benefits(29). Again however, larger trials and for longer treatment periods, are needed.

Potential benefits in diabetes:

Type 2 Diabetes mellitus is one of the major diseases of the 21st century, and is putting an increasing burden on health care budgets. While dietary education and interventions and exercise can assist, and oral hypoglycaemic drugs or insulin are often prescribed, other interventions to reduce drug medication needs and/or improve patient outcomes can have huge benefits.

Diabetes is primarily a condition of poor blood glucose control, but vascular dysfunction often develops and long term outcomes can include development of conditions such as retinal neuropathy and blindness, peripheral vascular disease leading to leg ulcers, and glomerulonephritis leading to deterioration in kidney function.

Various studies in animals suggest a possible role for ginkgo in protecting against such neuropathies. One in diabetic rats found that 4 weeks treatment with ginkgo and magnetised water protected type 2 diabetic rat kidneys from nephrotoxic damages, effects associated with reduced hyperlipidemia, uraemia, oxidative stress, and renal dysfunction(30). Another found ginkgo pretreatment improved neurological scores, and reduced cerebral infarct volume and acute cerebral ischemia‑reperfusion injury in diabetic rats(31). Improvement in cognitive function has been reported in elderly diabetic mice(32), as has reduced plaque lipid deposition and aorta atherosclerosis, and reduced expressions of cytokines and other inflammatory markers (33). Doses used in these animal studies, however, were generally significantly higher than those normally recommended in humans.

Few clinical trials have been undertaken to date and patient numbers were relatively small. Various trials involving a combined treatment of diabetic patients with a particular combination of various Chinese herbs and ginkgo reported improved outcomes, although the contribution of the relatively low dose of 24mg ginkgo extract used in these studies is unknown(34-36).

Another trial found an improved response through adding ginkgo to the oral hypoglycaemic drug metformin for 90 days(37). Blood levels of fasting glucose, insulin, and HbA1c (glycated haemoglobin), whose elevation is linked to risks of diabetic complications, showed a greater reduction in the combined ginkgo-metformin treatment group, than with metformin treatment alone.

Ginkgo would seem to offer various relevant potential benefits in the prevention and management also of Metabolic syndrome(38). This is an insidious cluster of conditions including high blood pressure, diabetes, obesity and high blood lipids, and associated with an increased risk of cardiovascular disease events. Given the increasing prevalence of Metabolic syndrome including in up to a third of American adults, herbal agents such as ginkgo with diverse but relevant pharmacological actions, should receive greater attention.

 

References:

  1. Kennedy DO et al, Psychopharmacology (Berl) 2000 Sep;151(4):416-23.
  2. Kennedy DO et al, Physiol Behav 2002 Apr 15;75(5):739-51
  3. Kaschel R et al, Phytomedicine 2011 Nov 15;18(14):1202-7
  4. Cieza A et al, Arch Med Res. Sep-Oct 2003;34(5):373-81.
  5. Wu Y et al, Phytomedicine. 2008;15:164–9.
  6. Saleem S et al, Stroke. 2008 Dec;39(12):3389-96.
  7. Lang D et al, Brain Res 2011 Nov 24;1425:155-63
  8. Tulsulkar J et al, Transl Stroke Res. 2016 Apr;7(2):120-31.
  9. Mdzinarishvili A et al, J Pharm Pharm Sci 2012;15(1):94-102).
  10. Oskouei DS et al, J Stroke Cerebrovasc Dis. 2013 Nov;22(8):e557-63.
  11. Li S et al, Stroke Vasc Neurol. 2017 Dec 18;2(4):189-197.
  12. Ji H et al, Medicine (Baltimore). 2020 Jan;99(2):e18568
  13. Rojas P et al, Nutrition. Nov-Dec 2012;28(11-12):1081-8.
  14. El-Ghazaly MA et al, Toxicol Ind Health. 2015 Dec;31(12):1128-43
  15. Wang YQ et al, Free Radic Res. 2015;49(9):1069-80
  16. Kuang S et al, Can J Neurol Sci. 2018 Mar;45(2):182-187
  17. Vijayakumaran S et al, Mol Cell Neurosci. 2019 Dec;101:103416.
  18. Mohammed N et al, Curr Pharm Biotechnol. 2020 Mar 20.
  19. Rojas P et al, Nutrition. 2009 Apr;25(4):482-5
  20. Johnson SK et al, Explore (NY). 2006 Jan;2(1):19-24
  21. Lovera JF et al, Neurology. 2012 Sep 18;79(12):1278-84
  22. Doozandeh A et al, J Ophthalmic Vis Res. Apr-Jun 2016;11(2):209-20.
  23. Martinez-Solis I et al, Planta Med. 2019 Nov;85(17):1292-1303.
  24. Cybulska-Heinrich AK et al, Mol Vis. 2012;18:390-402.
  25. Bungau S et al, Oxid Med Cell Longev. 2019 Feb 12;2019:9783429.
  26. Hirooka K et al, Curr Eye Res. 2004;28:153–7
  27. Shim SH et al, J Med Food. 2012 Sep;15(9):818-23
  28. Evans JR. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD001775.
  29. Moshetova LK et al, Vestn Oftalmol May-Jun 2015;131(3):34-44
  30. Zayed AE et al, Oxid Med Cell Longev. 2018 Jun 11;2018:1785614.
  31. Yan M et al, Mol Med Rep. 2020 Apr;21(4):1809-1818
  32. Guan ZF et al, Metab Brain Dis 2018 33(6):1887-1897.
  33. Tian J et al, Oxid Med Cell Longev. 2019 Mar 18;2019:8134678.
  34. An XF et al, Zhongguo Zhong Xi Jie He Za Zhi. 2016; 36(6):674-677.
  35. Zhao Y et al, Complement Ther Med. 2018 Oct;40:120-125.
  36. Shi R et al, Front Endocrinol (Lausanne). 2019 Feb 22;10:100
  37. Aziz TA et al, Drug Des Devel Ther. 2018 Apr 5;12:735-742
  38. Eisvand F et al, Phytother Res. 2020 Feb 25.

Covid -19: An Opportunity for the New Zealand economy

The Covid-19 pandemic is having and will continue to have a huge impact on the economic wellness of all countries. While effects are far-reaching and multiple industries will be impacted, two of New Zealand’s largest sources of employment and export earnings, have been hard hit by this clever virus, resulting in a sudden increase in financial stress and unemployment. The two industries being tourism and forestry.

With border restrictions and consequently less overseas visitors likely to continue for the foreseeable future, and in the global economic slowdown causing reduced demand for forestry products, the hit on these sectors of our economy from Covid-19 will be harsh. This will be particularly so for people living in New Zealand’s rural regions and small towns, where businesses based around tourism and forestry are often the foundation of the local economy. A re-evaluation of New Zealand’s competitive advantages and emerging opportunities to provide alternative sources of employment and exports in the ‘post Covid-19 world’, is therefore a priority for both the New Zealand government, and many businesses.

 

New Zealand’s Strategic Advantages:

The diversity and scale of our natural and rural landscapes and environment, is a key strength. This is not only appealing to tourists, but provides an ideal environment to grow a wide range of different plant types in different geographical regions. We already produce more food than is required for the local population, and export many products derived from plants and trees. Exports of wine, kiwifruit, avocados, apples, berries and other fruits, nuts and cereals, have all risen substantially over the past five years. The future of food will be more based upon plants and less on animal products, than it is now.

Another strategic advantage New Zealand has, is being a relatively small country with a low population density, and with a track record of adapting quickly to global economic changes and shifting market trends. This we have had to do several times in our past, each with good long term outcomes. Examples include the assignment of thousands of unemployed men to tree planting and further establishing a forestry industry during the Great Depression in the 1930’s, the shift to new markets after being too dependent on Britain for exports when that country joined the EU in 1973, and the early decisions by Air New Zealand to develop new and emerging markets and invest into more fuel-efficient planes, at a time when most airlines were becoming increasingly under stress early this century.

With Covid-19 being the latest global stressor to our economy, as well as future impacts of climate change and increasingly frequent droughts and floods, a fresh and forward thinking approach to rejuvenating regional and rural economies, is called for. In fact the non-native based forestry industry and elements of our tourism industry had already grown to the point of being unsustainable and having increasingly negative environmental and sociological impacts for some time. Some re-setting of their scale and our dependency on them was needed even before Covid-19. Nature has been protesting about the mounting negative impacts from carbon thirsty human activities for some time now, and there is a need to moderate our excessively animal based farming model for the wellness of both the planet and future generations.

 

Phytomedicines: The Big Opportunity

Many of our existing food and beverage products have health enhancing properties, but are just the tip of the iceberg in our potential to grow and add value to, a much wider range of plant-derived herbal or phyto (‘plant’) medicines.

Global demand for herbal medicines and their raw materials has been rising for many years due to a multitude of powerful market drivers, and Covid-19 has spurred this even more. This includes demand for products aimed at supporting immunity and stress, but also a wide range of other health and wellness applications.

Aging populations, increasing costs of new drugs and hospital care, and the associated budgetary constraints by government health agencies, are also catalysing increased interest in natural health products. Finally, the increasing evidence for the effectiveness of various phytomedicine interventions for a wide range of health conditions, supported by traditional use as well as modern science.

Covid-19 has dealt us a sudden reminder that drugs don’t always provide all the answers, and the void of antiviral drugs or vaccines to prevent or treat this virus, should be a wakeup call to us all. And then there’s that other closely related and worsening nightmare of antibiotic resistance, which already contributes to more than 700,000 deaths each year(1, 2), telling us again, that fresh approaches are called for in managing and preventing infectious diseases in humans.

New Zealand is currently one of the best placed countries in the world to build a rich natural health product industry that could make a much bigger contribution to our future exports and GDP. Apart from our natural resources, fertile soils and hard-working farmers, we have an enviable track record of research and development in biological and agricultural sciences, and pharmaceutical company development. Many intelligent people who work within universities, crown research institutes, private laboratories and as R&D providers have contributed to building and supporting a range of companies making products from plants that are competitive and premium quality, and in demand from overseas markets. As with other crops such as avocados, fruit and nuts, returns per hectare from growing medicinal plants are relatively high, although initial establishment costs such as growing systems and processing facilities can be significant, and benefit from economies of scale.

Growing ginseng in New Zealand pine forests has been shown to produce a premium quality (high ginsenoside-containing) and potentially very lucrative crop(3, 4). Rising demand for medicinal mushrooms through research supporting their usefulness in conditions such as cancer, immune conditions, viruses and lung inflammation(5), suggests research into some of the diverse introduced and native fungal species we see growing in our native and planted forests, would also be worthwhile.

While some early commercial operations into growing crops such as ginseng, green tea, ginkgo, saffron and mānuka as sources of medicines has revealed many challenges, others focussed on these and other medicinal plant species, have succeeded, and demand is now often outstripping supply. Further opportunities exist with cultivating high quality and sustainably grown phytomedicines such as saffron, rhodiola, false unicorn root and golden seal, all of which demand high prices due to being endangered in the wild yet highly sought after for their medicinal properties.

 

A Call to Action:

Covid-19 has jolted the world, and caused a sudden shift in the way we used to do things, and how the future will look. Like other countries, New Zealand needs to respond to this as a matter of some urgency, by identifying and pursuing new opportunities that have become even more apparent since this virus jumped into humans.

Businesses themselves will of course continue to develop innovative products and pursue emerging export market opportunities. However, support from government to enable more research and the development of increased local raw material production would both help facilitate increased exports by this fast growing and healthy industry. This would also help regenerate rural economies, and provide new sources of employment to those severely impacted by Covid-19.

A working group of industry, science, Māori, farming and government representatives should be formed to further explore options, and some of the regional development and other government funds that are being allocated to support business development and employment initiatives during the Covid-19 pandemic, could perhaps be allocated to this. An action plan to support new initiatives to help New Zealand leverage some of these large opportunities, could include the following:

  1. Investment in research into phytomedicines as well as that involving drugs, for Covid-19 and as antibiotic alternatives or adjuncts.
  2. A stocktake and comprehensive survey of various weeds, native plants and fungi that could be propagated and harvested as a secondary income earner for the forestry industry.
  3. Research into medicinal plants including field trials on selected species, to learn more about their agronomy, optimal growing conditions and geographical locations, and quality plus commercialisation considerations.
  4. Research into the phytochemistry, pharmacology and agronomy of New Zealand native plants and fungi, and an integrated approach to enable these being able to make a greater contribution to the future health care of both local communities, as well as wellness needs of our future generations and tamariki.
  5. Support for private sector businesses engaged in researching and establishing export markets for innovative, value added natural health products made from locally grown raw materials.
  6. Funding for clinical trials into phytomedicines that have the potential to be both grown in New Zealand, and make a valuable pharmaco-economic contribution to future health care treatments.

 

Finally, in writing this I’ve been taken back to remembering one of the children’s books I used to read to my son a few years ago,Dinosaurs (and all that rubbish)” by Michael Foreman. The book describes how the dinosaurs have taken over the Earth, after it not being treated kindly by humans, and one piece of it reads:

“As the rubbish was cleared

Green shoots appeared,

Bursting through cracks

And climbing over old forgotten walls.

Telegraph poles and iron pylons

Vanished beneath trailing blossoms,

And a fresh new forest

Of flowers and trees spread

Like a smile around the world”.

 

 

Phil Rasmussen

28 April 2020

 

 

withania seedlings 2016

 

References:

  1. https://www.fairr.org/article/resisting-resistance-investors-take-action-to-manage-risk-of-antibiotic-overuse-in-farming/
  2. Gerberding JL, First Opinion, 23 March, 2020. https://www.statnews.com/category/first-opinion/
  3. Chen W et al, Biomolecules 2020; 10(3):372.
  4. https://www.riddet.ac.nz/supercharged-ginseng-grown-on-new-zealands-fertile-volcanic-slopes/
  5. Chaturvedi VK et al, 3 Biotech. 2018 Aug; 8(8): 334.

 

CULINARY HERBS AND SPICES TO KNOW ABOUT, IN INFECTIOUS TIMES

Global panic has set in from the December 2019 outbreak of a new human form of coronavirus (SARS-CoV-2), responsible for causing the disease COVID-19 initially in China, and which has now become a pandemic as it spreads in multiple countries.

This virus is genetically closely related to the SARS-CoV-1 virus which first appeared in 2003, and is different to seasonal influenza. The mortality rate of COVID-19 is approximately 36 per 1,000 people, with highest rates in the elderly and those with pre-existing respiratory or cardiovascular disease, or diabetes. By comparison, the death rate from seasonal influenza is approximately 1 per 1,000 people (European Centre for Disease Prevention and Control (1).

As at the time of writing, at least 218,000 cases of COVID-19 and more than 8000 deaths have been reported globally, and numbers are increasing rapidly. No vaccine or proven drug treatment options are available, and panic buying in many countries has led to supermarket shelves been cleared of items such as toilet paper and hand sanitiser. Natural health products aimed at enhancing immunity, are also in high demand and supply shortages are becoming apparent.

It is therefore appropriate to start thinking about the various common herbs and spices, weeds and other plants available in our individual communities, that may be useful to support the need for greater ‘self care’ in the next few weeks or months.

This article will discuss some culinary herb and spice options, and will be followed by others on weeds and native plants, growing here in Aotearoa, New Zealand.

 

Part 1: Culinary spices and herbs:

Many well-known spices and herbs used in cooking have useful antimicrobial properties, and it is these in addition to their effects on the human palate, that made them very important and highly valued in early human trade. These include oregano, thyme, rosemary, ginger, garlic, onions, welsh onions, black mustard, cinnamon and blackseed.

While for the majority it is their antibacterial rather than antiviral actions that are most established, several seem to have effects that could be directly relevant to the prophylaxis or management of a COVID-19 infection.

While the COVID-19 situation is evolving rapidly and there is much not well understood, a large percentage of those who became severely ill or died from previous viral pandemics in 1918, 1957, 1968 and 2009, developed bacterial pneumonia, with Staph aureus and Strep pneumoniae being the most common bacterial pathogens (2). Evidence to date suggests that this virus is likely to be similar, and a significant proportion of SARS-1 and at least 10% of COVID-19 patients, develop such secondary bacterial infections in addition to infection with the virus itself (3).

These bacterial co-infections are associated with significant inflammation, and sometimes pneumonia and death. Pandemic viral infections make their development more likely, as viruses express bacterial adhesion receptors and can invoke an inflammatory response that can disturb the integrity of the respiratory tract’s normal physical barrier to bacteria (4). Recent studies in children also reveal complex interactions between viruses, the respiratory microbiome and the host’s immune response, which may have an impact on the pathogenesis and severity of respiratory virus infections (5).

While appropriate antibiotics can be life-saving and if available should be prescribed during serious bacterial lung infections and pneumonia, antibiotic resistance due to their overuse, and limited access to antibiotics for many, are seriously growing concerns for the human race. Therefore, herbs and spices that have traditional and/or scientific evidence of strong antibacterial activities, may be useful and should be considered. This is particularly likely to be the case, where their traditional use relates to conditions affecting the lungs or respiratory tract.

Some such culinary herbs and spices that spring to mind, are Garlic, Horseradish, Thyme and Oregano. These or other herbs traditionally used for congestion or infection of the lungs, may provide relief to some patients, and help lessen the risk of secondary bacterial infections and need for antibiotics or other drug-based medications.

 

Ginger (Zingiber officinale)

This is one of my favourites, for so many reasons. Much more than just a warming spice to add a bite to our food and smoothies, the rhizome and root of ginger has pronounced anti-inflammatory (6) and possibly some antiviral (7,8) properties, which may be useful.

High concentrations of a water extract of fresh but not dried ginger showed anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines, this activity being greatest when given before viral inoculation (9). A similar dose-related antiviral activity was measured in vitro against the avian influenza virus H9N2 (10).

Inhibition of Hepatitis C viral protease has been reported for both aqueous and methanol extracts of ginger (11). An Eqyptian clinical study found administration of a hydroethanolic extract to Hepatitis C patients decreased their viral load and improved liver function. These effects were enhanced when ginger was combined with blackseed (Nigella sativa) (12).

Zingiber montanum (Cassumuna ginger), a related Asian ginger species which is noxious in various countries, has been reported to more than halve the level of infectivity of the highly pathogenic avian influenza virus H5N1 in a cell-based assay (13).

Apart from potential antiviral effects, studies on animals suggest that modulation of the immune response to viral infections, may contribute to ginger’s beneficial effects (14, 15). One study for example, measured no inhibitory effect on the growth of influenza A virus for ginger root extract itself, but found it to produce activation of the macrophages leading to production of TNF-alpha (16).

While like other culinary herbs and spices specific anti-COVID-19 activity is unproven, there seems to be much to gain from preparing a hot drink by gently simmering a good few slices of the rhizome of this popular spice in a saucepan with the lid on it, then drinking this as a decoction. Particularly when stuck at home during an enforced winter lockdown!

 

Garlic (Allium sativum)

The reputation of garlic bulbs as an antimicrobial agent is strong, but this pertains mainly to antibacterial and antifungal activities, and the evidence it helps with viral infections such as colds and influenza, is mixed (17, 18).

One clinical trial in healthy volunteers found 90 days administration of an aged garlic extract to reduce the severity and symptoms, but not the frequency of colds and influenza (19).

Promising findings have however, been recently reported for a gold nanoparticle product made from garlic extract, as a potent inhibitor of the measles virus (20).

Like garlic, other Allium species such as onions, leek, shallot, scallion, and chives also show evidence of useful antimicrobial properties, and contain a plethora of bioactive compounds such as organosulfur compounds, polyphenols, saponins, fructans, and fructo-oligosaccharides (21). Green tops of Welsh onions (Allium fistulosum) for example, contain a fructan which showed inhibitory effects on replication of influenza A and enhanced antibody production against this virus in mice (22).

Garlic extracts show activity against Streptococcus pneumoniae and Klebsiella pneumoniae (23). Garlic’s antimicrobial activities are largely due to sulphurous compounds such as allicin (diallylthiosulfinate), a volatile compound produced when garlic is crushed. German researchers have shown allicin vapour to inhibit the growth of a range of lung pathogenic bacteria, including multi-drug resistant strains (24).

This suggests that frequent direct inhalation of crushed garlic may be useful to help combat bacterial lung infections, and could be a useful adjunct with oral antibiotics, where bacterial co-infection exists or is suspected.

 

Holy Basil (Tulsi) (Ocimum tenuiflorum, O sanctum) and Sweet Basil (Ocimum basilicum)

A popular aromatic herb used in cooking particularly by the Indian community, the leaves of Holy Basil or Ocimum tenuiflorum as well as other Ocimum species including the related so-called European or sweet Basil (Ocimum basilicum), are revered for their medicinal properties. Both these and other Ocimum species (but particularly Holy Basil) also contain the triterpenoid compound ursolic acid, which exhibits strong antiviral activity against a range of viruses such as herpes simplex, adenoviruses, rotavirus, coxsackievirus and enterovirus (25, 26).

A crude extract and terpenoid isolated from Holy Basil leaves has shown promising antiviral properties against H9N2 virus (27). In vitro activity against the HIV virus, has also been reported for the related Ocimum gratissimum (28).

Recent studies have also found an extract of sweet basil leaves to inhibit attachment and entry of the Zika virus into the host cell (29). Evidence of possible neuraminidase inhibitory activity against the H1N1 swine flu virus for the flavonoid compound apigenin, extracted from Holy Basil and found in a range of other medicinal plants, has also been reported (30).

While becoming out of season now in New Zealand, for those in warmer climates or with greenhouse growing options, planting lots of these two easy to grow herbs now, may pay dividends beyond their yummy flavours in the future.

 

Blackseed (Nigella sativa) or Ketza (black cumin)

This is a highly regarded traditional remedy used by many Asian, Middle Eastern and northern Africa ethnic groups in cooking and for a wide range of health issues, including to enhance immunity and to treat diarrhoea and various types of infections (31).

Protection against murine cytomegalovirus has been reported for blackseed oil (32). Eqyptian studies found blackseed administration to significantly reduce the viral load in patients with Hepatitis C (33), and to inhibit replication of this notoriously resilient virus (34). Six weeks administration of a combination of blackseed with echinacea also enhanced the immune response after vaccination against the H9N2 avian influenza virus, and reduced the pathogenicity of infection in stressed chickens (35).

 

Cinnamon (Cinnamonum zeylanicum)

The bark from various Cinnamonum species found in Sri Lanka, Indonesia and now cultivated in other Asian countries, has been traded for more than 2000 years, and was imported by Arabs to Eqypt, Venice and Europe, where it was used to preserve meats as well as for flavour. Control of the Cinnamon trade was a key factor in Portuguese (then Dutch) control of Sri Lanka, in the 16th century.

Potential benefits in fever management have been reported using an influenza virus infection model in mice (36), and antiviral effects against H1N1 Influenza A and herpes simplex viruses, as well as antibacterial effects against Staph aureus and Strep pneumoniae, shown for a blend of Cinnamomum zeylanicum, Daucus carota (wild carrot), Eucalyptus globulus (eucalyptus) and Rosmarinus officinale (rosemary) essential oils (37). A nanoparticular form of Cinnamomum cassia also exhibited promising activity against the H7N3 Influenza A virus (38). Trans-cinnamaldehyde, a major constituent of cinnamon essential oil exhibits in vitro antiviral activity against influenza A/PR 8 virus, and when given by nasal inhalation increased the survival rates of mice infected with a respiratory virus (39).

Cinnamon, its essential oil and its key constituents cinnamaldehyde and cinnamic acid also possesses strong antibacterial activity against a range of pathogenic bacteria (40), so incorporating some of this spice into your winter wellness warming beverage or mulled wine could be a good move.

 

Horseradish (Armoracia rusticana)

Not just a sought after culinary sauce, the roots of this strong and distinctive plant, have a long tradition of use particularly in Europe, for the treatment of bronchial infections.

Isothiocyanates from horseradish root exhibit broad spectrum antibacterial activity in vitro (41), and a mixture of horseradish when mixed with Nasturtium (Tropaelum majus), showed good activity particularly against Haemophilis influenzae, and intermediate activity against Staph aureus, Strep pneumoniae, Klebsiella pneumoniae and Strep pyogenes (42). Some evidence of prophylaxis against the H3N2 influenza virus has been reported in animal studies (43), though as with many of the herbs and spices I have mentioned, large doses are likely to be required.

While not widely grown here in New Zealand, it isn’t difficult to cultivate, and in fact can become ‘weedy’, not unlike how it grows in many locations in the U.K.

Other spices that may be useful, include Turmeric (Curcuma longa), and Black mustard (Brassica juncea). Both water and ethanolic extracts of black mustard have been reported by Korean researchers to exhibit in vitro activity against influenza virus A/H1N1 (44,45). Researchers in Thailand recently screened some Asian medicinal plant extracts and found ethanolic extracts of turmeric root as well as the leaf of guava (Psidium guajava), to have good in vitro activity against the H5N1 influenza virus (46).

While COVID-19 is a highly virulent and very challenging virus to combat and at the current time we have no research establishing the clinical efficacy of any of the herbs and spices I have mentioned, there is an urgent need to take an interest in this subject and what dietary interventions may perhaps assist, with infection prophylaxis at least. Similarly there are a number of weeds and native plants growing in our beautiful country that may also be helpful, and which I will discuss in subsequent postings.

I’m not lucky enough to be living in a bush area where the large, soft-leafed NZ native plant Rangiora (Brachyglottis repandra, “Bushman’s Friend”) is endemic and so if we run out of toilet paper will need to invoke other methods, but I’m feeling OK about having everyday plants on hand to take as teas or inhalations, should I or my family need to in the coming months.

 

References

  1. European Centre for Disease Prevention and Control https://www.ecdc.europa.eu/en
  2. Rynda-Apple A et al, Infection & Immunity 2015; 83(10):3764-3770.
  3. Huang C et al, Lancet 2020 Jan 24; epub ahead of print.
  4. Rossi GA et al, Pediatr Pulmonol. 2020 Apr;55(4):1061-1073.
  5. Diaz A Pediatr Infect Dis J. 2019 Jun;38(6S Suppl 1):S14-S19.
  6. Grzanna R et al, J Med Food. 2005 Summer;8(2):125-32.
  7. Denyer CV, J Nat Prod. 1994 May;57(5):658-62
  8. Bode AM, Dong Z, In: Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011. Chapter 7. Editors Benzie IFF, Wachtel-Galor S.
  9. Chang JS et al, J Ethnopharmacol 2013; 145(1):146-151.
  10. Rasool A et al, Pak J Pharm Sci 2017; 30(4):1341-1344.
  11. Sookkongwaree K et al, 2006 Aug;61(8):717-21.
  12. Abdel-Moneim A et al, EXCLI J. 2013 Nov 11;12:943-55.
  13. Klaywong K et al, Southeast Asian J Trop Med Public Health. 2014 Jan;45(1):62-74.
  14. Sultan MT et al, Crit Rev Food Sci Nutr 2014; 54(10):1298-1308.
  15. Sukumaran V et al, Fish Shellfish Immunol 2016; 57:362-370.
  16. Imanishi N et al, Am J Chin Med. 2006;34(1):157-69.
  17. Chavan RD et al, Pharmacognosy Res 2016; 8(2):105-11.
  18. Lissiman E et al,, Cochrane Database Syst Rev. 2014 Nov 11;(11):CD00620
  19. Percival SS, J Nutr. 2016 Feb;146(2):433S-436S
  20. Meléndez-Villanueva MA et al, 2019 Nov 30;11(12). pii: E1111. doi: 10.3390/v11121111
  21. Kothari D et al, Animals 2019; 9(12). pii. E1032.
  22. Lee NK et al, J Dairy Sci. 2014 Sep;97(9):5383-6.
  23. Dikasso D et al, Ethiop Med J 2002; 40(3):241-249.
  24. Reiter J et al, 2017 Oct 12;22(10)
  25. Chiang LC et al, Clin Exp Pharmacol Physiol. 2005 Oct;32(10):811-6.
  26. Tohme MJ et al, Int J Antimicrob Agents. 2019 Nov;54(5):601-609.
  27. Ghoke SS et al, BMC Complement and Altern Med 2018; 18(1):174
  28. Ayisi NI, Nyadedzor C. Antiviral Res. 2003 Mar;58(1):25-33.
  29. Singh P et al, Acta Virol 2019; 63(3):313-321.
  30. Alhazmi Bioinformation. 2015 Apr 30;11(4):196-202.
  31. Yimer EM et al, Evid Based Complement Alternat Med. 2019 May 12;2019:1528635
  32. Salem ML, Hossain MS. Int J Immunopharmacol. 2000 Sep;22(9):729-40
  33. Barakat EM et al, World J Gastroenterol. 2013 Apr 28;19(16):2529-36
  34. Oyero OG et al, Afr J Tradit Complement Altern Med 2016; 13(6):144-148.
  35. Eladl AH et al, Comp Immunol Microbiol Infect Dis. 2019 Aug;65:165-175.
  36. Kurokawa M et al Eur J Pharmacol 1998; 348(1):45-51.
  37. Brochot A et al, Microbiologyopen 2017; 6(5): doi:10.1002
  38. Fatima M et al, J Microbiol Biotechnol 2016; 26(1):151-159.
  39. Hayashi K et al, Antiviral Res 2007; 74(1):1-8.
  40. Vasconcelos NG et al, Microb Pathog. 2018 Jul;120:198-203
  41. Park HW et al, Biocontrol Sci 2013; 18 (3), 163-8
  42. Conrad A et al, Drug Res (Stuttg). 2013 Feb;63(2):65-8
  43. Oxford JS et al, Am J Ther 2007; 14(5):462-468.
  44. Lee JB et al, Food Chem 2012; 134(4):2164-8.
  45. Bae WY et al, BMC Complement Altern Med. 2019 Sep 11;19(1):253.
  46. Sornpet B et al, Asian Pacif J Tropical Med 2017; 10(9):871-876.

Optimising Immunity to Protect against Coronaviruses

The outbreak of a new human form of coronavirus (Wuhan novel coronavirus, 2019-nCoV) in December 2019 in the city of Wuhan in China, is spreading fear and alarm around the world.

Around 56 million people in China have been under lockdown since Chinese New Year, and the Chinese government has just completed the fast-tracked building of the first of two new hospitals in Wuhan, to help cope with a rapidly growing number of cases. As at Monday 3rd February, 20,438 confirmed cases have been reported across all regions in China as human to human transmission occurs, and 425 people have died following infection with the virus, 414 of which were in Hubei province where Wuhan is located. Cases have now been reported in at least 25 other countries, though only one death outside of China has been reported to date.

As with other serious virus outbreaks that have emerged over the past 45 years such as Ebola virus, Bird Flu (H5N1) and Swine Flu (H1N1) virus, this coronavirus seems to have originated in another animal species (probably a bat), and jumped the barrier to be able to replicate itself in humans.

China is now more prepared than it was back in 2002 when the SARS (Sudden Acute Respiratory Syndrome) virus emerged, killing 774 of the 8090 people reportedly infected. Also, while it is relatively early days, indications are that the death rate from 2019-CoV will be less than that of SARS, at around 2-3% of diagnosed cases, versus around 10% for SARS. However, like all viruses 2019-nCoV is likely to continue to mutate rapidly, and new more pathogenic forms are possible.

 

The Coronavirus

Coronaviruses are a fairly large family of viruses that cause illness ranging from the common cold (responsible for 15-30% of cases), to more severe diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). They typically infect the respiratory tract, though the gut can also be affected.

Human to human transmission of 2019-nCoV seems to be relatively easy, though we are still learning about the various means through which this can occur. A 7-14-day incubation period seems to occur before symptoms begin to show, although even asymptomatic cases can be infectious,

Most 2019-nCoV patients initially hospitalised in Wuhan had fever at the onset of symptoms, and well as dyspnoea (shortness of breath) and a cough. Myalgia (muscle pain) or fatigue also seem to be common symptoms. The main cause of death is from pneumonia and acute respiratory distress syndrome(1).

 

Treatment Options

There are no proven effective antiviral drug treatments for coronavirus infections, and our biggest protection against this new virus or others that may come our way, relies largely upon the execution of good Public Health measures. Restricting travel, wearing masks, washing hands frequently, the use of sanitising agents and the isolation of those with suspected infections, is the best current approach to help reduce the risk of spread to others.

In considering the nature of the virus and what is known about it so far, there would appear to be a number of possible pharmacotherapy (drug and/or herbal) approaches, namely:

  1. Enhancing immunity to help protect against infection, or if it takes hold, to improve the body’s ability to fight it.
  2. Antiviral actions to specifically inhibit the ability of 2019-nCoV to take hold and replicate.
  3. Lung and respiratory tract protective, healing and anti-inflammatory agents.
  4. Other agents such as febrifuges and systemic anti-inflammatories, to help reduce acute symptoms in some cases.

Since this virus hit the headlines a plethora of articles and social media posts promoting a whole range of natural including herbal treatments has appeared, although the quality of many of these leaves much to be desired.

Just as drug developers have found it challenging to make drugs that have clinically significant antiviral actions, the evidence for herbal remedies having the same, is slim. I am not saying they don’t exist, because I’m sure they do.

However, claiming an antiviral action of a herbal preparation based upon an in vitro antiviral activity shown against a virus completely unrelated to 2019-nCoV, by an individual phytochemical found in relatively low amounts in a whole herb, and usually about which little if anything is known on its bioavailability (ability to be absorbed from the gut after oral administration and distributed to the area in the body where it needs to act), is a very far reach.

A more likely efficacious and evidence-based approach to incorporating plant-based products to help reduce the potential impact of this new virus on human health, is therefore to focus on enhancing immunity. Herbs that help foster greater immunity or that protect or help heal the respiratory tract from the acute inflammation, shortness of breath, pneumonia and respiratory failure that are main causes of serious illness and death, are worthy of consideration.

 

Optimising immunity

As with all infectious diseases, the level of pre-existing immunity to the microbial pathogen, is a key factor known to influence the susceptibility to and severity of an infection, and immunocompromised patients are more vulnerable to viral infections. The largest factor in immunity to influenza and coronaviruses seems to be serum antibodies induced by prior infection or vaccination, which impart a strong and disease specific host resistance to the virus. However, it will take many months or even years to develop a vaccine, and even then, the virus may mutate further by that time.

Plants have much to offer in terms of optimising immunity in humans, and a healthy vegetable and fruit rich diet, is increasingly linked with favourable influences on the gut microbiome and immune function(2). Many plant and mushroom derived preparations have been shown to help enhance human innate immunity (resistance) to different viral and bacterial pathogens, and a full review of these is not possible here. However, I consider Echinacea (Purple coneflower) one of the most promising from both a traditional as well as evidence-based perspective.

 

Echinacea

Echinacea was an important traditional medicinal herb to Native Americans, and different species were used to treat animal bites and a wide range of infectious and inflammatory conditions(3,4). Early European settlers to the Midwest adopted Echinacea purpurea and Echinacea angustifolia as a treatment for wounds and glandular inflammation, and it was a preferred treatment by many clinicians for infections until discovery of penicillin. There are now more than 1200 scientific papers published on it, and its principle application over the last 50 years has largely been as a prophylactic or treatment for colds and influenza.

Several clinical trials have shown beneficial effects of echinacea during the treatment of colds and influenza, although others have had less favourable outcomes. However, evaluation of these is complicated by the use of a diverse range of product types, plant part(s) and doses used.

Immune enhancement and modulation, and anti-inflammatory effects, are principal actions of echinacea, and numerous studies have reported immunological changes associated with echinacea root usage. Key outcomes seem to be increased numbers of circulating white blood cells, monocytes, neutrophils and natural killer (NK) cells, and the abilities of these immune cells to engulf and inactivate harmful microbes or carcinogens. This enhancement of the non-specific immune response, is thought to improve the body’s ability to maintain immunosurveillance against a variety of potential viral or bacterial pathogens or spontaneous-developing tumours.

Canadian researchers found that normal mice given Echinacea purpurea root had significantly prolonged life spans versus non-immunized mice(5). NK cells were also elevated in leukaemic mice receiving echinacea in their diet versus those who didn’t(6). Japanese researchers found Echinacea purpurea to have a suppressive effect on spontaneously occurring leukaemia caused by a murine leukaemia virus, an effect related to enhancement of immune systems(7).

Stress is known to reduce immunity, and echinacea has shown beneficial effects on stress-induced immunosuppression by increasing splenocyte proliferation and NK cell activity, while modulating blood levels of inflammatory cytokines(8).

Secondary or co-existing bacterial infections are also a common cause of pneumonia and death in patients with viral infections of the respiratory tract, and have been reported in approximately 10% of 2019-nCoV hospitalised patients(1). Viral infections can express bacterial adhesion receptors, and the virus-induced inflammatory response can also disturb the integrity of the physical barrier to bacteria. Evidence suggesting echinacea may prevent virus-induced bacterial adhesion to cell membranes, and moderate an excessive inflammatory response (cytokine storm) sometimes seen with pandemic forms of viruses(9,10), may therefore contribute to improved host resistance against pathogenic viral infections.

Alkylamides (alkamides), found in highest concentrations in the root, are now regarded as major bioavailable and active immunomodulatory components in oral forms of echinacea(11). However, microbes known as endophytes that live in close association with echinacea, also exhibit strong antibacterial effects against respiratory pathogenic bacteria such as Klebsiella pneumonia, Burkholderia cepacia and Acinetobacter baumannii(12-14). Recent research also suggests that inulin-type fructans found in echinacea, which are prebiotic compounds that promote a health microbiome, may also contribute to beneficial immunomodulatory effects(15).

In summary, while the situation in China and elsewhere will continue to evolve rapidly over the coming weeks, given its seriousness and the limitations of drug treatment options at this point, herbal options such as echinacea to help optimise our immune system’s resistance to 2019-nCoV or other viruses that will continue to come our way, should be considered.

 

References:

  1. Huang C et al, Lancet 2020 Jan 24; epub ahead of print.
  2. Tomova A et al, Front Nutr. 2019 Apr 17;6:47.
  3. Felter HW. The Eclectic Materia Medica, Pharmacology and Therapeutics. Eclectic Medical Publications, Oregon, 1922.
  4. Smithsonian National Museum of Natural History, http://www.mnh.si.edu/lewisandclark/index.html?loc=/lewisandclark/home.html
  5. Brouseau M, Miller SC, Biogerontology. 2005;6(3):157-63.
  6. Currier NL, Miller SC, J Altern Complement Med. 2001;7(3):241-51.
  7. Hayashi I et al, Nihon Rinsho Meneki Gakkai Kaishi. 2001;24(1):10-20.
  8. Park S et al, J Med Food. 2018; 21(3):261-268.
  9. Rasmussen PL, Phytotherapy in an Influenza Pandemic: Swine Flu. Phytonews 32, 2009, June. Published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand. ISSN 1175-0251.
  10. Vimalanathan S et al, Virus Res. 2017; 2(233):51-59.
  11. Mudge E et al, J Agric Food Chem. 2011; 59(15):8086-94.
  12. Haron MH et al, Planta Med 2016; 82(14):1258-1265.
  13. Presta L et al, Res Microbiol 2017; 168(3):293-305.
  14. Chielleni C et al, Microbiol Res. 2017 Mar;196:34-43.
  15. Dobrange E et al, 2019 Oct 16;9(10). pii: E615.

ELECAMPANE, TO PROTECT OUR LUNGS DURING AN ERA OF INCREASING BUSHFIRES

The bushfires in Australia have worsened since I wrote about them a couple of weeks ago. Frequent exposures to hazy skies containing tiny airborne pollutants that are damaging to our lungs, have been incurred by millions of Australians, and also by many New Zealanders due to drift across the Tasman. Smoke from the Australian fires has also travelled to Argentina and across to the Atlantic, a stark reminder of how climatic events in one part of the world can have significant impacts on those living in completely different continents.

In addition to mucilaginous (polysaccharide hydrocolloid rich) and expectorant herbs such as Marshmallow (Althaea officinalis), Mullein (Verbascum thapsus) and the New Zealand native Hoheria (Hoheria populnea), evidence suggests that other herbal medicines can be beneficial for those forced to live or work in environments where exposure to smoke or fine-particulate matter containing and toxic haze from bush or forest fires, is unavoidable. Herbs with protective actions against airborne lung damaging and potentially carcinogenic compounds, are of particular interest.

One of the most promising herbs in this regard, is Elecampane (Inula helenium), the roots of which have long been traditionally used in treatments for coughs, chest infections, asthma and other lung conditions. Elecampane is an anti-inflammatory, antimicrobial and antioxidant herb, and contains various constituents exhibiting lung protective effects.

Research showing in vitro activity by elecampane against various forms of human cancer cell lines was first reported in 2002(1), and several further investigations into anticancer properties of elecampane and other Inula species, have produced favourable results(2-8). While having antitumour activity against cancer cells, no harmful effects have been measured on normal cells(3).

The sesquiterpene lactones alantolactone and isoalantolactone, key sesquiterpene lactone constituents in elecampane roots, undoubtedly contribute to these effects, having inhibitory effects against human lung, breast, prostate, colon and pancreatic cancer cells through a range of different mechanisms(10-13). Alantolactone also increases the sensitivity of lung cancer cells to the effects of the chemotherapy drugs doxorubicin and gemcitabine(9,10), suggesting a possible role as adjunctive therapy.

Isoalantolactone has also been shown to have marked anti-inflammatory effects and to reduce the extent of lung injury following exposure to lung damaging compounds in animal studies. Beneficial effects included suppression of pulmonary pathological changes, neutrophil infiltration, pulmonary permeability, and pro-inflammatory cytokine expression(14).

However, isoalantolactone and alantolactone seem to have low bioavailability when given orally to rats, possibly due to poor stability in gastrointestinal fluids and being subject to significant degradation by the liver after absorption through the so-called “first pass effect”(15,16). As such, alternative means of administration of elecampane apart from the usual oral route, particularly when the lungs are the target organ, are worth considering.

Many traditional applications of herbal medicine including Maori Medicine (Rongoā Māori), Ayurvedic, Chinese and European herbal medicine, utilised inhalation through the lungs as a popular method of administration. This pulmonary route of administration through inhalation or sprays, is also used widely in modern drug-based medicine as a means of treating conditions such as asthma or sore throats, or as a way to deliver drugs to the general blood circulation and treat other systemic conditions. Well-known examples include the pronounced bronchodilatory or anti-inflammatory effects through inhaling bronchodilatory or anti-inflammatory asthma drugs, relaxant and calming effects through inhalation of essential oil-rich preparations such as lavender or chamomile, and the well-known effects through inhaling preparations of plants such as cannabis and tobacco. The high permeability and large absorptive surface area of the lung alveolar epithelium, its good blood supply, the rapid onset of action and capacity for overcoming first-pass metabolism, can provide significant advantages of a pulmonary rather than oral route of administration(17-18).

With increasing evidence that acute or chronic environmental or occupational exposure to airborne carcinogens or lung-damaging compounds can have serious effects on human health, not only in an era of increasing bushfires but also amongst farmers handling pesticides, firefighters, painters and others working in dusty environments, the possible application of chemo-preventive and lung protecting herbs such as elecampane through the pulmonary route as an inhalation or spray, deserves more attention.

inula photo

Refs:

  1. Konishi T et al, Biol Pharm Bull 25(10):1370-1372, 2002.
  2. Spiridonov NA et al, Phytotherapy Res 19(5): 428-432, 2005.
  3. Dorn DC et al, Phytother Res. 2006 Nov;20(11):970-80.
  4. Wang GW et al, Expert Opin Investig Drugs. 2014 Mar;23(3):317-45
  5. Chun J et al, Phytother Res. 2018 Dec;32(12):2501-2509.
  6. Koc K et al, J Cancer Res Ther. 2018 Apr-Jun;14(3):658-661
  7. Zhang B et al, Mol Med Rep. 2018 Apr;17(4):5440-5448.
  8. Bar-Shalom R et al, Front Oncol. 2019 Apr 10;9:227
  9. Wang J, et al. Int J Mol Med. 2019. Sep;44(3):1026-1038
  10. Maryam A et al, Sci Rep. 2017 Jul 24;7(1):6242
  11. He R et al, Toxicol Appl Pharmacol. 2018 Oct 1;356:159-171.
  12. Liu J et al, J Food Biochem. 2019 Sep;43(9):e12972.
  13. Wang J et al, Int J Mol Med. 2019 Sep;44(3):1026-103
  14. Ding YH et al, Acta Pharmacol Sin. 2019 Jan; 40(1): 64–74.
  15. Lee JY, et al. Biopharm Drug Dispos. 2016. Apr;37(3):156-67
  16. Xu R et al, Eur J Drug Metab Pharmacokinet. 2019 Apr;44(2):295-303
  17. Patil JS, Sarasija S.Lung India. 2012 Jan;29(1):44-9.
  18. Gandhimathi C, 2015 et al. J Nanosci Nanotechnol