Overcoming Insomnia – Drug versus Herbal Solutions

So-called “Z drugs” such as zopiclone, were first approved as prescription sleeping tablets in the U.S. in 1993, and these are now more often used for insomnia than benzodiazepines such as Valium® (diazepam) or Mogadon® (nitrazepam)(5). However, whether these newer generation drugs which seem to act on different sites of the same GABA-A receptors as benzodiazepines, are in fact safer than their older cousins, is debatable. While their shorter duration of action and different receptor affinities may be associated with a slightly lower risk of dependency, they seem to be just as likely to lead to motor vehicle accidents & falls leading to fractures, particularly in older adults. These are major adverse events associated with the use of these drugs, and together with the risk of dependency, remain real concerns especially with ongoing use. Their prolonged use in young adults, can also compromise cognition, and have other negative adverse events in this age group. Finally, a range of other rare but serious adverse events from Z- drugs have been implicated in recent years, including dementia, infections, respiratory disease exacerbation and pancreatitis(6).

While the once widespread use of strong sedative antihistamine drugs to help knock out infants and children at night seems to have dissipated in recent years, other pharmaceutical drugs apart from benzodiazepines and Z drugs, are still widely used for stress management and associated sleeping difficulties. These include some powerful prescription-only drugs such as antipsychotics, antihistamines and opiates, which in many countries now, are being taken for sleep disorders and related ‘off label’ indications, and not just for their approved uses.

A cross-sectional study in 2015 also revealed that 42% of patients in the community taking a benzodiazepine or zopiclone for insomnia had experienced at least one adverse event, 52% had tried to stop, and that 23% of those taking Z drugs, wanted to stop taking the drug.

Given all of this, it is hardly surprising that many look for a herbal alternative to assist them to nod off and sleep soundly at night. However, while there seems to be a huge array of products out there said to help, including a large array of herbal teas with sleep-invoking names and packaging, when it comes to clinical trials showing that these actually work, there doesn’t seem to be a whole lot of compelling evidence.

A review of clinical trials of herbal products for insomnia, published in the December 2015 journal Sleep Medicine Reviews, evaluated 14 randomised clinical trials involving a total of 1602 participants with insomnia(7). The authors concluded that very few of these trials showed improved sleep quality and duration following herbal interventions. Of relevance perhaps, was that virtually all trials involved the use of herb combinations rather than individual agents. However, as is the case with such trials, the quality of the products involved, and doses used, varied enormously.

One of the best known herbs used traditionally for insomnia, is Valerian (Valeriana officinalis) root. While there has been a mixed appreciation of its value in recent years, and its taste and odour aren’t exactly pleasant, comments from the esteemed German medical practitioner and phytotherapist Rudolf Weiss, who widely prescribed Valerian and other herbs while in Russian captivity with limited drug supplies during World War 2, are salient:

“Valerian is beyond doubt a good and genuine sedative. There is however one aspect that has often been neglected: to be properly effective, valerian has to be prescribed in a sufficiently high dosage. It is almost pointless to give ten or twenty drops of valerian tincture; any effect here would be largely psychotherapy. The dose has to be very much larger, at least a whole teaspoonful of the tincture in water or on sugar…..the single dose of one teaspoonful may, if necessary, be repeated two or three times at short intervals. The greater effectiveness of some proprietary valerian preparations is due to the fact that this has been taken into account, with the dosage made sufficiently high”(8).

Medical conditions or other physical ailments, can also be partly or largely contributory to a poor night’s sleep, and identifying and trying to manage these with appropriate herbal medicines, can also be worthwhile. These include menopause, depression, aches and pains due to arthritis or injury, migraines, alcohol or drug withdrawal, or adverse effects to drugs such as prednisone or methamphetamine.

Clinical trials have shown Valerian and a combination of Valerian with Lemon Balm to improve the quality of sleep in postmenopausal women(9,10). Valerian with acupressure also improved the quantity and quality of sleep in patients with acute coronary syndrome(11). Another trial found Valerian to improve sleep in HIV patients taking the antiviral drug efavirenz(12), and a combination of Valerian, Hops and Zizyphus, to improve both total sleep time and night awakenings frequency(13).

There is in fact much more in the way of good quality published research supporting the benefits of herbal interventions in cases of anxiety or associated conditions, than straight insomnia. Evidence from clinical trials and other studies of anxiolytic as opposed to sedative effects for various medicinal herbs, is already substantive, and growing. As discussed in my February 2017 blog, there are many herbs which have been successfully traditionally used for anxiety. They include Chamomile, Lavender, Skullcap, Passionflower, Valerian, Kava, Lemon balm, Zizyphus, Hops and Withania.

Extracts of the Polynesian plant Kava (Piper methysticum) became popular towards the end of last century, for the management of anxiety disorders and related insomnia. While product type and phytochemistry, and doses used in clinical trials have been highly variable, a clear benefit has been shown in most cases.

Taking adequate doses of these anxiolytic herbs can certainly help promote a better quality sleep, and provide some relief to debilitating insomnia. Most anxiolytic drugs and sedative drugs work on the same GABA receptors, and it is not surprising that the same mode of action probably applies also to herbal medicines. By acting to help ease tension, anxiety and stress, they can effectively address some of the underlying and contributory factors to lack of sleep.

It is clear that more clinical studies to better determine efficacious herbal medicines and optimal doses, are sorely needed for the management of sleep disorders. However, their ability to help prevent insomnia, or avoid the need to take pharmaceutical drugs with a relatively high risk of adverse events, is well established. It is this ability of herbal medicines when properly selected and prescribed to address more than the outcome of a long-standing or acute underlying imbalance in health, but rather to help rebalance overall health and overcome weaknesses in several contributory areas, that makes them such excellent prophylactics. And after all, a prophylactic is preferable to a sticking plaster, especially one that is prone to fall off or leak when left on too long.

Refs:

1. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Institute of Medicine (US) Committee on Sleep Medicine and Research; Colten HR, Altevogt BM, editors. Washington (DC): National Academies Press (US); 2006. The National Academies Collection: Reports funded by National Institutes of Health.
2. Brzecka A et al, Front Neurosci. 2018 May 31;12:330.
3. Zitting KM Sci Rep. 2018 Jul 23;8(1):11052
4. Bordoloi M, Ramtekkar U. Med Sci (Basel) 2018 Sep 14;6(3).
5. Pollmann AS et al. BMC Pharmacology and Toxicology 2015; 16:19.
6. Brandt J et al, Drugs RD 2017 Dec;17(4):493-507.
7. Leach MJ, Page AT, Sleep Med Rev 2015;24:1-12.
8. Weiss Rudolf Fritz Lehrbuch der Phytotherapie (Herbal Medicine): Published by Hippokrates Verlag, Stuttgart, Germany, 1960. English edition first published 1988.
9. Taavoni S et al, Menopause. 2011 Sep;18(9):951-5
10. Taavoni S et al, Complement Ther Clin Pract. 2013 Nov;19(4):193-6.
11. Bagheri-Nesami M. J Tradit Complement Med. 2015 Jan 31;5(4):241-7
12. Ahmada M et al, Ann Pharmacother. 2017 Jun;51(6):457-464
13. Palmiera G, Nat Sci Sleep. 2017 May 26;9:163-169

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PROMISING NEW FINDINGS FOR ROSEMARY

The leaves and sprigs of Rosemary (Rosmarinus officinalis), have been widely used in food preparation and preservation and also for many medicinal purposes, almost as far back as human history began. As a popular plant that is easy to use and often readily accessible, its reputation as a meat preserver and an alleged hair restorer, are fairly well known in herbal folklore.

As with other long-esteemed herbaceous plants, rosemary’s diverse medicinal capabilities and their relevance to the needs of a modern-day world are being increasingly validated by modern research.  Rosemary is now known to have some powerful pharmacological actions, including antioxidant, hepatoprotective, anti-cancer, antimicrobial and potential antidepressant activities(1).

Further possible medicinal uses for this well-known plant have now emerged, following results from recent research.

Preservative actions have long been assigned to rosemary, and scientific evidence supporting an antimicrobial application is very encouraging(2,3). An ethanolic rosemary extract was recently reported to have promising antibacterial activity against different pathogenic bacteria, with particularly good activity against Klebsiella pneumoniae(4). The essential oil of rosemary also exhibits powerful bactericidal (bacteria killing) and anti-biofilm activity against Staphylococcus aureusand Staphylococcus epidermidis(5), common causes of infections such as UTI’s and those from medical devices such as catheters.

Another study by veterinarian researchers recently, found that rosemary essential oil improved the motility of sperm collected from roosters, during its storage at 4 degrees C. These benefits were particularly seen when low concentrations of 8.7 and 87 ug/ml of rosemary essential oil were used. This suggests potential uses in animal fertilisation, and in human fertility clinics and procedures(6). With declining rates of sperm counts and motility, anything that gives sperm a greater chance of successfully fertilising an egg, can only be a good thing. As such it is conceivable that humans (or prehumans) may become exposed to this remarkable herb even before conception itself in the future!

Rosemary also has a reputation for helping prevent cancer, and application of rosemary or its phenolic acid constituents carnosol and ursolic acid were first shown to inhibit skin cancer formation in 1994(7).  Such actions have since been extended to other forms of cancer cells, including most recently the growth of human colon adenocarcinoma(8), and three other gastrointestinal cancer cell lines(9).

Benefits on heart health are also associated traditionally with regular ingestion of this herb, and recent studies on rodents have provided some support for this.  Pre-treatment with an aqueous rosemary extract protected mice against cardiotoxicity and hepatotoxicity(10). Supplementation of the diet of rats with 0.02% rosemary for three months improved diastolic function, and reduced the degree of hypertrophy after a heart attack (myocardial infarction). These effects were associated with improved energy metabolism and decreased oxidative stress(11). Rosmarinic acid has also shown a cardioprotective effect against myocardial infarction and arrhythmia in rats(12).

Collectively, these recent studies supportfurther investigations into the potential use of rosemary as adjuvant therapy with other cardiac drugs in those at risk of a heart attack, or to be taken immediately following such life-threatening cardiac events.

Finally, rosemary is also used in traditional medicine to alleviate rheumatic and abdominal pain. In a rat model of painful diabetic neuropathy, rosemary extract improved hyperglycemia, hyperalgesia and motor deficit(13). Triterpene constituents of an ethanolic extract also reduce abdominal pain in mice(14). These findings suggest rosemary may have analgesic and neuroprotective effects in painful diabetic neuropathy as well as abdominal pain in humans. Rosmarinic acid is likely to contribute to these effects, as other recent studies found it effective in a rat model of neuropathic pain(15-17). Analgesic properties have also previously been reported for rosemary essential oil (18).

Rosmarinic acid is a highly valued phenolic compound found not only in Rosemary, but also in many other well-known plants in the Lamiaceaeand Boraginaceaefamilies, such as Sage, Lemon balm, and Perilla (Perilla frutescens). Potentially beneficial pharmacological properties of this natural compound include anticancer, anti-angiogenic, anti-inflammatory, antioxidant, and antimicrobial activities(19,20). This has lead to increasing demands for it from the pharmaceutical industry. As a result, methods to chemically synthesise rosmarinic acid or produce it by biotechnological methods, are now being actively explored(19).

Beyond rosmarinic acid, however, the cumulative research into the diverse pharmacological actions of the reliable rosemary, show that other phenolic acids, triterpenoids, essential oil and other constituents, also seem to make powerful contributions to its many potential medicinal uses.

 

References:

  1. Andrade JM et al, Future Sci OA. 2018 Feb 1;4(4):FSO283.
  2. Ahn J et al, Food Microbiol. 2007 Feb;24(1):7-14
  3. Nieto Get al, Medicines (Basel).2018 Sep 4;5(3).
  4. Javed H 1stal, Pam J Pharm Sci 2018; 31(3):933-939.
  5. Jardak M et al, Lipids Health Dis.2017 Oct 2;16(1):190.
  6. TouaziL et al, Vel World 2018; 11(5):590-597.
  7. HuangMT et al, Cancer Res.1994 Feb 1;54(3):701-8.
  8. Jaksevicius A, et al, Nutrients. 2017 Sep 21;9(10).
  9. Karimi N, Gastroenterol Hepatol Bed Bench. 2017 Spring;10(2):102-107.
  10. Hamed H et al, Appl Physiol Nutr Metab.2018 Apr 9. doi: 10.1139/apnm-2017-0786. [Epub ahead of print]
  11. Murino Rafacho BP, PLoS One. 2017 May 11;12(5):e0177521
  12. Javidanpour Set al, 2017 Dec;51(11-12):911-923.
  13. Rasoulian B et al, J Physiol Sci 2018; May 12 (epub ahead of print).
  14. Martinez AL et al, J Ethnopharmacol 2012; 142(1):28-34.
  15. Rahbardar GM et al, Biomed Pharmacother. 2017 Feb;86:441-449
  16. Rahbardar MGet al 2018 Feb 1;40:59-67
  17. Di Cesare Mannelli L et al,Sci Rep. 2016 Oct 7;6:34832.
  18. Raskovic A, et al, Eur Rev Med Pharmacol Sci. 2015 Jan;19(1):165-72.
  19. Swamy MK et al, Appl Micriobil Biotechnol 2018.
  20. Shekarchi M et al, Pharmacognosy Mag 2012; 8(29):37-41.

WITHANIA: A USEFUL ADJUNCT WITH ANTIPSYCHOTIC MEDICATIONS

Antipsychotic drugs are strong medicines, and while they can successfully alleviate symptoms of psychosis and prevent relapse of schizophrenia and related conditions, like all drugs they are not without side effects.

There are two types of antipsychotics, older generation ones such as chlorpromazine or haloperidol developed in the 1960s, and so called ‘atypical’ antipsychotics such as olanzapine, clozapine and quetiapine developed in the 1990s, with a different side effect profile. While atypical newer generation antipsychotics are less likely than older generation ones to produce the extrapyramidal or Parkinson’s disease-like side effects, they can cause weight gain and precipitate or worsen metabolic syndrome or diabetes, and both types increase the risk of sudden cardiac death. Over-use and mis-use of antipsychotics is also of growing concern in the elderly(1).

Despite these risks, in a world in which the incidence and predominance of mental health conditions is rising, prescribing rates for antipsychotic drugs are increasing. Nearly seven million Americans take antipsychotic medications, and a recent study revealed a 49% rise in the use of anti-psychotic drugs by New Zealanders between 2008 and 2015. New Zealanders are now 60% more likely to be prescribed such drugs than Australians, with one in 36 New Zealand adults, or 2.81% of the population, being prescribed antipsychotic medication in 2015(2).

This recent New Zealand study also suggests that in a significant and probably increasing number of cases, these strong prescription-only drugs are being used to help with stress and associated sleep problems, rather than for their primary indication for conditions such as schizophrenia and bipolar disorders. Such ‘off label’ uses for prescription-only antipsychotics such as olanzapine, is something that has landed pharmaceutical companies in court in the U.S., in a number of prominent cases.

Herbal medicine offers an array of potential treatments for insomnia and stress-related conditions(3). One of the most suitable of these is Withania somnifera (Withania), known as Ashwagandha in India. The roots of Withania have a subtle but powerful nervous system and adrenal tonic action which insulates the nervous system from stress, enabling it to be better prepared to respond appropriately to the ‘fight or flight’ response. Many studies now support its applications for stress-associated anxiety conditions, including several human clinical trials(3).

Another possible application for Withania became apparent recently, through an American clinical trial where it was used as an adjunctive treatment alongside antipsychotic drug treatment in patients with schizophrenia(4). A total of 66 patients who had recently experienced an exacerbation of their schizophrenia symptoms, were given Withania or placebo alongside their usual antipsychotic drug medications, for a 12 week period. Outcomes were change from baseline to end of treatment on the “Positive and Negative Syndrome Scale” (PANSS), which measures total, positive, negative, and general symptoms of schizophrenia, and indices of stress and inflammation.

Patients given Withania were significantly more likely to achieve at least 20% improvements in PANSS negative, general, and total symptom scores, but not positive symptom scores, compared to those assigned to placebo. They also showed a significant improvement in stress scores compared to placebo. Additionally, only two of the Withania-treated subjects required an increase in their antipsychotic drug dosage, whereas nine of the placebo-assigned subjects either had their antipsychotic drug dosage increased or had a second antipsychotic drug added. These improvements were first noted at 4 weeks, and continued through the 12-week study period.

This is not the first time that Withania has been shown to be useful when taken alongside antipsychotic drugs. A one month clinical trial involving 30 schizophrenia patients with metabolic syndrome who had taken second generation antipsychotics for more than 6 months, found that adding Withania to their normal antipsychotic medication reduced serum triglycerides and fasting blood glucose, thus improving these metabolic syndrome symptoms(5).

Apart from Withania, clinical trials have shown appropriate doses of other high quality herbal medicines to benefit patients receiving antipsychotic drugs. Ginkgo was found to both increase the response rate to haloperidol when taken alongside it for 12 weeks(6), and to reduce the incidence of extrapyramidal side effects(7, 8). Similar effects have also been reported using Ginkgo alongside olanzapine(9).

Another U.S. study has shown American Ginseng (Panax quinquefolium) to have positive effects on memory function in individuals with schizophrenia, and to reduce the occurrence of extrapyramidal symptoms in patients on antipsychotic medications(10).

While underlying reasons for the high and increasing level of antipsychotic drug use in New Zealand and other countries should be further examined and addressed, clinical trials suggest that adjunctive herbal medicines such as Withania, Ginkgo and American ginseng, can play a role to help reduce some of the adverse events, and improve their response rates. Larger and longer term trials, are warranted.

References:
1. Bjerre LE; Canadian Fam Physician 2018; 64(1):17-27
2. Wilkinson S, Mulder RT. NZ Med J 2018 Aug 17; 131(1480):61-67.
3. Rasmussen PL, Feb 2017; Why Herbs should be the first choice of treatment for acute    anxiety. http://www.herbblurb.com
4. Chengappa KNR et al, J Clin Psychiatry 2018 Jul 10;79(5).
5. Agnihotri AP et al, Indian J Pharmacol 2013; Jul-Aug;45(4):417-8
6. Zhang XY et al, Psychopharmacology 2006; 188(1):12-17.
7. Zhang XY et al, J Clin Psychiatry 2001; 62(11):878-883.
8. Chen X et al, Psychiatry Res 2015; 228(1):121-127.
9. Atmaca M et al, Psychiatry Clin Neurosci 2005; 59(6):652- 656.
10. Chen EY et al, Phytother Res. 2012 Aug;26(8):1166-72

Echinacea – a useful herb for allergies

The best known use for the root of Echinacea (also known as Purple Coneflower), is the prevention or treatment of upper respiratory tract infections, such as influenza and the common cold, and its pharmacological activity is often simplified down to being regarded as an ‘immuno-stimulant’.

A close look at the traditional applications for Echinacea however, suggest its most prominent uses were to reduce inflammation. The traditional uses by North America Indians and early European settlers, included inflammatory conditions such as snake bites, sore throats, swollen gums and abscesses, and other conditions where a high level of localised or systemic inflammation is characteristic. Much of Echinacea’s established pharmacology therefore also relates to an anti-inflammatory mode of action, with tongue-tingling alkylamides being the key active phytochemicals (1, 2).

Inflammation is also a major component of many allergic and autoimmune conditions, including asthma, hay fever or systemic lupus erythematosus. Anti-inflammatory drugs such as prednisone, beclomethasone and flumethasone are frequently prescribed to reduce the symptoms of these. The concept of Echinacea being used for such conditions can be hard to grasp, particularly when influential texts such as the German ‘The Complete Commission E Monographs’, the European Pharmacopoeia and websites presenting information on medicinal herbs, make statements such as:

“Because of its immunostimulating activity, Echinacea must not be used in cases of progressive systemic disorders (tuberculosis, sarcoidosis), autoimmune diseases (e.g.: collagenoses, multiple sclerosis), immunodeficiencies (e.g.: HIV infection; AIDS), immunosuppression (e.g.: oncological cytostatic therapy; history of organ or bone marrow transplant), diseases of the white blood cell system (e.g.: agranulocytosis, leukemias) and allergic diathesis (e.g.: urticaria, atopic dermatitis, asthma).

Despite such statements, there is in fact no substantiated evidence of Echinaceas absolute contraindication in any of the above immunological or autoimmune conditions, making this precautionary statement a potential theoretical, rather than clinically proven one.

Something else that European regulators are overly sensitive about is the likelihood of Echinacea triggering allergic reactions, to the point of advising against its use in children under the age of 12. The background to this however, is likely attributable to the greater prevalence in Europe of products containing either the whole plant or flowering tops of Echinacea, rather than just the root. Using just the root is more often seen in Australia, New Zealand and North America. Products made using flowering Echinacea tops contain higher pollen levels, and are therefore more likely to be associated with allergic reactions in atopic subjects, as seems to have been the case in Europe(3).

Further insight into whether Echinacea is or isn’t safe to use in autoimmune conditions, was provided by a recent American study which investigated its effects on mast cells(4).  Mast cells are a type of white blood cell and known to be important mediators of allergic and inflammatory responses. Upon exposure to an allergen and release of immunoglobulin E (IgE) antibodies, an influx of calcium occurs resulting in mast cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes, and other pro-inflammatory cytokines. These actively contribute to allergic reactions and the subsequent inflammatory response, including those seen in asthma and allergic rhinitis (hay fever). The main mechanism of drugs such as sodium cromoglycate, used as an inhalation for hay fever and asthma, is to reduce mast cell release of histamine and other inflammatory mediators.

Effects of an ethanolic extract of Echinacea purpurea root were evaluated on mast cell degranulation, calcium influx, cytokine and lipid mediator production, using both bone marrow derived mast cells and a rat basophilic leukemia mast cell lines. As well as the crude Echinacea root extract, a purified alkylamide (dodeca-2E,4E-dienoic acid isobutylamide), and fractions containing both low and high alkylamide levels, were also tested for effects on mast cell function.

The Echinacea extract and isolated dodeca-2E,4E-dienoic acid isobutylamide, inhibited degranulation from both mast cell types after treatment with a calcium ionophore, as well as after stimulation with IgE. Histamine release from the rat basophilic leukaemia mast cell lines, was reduced by 47%, and that of TNF-alpha and prostaglandin E2 (PGE2), but by a lesser degree. Inhibition of calcium influx by Echinacea and its alkylamides, was implicated as a mechanism of action, and as similar actions were shown also on non-mast cells, other possible pharmacological actions of benefit in both inflammatory and autoimmune conditions, are likely.

Inhibition of mast cell degranulation and calcium influx was observed by Echinacea purpurea extracts and Echinacea fractions with high alkylamide content, but not by fractions with little to no detectable alkylamide levels. This implicates alkylamides in the anti-allergic actions of Echinacea purpurea root extract, and adds to the large existing body of evidence that they contribute significantly to the overall immunomodulatory and anti-inflammatory actions of this plant.

The combined effects of Echinacea purpurea on mast cell activation, considered together with research showing it reduces the release of inflammatory cytokines from macrophages, suggests the possible application of high alkylamide-containing Echinacea purpurea extracts for limiting inflammation associated with allergic responses, in addition to that associated with infections.

Further evidence of Echinacea’s anti-allergic effects was provided recently from results of a study by Hungarian and German researchers, who found an alkylamide-rich Echinacea extract to exert strong anti-inflammatory effects and help restore the epidermal lipid barrier, in patients with atopic (allergic) eczema. Topical application of an Echinacea cream, reduced both pruritis (itchiness) and redness in an 85 day clinical trial involving patients with atopic eczema, particularly from days 57 to 85(5).

Refs:

  1. Rasmussen PL, Phytonews 14 , Evaluation of anti-inflammatory effects of Echinacea purpurea and Hypericum perforatum, ISSN 1175-0251, published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand, Dec 2002
  2. Rasmussen PL, Phytonews 24 , Effects of Echinacea on virus-induced respiratory cytokines, ISSN 1175-0251, published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand, Feb 2006
  3. Rasmussen PL, Phytonews 38 , Safety of Echinacea in Children, ISSN 1175-0251, published by Phytomed Medicinal Herbs Ltd, Auckland, New Zealand, Dec 2012
  4. Gulledge TV, Mast cell degranulation and calcium influx are inhibited by an Echinacea purpurea extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide. J Ethnopharmacol. 2018 Feb 15;212:166-174.
  5. Oláh A et al, Echinacea purpurea-derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema. J Dermatol Sci. 2017 Oct;88(1):67-77.

 

Herbs and Cancer

A diagnosis of cancer is a highly stressful experience and increasingly, a common reason for people to consult a medical herbalist. With ongoing environmental exposures to carcinogenic agents, genetic predispositions and aging populations, this is likely to continue in coming decades.

Pharmaceutical company expenditure on research into new cancer drugs far outweighs that spent on developing new antibiotics or antidepressants, and advances in diagnosis, surgery, chemotherapy, radiotherapy and other cancer treatments, continue to be made. These can be expensive however, and waiting lists unacceptably long, in an increasingly stressed healthcare system. Also, conventional medicine is not always effective in the treatment of cancer and in many patients, its adverse effects and a relatively poor risk versus benefit rationale, are reasons for exploring herbal and other natural treatments.

Consequently, there is a huge amount of material on the subject available online, in magazines and books, including websites offering cancer cures through expensive clinic programmes, or ‘ready to take’ products that are heavily marketed. Soon after informing friends, colleagues and family, newly diagnosed patients tend to be inundated with suggestions and recommendations to take a wide range of ‘herbal remedies’, ‘dietary supplements’, ‘superfoods’ and other ‘alternative treatments’, several promising a cure, and strongly advocating against conventional treatments.  Care should be taken with all of these.

It’s fairly well known that a large percentage of chemotherapeutic drugs for cancer and leukaemia treatment are molecules identified and isolated from plants or their synthetic equivalents or close derivatives. Research on herbs has led to the development of anti-cancer drugs such as vincristine, vinblastine, paclitaxel, docetaxel, etoposide, teniposide and more.

These are however, strong and individual chemicals found in or derived from plants, they are not the plants themselves. It is inappropriate to extrapolate from the anticancer effects of large doses of these drugs (often given by injection rather than orally), and to claim that a plant extract from which chemotherapy drugs have been developed will also exhibit significant anticancer properties. Also, successful traditional uses of most of these plants for the treatment (as opposed to prevention) of cancer in humans is in fact poorly established. Finally, the likelihood of something that kills cancer cells in vitro (in laboratory cultures) doing the same thing when taken orally by human patients, is actually pretty low, just as the diabetes drug insulin is poorly absorbed when taken orally, and needs to be administered by injection.

Of more relevance from a scientific evidence-based perspective, are herbs and natural products that show useful outcomes (efficacy) when used in studies involving rats and mice (rodents). We now know that the mouse and human genomes are approximately 85% identical, meaning that if something works in mice, it has a reasonable chance of also working in humans. A 2005 Canadian study that found daily oral ingestion of Echinacea purpurea root from the age of 6 weeks until death from natural causes (‘old age’) reduced the incidence of spontaneous tumours and prolonged the life expectancy of mice, is therefore highly relevant(1, 2). This type of study should be given more prominence than claims that oral administration of Madagascar periwinkle (Catharanthus roseus, the source of the anti-cancer drugs vincristine and vinblastine), can help fight cancer.

The best contribution that most herbs make is in fact related to their preventive effects against human cancers, just as a diet rich in vegetables and low in or excluding red meat is now well established to do the same. Well-known herbs and spices such as ginger, garlic, turmeric, rosemary, nasturtium and watercress, are just some for which compelling evidence now exists as to their prophylactic properties. Incorporating these and many others into the diet or taking as a tonic on a regular basis, is likely to help reduce the likelihood of developing many different types of cancer.

When it comes to management of patients with a cancer diagnosis, one of the most promising contributions that herbs can make, is as adjunctive treatments to be taken alongside the anti-cancer drugs and other conventional interventions that modern medicine now has available. Evidence from a large number of animal studies and a growing number of human clinical trials, now strongly supports this approach, key outcomes being to help increase the chances of achieving remission, and/or reduce the likelihood of treatment-related adverse effects such as infertility and fatigue. Sadly, however, most of my cancer patients don’t come to see me until either after they have undergone chemotherapy, or where it is no longer an option, and a small number firmly opt against conventional treatment. This is perfectly their right and completely understandable, but may not have been their decision if they had been informed of the valuable contribution an individualised concurrent herbal treatment regimen can sometimes make.

It is in fact a reflection of the widespread lack of acknowledgement and appropriate regulation of highly trained medical herbalists, that most people’s view of virtually all herbs and herbal products, is that they are only things to be sourced from ‘over the counter’ (OTC) or internet outlets. This is a far cry from their view of drugs, where when suffering from most debilitating or serious conditions, the prescribing expertise of a medical practitioner or specialist such as an oncologist, is sought prior to embarking upon drug treatments.

While proactive selfcare should be actively encouraged as the best preventive approach to cancer and other illnesses. However, once cancer is diagnosed, while herbs are rarely a magic cure, seeking the best professional advice rather than relying on google apps or recommendations from those not trained in herbal medicine, is highly recommendable.

 

Refs:

 

  1. Brousseau M, Miller Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth. Biogerontology. 2005;6(3):157-63.

 

  1. Miller Echinacea: a miracle herb against aging and cancer? Evidence in vivo in mice.

Evid Based Complement Alternat Med. 2005 Sep;2(3):309-14.

 

 

Valerian –  favourable effects on cognitive function

Valerian (Valeriana officinalis) root is well known for its applications in anxiety or insomnia, for which it has been used for thousands of years. Its anti-anxiety (anxiolytic) and sedative effects are mainly attributed to modulation and enhancement of the neurotransmitter GABA (gamma amino butyric acid), which prevents overstimulation of neurons implicated in anxiety and seizure disorders such as epilepsy. Behavioural studies in mice and clinical trials in humans are now expanding our understanding of this notable herb, and revealing other potential applications of relevance to modern day health gaps and needs.

One of these was a behavioural study in aged mice using a water maze performance test, reflective of spatial memory and the ability to cope with stress(1). Administration of valerian or valerenic acid improved the preferential exploration of new objects in a test of object recognition, and enhanced escape latency, swimming speeds, platform crossings, and a spatial preference for the target quadrant. These changes were accompanied by reduced blood levels of the stress-induced adrenal hormone corticosterone, and increased growth of nerve cell precursors (neuroblasts). The results suggest Valerian may help performance in stressful situations and moderate some of the less desirable neurological and physiological changes associated with becoming elderly, such as reduced cognitive function and confidence. This suggests adaptogenic (improved stress-coping ability) and possible nootropic (cognitive enhancing) properties for Valerian.

Other studies reporting anticholinesterase (cholinergic enhancement) activity, thought to be a mechanism of anti-dementia effects, and nerve growth stimulation by various Valerian iridoid and sesquiterpenoid constituents, further support such actions(2, 3).

Potential benefits of Valerian on cognitive function in patients undergoing certain forms of surgery, have also been revealed in a recent clinical trial(4).  Surgery is a stressful event, particularly so for patients with cardiovascular disease undergoing coronary artery bypass surgery. The trial involved 61 patients aged 30-70 years who underwent elective coronary artery bypass graft surgery using cardiopulmonary bypass. Patients received either one valerian capsule containing 530 mg valerian root extract (1,060 mg/daily), or a placebo capsule twice daily for 8 weeks. Cognitive brain function was evaluated prior to surgery then at 10 days and 2 months post surgery, using a test known as “Mini Mental State Examination (MMSE)”.

Following Valerian treatment, the mean MMSE score dropped from 27.03 in the preoperative period to 26.52 at the 10th day, then increased to 27.45 at the 60th day. This return to a normal MMSE was greater than that measured in the placebo group, in which the mean MMSE score fell from 27.37 at  baseline to 24 at day 10, and increased only slightly to 24.83 on the 60th day. This clinical trial provides evidence that Valerian may prevent early postoperative cognitive dysfunction after coronary artery bypass surgery. Given the high burden on the healthcare system and patients of such surgical procedures, further investigations using adjunctive Valerian in this and other forms of surgery, are warranted.

While unlike most sedative drugs Valerian shows little signs of impeding performance or producing an unwanted hangover effect the next day, until recently no study has specifically investigated these potential adverse effects.  Outcomes from a placebo-controlled clinical trial by Californian researchers in which participants received a dose of either 1600mg valerian or placebo then underwent a driving simulator, field sobriety and other tests of visual reactions and performance, are therefore of interest(5). No significant differences were recorded between groups in the simple visual reaction test or sleepiness scales, standardised field sobriety test total and individual test failure rates. This suggests a single dose of 1600mg valerian is unlikely to impair driving performance, in the way that alcohol or sedative drugs are known to do.

Finally, it is noted that Valerian’s reputation as a useful medicine in humans has attracted the attention of U.S. biotechnology researchers recently, who in a quest for new anti-anxiety agents have genetically engineered a strain of the E coli bacteria, to produce substantial quantities of the valerenic acid precursor valerenadiene(6, 7).

 

Refs:

  1. Nam SM et al, Exp Gerontol. 2013;48(11):1369-77
  2. Chen HW et al, 2016;110:142-9.
  3. Dong FW et al, Phytochemistry 2015; 118: 51-60.2015
  4. Hassani S et al, Psychopharmacology (Berl). 2015;232:843-50
  5. Thomas K, Accid Anal Prev 2016; 92:240-244.
  6. Nybo SE et al, J Biotechnol. 2017 Nov 20;262:60-66. doi: 10.1016/j.jbiotec.2017.10.004. Epub 2017 Oct 5.
  7. Ricigliano V et al, Phytochemistry 2016; 125:43-53.

Medicinal Uses of Nasturtium

With spring upon us, the New Zealand countryside and our gardens are rich with budding and flowering plants, many of them normally regarded as weeds, but in fact highly medicinal.

One of these is Nasturtium (Tropaelum majus; Indian cress), a plant with water lily like circular leaves and bright yellow, orange and red flowers which is native to South America but established in many warmer areas of New Zealand and Australia. While it can certainly be very weedy in some situations, it also makes a useful plant on the edges of the vegetable garden to attract bees and other beneficial insects. It can also act as a decoy by attracting cabbage white butterflies and drawing these pests away from brassicas.

What many people don’t realise, however, is that all parts of Nasturtium are edible, with its leaves and flowers making a decorative, peppery addition to salads, and the fruits when pickled with vinegar serving as a tasty alternative to capers. It also has outstanding antioxidant activity due to its rich content of phenolic compounds, including anthocyanin and vitamin C. Like many ‘weeds’ readily available in the New Zealand environment, Nasturtium is also a highly medicinal plant.

Traditionally it was used to help ward off and treat various infections, particularly those affecting the lungs and the urinary tract. The pungent compounds known as isothiocyanates found in all parts of nasturtium and roots of horseradish (Armoracia rusticana), have powerful and fairly broad spectrum antibacterial activities particularly against Haemophilus influenza and Moraxella catarrhalis, a common cause of middle ear infection (otitis media) and sinusitus in children(1). These isothiocyanates have also recently been reported to have good activity against both developing and mature biofilms of Pseudomonas aeruginosa, a bacterial pathogen associated with many serious human illnesses(2). Importantly also, they have also been shown to be well absorbed into the bloodstream following oral ingestion of nasturtium in humans(3).

Nasturtium was used in folk medicine as a remedy against scurvy, and can be used as a natural, warming remedy to help the body overcome and prevent the common cold and influenza. It was also used traditionally to treat muscular pain, and it’s antimicrobial properties extend to its use as a topical treatment for bacterial infections and minor scrapes and cuts.

Possible applications in the prevention or treatment of various cancers are also likely, due to conversion of a key constituent glucotropaeolin to benzyl isothiocyanate, within the body. This compound, formed also from isothiocyanates found in brassica (cruciferous) vegetables, exhibits anticancer activity against cultured lung, breast, liver, prostate, brain, melanoma, oral & ovarian cancer cells in vitro, and prevents chemically induced carcinogenesis in rodents(4-10).

Potential benefits in fluid retention, hypertension and other cardiovascular conditions, have been suggested by Brazilian research showing diuretic, hypotensive and lipid-lowering activities for a hydroethanolic extract in rats(11-13). Angiotensin converting enzyme (ACE) inhibition was implicated as a possible mechanism for these effects, in a similar manner to how ACE inhibitor drugs work to help manage hypertension and other cardiovascular conditions(14). Unlike many other conventional diuretic drugs, however, no unwanted effects on urinary calcium or potassium excretion seem to occur, suggesting valuable potassium and calcium-sparing properties. These findings indicate possible applications also to help prevent osteoporosis, which is supported by another Brazilian study in menopausal rats(13).

Nasturtium may also be useful to help prevent or manage obesity, according to findings from a Korean study published in the June 2017 issue of the journal Food and Nutrition Research(15). The study investigated the effects of a nasturtium ethanolic extract on a mouse cell line with adipocyte-like characteristics, used in research on adipose (fat) tissue. Treatment of cells with nasturtium extract produced a concentration-dependent reduction in lipid accumulation, and inhibited the expression of various proteins associated with differentiation of fat cells. This suggests potential usefulness also, in the prevention and treatment of obesity.

With these compelling research findings, incorporation of nasturtium into the diet or herbal treatments of a range of human conditions common in the 21st century, should overtake our view of it simply as a bothersome weed.

References:

  1. Conrad A et al, Drug Res (Stuttg). 2013 Feb;63(2):65-8.
  2. Kaiser SJ et al, 2017 Jun;119:57-63.
  3. PPlatz S et al, Mol Nutr Food Res. 2016 Mar;60(3):652-60..See comment in PubMed Commons below
  4. Wattenberg LW. J Natl Cancer 1977 Feb;58(2):395-8.
  5. Hecht SS et al. J Nutr. 1999 Mar;129(3):768S-774S.
  6. Cho HJ et al, Int J Mol Sci 2016 Feb 22; 17(2):264
  7. Shang HS et al, Environ Toxicol 2016 Dec; 31(12):1751-1760.
  8. Yeh YT et al. Food Chem Toxicol. 2016 Nov;97:336-345.
  9. Zhu M et al J Cancer. 2017 Jan 15;8(2):240-248.
  10. Lai KC et al, Int J Oncol. 2017 Sep;51(3):832-840.
  11. Gasparotto Junior A et al. J Ethnopharmacol. 2009 Apr 21;122(3):517-22.
  12. Gasparotto Junior A et al. J Ethnopharmacol. 2011 Mar 24;134(2):210-5.
  13. Barboza LN et al, Evid Based Complement Alternat Med 2014; 2014:958291.
  14. Gasparotto Junior A et al J Ethnopharmacol. 2011 Mar 24;134(2):363-72. (2011a)
  15. Kim GC et al,.Food Nutr Res. 2017 Jun 14;61(1):1339555.

 

Antibiotics and their effects on Plants

Soil bacteria and fungi are a rich source of natural antibiotics, but the prevalence of human-made antibiotics and antibiotic resistance genes in soils, is an emerging concern. Antibiotics are widely used to promote livestock growth in modern non-organic agriculture, with poultry, cattle and pigs, being regularly treated with these antibacterial drugs. Millions of kilograms of antibiotics are released into the environment annually, much in the excrement of grazing animals, or through application of manure to agricultural fields(1). Discharge of human waste into waterways and the use of contaminated irrigation water or sewerage sludge to fertilise crops in many countries, is also a contributory cause. As a result, a higher level of antibiotic resistance is now apparent in conventional agricultural versus natural forest soils(2).

Soil and water-containing antibiotics constitute a potential route of human exposure to antibiotic resistance genes through their uptake by plants(3-8).  Uptake by plants can also have other effects, such as the accumulation of nitrofuran-type antibiotics in the edible parts of spring onions, and the subsequent metabolism of these into genotoxic and potentially carcinogenic hydrazine-containing metabolites(9).

The other consideration is the effects these human-made antibiotics have on the soil or plants themselves.  With human and animal health being intrinsically connected to that of plants and soil, and increasing research showing the many symbiotic and complex relationships between living organisms and their environment, effects of human-made antibiotics on plant health, should also be considered.

The high level of contamination with antibiotic residues and transferable resistance genes in pig manure applied to soil, has been shown to change the antibiotic resistant gene reservoir of the plant microbiome(10).  Carrots and lettuce can uptake amoxicillin and tetracycline(4), and tetracycline residues have toxic effects on both root and stems of germinating lettuce seedlings(11).  Oxytetracycline residues from cattle manure have also been shown to affect the diversity and type of nitrogen-fixing soil bacteria communities(12).

A recent European study has shown that even small amounts of antibiotics can have a range of potentially negative effects on plant traits(13). The comprehensive study examined the effects of three antibiotics (penicillin, tetracycline and sulfadiazine), on germination and growth of four plant species. These included two cultivated species (rapeseed, Brassica napus and common wheat, Tricicum aestivum), and two non-crop (herb) species (Shepherd’s purse, Capsella bursa-pastoria and Common Windgrass, Apera spicaventi). In farmland fertilised with manure containing antibiotic concentrations as typically found in agricultural soils, various effects on the plants were observed.

Main effects were delayed germination or reduced plant biomass. These effects varied markedly depending on the plant species concerned, but were most pronounced in the two herb species, particularly by penicillin and sulfadiazine. This suggests that different antibiotics could potentially affect the prevalence and types of species, and the diversity of natural plant communities near agricultural fields. Furthermore, these species-specific responses may not only alter the competitive abilities and makeup of the plant community, but also have secondary effects on other species such as pollinating and herbivorous insects(13).

Petrochemical residues and the use of non-organic agricultural pesticides and insecticides, are also starting to come under the spotlight as likely contributors to multi-drug antibiotic resistance among soil bacteria. A recent Chinese study has demonstrated that petrochemical residue -polluted soils were more than 15 times more likely than less-contaminated ones, to contain antibiotic resistance genes. This strong association of soil pollution with polycyclic aromatic hydrocarbons, suggests these may also be contributing to the growing amounts of antibiotic resistant genes in human-impacted environments(14).

In non-organic agriculture, soil bacteria can be continuously exposed to synthetic pesticides at sub-lethal concentrations, and a recent Indian study has found that insecticide-contaminated soil may have contributed to development of resistance to a range of different antibiotics, by several Bacillus species(15).

Silver nanoparticles are also now widely used in antibacterial products, and these inevitably discharge into aquatic environments and have been shown to affect the nitrogen cycle in phytoplankton and aquatic plant life(16).

Antimicrobial chemicals such as triclosan and triclocarban, which are used in some liquid soaps and toothpastes, can take a long time to break down in the environment and have been shown to have detrimental effects on aquatic organisms, and potentially contribute to antimicrobial resistance(17-19).

Soil and plant health are pivotal to the health of the planet and all its living organisms, and antibiotic drugs have saved many millions of lives. However, the widespread use of antibiotics in non-organic agricultural production systems particularly those involving animals, should be curtailed.

Refs:

  1. Popova IE et al, J Environ Sci Health B 2017; 52(5):298-305.
  2. Popowska M et al, Antimicrob Agents Chemother 2012; 56(3):1434-1443.
  3. Grote M. et al, Landbauforschung Volkenrode 2007; 57: 25-32.
  4. Azanu D et al, Chemosphere 2016; 157:107-114.
  5. Rahube TO et al, Can J Microbiol 2016; 62(7):600-7.
  6. Pan M et al, J Agric Food Chem 2014; 62:11062-11069.
  7. Kang DH et al, J AGric Food Chem 2013; 61:9992-10001.
  8. Kumar K et al, J Environment Qual 2005; 32:2082-2085.
  9. Wang Y et al, J Agric Food Chem 2017; 65(21):4255-4261.
  10. Wolters B et al, Appl Microbiol Biotechnol 2016; 100(21):9343-9353.
  11. Pino MR et al, Environ Sci Pollut Res Int 2016; 23(22):22530-22541.
  12. Sun J et al, Bioresour Technol 2016; 801-807, epub May 21.
  13. Minden V et al, AoB Plants 2017; 9(2):plx020.
  14. Chen B et al, Environ Pollut 2017; 220(Pt B):1005-1013.
  15. Rangasamy K et al, Microb Pathog 2017; 103:153-165.
  16. Jiang HS et al, Environ Pollut 2017; 223:395-402.
  17. Falisse E et al, Aquat Toxicol 2017; 189:97-107.
  18. McNamara PJ, Levy SB. Antimicrob Agents Chemother 2016; 60(12):7015-7016.
  19. Tremblay Louis, Environmental toxicologist, Cawthron Institute, Nelson, New Zealand Herald, 23 June 2017.

Manuka and Myrtle Rust

Last week I attended a two day workshop organised by scientists at Plant and Food Research Ltd and Massey University in Palmerston North, to discuss a range of recent scientific and biosecurity developments, concerning Manuka (Leptospermum scoparium), an important plant in New Zealand’s natural environment and economy. As with the two day Hui on ‘Manuka and More’ in Ruatoria and Te Araroa in November last year, this was an excellent event in which more than 30 scientists working actively on Manuka research presented on a diverse range of subjects and discussed where there could be gaps in our knowledge or research needs for this plant. While Manuka Honey and essential oil are currently the main two medicinal products produced from Manuka, numerous other therapeutic applications and potential contributions to preserving our environment, are found within this plant.

Jacqui Horswell and colleagues from the Institute of Environmental Science and Research, have shown that Manuka and other myrtaceaeous plants seem to be capable of killing the faecal bacterial pathogen Enterobacter coli (E. coli), by enhancing the die-off of this and other pathogenic organisms that pass through their root systems. A field trial involving riparian planting of Manuka is just getting going, to see whether laboratory results extend to helping to reduce animal effluent flows into a polluted lake. A lake which was once pristine and a treasured swimming area, but in recent years has changed into a green and dirty waterway due largely to dairy industry runoff, has been selected for this trial.

Hayley Ridgway from Lincoln University presented some interesting findings concerning novel and potentially useful mycorrhizae (fungi) and endophytic bacteria associated with the roots of Manuka, some of which I wrote about in my previous blog. Inoculation of Manuka plants with different mycorrhizae causes significant alterations in their growth rates and essential oil composition, highlighting the complex inter-relationships between microbes associated with Manuka, and its production of phytochemicals including some with bioactive properties.

Other presentations were made on experiences to date involving plantations of Manuka which have been established at a number of North Island sites in recent years. Challenges include site access, weeds, pests, and the relative attractiveness of different genetic lines to bees. A comment made by one of the presenters that while humans have had multiple generations of experience with cultivation and enhancing performance characteristics of crops such as wheat and rice, our experience with Manuka plantations spans less than 10-15 years to date.

The hottest topic at the workshop, however, was the recent finding of isolated outbreaks of Myrtle Rust (Austropuccinia psidii) in New Zealand nursery and garden grown specimens of Manuka and the native tree, Ramarama (Lophomyrtus bullata). This pathogenic fungi originated from Brazil where it causes guava rust, but spread internationally into North America in the 1880’s, and was first reported in Australia in 2010.  Australia is home to around half of the world’s Myrtaceae (Myrtle family) plant species, including Eucalyptus (850 species), Melaleuca (176 species) and Callistemon species.

Outbreak of Myrtle rust has had a devastating effect on much of the east coast as well as other areas of Australia, where it has resulted in ecosystem collapse for certain plant species. To date it has only been found in isolated locations in Northland, Waikato, Bay of Plenty and Taranaki, although it is widespread on Raoul Island in the Kermadec group, about 1,100km to the north-east of New Zealand.

Myrtle rust spores can easily spread across large distances by wind, or via insects, birds, people, or machinery, and it is thought the fungus arrived in New Zealand carried by strong winds and significant weather events from Australia.

The Myrtle Rust Strategic Science Advisory Group is working hard to assess and try to ameliorate the widespread environmental, economic, social and cultural impacts this plant pathogen could have on New Zealand. Apart from Manuka and Ramarama, other indigenous Myrtaceae species such as Pohutakawa (Metrosideros spp) and Swamp Maire (Syzygium maire), are under risk. Priorities including acceleration of scientific research into the biology of the pandemic strain detected here, pathways of spread, surveillance, management, exploring plant susceptibility and resistance, and coordinating and communicating a management plan that has widespread engagement by communities, scientists, industry and Maori stakeholders and landowners, councils and government.

The Ministry for Primary Industries (MPI) and the Department of Conservation (DOC), with the help of local iwi, the nursery industry, and local authorities are running an operation to determine the scale of the situation and to try and contain and control myrtle rust in the areas it has been found. However, emergence of the infection and appearance of the distinctive yellow or brown leaf discolouration may not become fully apparent until the spring, and a better assessment of the number of infection sites and their extent, may not be possible until then.

The arrival of Myrtle Rust in New Zealand means that the task of collecting and storing seed of New Zealand indigenous Myrtaceae including Manuka, has now become urgent. The NZ Indigenous Flora Seed Bank (NZIFSB), a collaborative project between Massey University, AgResearch, Landcare and the Department of Conservation, with support from the NZ Plant Conservation Network and the Millennium Seedbank at Kew in the UK, was established in 2013. NZFISB has been doing some really valuable work to collect and store seeds aimed at preserving a wide range of biodiversity within New Zealand native plant species. More than 130 volunteer seed collectors have been trained to date, and plans are underway to extend this and the level of community participation, to try to better protect our native plants for generations to come.

Refs:

http://www.nzpcn.org.nz/page.aspx?conservation_seedbank

http://www.mpi.govt.nz/protection-and-response/responding/alerts/myrtle-rust/

Antimicrobial Endophytes in Echinacea, Olive and Manuka

While plants are being extensively explored for new therapeutic properties and pharmacological activities, the communities of live fungi and bacteria known as endophytes that live between living plant cells, are also now being regarded as having many useful potential medicinal applications. Ironically, in recent years it is these microorganisms associated with plants rather than plants themselves, which seem to be receive much research interest.

Endophytes are microorganisms that live within a plant for at least part of their life cycles, without causing apparent disease or infections in the plant. Different endophytes seem to have affinities for particular plants, with which they have distinctive and cherished but complex interactions while each of them grows. They are for instance known to sometimes enhance host growth and nutrient gain, improve the plant’s ability to tolerate various types of stressors, and enhance the its resistance to insects and pests. The rrelationships that these bacteria and fungal communities have with their host plant varies from symbiotic to parasitic, to bordering on pathogenic.
Some very unusual and valuable bioactive substances are sometimes produced by these endophytes, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids, and these are increasingly being recognized as sources of novel compounds which may help to maintain or solve not only the plant’s health challenges, but can also have applications in human and animal health problems.
Over the past few decades, some highly medicinal compounds produced by endophytic microbes lead to novel drug development. These include Taxol (paclitaxol), a complex diterpene alkaloid produced by the endophyte Metarhizium anisopliae found in the bark of the Pacific Yew (Taxus brevifolia) tree, and one of the most promising anticancer agents ever developed. Also streptomycin, an antibiotic produced from the bacterial endophyte Streptomyces.

Other endophytes possess antibacterial activities which may be useful in treating various infections, and in a world where antibiotic resistance is becoming a major public health threat, these are obviously of great interest. Exploring and bioprospecting these for potential antimicrobial compounds may well yield valuable new natural products or drugs to help in the fight against resistant organisms(1,2,3,4).

It now seems that bacterial communities colonizing Echinacea purpurea contribute to its well-known immune enhancing activity(5). American researchers have reported that Echinacea’s stimulating activity on monocytes (a type of white blood cell involved in engulfing and destroying harmful microbes), could be solely if not partially accounted for by the activities and prevalence of Proteobacteria, a family of bacteria found in the bacterial community associated with this medicinal plant.
A screen of 151 different endophytic bacteria isolated from three different compartments of Echinacea purpurea, revealed that several bacteria isolated from the roots are strong inhibitors of Burkholderia cepacia complex bacteria, a serious threat particularly in immune-compromised cystic fibrosis patients(6). One of these bacterial strains also showed antimicrobial effects against Acinetobacter baumannii, a pathogenic bacteria mainly associated with hospital-acquired infections, and Klebsiella pneumoniae, also increasingly incriminated in hospital infections(7). Interestingly, the type of bacteria and their antimicrobial effects varied considerably, according to which part of the plant (root, stem, leaves etc) they were associated with. This has resemblances to different plant parts of Echinacea having different phytochemical and thus pharmacological activities, such as Echinacea roots being richest in alkylamides and thus anti-inflammatory activities.

Endophytic fungi including Penicillium commune and Penicillium canescens (related to the Penicillium notatum mould from which the first antibiotic penicillin originated), have also been isolated from the leaves of olive (Olea europaea) trees, and several of these have also shown antibacterial as well as antifungal activities in recent work(8).

Finally, a rich endophyte community has recently been identified by Lincoln University researchers for the New Zealand native plant Manuka (Leptospermum scoparium). A total of 192 culturable bacteria were recovered from leaves, stems and roots, including some showing activity against the bacterial pathogen, Pseudomonas syringae pv. actinidiae(9), otherwise known by Kiwifruit growers as Psa. With Psa being a serious risk to the health of the Kiwifruit vine, it could be that these endophytic bacteria found within Manuka will make a useful contribution to ensuring the future health of the Kiwifruit industry.
While very few of all of the world’s plants have had their complete complement of endophytes studied, these are just three well established medicinal plants from which some highly active cohabitating bacteria and fungi have been sourced. Undoubtedly this area of research will receive much more attention due to growing concerns about antibiotic resistance, as there would seem to be a huge opportunity to find new and interesting endophytes among the wealth of different plants growing not only in soil, but also in waterways and oceans.
Refs:
1. Alvin A et al, Microbiol Res 2014; 169(7-8)L483-495.
2. Martinez-Klimova E et al, Biochem Pharmacol 2016; Oct 27.
3. Kealey C et al, Biotechnol Lett 2017; Mar 8 (epub ahead of print)
4. Tanwar A et al, Microbiol Path 2016;101:76-82
5. Haron MH et al, Planta Med 2016; 82(14):1258-1265.
6. Chiellini C et al, Microbiol Res 2017; 196:34-43.
7. Presta L et al, Res Microbiol 2017; 168(3):293-305.
8. Malhadas C et al, World J Microbiol Biotechnol 2017; 33(3):46.
9. Wicaksono WA et al, PLoS One 2016; 11(9):e0163717.