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.

 

 

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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.

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.