Herbal Medicines Diabetes Cancer—A Global Perspective · Euphorbia prostrata and Fumaria parviflora, Taraxacum officinale and Eribotry japonica. These plants include Momordica foetida,9

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www.asiabiotech.com Clinical Application

Herbal Medicines for Diabetes and

Cancer—A Global Perspectiveby Peter Natesan Pushparaj

D iabetes mellitus is a principal cause of morbidity and mortality inhuman populations. It is a syndrome characterized by hyperglycemia,polydipsia and polyuria and causes complications to the eyes, kidneys

and nerves. It is also associated with an increased incidence of cardiovasculardisease.1 The clinical manifestations and development of diabetes often differsignificantly between countries and also between racial groups within a country.For example, diabetes currently affects an estimated 15.1 million people inNorth America, 18.5 million in Europe, 51.4 million in Asia, and just under

one million in Oceania.2 It is estimated that globally, the numberof people will rise from 151 million in the year 2000 to 221 millionby the year 2010,3 and to 300 million by 2025.4 However, diabetesmellitus is becoming increasingly common in the Singaporepopulation. The prevalence of type 2 diabetes doubled between1984 and 1992 in Singaporean Chinese.5 This increase can beattributed to many factors, including a stressful lifestyle as well asimproper dietary habits. This is of economic concern as the diseaserequires life-long treatment and associated with high morbidity fromthe resulting complications.

Introduction

Herbal remedies typically are part of traditional and folk healingmethods with long histories of use. Some forms of the herbalmedicines are found in most areas of the world and across allcultures historically. Before the advent of insulin, diabetes wastreated with plant medicines. In 1980, the World HealthOrganization (WHO) urged researchers to examine whethertraditional medicines produced any beneficial clinical results. Theplant kingdom represents a largely unexplored reservoir of

biologically active compounds not only as drugs, but also as unique templatesthat could serve as a starting point for synthetic analogs and an interesting toolthat can be applied for a better understanding of biological processes. Folkloricuses are supported by a long history of human experience. Numerousbiologically active plants are discovered by evaluation of ethnopharmacologicaldata, and these plants may offer the local population immediately accessibletherapeutic products.6

The earliest known documentation of plant-derived treatments for diabetesis found in the Ebers Papyrus of about 1550 BC. Since then, multitudes ofherbs, spices and other plant materials have been described for the treatmentof diabetes throughout the world.7 Traditional anti-diabetic plants might providea useful source of new oral hypoglycemic compounds for development aspharmaceutical entities, or as simple dietary adjuncts to existing therapies.However, since the availability of insulin, folklore medicines for diabetes havealmost disappeared from occidental societies, although they continue to bethe cornerstone of therapy in underdeveloped regions. Renewed attention toalternative medicines and natural therapies has stimulated a new wave of

Herbal Remediesfor Diabetes

Mellitus

Averrhoa bilimbi plant

apbn.v8n23.Pushparaj15 15/12/04, 10:42 am1307

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research interest in traditional practices. In the last 20 years,scientific investigation has confirmed the efficacy of many of thesepreparations, some of which are remarkably effective. Mentionedhereafter are those plants that appear most effective, are least toxicand have substantial documentation of efficacy.

More than 400 different plants and plant extracts have beendescribed for the diabetic patient. From these, various molecularspecies with hypoglycemic activity have been identified, includingalkaloids, flavonoids, glycosides, and polysaccharides. For example,castanospermine, an alkaloid isolated from seeds ofCastanospermum australe; epicatechin, a flavonoid isolated fromthe heartwood of Pterocarpus marsupium; and neomyrtillin, aglycoside isolated from Vaccinium myrtillus, were claimed to exerthypoglycaemic effect.8 Like the sulfonylureas, some plants act byincreasing the release of insulin and require a minimum of β-cellsto exert their action. These plants include Momordica foetida,Euphorbia prostrata and Fumaria parviflora, Taraxacum officinaleand Eribotry japonica. These plants include Momordica foetida,9

Euphorbia prostrata and Fumaria parviflora,10 Taraxacum officinale11 and Eribotry japonica.12 Some are shown to correct complicationsof diabetes, for example, masoprocol, a pure compound isolatedfrom Larrea tridentata, which decreases the elevated levels of serumcholesterol, free fatty acids and triglycerides in fat-fed/diabetic rats.13

Even with the use of these herbs, which possess blood glucoselowering effects, proper and effective natural treatment of diabeticsrequire careful integration of diet, nutritional supplements, lifestyleand botanical medicine.

Although many herbal remedies are claimed to have anticancereffects, only a few have gained substantial popularity as alternativecancer therapies. For decades, Essiac has been one of the mostwell-known herbal cancer alternatives in North America. It wasdeveloped by a Native healer from Southwestern Canada, it waspopularized by a Canadian nurse, Rene Caisse (Essiac is Caissespelled backwards). Essiac comprises four herbs: burdock, Turkeyrhubarb, sorrel and slippery elm. Conversely, researchers at theNational Cancer Institute of USA (NCI) and other institutes foundthat it has no anticancer property. Even though Essiac is illegal inCanada, it is widely available in American pharmacies and healthfood stores.14, 15

A derivative of mistletoe, called Iscador, is a popular cancerremedy in Europe, where it is said to have been in continuous useas folk treatment since the druids. Iscador is available in manymainstream European cancer clinics. European governments havefunded studies of iscador’s effectiveness against cancer, butdefinitive data have not emerged.14–17

Pau d’arco tea is said to be an old Inca Indian remedy formany illnesses, including cancer. Made from the bark of anindigenous South American evergreen tree, its active ingredient,lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphtho-quinone),has been isolated. Although lapachol showed antitumor activity inanimal studies conducted in the 1970s, it does not appear to affect

Herbal Remediesfor Cancer

Averrhoa bilimbi(Family: Oxalidaceae, Common Name: Bilimbi)

A common plant in Asia, which has been

widely used in traditional medicine as a cure

for cough, cold, itches, boils, rheumatism,

syphilis, diabetes, Whooping cough, and

hypertension. In addition, A. bilimbi has been

widely reported for its anti-inflammatory, anti-

scorbutic, astringent, anti-bacterial, and post-

partum protective properties. In Indonesia, it

has a considerable medicinal reputation as a

potent folk remedy for the treatment of

diabetes mellitus.

Fruits of Averrhoa bilimbi


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human malignancies. The tea does induce nausea and vomiting.Despite the absence of efficacy, pau d’arco tea is sold as a cancerremedy in health food stores, by mail, and on the internet.14

Herbal remedies in Asia show greater promise. For example,in Japan, several mushroom-derived compounds are approved foruse as cancer treatments. PC-SPES (PC for prostate cancer; SPES isthe Latin word for hope), a combination of eight herbs, all but twofrom traditional Chinese medicine, was found to reduce prostate-specific antigen (PSA) levels in men with advanced prostate cancer.The recipe came from a great-grandfather of one of the researchers,that ancestor having been a physician to the Chinese emperor.Estrogenic side effects occurred with PC-SPES, and its mechanismof action, although uncertain, may relate to its phytoestrogeneffects.18–21

Chinese medicinal herbs (CMH) can improve chemotherapytreatment in lung cancer according to researchers at the JiangxiCancer Hospital, Nanchang. The researchers observed the effect ofChinese medicinal herbs (CMH) and chemotherapy on non-smallcell lung cancer. Comparing the therapeutic effects of three treatmentregimens on 110 patients diagnosed with advanced non-small celllung cancer patients — 58 patients were treated with CMH pluschemotherapy, 28 cases treated with chemotherapy only and 24cases treated with CMH alone. The results showed that the effectiverates (i.e. partial remission or complete remission) were 22.9% inCMH and chemotherapy (CT) group, but just 13.6% both inchemotherapy and in the CMH groups. The survival rate of boththe CMH and chemotherapy group and the CMH group weresignificantly higher than that of the chemotherapy group but therewere no significant differences between CMH and CMH + CT group.The researchers concluded that Chinese medicinal herbs werehelpful to improve average survival times and survival rates ofpatients with advanced non-small cell lung cancer. The herbs couldbe used in conjunction with chemotherapy and the evidencesuggests that they may be equally effective used alone which wouldmean that patients may be able to avoid the side effects ofchemotherapy treatment.22

A study developed by researchers at the University of Californiaat San Francisco Breast Cancer Center involves patients from thatinstitution and from the Memorial Sloan-Kettering Cancer Center.Women with advanced metastatic breast cancer, receiving a Tibetanherbal formula, are being followed for clinical outcome, includingsurvival. These investigations suggest that historic herbal cancerremedies, pre-tested to insure purity and consistency of productand studied carefully, may produce potentially useful, non-toxiccancer treatments. The difficulty with time-honored herbal remediesis that they are rarely tested for purity, examined for consistency, orstudied carefully. They are, nonetheless, in common use. Herb salesin drugstores and food stores increased 35% from 1993 to 1994,totaling US$106.7 million for the year.23

Vinca rosea(Family: APOCYNACEAE, Common Name: Rosy

Periwinkle)

It is also known as Madagascar periwinkle.

Madagascar periwinkle’s traditional use as a

treatment for diabetes has led to extensive

investigation into its properties. Vincristine

and vinblastine are powerful anticancer

agents, and are two of the most important

medicinal compounds found in plants in the

last 40 years. Vincristine has proved most

effective in treating childhood leukemia;

vinblastine in treating testicular cancer and

Hodgkin’s disease (cancer of the lymphatic

system). Like many drugs used in

chemotherapy, both alkaloids produce such

side-effects as nausea and hair loss.

Long before modern researchers learned

of the plant’s valuable and varied properties,

folk healers in faraway places were using the

Madagascar periwinkle for a host of

medicinal purposes. In India, they treated

wasp stings with the juice from the leaves.

In Hawaii, they prescribed an extract of the

boiled plant to arrest bleeding. In Central

America and parts of South America, they

made a gargle to ease sore throats and chest

ailments. In Cuba, Puerto Rico, Jamaica, and

other islands, an extract of the flowers was

commonly administered as a soothing

eyewash. Periwinkle is used in folk medicine

in the Philippines as a remedy for diabetes.

Most of these practices are still followed.

Vinca rosea


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No legal standards exist for the processing or packagingof herbs. Quality-control standards and reviews are needed.Because they are not mandatory, however, few foodsupplement companies voluntarily self-impose qualityevaluation and control. Consumer protection andenforcement agencies cannot provide protection againstcontaminated or falsely advertised products. Current federalregulations do not permit such oversight, and regulatorycapability would prohibit full analysis and ongoing oversightof the estimated 20,000 food supplement items now soldover the counter. Cancer patients use over-the-counter herbalproducts in addition to or instead of those promotedspecifically as cancer treatments. It is therefore important torecognize herbal remedies that may help cancer patients andthose that are toxic or interact with other medications.Because neither the US Food and Drug Administration (FDA)nor any other agency examines herbal remedies for safetyand effectiveness, few products have been formally testedfor side effects or quality control, but information is beginningto emerge on the basis of public experience with over-the-counter supplements.

Recent reports emphasize the fact that “natural”products, contrary to apparent consumer belief, are notnecessarily safe or harmless. Most members of the publicapparently are not well aware that herbs are dilute naturaldrugs that contain scores of different chemicals, most ofwhich have not been documented. Effects are not alwayspredictable. Moreover, the potential for herb-drug interactionis sufficiently problematic that patients on chemotherapyshould be told to stop using herbal remedies during treatment.Similar cautions are necessary for patients receiving radiation,as some herbs photosensitize the skin and cause severereactions. Patients scheduled for surgery should be alertedto the fact that some herbs produce dangerous blood pressureswings and other unwanted interactions with anesthetics.Herbs such as feverfew, garlic, ginger and ginkgo have anti-coagulant effects and should be avoided by patients oncoumadin, heparin, aspirin, and related agents. The risk ofherb-drug interactions appears to be greatest for patients withkidney or liver problems.

Moreover, botanical remedies are sold in many forms,including capsules, liquids and tea leaves. They may containone or a collection of herbs and other ingredients, whichtypically are not described and often are unknown. Accordingto research conducted by Consumer Reports, the content ofherbal remedies often differs widely from one bottle to thenext, even within the same brand, as well as from claimsmade on the label. The California Department of Healthfound unsafe levels of mercury and other toxic metals inmore than a third of Asian patent medicines studied. Severalinstances of heart problems resulting from digitalis-contaminated supplements have been reported. Concernshave been raised recently even about dietary antioxidants,

Safety and Regulatory Issues onHerbal Medicines


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which may interact with chemotherapeutic agents.Hence, Canada is establishing a federal office toevaluate and regulate herbal remedies, which theywill treat as a new category distinct from drugs andfoods. Organizations such as the American MedicalAssociation and the American Cancer Society haveproduced position papers, and hearings have beenheld on food supplement issues by the FDA.24

In conclusion, the enormity and seriousnessof the problem probably will lead to theestablishment of government programs, despite theanticipated efforts on the part of the foodsupplement industry to block efforts that could leadto regulation of herbal products.

References

1. Steppan CM, Bailey ST, Bhat S, Brown EJ,

Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA,

The hormone resistin links obesity to diabetes, Nature

409(6818):307–312, 2001.

2. Kuhlmann J, Introduction, in Kuhlmann J, Puls W (eds.),

Oral Antidiabetics, Springer-Verlag, Berlin, Germany, Chap.

1, 1996.

3. Amos A, McCarty D, Zimmet P, The rising

global burden of diabetes and its complications: estimates

and projections to the year 2010, Diab Med 14:S1–S85,

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4. King H, Aubert R, Herman W, Global burden of diabetes,

1995–2025. Prevalence, numerical estimates and

projections, Diab Care 21:1414–1431,1998.

5. Chen KT, Gregg EW, Williamson DF, Narayan

KMV, High prevalence of impaired fasting glucose and

type 2 diabetes in Pehghu Islets, Taiwan: evidence of a

rapidly emerging epidemic? Diab Res Clin Pract 44:59–69,

1999.

6. Aquino R, De Simone F, De Tommasi N, Piacente S, Pizza

C, Structure and biological activity of sesquiterpene and

diterpene derivatives from medicinal plants, in Hostettmann

K, Maillard M, Hamburger M (eds.), Phytochemistry of

Plants Used in Traditional Medicine, Oxford University

Press, New York, USA, pp. 249-278, 1995.

7. Bailey CJ, Day C, Traditional plant medicines as treatments

for diabetes, Diab Care 12:553–564, 1989.

8. Day C, Hypoglycaemic compounds from plants, in Bailey

CJ, Flatt PR (eds.), New Antidiabetic Drugs, Smith-Gordon

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26, 1990.

9. Marquis VO, Adanlawo TA, Olaniyi AA, The effect of

foetidin from Momordica foetida on blood glucose level

of albino rats, Planta Med 31:367-374, 1977.

10. Akhtar MS, Khan QM, Khaliq T, Effects of

Euphorbia prostrata and Fumaria parviflora in

normoglycaemic and alloxan-treated hyperglycaemic

rabbits, Planta Med 50(2):138–142, 1984.

11. Akhtar MS, Ali MR, Study of hypoglycaemic

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diabetic rabbits, Planta Med 51(2):81–85, 1985.

12. Noreen W, Wadood A, Hidayat HK, Wahid SA,

Effect of Eriobotrya japonica on blood glucose levels of

normal and alloxan-diabetic rabbits, Planta Med 54:196–

199, 1988.

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Brignetti D, Luo J, Khandwala A, Reaven GM, Effect of

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model of Type II diabetes, Diabetologia 42:102–106, 1999.

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DC, USA, OTA-H-405, pp. 71–75, 1990.

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2(3):19–23, 2000.

16. Mistletoe, in Murray MT (ed.), The Healing Power of Herbs,

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Dr PETER Natesan Pushparaj is currently teaching at the Department of

Biochemistry, Faculty of Medicine, National University of Singapore,Singapore. He has extensive experience in teaching Biochemistry. His researchhas cast new light upon the anti-diabetic properties of Averrhoa bilimbi.Dr Pushparaj has identified and characterized the active com-ponents,nicotinic acid (NA) and magnesium (Mg) in A. bilimbi which is believed toimprove the blood glucose tolerance in diabetes. He has published scientific

articles in many international journals and a book chapter in Herbal Medicines:Molecular Basis of Health and Disease (published by Marcel Dekker Inc.,August 2004).

About the Author

Contact Details:

Dr Peter Natesan PushparajAddress: Department of Physiology

Faculty of Medicine,10 Kent Ridge Crescent,National University of

Singapore, Singapore 119260Tel: +65 6874 1668Email: [email protected]

19. Small EJ, Frohlich MW, Bok R, et al., Prospective trial of

the herbal supplement PC-SPES in patients with progressive

prostate cancer, J Clin Oncol 18(21):3595–3603, 2000.

20. De la Taille A, Buttyan R, Hayek O, et al., Herbal therapy

PC-SPES: in vitro effects and evaluation of its efficacy in

69 patients with prostate cancer, J Urol 164(4):1229–1234,

2000.

21. Sovak M, Seligson AL, Konas M, et al., Herbal composition

PC-SPES for management of prostate cancer: identification

of active principles, J Natl Cancer Inst 94(17):1275–1281,

2002.

22. http://www.internethealthlibrary.com/Health-problems/

lungcancer-tcm-research.htm.

23. http://www.cbcrp.org/research PageGrant.asp?grant_id=90

24. MEDWATCH 2002 Safety Alerts for Drugs, Biologics,

Medical Devices and Dietary Supplements, Food and Drug

Administration, 2002.


Documents

Herbal Medicines Diabetes Cancer—A Global Perspective · Euphorbia prostrata and Fumaria parviflora, Taraxacum officinale and Eribotry japonica. These plants include Momordica foetida,9