Number 20
May/June 1999

Herbs in this issue:

Nuzhenzi (Ligustrum lucidum)

Mahuang and mahuanggen




A Note From Dr. Leung


Exotic dietary supplements – Are they safe?


     Are there such things as “exotic dietary supplements” which are so rare that our human body has so far had little experience in dealing with them on a continuous daily basis?  Under the current Dietary Supplement Health and Education Act (DSHEA), there certainly are, especially when sold as part of an “extract.”  These include ephedrine, synephrine, huperzine A, silymarin, epigallocatechin gallate, epicatechin, ginsenoside Rb1, ginsenoside Rg1, glycyrrhizin, etc.  While some are derived from well-known herbs that have been widely and safely consumed over centuries as part of our regular diet or at least as occasional supplements to our diet, others (such as ephedrine, synephrine, huperzine A, and silymarin) are from herbs that either have never been used as part of our diet or contain these chemicals in very minor amounts but which are now selectively extracted for specific therapeutic aims.  These highly purified phytochemicals are legal dietary supplements, despite the fact that they are either known to be toxic or


Dr. Leung is author of the Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics (Wiley-Interscience), which was published in 1980 and revised in 1996. He is also creator of PHYTOMED, a prototype computer database on Chinese herbal medicine developed under contract with the National Cancer Institute.


their long-term toxicity has not yet been determined.  We are ingesting these chemicals into our bodies in amounts many times (some thousands) the usual levels to which they have been accustomed.  This is possible because of the DSHEA.  These compounds (drugs) have effectively eluded the existing drug laws by being passed off as dietary supplements.  My concern is where and when do we draw the line in accepting these exotic dietary supplements?Let’s consider the following 2 cases.  (1) Take the well-known angelica root (Angelica archangelica).  It contains dozens of biologically active chemical constituents, including volatile components (such as d-α-phellandrene, α-pinene, limonene, β-caryophyllene, linalool, borneol, acetaldehyde, ω-tridecanolide, 12-methyl-ω-tridecanolide, ω-pentadecanolide, ω-heptadecanolide, etc.), coumarins (osthol, angelicin, osthenol, umbelliferone, archangelicin, bergapten, ostruthol, imperatorin, umbelliprenine, xanthotoxol, xanthotoxin, oxypeucedanin, oreoselone, phellopterin, marmesin, byakangelicol, etc.), plant acids (angelic, aconitic, malonic, caffeic, chlorogenic, quinic, myristic, pentadecanoic, behenic acids, etc.), archangelenone, β-sitosteryl palmitate, etc.  Despite its high content of coumarins, some of which are toxic, angelica root is considered a GRAS (generally recognized as safe) substance in the United States and has been safely used for decades as a flavoring agent in foods as well as a botanical medicine.  The reason it is safe is due to the fact that in its natural state, the dozens of chemicals present are ingested in the proportions as they naturally occur in the plant, and therefore no one single chemical is being consumed in excessive quantities.  This prevents the over-consumption of a particular potentially toxic chemical; there also may exist a mutually ameliorating effect among these potentially toxic compounds.  However, once a minor chemical is selectively isolated from the mixture of these bioactive components and introduced as a dietary supplement, we will be exposed to a specific compound in a way we have never before been subjected.  Even though this compound is from a GRAS herb, it is now being ingested in such relatively high doses that its intake can no longer be considered normal consumption.  This compound is now basically no different than a new drug or food additive whose toxic side effects will take time (perhaps decades) to surface.  (2) Take the case of jungle medicines.  After losing millions of investors’ money and failing to introduce chemicals isolated from jungle plants as drugs, a natural products company recently entered the dietary supplements field with the following claim by its president, who, not unlike other executives of many failed public companies, has pocketed millions: “We are a powerful force entering the industry.  I have no doubt we will be No. 1 in introducing novel supplements.”1  I am sure you can guess what was meant by “novel supplements.”  They want to have their cake and eat it too.  In my opinion, unless a chemical is either a major active component of a commonly used herb, or is ubiquitously present in the plant kingdom, it does not qualify as a true dietary supplement.  And I have serious doubts about the safety and relevance of these “novel supplements” from the jungle being used as part of our daily diet, especially if the compounds are of novel or rare chemical structures.  No matter how you view it, this company, like many others, is trying to take advantage of the faulty DSHEA, and bypassing the food and drug laws by introducing new drugs or food additives as dietary supplements. Why is it that no one seems to see the potential danger to the public of this new trend?  It may be because money and conscience are so intertwined that nobody is free to speak up anymore. 

(1) Natural Business, March 1999, p. 6.



Wisdom in Herb Processing


        Certain fundamental differences exist between Chinese and Western herbs:  Chinese herbs normally undergo further processing beyond simply cleaning and drying [Issue 7, pp. 1,2].  They are commonly used in combinations; and a large number are used for their subtle and balancing effects, even in the treatment of specific diseases or symptoms; this latter practice has resulted in a unique class of herbs called tonics.  On the contrary, Western herbs rarely undergo further physical or chemical treatment beyond washing and drying.  They are often used fresh and are traditionally rarely used in combinations.  Unlike Western herbs, Chinese herbs are very specifically defined.  Simply stating the correct species is not enough, even if the appropriate plant part is included.  This is why so much confusion still exists, a result of too many publications by botanists, Western herbalists, and chemists who have not learned the intricacies of traditional Chinese herbs.  For example, mahuang is the herb-like stem of one of 3 major Ephedra species.  It promotes perspiration and is used in treating asthma, cold, flu, and other conditions.  On the other hand, the root and rhizome of this plant, called mahuanggen, are used both internally and externally to stop perspiration.  Thus, an uninformed herbalist, botanist, chemist or pharmacist, who may be highly knowledgeable in botanical identification but not knowledgeable in Chinese herbs, may miss the point, and will continue to refer to mahuang as if it were the plant itself.  This would not only perpetuate the dissemination of inaccurate information, but also impact quality of the raw herb.  For example, in this case, if you don’t know the nature of the 2 distinctly different herbal drugs from the same Ephedra plant, you might not consider mahuang (the stem) that contains large amounts of the root and rhizome as adulterated, and vice versa.  The fact is that the quality of a shipment of mahuang containing 5% root/rhizome is quite different from one that contains 25% of root/rhizome!  Yet to the casual or untrained analyst, the two shipments may not look that different.  This is just one example of many potential problems in dealing with Chinese herbs.  Further, let’s say you have the right plant species with its correct plant part, you are not out of the woods yet.  Depending on how it is processed, the herbal drug often yields 2 or more different drugs with distinctly different properties, which are used for different purposes.  Thus, even with mahuang, the raw herb (cleaned and dried) has stronger diaphoretic properties and is not recommended for persons with a weak constitution, while the cured herb (processed with licorice, honey, etc.) is milder in its diaphoretic effect but stronger in its anti-asthmatic and anti-tussive properties.  These effects were observed many centuries ago, and were scientifically verified only in recent years.  A much more dramatic change in properties after processing is seen in the herb, heshouwu (commonly known here as fo-ti), which is the root tuber of Polygonum multiflorum Thunb., a knotweed or fleeceflower.  The raw herb is a strong detoxicant and is cathartic as well as toxic, while the cured herb is a tonic that is often used in cooking [Issue 12, p. 2; 13, p. 3; 14, p. 2].  Not being specific about its source can result in serious consequences.  For example, knowingly or unwittingly using the cheaper raw fo-ti instead of cured fo-ti in a product intended as a general tonic may result in many trips to the bathroom for the consumer and a misconception of Chinese tonics. 

        It is quite clear how important processing is in the use of traditional Chinese herbs.  Two of the major objectives of processing are (1) to reduce toxicity of the herb and (2) to modify or improve the herb’s function(s).  The Chinese started this tradition thousands of years ago.  Initially, it was used to render toxic herbs less toxic, with earliest documentation in the Wu Shi Er Bing Fang (Prescriptions for Fifty-two Diseases) published around 11th-8th century B.C.  Later, an additional objective of processing was to modify the herbs’ action while simultaneously reducing their toxic effects. The first book exclusively devoted to this subject, called Lei Gong Pao Zhi Lun (Lei Xiao’s Principles of Processing), was published during the 5th century A.D.  By the 15th century, herb processing had become routine and methods for most herbs are described in Li Shi-Zhen’s Ben Cao Gang Mu.  Thus, through centuries of practical experience, coupled with keen observations, the Chinese have discovered ways to make a toxic herb less toxic and to modify an herb’s properties for specific applications.  For example, prolonged heating, treatment with wine or vinegar, and frying or steaming with adjuvants (honey, salt, bran, licorice, and other herbs) are often used to enhance an herb’s functions, as in the case of ligustrum or nuzhenzi (Ligustrum lucidum fruit), an age-old yin tonic, first described in the Shan Hai Jing around 800 BC. 



Recent Findings in Effects of Processing

         Effects of Processing of Nuzhenzi (Ligustrum lucidum Fruit) on Lipid Peroxidation [Zhejiang Zhongyi Zazhi, 33(11): 522-523(1998)].  Decoctions (representing 500 mg/mL of herb) of raw and cured nuzhenzi were studied for their in vitro inhibition of lipid peroxidation in rat liver tissue.  The inhibitory effects of 3 different concentrations (0.25 mg/mL, 0.5 mg/mL and 1.0 mg/mL) of the decoctions on the formation of malonyldialdehyde (MDA), a product of lipid peroxidation, were measured.  The following 6 types of cured nuzhenzi were studied:  (1) steamed and dried; (2) brine-treated, steamed and dried; (3) vinegar-treated, steamed and dried; (4) white-wine-treated, steamed and dried; (5) yellow-wine-treated, steamed and dried; and (6) yellow-wine-treated and stir-fried.  Using decoctions of rhodiola (rhizome of Rhodiola species) as positive control, results showed that the inhibitory effects on lipid peroxidation of the decoctions of rhodiola and cured nuzhenzi at 0.25 mg/mL was 3.7 to 4.7 times stronger than those of raw nuzhenzi.  However, as the concentrations of the decoctions increased, the difference in their inhibitory effects became progressively less (only 17%-33% higher at 0.5 mg/mL; and negligible at 1.0 mg/mL).  In all cases the percent inhibition of MDA formation ranged from 17.09 for raw nuzhenzi to 81.05 for brine-treated/steamed nuzhenzi at 0.25 mg/mL; 68.16 for raw nuzhenzi to 90.94 for vinegar-treated/steamed nuzhenzi at 0.5 mg/mL; and 87.69 for raw nuzhenzi to 95.56 for steamed nuzhenzi at 1.0 mg/mL.

        As described earlier (Issue 10, p. 2), nuzhenzi is one of the most important Chinese yin tonics, with a recorded use history dating back to around 800 B.C.  As a tonic herb, it is often processed different ways (involving steaming and drying), and its biological functions are multifaceted (immunomodulating, antioxidant, hypolipemic, anti-atherosclerotic, anti-inflammatory, anti-allergic, liver protectant, sedative, hypoglycemic, etc.).  Some of its known active principles include polysaccharides (6.8%-17.8%), p-tyrosol (0.31%-0.94%), and oleanolic acid (0.7%-4.3%).2  Among other effects, oleanolic acid lowers SGPT, hence is liver protectant.  Curing (especially wine-steamed) increases this effect, which correlates to an increase in oleanolic acid.3  Incidentally, oleanolic acid is a triterpene that is ubiquitously present in plants (common jujube, hawthorn, olives, forsythia, mume, thyme, etc.).  Even though it is an “old” chemical structure that is normally of little interest to chemists, oleanolic acid has a tremendous potential of being developed into a safe dietary supplement (“nutraceutical”).  Unlike ephedrine and related amphetamine-type compounds (e.g., synephrine), oleanolic acid has routinely been part of our diet for millennia, and has been demonstrated to have broad biological activities that are beneficial.

(2) J.H. Xu et al., “Active Components of Nuzhenzi (Ligustrum lucidum Ait. Fruit) and Xiaola Fruit (Ligustrum sinense Lour.),” Zhongcaoyao, 29(3): 167-169(1998);  (3) Y.S. Yin and C.S. Yu, “Experimental Study on the Effects of Curing on the Chemistry and Liver-Protectant Effects of Ligustrum lucidum fruit,” Zhongchengyao, 15(9): 18-19(1993); Leung, A.Y., and S. Foster, Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, Wiley-Interscience, New York, 1995, pp. 227-229, 250-253, 350-352; Leung, A.Y., Better Health with (Mostly) Chinese Herbs & Food, AYSL Corp., Glen Rock, NJ, 1995, pp. 28-29, 58.



Herb Notes


        Periodically, the Zhongyi Zazhi (Journal of Traditional Chinese Medicine) publishes a special issue dealing with results of the uncommon use of a specific herb in treating mostly common ailments.  In last year’s June issue [39(6): 325-327(1998)], a report from Daxian Hospital of Traditional Chinese Medicine, Sichuan Province, describes the use of high doses of schisandra for treating the following conditions. 


          Chronic fatigue syndrome due to excessive exercise.  A 21-year-old basketball player complained of general stiffness and soreness after a rigorous practice, accompanied by excessive dreams, languor, and listlessness, which persisted even after a 2-week rest.  During one game, he had to force himself to substitute for an injured teammate, but had to stop after only a few minutes, due to profuse perspiration and lack of energy.  A complete check-up resulted in the above diagnosis.  The patient was treated with the following tea: 150 g schisandra berries and 10 g Chinese ginseng rootlets were boiled together and the liquid is drunk as a tea.  After only 1 dose (not clear whether it was during the course of 1, 2 or 3 days), the patient’s fatigue was greatly relieved, and after 3 doses, his strength returned.  He was then able to play in major games without requiring substitution.  During the next few years’ follow up, his problem occasionally recurred, which was quickly relieved with the same tea.


           Menopausal syndrome.  At age 53, the patient had undergone menopause 3 years earlier.  Since then, she had been irritable, argumentative, and short-tempered, as well as suffering from serious memory loss.  Menopausal syndrome was diagnosed at a university hospital and was treated unsuccessfully.  At the time she consulted TCM, she had difficulty sleeping and had frequent nightmares.  She was treated with schisandra alone:  100 g boiled with water and drunk as tea; 1 dose per day.  After 2 weeks, the patient’s temper mellowed and her memory improved.  Treatment was continued for another month and follow-up several times since revealed no recurrence of hot temper and memory loss.


        Being a typical tonic (or adaptogen), schisandra berry has normalizing effects.  Depending on a person’s physical and mental state, it exerts either central stimulant or tranquilizing effects, in addition to numerous other activities (antioxidant, immunomodulating, antimutagenic, liver protectant, etc.)[Issue 7, pp. 2,3; 16, p. 3].  It is a fairly common ingredient in formulas for insomnia, persistent cough and wheezing, night sweat and spontaneous perspiration, and male inadequacy problems.  Its effects in improving the endurance and work performance of healthy humans and animals (e.g. race horses) have been reported. 

        The daily therapeutic dose of schisandra berry is normally no more than 10 g, and it can be as low as 1.5 g, as specified in the Chinese Pharmacopoeia.  The dosage used in the above 2 cases were 10 to 15 times above normal.  Although I am not aware of any serious toxic side effects due to the ingestion of schisandra berries, I don’t recommend anyone without certain knowledge and proficiency in the practice of TCM to go ahead and use the above methods and high doses in treating above conditions.  Furthermore, there is another issue regarding the use of schisandra berries, which has never been expressly addressed by any book or by the Chinese Pharmacopoeia.  This is the fact that most schizandrins (one group of its various active components) are present in the seed.  When used as a powder, there is no confusion as to whether the right dosage is taken, because the seed is present in its powdered form that will allow the schizandrins to be extracted and absorbed inside the body.  The lower dosage indicated usually refers to the powdered herb to be swallowed with water.  On the other hand, when an amount is specified to be taken after being decocted, there is potentially a great discrepancy in schisandra’s intended effects [Issue 16, p. 3], depending on whether the whole or ground form of schisandra is used.  For example, the amount of schizandrins extracted from 1 g of whole berries would be considerably less than that from 1 g of the powder.  Until this issue is resolved, we should accept biological and clinical data on schisandra with reservations.  In the case of the above 2 reports, if the berries were decocted whole, I see little problem of overdosing.  On the other hand, if one ground the berries first and then made a tea of the ground material, that would be quite a different story.  In any case, I urge my colleagues who are in a position to recommend or specify dosages for schisandra fruit to be specific in stating whether the whole or the powdered fruit is used. 

Leung, A.Y., and S. Foster, Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, Wiley-Interscience, New York, 1995, pp. 469-472; Leung, A.Y., Better Health with (Mostly) Chinese Herbs & Food, AYSL Corp., Glen Rock, NJ, 1995, pp. 83.