LEUNG'S
(CHINESE) HERB NEWS
Number 31
March/April 2001

Herbs in this issue:

Astragalus

Bai-zhu atractylodes

Siler

‘Bamboo leaf’

Common purslane

 

A Note From Dr. Leung

 

Pharmacokinetics and bioavailability … of what?

 

     I am talking about pharmacokinetics (PK) and bioavailability (BIO) of botanicals (often casually and wrongly referred to as pure chemical drugs).  Whenever there is a scientific discussion on the safety and efficacy of a botanical, these topics invariably come up.  I hope my writing this would stir up debate among my colleagues about this issue, because much of our tax dollars are being, and continue to be, wasted if we, as ‘scientists,’ don’t get it straight.  This is especially true for those of us who are in powerful positions in government with authority to dispense our tax money for research in botanical ‘drugs.’  I may be PK- and BIO-challenged, but I don’t believe PK or BIO can apply to anything other than well-defined chemicals that include chemical drugs like methotrexate, morphine, codeine, synephrine, and ephedrine, or nutritional chemicals like vitamins (A, B, C, D, E, etc.) and amino acids.  They cannot apply to botanicals despite the fact that they are often mistakenly referred to as pure-chemical drugs and not herbal drugs.   

 

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.


 

There are standard methods for analyzing chemical compounds as well as their metabolites.  Hence, we can determine the PK and BIO of these chemicals.  On the other hand, foods and many botanicals (whether one calls them tonics, foods, supplements, or drugs) don’t yield well-defined compounds that can be readily measured which are relevant to the total biological activities of these materials.  There are simply too many chemicals present.  Thus, how can you determine the PK and BIO of broccoli, cauliflower, and prune?  Or of eleuthero, Asian ginseng, feverfew, and St. John’s wort, when we don’t know what specific chemicals are responsible for their activities?  Thus, have you heard scientists talk about the PK or BIO of broccoli?  I haven’t.  Yet I have often heard them insist on requiring PK and BIO for ginseng, eleuthero, feverfew, and other botanical ‘drugs’ as if these botanicals were single-chemical entities.  The fact is, as far as the complexity of their chemical composition is concerned, broccoli and ginseng or eleuthero all have multiple chemical components, none of which alone represents broccoli, eleuthero, or ginseng.  Hence, it is plain silly to have PK and BIO performed on them.  Sure, for lack of something on which to utilize our knowledge that we have spent years to learn in graduate school, we can use chemical markers like citric acid (or maybe malic acid or ascorbic acid) for prune and one of the numerous sulfur compounds for broccoli and cauliflower.  For eleuthero, we can use one of the numerous ‘eleutherosides’ (the sterol daucosterol, the phenylpropanoid syringin, an isofraxidin glucoside, one of the coumarins, one of the lignans, or one of the triterpenes).  And for ginseng, we have the now well-known ginsenosides; we can use one of about 2 dozen of these compounds, or perhaps one of the other ginseng components such as choline, one of the polyacetylenes (e.g., panaxynol), nicotinic acid, pantothenic acid, biotin and other vitamins, or perhaps b-sitosterol.  How about feverfew and St. John’s wort?  They appear simpler, because we can use parthenolide for the former and hypericin (or hyperforin) for the latter.  However, the problem with arbitrarily selecting any of these compounds for PK and BIO determination is that whatever results obtained will be largely short-lived or meaningless unless these compounds have been proven for sure to represent the bioactivity or efficacy of the botanicals concerned.  In fact, we now know that parthenolide is not the only active component of feverfew, nor is  hypericin or hyperforin solely responsible for the activity of St. John’s wort.  My concern is while we are chasing after parthenolide, for example, what happens to the other still-to-be-identified active chemical compound(s) that we have not included in our PK and BIO studies?  Also, the bioactivity or efficacy must be clearly defined, otherwise it would be like comparing oranges with apples.  For example, if you picked 1 of the 2 dozen ginsenosides in ginseng, say ginsenoside Rb1, as the target/marker compound for PK and BIO studies, you better be sure that this was selected for a very specific activity.  Thus, if ginsenoside Rb1 in ginseng were selected for its CNS-tranquilizing effect, it had better be clearly demonstrated to be responsible for all or most of this activity in ginseng.  If not, one would obtain meaningless or, at best, misleading results, because sooner or later, another compound (or compounds) in ginseng would be found to have effects that negate those of Rb1, as it has been found in another compound in ginseng (ginsenoside Rg1), which has CNS-stimulant effect.  These kinds of misleading or meaningless results are nothing new when we apply our conventional scientific approach to the study of herbal medicines, treating them as if they were conventional single-chemical drugs and out of their traditional context.  This is the major reason why many of the research studies and clinical trial results on herbal medicines cannot be duplicated, thus wasting much of the little amount of taxpayers’ money allocated to the study of herbal supplements.  As long as scientists can’t tell the difference between an herbal drug and a single-chemical drug, research in PK and BIO of herbal medicines will not produce meaningful or useful results.  It seems to me such an elementary concept, yet I keep encountering ‘experts’ in our field in government, academia, and industry continue to go about their business as usual, without distinguishing an herb from a conventional chemical drug!  I would love to hear from my colleagues regarding this.

  

Encyclopedia of Traditional Chinese Prescriptions (Zhong Yi Fang Ji Da Cidian)

        In the last issue (Issue 30, pp. 1-3), I reviewed the most recently published 10-volume Chinese herbal, Zhonghua Bencao (The Chinese Herbal), which provides detailed monographs on almost 9,000 traditional Chinese drugs, and is easily the most extensive work to date on materia medica in any language. 

         The total number of plant species used in traditional Chinese medicine (TCM) recorded in the Quanguo Zhongcaoyao Mingjian, published in 1996, is close to 11,500 (from 369 families).  Considering that a single plant species generally yields more than 1 drug and sometimes up to 4 or 5 (e.g., root, leaf, stem, bark, fruit, or flower), it is a conservative estimate that the number of actual herbal drugs derived from these plants can easily be twice the number of plant species recorded – or over 22,000!  Since herbs in TCM are usually used in combinations, the number of permutations derived from combining these documented plant drugs can be astronomical (Issue 21, p. 2).  Indeed, my estimate of even only the documented Chinese herbal formulas is at least 200,000.  Thus, in the Encyclopedia of TCM Prescriptions alone, 100,000 formulas are documented.  These are primarily from the classical literature with only a minor number from the modern practice of TCM.  There are countless formulas documented in regional and local publications which are not included in this work, not to mention the unpublished formulas handed down over generations from parent to child and from master to disciple.  And the Chinese population is over 1.2 billion, most of which still relies on TCM as its major health care system. 

         The Encyclopedia of TCM Prescriptions was published between 1993 and 1997, in 11 volumes, by Renmin Weisheng Chubanshe (Peoples’ Health Press), Beijing.  Volumes 1 through 10 describe close to 100,000 named prescriptions from 1,800 major classical works on formulas written during a 2,000-year period, starting with the Qin/Han era up until 1986.  The prescriptions are listed in increasing order of strokes based on the first character (word) of the formulas’ names.  Volume 11 consists of an index of the formulas based on standard names and another based on other names.  It also contains an index of diseases treated by these formulas, a section dealing with the comparison between ancient and modern measurements, a list of references from which the formulas are derived, and an addendum of correction of errors in the Encyclopedia

         It is worth noting that many prescriptions have the same names.  Hence, if one wants to be precise, it is important to specify exactly from where a particular formula originates (formulary, date, etc.) 

         Information provided for the prescriptions in the Encyclopedia includes the following 12 categories: origin of prescription, other name(s), composition, method(s) of administration, action, diseases treated, precautions, modification (addition or subtraction of ingredients depending on nature of disease), theoretical comments from selected TCM classics, clinical use examples, modern research, and additional comments.  Most monographs contain only basic information, such as the origin of the prescription, composition, method(s) of administration, action, diseases treated, and precautions.  However, the more commonly used formulas contain information on most of above 12 categories.  The following 2 examples will serve to demonstrate the typical information provided in this Encyclopedia for better-known formulas:

Yu Ping Feng San (‘Jade Screen Powder’) – There are 3 formulas with the same name described in the Encyclopedia.  The first one comes from Yi Feng Lei Ju (circa 1445), the second from Ma Ke Huo Ren Quan Shu (circa 1748), and the third from Bi Hua Yi Jing (circa 1824).  The first one is the most well-known and is the one generally being referred to when one talks about the Yu Ping Feng formula (Issue 17, p. 3).  As described in its monograph, it consists of 1 part of siler (Saposhnikovia divaricata root - fang feng,) and 2 parts each of honey-cured astragalus (huang qi) root and bai-zhu atractylodes (Atractylodes macrocephala rhizome).  Information is provided for 8 of the 12 categories listed above, the missing categories being ‘other names,’ ‘precautions,’ ‘modifications,’ and ‘additional comments.’  Three clinical case examples are given.  So are findings from modern research in immunoregulation and effects on renal function.  In contrast, the information on the other 2 prescriptions is minimal, including only ‘origin,’ ‘composition,’ ‘methods of administration,’ and ‘diseases treated.’

Yin Qiao San (Honeysuckle Forsythia Powder) – There are 3 prescriptions bearing the same name.  The first one comes from Wen Bing Tiao Bian (circa 1798), the second from Hao Jing Zhi Zhi Yi Fang (circa 1907), and the third from a 1962 compilation.  Yin Qiao San is one of the most commonly used formulas for treating cold and flu in China.  Although all 3 formulas are based on honeysuckle flower and forsythia fruit, the first one is the most widely used and researched.  Its basic formula consists of the following 9 herbal drugs as listed in its monograph under ‘composition’ with my clarification or comments in parenthesis:  (1) lian qiao [forsythia fruit, Fructus Forsythiae]; (2) yin hua [jin yin hua or honeysuckle flower, Flos Lonicerae]; (3) ku jie geng [another name for jie geng, platycodon root or Radix Platycodi]; (4) bo he [a variety of field mint or Japanese mint – Mentha haplocalyx Briq., Herba Menthae]; (5) zhu ye [literally translated as ‘bamboo leaf’.  Most other sources list dan zhu ye, meaning ‘bland-tasting bamboo leaf,’ as a component of this formula.  Dan zhu ye is also the name of the plant, Lophatherum gracile Brongn.  The drug derived from this plant is also called dan zhu ye which consists of the plant’s stems and leaves, or Herba Lophatheri – Lophatherum herb.  Zhu ye is the leaf of another bamboo plant called ‘dan zhu,’ (without the ye or leaf) which is Phyllostachys nigra (Lodd.) Munro var. henonis (Mitf.) Stapf ex Rendle.  Various parts of this plant are used in medicine and its leaf is called zhu ye or dan zhu ye (zhu=bamboo; ye=leaf; dan=bland).  Is that confusing enough yet?  The 2 herbs have obviously been used interchangeably for centuries, sometimes knowingly, while other times unknowingly]; (6) sheng gan cao [raw licorice root, Radix Glycyrrhizae]; (7) jing jie [schizonepeta herb, Herba Schizonepetae]; (8) dan dou chi [fermented soy bean, Semen Sojae Praeparatum]; and (9) niu bang zi [burdock fruit or Fructus Arctii].  Information is provided in all the above 12 categories with the exception of ‘precaution’ which is not given, probably due to the general safety of this formula. 

Clinical use examples are cited from 4 modern sources, including 3 regional TCM journals, 1 each from Guangdong, Hubei, and Fujian Provinces.  The diseases successfully treated with this formula include influenza (1,150 cases – all recovered in 2-4 days), childhood pneumonia (25 cases – all recovered in 3-5 days, with negative X-ray; authors of report opined that this prescription should be most valuable in antibiotic-resistant pneumonia), early-stage measles (55 cases – with fever gone in average 7.00.24 days, compared to 8.410.22 days in 101 patients treated with conventional drugs), and various febrile diseases (wen bing) at their onset, such as acute bronchitis, pneumonia, influenza, pertussis, parotitis, measles, chickenpox, and acute laryngitis (over 100 cases – all satisfactory). 

         Under ‘modern research’ Yin Qiao San’s fever-lowering and immunologic effects are described, citing literature up to 1986. 

         Under ‘additional comments,’ 3 recent formulas in pill, tablet, and ointment forms are derived from the original Yin Qiao SanYin Qiao Jie Du Wan (jie du means detoxifying, and wan means pill); Yin Qiao Jie Du Pian (in tablet form – this version is official in the Chinese Pharmacopoeia); and Yin Qiao Jie Du Gao (ointment). 

         Compared to The Chinese Herbal (Zhong Hua Ben Cao), reviewed in the last issue of this Newsletter, the depth of treatment of this compilation in terms of modern findings is minimal.  But considering the number of formulas described in this Encyclopedia, which is over 10 times the number of traditional drugs described in the former, it is understandable the treatment needs to be much briefer. 

  

Common Purslane (Portulaca oleracea; machixian)

        I wrote about this herb before in the November/December 1997 Issue of this newsletter (Issue 11, p. 3).  It is also one of the botanicals described in my Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics.  This is such a ubiquitous and potentially very useful plant that I wish someone would commercialize it in North America as a vegetable or salad green.  As a salad green, it tastes slightly tart and quite refreshing.  I would buy it if it were available at supermarkets.  This would eliminate the uncertainty of collecting enough of it from one’s own yard.

The plant grows in many parts of the United States and southern Canada.  Here in New Jersey, it grows as a weed on many nonprofessionally cared-for lawns and waste places.  The aboveground part is used as a vegetable and salad green in many parts of the world.  It is rich in nutrients (vitamins A, B1, B2, C, niacinamide, nicotinic acid, a-tocopherol, b-carotene, omega-3 acids, glutathione, flavonoids) and also contains high concentrations of l-noradrenaline or l-norepinephrine (0.25% in fresh herb reported). 

In TCM, the whole herb is considered cold-natured and has detoxicant and heat-dispersing properties.  Traditionally, it is used internally to treat headache, stomachache, painful urination, dysentery, enteritis, mastitis, bleeding, etc., as well as externally to treat burns, insect stings, inflammations, eczema, pruritus, vitiligo, and skin sores.  Modern uses include the treatment of colitis, diabetes, shingles, and dermatitis. 

         To treat shingles, simply apply the expressed juice from the fresh herb to the afflicted areas as many times as necessary.  For severe cases, boil 250 g of the fresh herb in water and drink the liquid, once daily, in addition to the external treatment.  It is claimed that most patients were cured in 2-3 days, without adverse effects.1  Certainly won’t hurt to give it a try.

For diabetes, simply eat it regularly as a vegetable when in season or dry it for use in winter.  The dried herb (100 g daily) is boiled in water and the decoction drunk.  According to a 1990 report, the latter method was effective in normalizing blood sugar levels usually in 1-2 weeks.2

In a recent review, fresh purslane herb (juice or poultice) is reported to be effective in treating numerous skin conditions when applied topically, including urticaria (hives), psoriasis, flat warts, wasp stings, vitiligo, and ringworm of hand and foot.3 

In another report, rabbits (2-2.5kg body wt.) fed dried purslane herb powder (8g daily for 11 weeks) showed significant increase in their serum superoxide dismutase (SOD) activity and decreased production of malonyldialdehyde (MDA), indicating strong antioxidant activities.4

1.  F.S. Huang, “Treatment of Herpes Zoster with Fresh Purslane Herb,” Zhejiang Zhongyi Zazhi, 29(8): 351(1994);  2. H. Wang, “Single-herb Purslane for Treating Diabetes,” Zhejiang Zhongyi Zazhi, 25(11): 516(1990);  3. Z. Yang and L. Huang, “Recent Developments and Future Prospects in Purslane Research,” Fujian Zhongyiyao, 31(5): 43-44(2000);  4. S.W. He et al., “The in vivo Antioxidant Effects of Purslane Herb in Rabbits,” Zhongcaoyao, 28(5): 284-285(1997);  Leung, A.Y., and S. Foster, Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, Wiley-Interscience, New York, 1996, pp. 548-549.