[First published in Leung’s Chinese Herb News (LCHN-19), Mar/Apr, 1999; reprinted in My Life & Rollercoaster Career (MLRC), 2018, pp. 330-334]
Too many scientists and researchers investigating botanical medicines frequently treat herbal materials as if they were pure single-component drugs. This has resulted in countless numbers of publications that are meaningless (Issue 18), which in turn has wasted considerable amount of our precious resources and mental energy in disseminating and/or debunking. To help scientists and writers/editors who are not familiar with the intricacies and complexities of natural product research, the following are some guidelines for evaluating and accepting natural products for study or manuscripts for publication. They also will serve as basic information for abstractors to include in their abstracts of published papers. I have divided them into 2 standard levels. The higher-level criteria should be ones whose attainment is our ultimate goal. With this higher standard, results of investigations in this field are more likely to be consistently duplicated. On the other hand, the minimal-level criteria are ones that should constitute the basic requirements for accepting a natural product for research or a manuscript for publication as well as minimal information to be included in abstracts. This lower standard is necessary for now because, at present, there are not too many publications that meet the ideal criteria. However, as researchers not trained in the comprehensive aspects of natural products research get acclimated to this field, the ideal criteria naturally will then be adopted.
1. Commercial products without disclosure of formulas. Frequently, researchers publish reports based on a commercial or proprietary product, without revealing what the product is. In the Chinese herbal/medical literature, there are many publications of this type. The information in them is meaningless and useless, except to manufacturers and marketers of the investigated products.
Minimal (to allow traceability):
• Name and address of manufacturer
• Concentration(s) used in the study
• Method(s) of administration
• Source of financial support if other than manufacturer/marketer
Ideal:
• Reject the material or manuscript
2. Pure natural compounds. They should be treated as any pure natural
chemicals (e.g., caffeine, ephedrine, huperzine A, synephrine), with indication of whether they are isolated from plants or chemically synthesized.
Minimal:
• Chemical name
• Purity
• Concentration(s) used in study
• Method(s) of administration
Ideal (all above, plus):
• Plant source (Latin binomial), with authenticating authority
• Plant part (s), with authenticating authority
3. Purified extracts containing artificially high concentrations of specific chemical compounds or groups of chemicals. They include extracts of green tea with high amounts (e.g., 90%) of certain polyphenols (catechin, epigallocatechin, epigallocatechin gallate, etc.), of Asian ginseng with high total ginsenoside content (e.g., 80-90%), of grape seed or pine bark with high proanthocyanidin content (e.g., >80%), and of milk thistle with silymarin. Since the contained chemicals are present in such artificially high levels, they no longer bear resemblance to the botanicals from which they are extracted. These extracts are the ones that can cause the most problems. Unless the whole extraction process (including solvents) is revealed, there is no easy way to ascertain, besides the named chemicals (markers or actives), what else is present in the extract. For example, does the remaining part of the extract contain other even more active components from the botanical drug, or is it made up of only excipients? What is the chemical profile of the extract? Is this chemical profile consistent and how comparable is it to ones previously reported? Variations among these factors can greatly affect the biological activities of these extracts. The more precisely we identify these parameters, the more likely can the results be duplicated by future studies. To perform scientific studies on these natural materials without addressing these issues would not yield consistent and meaningful results.
Minimal:
• Plant source(s) (Latin binomials), with authenticating authority
• Plant part(s), with authenticating authority
• Percent purity of marker(s)/active(s) in extract
• Chemical profile of marker(s)/active(s) (minimum 2 of: HPLC,
TLC, GC, etc.)
• Concentrations used in study
• Method(s) of administration
Ideal (all above, plus):
• Nature of extract (solvents used and ratios)
• Total chemical profile of extract (minimum 2 of: HPLC, TLC, GC, etc.)
• Excipients used in extract
4. Standardized extracts. These are extracts with a standardized amount of one or more marker or active compounds. There are 2 major types: total extracts containing specified amounts of markers or actives plus other compounds also naturally present; and partial extracts containing specified amounts of markers and actives, but lacking other components present in total extracts. As with purified extracts containing high concentrations of specific markers or active compounds, the same types of issues relating to solvents used and consistency of chemical profile apply.
Minimal:
• Plant source(s) (Latin binomials), with authenticating authority
• Plant part(s), with authenticating authority
• Percent purity of marker(s)/active(s) in extract
• Total chemical profile of extract (minimum 1 of: HPLC, TLC, GC, etc.)
• Concentrations used in study
• Method(s) of administration
Ideal (all above, plus):
• Nature of extract (solvents used and ratios)
• Chemical profile of marker(s)/active(s) (minimum 2 of: HPLC,
TLC, GC, etc.)
• Total chemical profile of extract (1 more of: HPLC, TLC, GC, etc.)
• Excipients used in extract
5. Regular extracts. These are extracts with no standardized amounts of marker or active compounds. Their strength may be expressed in ratios between raw herbs and extracts (e.g., 4:1, meaning 1 kg of extract is derived from 4 kg of raw herb) or as percent of herb material in a specific solvent (e.g., 20% extract in 70% ethyl alcohol, meaning 100 g or mL of the hydroalcoholic extract is derived from 20 g of crude herb). However, these strengths are meaningless unless solvents used in their extraction are given. For example, a strength of 10:1 to describe extracts of astragalus root or Asian ginseng root is meaningless, unless the solvent(s) are clearly stated, because a normal exhaustive extraction of either herb with water will result in extracts of no more than a 3.5:1 strength. On the other hand, an extraction with 1-butanol would yield very little extractives and thus would result in extracts of high strength (e.g., 10:1). However, these extracts do not represent these botanicals in traditional properties or in chemical profiles.
Minimal:
• Plant source(s) (Latin binomials), with authenticating authority
• Plant part(s), with authenticating authority
• Type of extract (tincture, fluid extract, solid extract, powdered
extract, etc.)
• Solvent(s) used and ratios
• Strength (ratio of crude herb to extract)
• Concentration(s) used in study
• Method(s) of administration
Ideal (all above, plus):
• Total chemical profile of extract (minimum 2 of: HPLC, TLC, GC, etc.)
• Dosage form used (tablets, capsule, syrup, drink, etc.)
6. Crude botanicals. Sometimes powdered herbs and fresh herbs or juices are used in studies. It is important to be sure the following minimum information is provided.
• Plant name(s) (Latin binomials), with authenticating authority
• Plant part(s), with authenticating authority
• Form used (fresh, juice, dried, dried after processing, etc.)
• Dosage form used (capsule, tablet, drink, etc.)
• Method of administration or application (oral, topical, etc.)
• Amount(s) used in study
The above guidelines I have provided are by no means complete. But at least they can serve as a start. I am sure some of my esteemed colleagues who are well versed in this field will provide further suggestions and comments. However, there are several caveats. Thus, despite all these criteria, an uninformed investigator could always provide a plant name (Latin binomial) even though he/she may have no idea of its authenticity. Consequently, it is imperative that the authority who authenticated the plant material be identified in the publication. Also, fundamental problems relating to the influences of growing location, time of harvest, and age of plant at harvest, as well as other geographical and climatic factors, need to be addressed on an ongoing basis until resolution is achieved. I am not the only scientist who sees as a major threat to natural product research, the use of dubious plant materials, which leads to the proliferation of published information that is biased, dubious, and often plain wrong. As the few examples described in the last issue of this newsletter [Issue 18] demonstrate, we, as responsible scientists, must take the challenge and responsibility to stop this “cancer” that is growing out of control. We need to have relevant organizations such as the American Society of Pharmacognosy (ASP) take the lead in refining these guidelines and promoting their adoption by fellow scientists. ASP should itself encourage its own members to follow them as well as enforcing them in its own publication and publications of its sister organizations. If we, as a small group of scientists who understand the complexities of natural product research, do not take the lead, the scientific and medical fields would be drowned in quasi-scientific herbal gibberish in 10 years. Just look at the sudden proliferation of books, journals, magazines, and newsletters on this subject over the past 5 years! Too much damage has already been done!