Developing a Library of Authenticated Traditional Chinese Medicinal (TCM) Plants

for Systematic Biological Evaluation - Rationale, Methods and Preliminary Results

from a Sino-American Collaboration

 

David M. Eisenberg, Eric S.J. Harris, Bruce A. Littlefield, Shugeng Cao,

Jane A. Craycroft, Robert Scholten, Peter Bayliss, Yanling Fu, Wenquan Wang,

Yanjiang Qiao, Zhongzhen Zhao, Hubiao Chen, Yong Liu, Ted Kaptchuk, William C. Hahn,

Xiaoxing Wang, Thomas Roberts, Caroline E. Shamu, Jon Clardy

 

Abstract

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While the popularity of and expenditures for herbal therapies (aka ”ethnomedicines”) have increased globally in recent years, their efficacy, safety, mechanisms of action, potential as novel therapeutic agents, cost-effectiveness, or lack thereof, remain poorly defined and controversial. Moreover, published clinical trials evaluating the efficacy of herbal therapies have rightfully been criticized, post hoc, for their lack of quality assurance and reproducibility of study materials, as well as a lack of demonstration of plausible mechanisms and dosing effects. In short, clinical botanical investigations have suffered from the lack of a cohesive research strategy which draws on the expertise of all relevant specialties.

With this as background, US and Chinese co-investigators with expertise in Traditional Chinese Medicine (TCM), botany, chemistry and drug discovery, have jointly established a prototype library consisting of 202 authenticated medicinal plant and fungal species that collectively represent the therapeutic content of the majority of all commonly prescribed TCM herbal prescriptions. Currently housed at Harvard University, the library consists of duplicate or triplicate kilogram quantities of each authenticated and processed species, as well as “detanninized” extracts and sub-fractions of each mother extract. Each species has been collected at 2-3 sites, each separated geographically by hundreds of miles, with precise GPS documentation, and authenticated visually and chemically prior to testing for heavy metals and/or pesticides contamination. An explicit decision process has been developed whereby samples with the least contamination were selected to undergo ethanol extraction and HPLC sub-fractionation in preparation for high throughput screening across a broad array of biological targets including cancer biology targets. As envisioned, the subfractions in this artisan collection of authenticated medicinal plants will be tested for biological activity individually and in combinations (i.e., “complex mixtures”) consistent with traditional ethnomedical practice.

This manuscript summarizes the rationale, methods and preliminary “proof of principle” for the establishment of this prototype, authenticated medicinal plant library. It is hoped that these methods will foster scientific discoveries with therapeutic potential and enhance efforts to systematically evaluate commonly used herbal therapies worldwide.

1. Introduction
2. Relevance of herbal and TCM products.
3. Epidemiology and market relevance of herbal and TCM products
4. Rationale to build a prototype library based on challenges and lessons learned
   1. Lessons learned from selected clinical trials
   2. Lessons learned from the vantage point of drug discovery and ethnobotan
   3. Considerations in the development of a prototype authenticated TCM plant library
5. Methods
   1.   Criteria for inclusion
      1. Monograph summarizing relevant information of each plant
   2.  Collection protocol
   3.  Authentication and quality assessment
   4. Testing for heavy metals and pesticides
   5. Shipping, import, export and maintenance of plant materials
   6. Selecting one of three samples for initial extraction and fractionation
      1. Extraction and fractionation procedures
      2. Preparing extract fractions for screening
   7.  Construction of electronic database
   8. Initial screening strategies
   9.   Description of selected (initial) screens involving cell based and whole organism (e.g. Zebra fish) assays
      1. LC/MS and NMR techniques for compound characterizatio
      2. International collaboration agreements
6. Results
   1. Current status of the authenticated TCM library
   2. Summary of plant species included
   3. Heavy metal and pesticides screening
   4. Quality assurance results
   5. Shipment experience
   6. Reproducibility of extraction process
   7. Initial high-throughput screening target
   8. Examples of selected initial screens as “proof of principle:” cytotoxicity screens and zebra fish assay
7. Discussion
8. References

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