Modern Clinical Applications Related to Chinese Traditional Theories of Drug Interactions

MODERN CLINICAL APPLICATIONS RELATED TO CHINESE TRADITIONAL THEORIES OF DRUG INTERACTIONS E. LEONG WAY* and CHIEH-FU CHENf For over two millennia, by trial error and serendipity, the Chinese recorded the biologic actions of thousands of products derived from plants, animals, and minerals. They thought about and tried to explain their pharmacologic effects. In so doing, there evolved a rationalization process relating man's relationship with the universe and laws of nature, and these ideas were coupled with the empirical findings to formulate a system of medicine that is still extant. The efforts culminated in the emergence ofproto-disciplines related to botany, physiology, biochemistry, and psychology, as well as to drug-related fields such as pharmacognosy, pharmacy, endocrinology, toxicology , immunology, and forensic medicine. Such notions led to the use of a vast number of agents to prevent, diagnose, cure, and alleviate illness. In the process, amazing insight and perspicacity were displayed with respect to factors that may alter drug action, including host facets concerned with age, sex, mood, and pathologic states, as well as environmental conditions related to daily and seasonal alterations on circadian rhythm. Medicinal agents were understood to act not by creating new functions but by correcting an underlying pathologic process. Especially intuitive were the concepts evolved concerning drug interactions that could alter drug efficacy and toxicity. In recent years, there has been an enormous effort to validate ancient Chinese recipes for treatment of medical conditions by Western methodology . Current efforts are directed mainly towards identification of the active substances in the prescription by chemical and bioassay procedures. The work involves isolation and identification of the various ingredients and Part of this material was presented at the 4th Annual Meeting of the Mutual Ocean Strait Societies and Hong Kong Society, held at Chengdu, China, 18-21 August 1998. Generous support was provided by the Chang Ching Kuo and the Song Foundations. *Departments of Cellular and Molecular Pharmacology and Pharmaceutical Chemistry, Schools of Medicine and Pharmacy, University of California, San Francisco, CA 94143, and fNational Research Institute of Chinese Medicine, Taipei Hsien, Taiwan 23177, R.O.C.© 1999 by The University of Chicago. All rights reserved. 0031-5982/99/4204-1117$01.00 512 F. Leong Way and Chieh-Eu Chen ¦ Chinese Traditional Theories then attempt to characterize their pharmacologic properties [1, 2]. Although considerable information, basic and practical, has been provided, such an approach ignores the original reason for combining drugs, and there is no question that under certain conditions, various plant, animal, and mineral products may interact and influence each other beneficially or adversely. The Chinese have known this for centuries and have exploited this knowledge to preferentially compound and dispense prescriptions containing more than one natural product, mostly vegetative in origin. Morever , based on their clinical observations, they conceptualized a rationale for combining drugs that appears relatable to modern practice. An attempt will be made to provide some insight as to how the Chinese theories of drug interactions, conceived about two thousand years ago, anticipated Western concepts that have only been recently developed—indeed , not until well into the 20th century. Although the Chinese notions are descriptive and may appear qualitative, they could only have been developed after astute and thorough clinical observations that must have been at least semi-quantitative. In addition, we should like to offer how the experimental approaches of contemporary pharmacology might be applied to validate possible interactions between the constituents contained in the natural products of traditional recipes. Legendary and Early History Legend ordains the founders of Chinese traditional medicine as two reputed mythical emperors, Huangdi and Shennong, said to have lived about five thousand years ago. Each is alleged to have authored a classic medical compendium that bears their name, Huangdi neijing ("The Yellow Emperor 's Manual on Corporeal Medicine") and Shennong ben caojing ("Classical Pharmacoepeia of the Heavenly Husbandman"), but no original copies exist [3]. There is consensus among scholars that the Neijing, even though it may contain earlier information from the latter part of the Late Zhou dynasty (722-221 bc), could only have been written by unknown authors after the Qin dynasty (202 bc-ad 9), when the Chinese language became standardized and stylized [3-6]. Likewise...