Importance of Metabolic Activation Study to the Safe Use of Chinese Herbal Medicines

Author(s): Bin Ma, Na Li, Ge Lin

Journal Name: Current Drug Metabolism

Volume 13 , Issue 5 , 2012


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Abstract:

The number of new drugs approved for clinical use per year is falling in the last decade. One approach to reduce the high rate of attrition during early drug development is to systematically determine the toxic metabolites on the mechanism basis. Traditional Chinese herbal medicines (CHM) have been used extensively for disease treatment and health care. Recently, they have also been used as raw materials for preparation of herbal dietary supplements and nutraceuticals worldwide. However, problems arise due to the adverse effects caused by CHM and their derived products. Similar to synthetic drugs, among the diverse mechanisms the metabolism-induced adverse effect/toxicity is an important safety issue of CHM. For safe use of CHM and herbal products, it is also necessary to study herbinduced toxicities using the mechanism-based approach. CHM consist of multi-ingredients, which makes the study of toxic metabolites more difficult and challenging than that of synthetic drug-induced toxicity. In this mini-review, using hepatotoxicity and nephrotoxicity induced respectively by metabolic activation of pyrrolizidine alkaloids and aristolochic acid present in CHM as examples, we address the significance of metabolic study of CHM and how it contributes to the delineation of the toxic mechanisms, development of mechanismbased biomarkers for the diagnosis and assessment of adverse effect/toxicity of CHM, prediction of toxic dosage, and reduction and prevention of toxicity of CHM.

Keywords: Safety of Chinese herbal medicines, Metabolic activation, Protein/DNA adducts, CHM, pyrrolizidine alkaloids, aristolochic acid, DNA adducts, alkaloids, intrinsic toxicity, GMP, herbal dietary supplements

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Article Details

VOLUME: 13
ISSUE: 5
Year: 2012
Published on: 08 May, 2012
Page: [652 - 658]
Pages: 7
DOI: 10.2174/1389200211209050652
Price: $65

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