Application of bioactivity database of Chinese herbal medicine on the therapeutic prediction, drug development, and safety evaluation

• Published in: Journal of ethnopharmacology Vol. 132; no. 2; pp. 429 - 437
• Main Authors: Cheng, Hui-Man, Li, Chia-Cheng, Chen, Calvin Yu-Chian, Lo, Hsin-Yi, Cheng, Wen-Yu, Lee, Chang-Hsien, Yang, Shi-Zhe, Wu, Shih-Lu, Hsiang, Chien-Yun, Ho, Tin-Yun
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 11.11.2010; Amsterdam; New York: Elsevier; Elsevier
• Subjects: animal models; Animals; bioactive properties; biochemical pathways; Biological and medical sciences; Cardiovascular diseases; Chemicals; Chinese herbs; cytochrome P-450; Databases, Factual; DNA microarray; Drug Evaluation, Preclinical; drug interactions; Drugs; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - toxicity; enzyme activity; Formulae; gene expression; Gene Expression - drug effects; Gene Expression Profiling; General pharmacology; glutathione; glutathione transferase; glycosyltransferases; growth factors; herbal medicines; Kidney; Kidney - drug effects; kidneys; Liver; Liver - drug effects; Liver - metabolism; mechanism of action; Medical sciences; Metabolic Networks and Pathways - drug effects; Metabolism; Mice; microarray technology; nephrotoxicity; Oligonucleotide Array Sequence Analysis; oral administration; Oriental traditional medicine; oxidation; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; protein phosphorylation; signal transduction; Signal Transduction - drug effects; Transcription, Genetic; transcriptome; Transcriptomic; transcriptomics; China; Asia; PBS; Chinese herbs; UGT; MeSH; IGF; GSTs; SHXXT; CCCTS; DNA microarray; MHC-I; Formulae; Transcriptomic; EDGE; Drug; Evaluation; Pharmacognosy; Toxicity; Prediction; Research and development; Medicinal plant; Chinese medicine; Treatment; Folk medicine; DNA; Plant origin; Database
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.08.022

We applied transcriptomic tools as a novel platform of translational medicine for Chinese herbal medicine. The usefulness of this platform was illustrated by analyzing the biological events induced by formulae, predicting the therapeutic potential of formulae, and evaluating the safety of formulae. Chinese herbal medicine has been used for the treatments of various diseases for years. However, it is often difficult to analyze their biological activities and molecule mechanisms because of their complex nature. In this study, we applied DNA microarray to analyze the biological events induced by herbal formulae, predict the therapeutic potentials of formulae, and evaluate the safety of formulae. Mice were administrated orally with 15 formulae for 7 consecutive days, and the gene expression profiles in liver or kidney were further analyzed by transcriptomic tools. Our data showed that most formulae altered the metabolic pathways, such as glutathione metabolism and oxidative phosphorylation, and regulatory pathways, such as antigen processing and presentation and insulin-like growth factor signaling pathway. By comparing the gene expression signatures of formulae with those of disease states or drugs, we found that mice responsive to formula treatments might be related to disease states, especially metabolic and cardiovascular diseases, and drugs, which exhibit anti-cancer, anti-inflammatory, and anti-oxidative effects. Moreover, most formulae altered the expression levels of cytochrome p450, glutathione S-transferase, and UDP glycosyltransferase genes, suggesting that caution should be paid to possible drug interaction of these formulae. Furthermore, the similarities of gene expression profiles between formulae and toxic chemicals were low in kidney, suggesting that these formulae might not induce nephrotoxicities in mice. This report applied transcriptomic tools as a novel platform of translational medicine for Chinese herbal medicine. This platform will not only for understanding the therapeutic mechanisms involving herbal formulae and gene interactions, but also for the new theories in drug discovery.