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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Cheng
Hui-Man
HM
Graduate Institute of Integration of Traditional Chinese and Western Medicine, China Medical University, Taichung 40402, Taiwan.
Li
Chia-Cheng
CC
Chen
Calvin Yu-Chian
CY
Lo
Hsin-Yi
HY
Cheng
Wen-Yu
WY
Lee
Chang-Hsien
CH
Yang
Shi-Zhe
SZ
Wu
Shih-Lu
SL
Hsiang
Chien-Yun
CY
Ho
Tin-Yun
TY
D000818:Animals; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic
D004365:Drugs, Chinese Herbal