Application of Bioactivity Database of Chinese Herbal Medicine on the Therapeutic Prediction, Drug Development, and Safety Evaluation

 

By Hui-Man Cheng, Chia-Cheng Li, Calvin Yu-Chian Chen, Hsin-Yi Lo, Wen-Yu Cheng, Chang-Hsien Lee, Shi-Zhe Yang, Shih-Lu Wu, Chien-Yun Hsiang, Tin-Yun Ho

 

 

Abstract

---

Aim of the study: 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 micro array to analyze the biological events induced by herbal formulae, predict the therapeutic potentials of formulae, and evaluate the safety of formulae.

 

Materials and 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 cytochromep450, 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.

1. Introduction
2. Material and Methods
   1. Animal experiments
   2. Total RNA isolation
   3. Microarray and pathway analysis
   4. Connection analysis of formulae-altered genes and diseases-altered genes
   5. Connectivity Map analysis of formulae-altered genes and small molecules-altered genes
   6. Analysis of expression levels of genes associated drug metabolism and toxicity
3. Results
   1. Pathway analysis of formulae-regulated gene expression profiles in livers
   2. Gene expression connection between formula treatments and disease states
   3. Gene expression connection between formula treatments and drugs
   4. Formulae affected the expression levels of several genes involved in drug metabolism
   5. Analysis of nephrotoxicities of formulae
4. Discussion
5. Conclusion
6. References

 

Join our member to get full-text article! Join Free!