A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy

BACKGROUND: Traditional Chinese medicine (TCM) has been widely used in treating various diseases in eastern Asia for several thousand years, and is becoming increasingly popular in western countries. Gubentongluo (GBTL) decoction, as a classic TCM formula, is commonly applied to treat IgA Nephropathy (IgAN) in China. To date, however, the pharmacological/molecular mechanisms of GBTL have not been fully elucidated. METHOD: In the present study, we used a system biological approach to explore these mechanisms acting on IgAN. RESULTS: First, we found 3876 potential target proteins for GBTL (based on TCMID) and 25 known IgAN associated biomarkers (based on the OMIM or IPA database).16 of the latter biomarkers were direct targets of 6 of the 9 herbs in GBTL, suggesting that these components play a vital role in treating IgAN. Second, we showed that these 6 herbs mainly regulate the immune system and renin-angiotensin system, imbalance in which is the main factor leading to IgAN. Importantly, HUANG QI links with 14 biomarkers, indicating that it is the most important herb in GBTL for treating IgAN. Also, relationships of other herbs with IgAN were explored. Third, we demonstrated that the remaining 9 IgAN associated proteins are responses to biological processes, such as antigen processing, protein ubiquitination and cell cycle regulation, which are crucial for IgAN development. Finally, we found that GBTL could induce a significant increase in the levels of two target gene: TNF and NOS2. CONCLUSIONS: Further studies are called to develop/modify the formula of GBTL, in order to enhance its effect on IgAN. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-016-1268-9) contains supplementary material, which is available to authorized users.