Use of Chou's 5-Steps Rule to Reveal Active Compound and Mechanism of Shuangshen Pingfei San on Idiopathic Pulmonary Fibrosis.

Abstract

Shuangshen Pingfei San (SPS) is the derivative from the classic formula Renshen Pingfei San in treating idiopathic pulmonary fibrosis (IPF). In this study, Chou's 5-steps rule was performed to explore the potential active compound and mechanism of SPS on IPF. Compound-target network, target- pathway network, herb-target network and the core gene target interaction network were established and analyzed. A total of 296 compounds and 69 candidate therapeutic targets of SPS in treating IPF were obtained. Network analysis revealed that the main active compounds were flavonoids (such as apigenin, quercetin, naringenin, luteolin), other clusters (such as ginsenoside Rh2, diosgenin, tanshinone IIa), which might also play significant roles. SPS regulated multiple IPF relative genes, which affect fibrosis (PTGS2, KDR, FGFR1, TGFB, VEGFA, MMP2/9) and inflammation (PPARG, TNF, IL13, IL4, IL1B, etc.). In conclusion, anti-pulmonary fibrosis effect of SPS might be related to the regulation of inflammation and pro-fibrotic signaling pathways. These findings revealed that the potential active compounds and mechanisms of SPS on IPF were a benefit to further study.