Active Compounds Derived from Fuzheng Huayu Formula Protect Hepatic Parenchymal Cells from Apoptosis Based on Network Pharmacology and Transcriptomic Analysis

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 2; p. 338
• Main Authors: Wu, Rong, Dong, Shu, Cai, Fei-Fei, Chen, Xiao-Le, Yang, Meng-Die, Liu, Ping, Su, Shi-Bing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.01.2019; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; BAX protein; Caspase-3; Cell activation; Cell Survival - drug effects; Chinese medicine; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacokinetics; Drugs, Chinese Herbal - pharmacology; Fibrosis; fuzheng huayu formula; Gene Expression Profiling; Gene Expression Regulation - drug effects; hederagenin; Hepatocytes - drug effects; Hepatocytes - metabolism; Herbal medicine; Inflammation; Liver; Liver cirrhosis; luteolin; Male; Metabolism; Network analysis; network pharmacology; Pharmacology; Proteins; Rats; Signal Transduction - drug effects; tanshinone IIA; Tanshinones; Transcriptome; Transforming growth factor-b1; Tumor necrosis factor-TNF; Tumor necrosis factor-α; fuzheng huayu formula; luteolin; apoptosis; tanshinone IIA; hederagenin; network pharmacology
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24020338

Fuzheng huayu formula (FZHY), an antifibrotic traditional Chinese medicine, is frequently used for the treatment of liver fibrosis. In this study, network analysis, transcriptomic analysis, assays of cell apoptosis, viability and protein expression were used for investigating the effects and mechanisms of compounds derived from FZHY on hepatic parenchymal cell (HPC) protection and hepatic stellate cell activation. Network pharmacology analysis found that 6 major compounds and 39 potential targets were important network nodes. Our analysis predicted that the active compounds of FZHY, including hederagenin, luteolin and tanshinone IIA inhibited cell apoptosis ( < 0.05), increased PI3K expression and reduced cleaved caspase 3 expression and the Bax/Bcl-w ratio ( < 0.05) in L02 cells that had apoptosis induced by TNF-α. Few significant changes caused by FZHY, hederagenin, luteolin and tanshinone IIA were observed in hepatic stellate Lx2 cells upon TGF-β1 induction. These data suggest that FZHY is active against liver fibrosis, protects hepatic parenchymal cells from apoptosis, and recovers liver function, possibly through the effects of its active compounds hederagenin, luteolin and tanshinone IIA and is involved in the inhibition of apoptosis in HPCs, possibly through regulating the PI3K, ERK, cleaved caspase 3 and Bax/Bcl-w levels.