Yinchenhao decoction (YCHD) is a classical
Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of
liver fibrosis caused by
chronic hepatitis B and
jaundice for more than 1800 years. The purpose of this study was to investigate the apoptosis regulation mechanisms of YCHD and its active components suppresses
liver fibrosis. The active components and putative targets of YCHD were predicted by network pharmacology approach. Functional and pathway enrichment analysis were presented in the present study by using clusterProfiler. Further, experimental validation was done by using
terminal deoxynucleotidyl transferase (TDT) dUTP nick end labelling (TUNEL) assay and western blotting in
dimethylnitrosamine (DMN)-induced
liver fibrosis rats, and cell proliferation assay, apoptosis assay, and western blotting in human hepatic L02 cells and LX2 cells. 45 active compounds in YCHD formula, 592 potential target
proteins and 1191
liver fibrosis-related human genes were identified. Functional and pathway enrichment analysis indicated that YCHD obviously influenced TNF, PI3K-Akt signaling pathways. Further, In vivo experiment indicated that YCHD treatment not only attenuated the symptoms of
liver fibrosis, but also decrease the apoptosis of hepatic parenchyma cells. Moreover, in vitro experiments showed that
rhein,
kaempferol and
quercetin treatments remarkably decreased the
protein levels of cleaved
caspase-3 and increased p-ERK1/2, PI3K and
Bcl-XL protein expression in TNF-α-stimulated L02 cells. On the contrary,
rhein,
kaempferol,
aloe-emodin and
quercetin inhibited the proliferation of LX2 cells and up-regulated the
protein levels of Bax and cleaved
caspase-8. In conclusion, 45 active components and 296 potential targets of YCHD against
liver fibrosis were identified by the analysis of network pharmacology and transcriptomics combination. The mechanisms of YCHD against
liver fibrosis were involved in the regulation of multiple targets, especially affecting the apoptosis-related signaling pathways.