The incidence of
pulmonary fibrosis (PF), a progressively fatal disease, has increased in recent years. However, there are no effective medicines available. Previous results have shown that
sinensetin probably has some curative effects on PF. Therefore, this paper aims to predict the targets of
sinensetin using a network pharmacology method and to confirm its effects and functional targets in PF using a mouse PF model. First, network pharmacology analysis showed that
sinensetin has 105 functional targets, and 1,698 gene targets closely relate to PF. The intersection of the functional targets and gene targets produced 52 targets for the treatment of PF with
sinensetin. The PPIs (
protein-
protein interactions) led to several potential key target genes, including MAPK1, EGFR, SRC, and
PTGS2. The results of GO and KEGG analyses suggested the crucial function of apoptosis in PF and its involvement in the PI3K signaling pathway. Subsequently, we tested the molecular docking of
sinensetin with the PI3K
protein using the AutoDock4 software. The results showed that
sinensetin could fit well into several binding sites of the PI3K
protein. Furthermore, we constructed a PF mouse model through one-off intratracheal instillation of
bleomycin and then intragastrically administered different concentrations of
sinensetin to the model mice. Twenty-eight days later, the mice were sacrificed, and the lung tissues, serum, and bronchoalveolar lavage fluid (BALF) were collected. The in vivo tests showed that the
body weight of model mice increased slightly compared with that of PF mice after intragastric
sinensetin. HE and Masson staining suggested a certain extent of reduction in the pathology of lung tissues. The expression of
collagens I and III, as well as
hydroxyproline in the lung tissues, was reduced to a certain extent.
IL-6 levels in the serum and BALF decreased markedly. The expression of
vimentin and α-SMA in pulmonary tissues decreased. Cell apoptosis, as well as P-PI3K and P-AKT levels, in lung tissues also reduced. In summary, network pharmacology and in vivo test results suggest
sinensetin causes an effective delay in the progression of
pulmonary fibrosis, and the functional mechanism is likely related to PI3K-AKT signaling.