Antifibrotic action of Yifei Sanjie formula enhanced autophagy via PI3K-AKT-mTOR signaling pathway in mouse model of pulmonary fibrosis

• Published in: Biomedicine & pharmacotherapy Vol. 118; p. 109293
• Main Authors: Yu, Jing-Ze, Ying, Yi, Liu, Yang, Sun, Chun-Bin, Dai, Chen, Zhao, Shan, Tian, Shou-Zheng, Peng, Jing, Han, Ni-Ping, Yuan, Jia-Li, Yan, Jin-Yuan, Yang, Zhong-Shan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2019; Elsevier
• Subjects: Animals; Autophagosomes - metabolism; Autophagosomes - ultrastructure; Autophagy - drug effects; Collagen - metabolism; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Inflammation - complications; Inflammation - pathology; Lung - pathology; Male; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary Fibrosis - complications; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; Transforming Growth Factor beta1 - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109293

[Display omitted] •Yifei Sanjie formula (YFSJF) reduces the inflammatory injuring and collagen deposition in BLM-induced PF mice.•Autophagy is triggered by YFSJF and inhibition of autophagy may contribute to the promotion of lung fibrosis.•YFSJF inhibits the PI3K-AKT-mTOR signaling pathway in BLM-induced PF mice.•Crippling of PI3K-AKT-mTOR signaling pathway induces autophagy and reduces the expression of collagens. Pulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determined. Here we investigate the contribution of YFSJF in BLM-induced PF mice. Administration with YFSJF significantly alleviated the degree of BLM-induced collagen I and III deposition and the inflammatory injuring in the lungs and suppressed hydroxyproline release in PF animals. The active components of YFSJF are comprised with flavonoid, amino acids, saponins, oligosaccharide, organic acid, vitamin, esters, purine nucleosides. Additionally, there was a significant increase in autophagosomes, after treatment with YFSJF in PF animals. Interestingly, autophagy dysfunction by the blocker chloroquine (CQ) resulted in collagen deposition and inducing the expression of fibrosis-related genes. In addition, YFSJF-induced autophagy is mediated by the PI3K-AKT-mTOR pathway, and knockdown of PI3K by siRNA up-regulated the expression of autophagy-related genes and down-regulated the expression of collagen in human lung fibroblasts (HLF). Our findings provide a detailed understanding that YFSJF-antifibrotic effects are mainly mediated by triggering autophagy, and suppressing phosphorylation of the PI3K-AKT-mTOR pathway is required for YFSJF-curative effect.