Inhibitory effects of Schisandrin C on collagen behavior in pulmonary fibrosis

Abstract

Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β1 to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of α-SMA, FN, MMP2, MMP9, TIMP1 and collagen proteins such as Col 1A1, and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β1/Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX.

Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained from Salvia castanea Diels f. tomentosa Stib. using a scalable process

“…In pulmonary fibrosis, snail is involved in the TGF-β1-induced endothelial−mesenchymal transition ( Hashimoto et al, 2010 ), the promotion of epithelial cell apoptosis and the inhibition of fibroblast and myofibroblast apoptosis ( Mo et al, 2015 ). Collagen I and III, which are the major water-insoluble fibrous proteins in the body, are present in the ECM, and their excessive deposition and abnormal degradation impede injury healing and lead to fibrosis ( Devos et al, 2023 ; Xu et al, 2023 ). In this report, we used collagen-Ⅰ, collagen-Ⅲ, α-SMA, vimentin, and snail as biochemical indicators to evaluate the degree of pulmonary fibrosis.…”