Researchers determined that schisandrol A, the main active lignan of the schisandrae chinensis fructus (SCF) herb, might inhibit idiopathic pulmonary fibrosis (IPF) by suppressing aberrant transforming growth factor β (TGF-β) signaling, as published in the Journal of Ethnopharmacology.

“Transforming growth factor-β [TGF-β] is a key player in the process of fibrosis,” the authors wrote. “Under physiological conditions, TGF-β is necessary for lung morphogenesis and homeostasis while aberrant TGF-β signaling has been shown to be central to pulmonary fibrosis.”

These processes can lead to increased lung tissue rigidity, thickening of the alveolar-capillary barrier, and a corresponding decline in alveolar gas exchange. In addition, damage to alveolar epithelial cells leads to the release of inflammatory cytokines which, in turn, generate fibroblasts that secrete and deposit excess proteins into the extracellular matrix.

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There is no known treatment for IPF; however, in related studies, lignans from SCF have been shown to improve quality of life, reduce symptoms, and increase exercise tolerance in patients with IPF by inhibiting inflammatory processes and reducing cell proliferation and migration. SCF has a long history of use in China for other inflammatory conditions such as asthma and cough.

The research team administered SCF to rats for 7 days and then employed ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry to identify 13 lignans, including schisandrol A, along with 65 metabolites.

Network pharmacology, serum pharmacochemistry, and a molecular docking analysis revealed that schisandrol A alleviated fibrosis in the rats by regulating the expression of α-smooth muscle actin and E-cadherin via the TGF-β signaling pathway, and in vivo experiments showed that schisandrol A reduced bleomycin-induced deposition of collagen, thus reducing pulmonary fibrosis in the rats.

Reference

Wu Z, Jia M, Zhao W, et al. Schisandrol A, the main active ingredient of Schisandrae Chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-β signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification. .J Ethnopharmacol. Published online January 26, 2022. doi:10.1016/j.jep.2022.115031