Inhibitory Effect of Corilagin on miR-21-Regulated Hepatic Fibrosis Signaling Pathway

Abstract

Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague–Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), [Formula: see text]-smooth muscle actin ([Formula: see text]-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor-[Formula: see text]1 (TGF-[Formula: see text]1) in LX2 cells and liver tissues were determined. Furthermore, gain-of and loss-of function of miR-21 in miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway were analyzed in LX2 cells. Liver tissues and serum were collected for pathological analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Corilagin treatment reduced mRNA or protein levels of miR-21, CTGF, [Formula: see text]-SMA, TIMP-1, TGF-[Formula: see text]1, COL1A1, p-Smad2, p-Smad3, and p-Smad2/3 both in vitro and in vivo. While corilagin increased mRNA and protein levels of Smad7 and MMP-9. After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of [Formula: see text]-SMA and COL1A1 in liver tissues and TGF-[Formula: see text]1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis.