Mechanism of the anti-liver fibrosis effect of Periplaneta americana extracts that promote apoptosis of HSC-T6 cells through the Bcl-2/Bax signaling pathway

Abstract

Periplaneta americana L. (Blattidae) extract (PA-B) possesses anti-oxidant, anti-inflammatory, and hepatoprotective properties; however, its mechanism of action in liver fibrosis remains unclear. Herein, we investigated the hepatoprotective effect and mechanism of action of PA-B. HSC-T6 cells treated with PA-B were stimulated with TGF-β1, and immunofluorescence, western blotting, Hoechst 33342 staining, confocal laser scanning microscopy, and flow cytometry were performed. Furthermore, the effects of PA-B were verified in a rat model of hepatic fibrosis established using 40% carbon tetrachloride (CCl4). PA-B induced apoptosis of HSC-T6 cells by inhibiting proliferation (maximum inhibition ratio 99.08%), reducing mitochondrial membrane potential, and ameliorating apoptosis-related proteins (P < 0.01). PA-B (120 mg/kg) significantly alleviated CCl4-induced hepatic histopathological fibrosis and reduced the levels of aspartate aminotransferase (from 27.68 to 20.58 U/L) and alanine aminotransferase (from 16.88 to 5.93 U/L; P < 0.05 or P < 0.01). Immunohistochemistry and western blotting showed that α-SMA levels were reduced (from 0.49 to 0.23) and that the Bcl/Bax signaling pathway was significantly inhibited by PA-B (120 mg/kg; P < 0.05 or P < 0.01). PA-B exhibits anti-fibrotic effects by mediating the Bcl-2/Bax pathway and promoting HSC-T6 cell apoptosis, providing a basis for its development as a drug to treat liver fibrosis.