Molecular mechanisms of Agardhiella subulata attenuates hepatic fibrosis by modulating hepatic stellate cell activation via the reduction of autophagy

Abstract

In this study, we investigated the effects of Agardhiella subulata extract (ASE) and its underlying mechanisms in vivo and in vitro. Rats induced hepatic fibrosis with CCl4 and transforming growth factor-β1 (TGF-β1) activated rat hepatic stellate cell line (HSC-T6) was used. The results showed that ASE (oral, 10 or 50 mg/kg) effectively attenuated liver fibrogenesis in the rats. This was evidenced by decreases in serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels, histopathological changes, decreased collagen deposition, and extracellular matrix formation. ASE significantly reduced hepatocyte apoptosis, Kupffer cell activation, and the levels of fibrogenic molecules such as alpha-smooth muscle actin and collagen. Furthermore, ASE downregulated the TGF-β1/Smad signaling pathway and concomitantly inhibited the activation of hepatic stellate cells by reducing autophagy and inducing the regeneration of lipid droplets both in vivo and in vitro. Overall, ASE inhibited various mechanisms that are important targets in the prevention of hepatic fibrosis.

Keywords

• Agardhiella subulata
• Autophagy
• Lipid droplet
• Hepatic stellate cell
• Hepatic fibrosis