PMC

Proposed mechanisms indicate the effects of mulberrin on liver fibrosis. In brief, under fibrotic stimuli, TRIM31-mediated activation of Nrf2 signaling pathway was restrained, resulting in inflammatory response and oxidative stress in hepatocytes, which contributed to the HSC activation and hepatic fibrosis. Notably, mulberrin treatment could improve TRIM31/Nrf2 signaling to ameliorate hepatic inflammation and ROS production, consequently attenuating liver fibrosis.

(a) Two-dimensional scheme of the interaction between mulberrin and the 4ZZJ complex, generated by LigandScout 4.2. (b) The structure of mulberrin and 4ZZJ complex shown as a mesh surface image, generated by LigandScout (hydrophilic, blue; hydrophobic, grey). The interaction between (c) quinine, (d) quinidine, and (e) gartanin, with the 4ZZJ []. Figure reproduced by permission.

Mulberrin ameliorates hepatic dysfunction in CCl₄-induced mice. (A) The experiment design scheme. (B) Body weights of each group of mice. (C) Survival rate of mice from all groups was quantified. Serum (D) TBIL, (E) ALT, AST, ALP, and (F) LDH levels were examined. Representative data were expressed as mean ± SEM (n = 10 per group). **P < 0.01 and ***P < 0.001 vs the Oil/Veh group; +P < 0.05 and ++P < 0.01 vs the CCl₄/Veh group.

Hepatic protective effects of mulberrin are TRIM31-dependent in vivo. (A) Body weights of TRIM31^Flox or TRIM31^Hep-cKO mice were recorded. Serum (B) TBIL, (C) LDH levels, (D) ALT, AST, ALP contents, (E) hyaluronic acid, (F) PC III, and (G) Collagen IV levels were examined. Representative data were expressed as mean ± SEM (n = 9 per group). ^#P < 0.05, ^##P < 0.01 and ^###P < 0.001; ns, no significant difference.