Glabridin inhibits liver fibrosis and hepatic stellate cells activation through suppression of inflammation and oxidative stress by activating PPAR? in carbon tetrachloride-treated mice

Glabridin is an active ingredient extracted from the root of Glycyrrhiza glabra. Previous studies showed that glabridin had potent hepatoprotective effect, however, the effect of glabridin on liver fibrosis and its potential mechanisms remain largely unknown. The present study was aimed to study the effect and potential mechanisms of glabridin on liver fibrosis in carbon tetrachloride (CCl4)-treated mouse livers. Glabridin attenuated the liver injury and improved pathological changes in CCl4-treated mouse livers. Glabridin suppressed the liver fibrosis in CCl4-treated mouse livers, as shown by the decreased collagen deposition, the reduced hydroxyproline level together with the decreased mRNA and protein expression of alpha-SMA, fibronectin and alpha 1(I)procollagen in mouse livers. Interestingly, glabridin increased the mRNA and protein expression of proliferator-activated receptor gamma (PPAR gamma) in CCl4-treated mouse livers. In addition, both immunohistochemistry and tissue immunoflu-orescence showed that glabridin upregulated the expression of PPAR gamma in CCl4-treated mouse livers. Glabridin evidently reduced the levels of pro-inflammatory factors and increased the level of anti-inflammatory factor in CCl4-treated mouse livers and sera. In addition, Glabridin inhibited the level of MDA and increased the level of GSH as well as the total antioxidant capacity (T-AOC) in CCl4-treated mouse livers. In vitro study showed that glabridin reduced the cell viability of PDGF-BB-stimulated JS-1 cells. Noteworthy, glabridin showed no obvious toxicity on normal JS1 cells. Glabridin inhibited the protein expression of alpha-SMA, fibronectin and alpha 1(I)pro-collagen, and increased the expression of PPAR gamma in stimulated JS-1 cells. Furthermore, disruption of PPAR gamma attenuated the anti-inflammatory and anti-oxidative stress effects of glabridin in stimulated JS-1 cells. Collec-tively, glabridin inhibited the liver fibrosis and hepatic stellate cells activation by suppressing inflammation and oxidative stress through activation of PPAR gamma in carbon tetrachloride-treated mice.