Esculin protects against methionine choline-deficient diet-induced non-alcoholic steatohepatitis by regulating the Sirt1/NF-κB p65 pathway

Context: Esculin, an active coumarin compound, has been demonstrated to exert anti-inflammatory effects. However, its potential role in non-alcoholic steatohepatitis (NASH) remains unclear. Objective: This study explored the hepatoprotective effect and the molecular mechanism of esculin in methionine choline-deficient (MCD) diet-induced NASH. Materials and methods: Fifty C57BL/6J mice were divided into five groups: control, model, low dosage esculin (oral, 20 mg/kg), high dosage esculin (oral, 40 mg/kg), and silybin (oral, 105 mg/kg). All animals were fed a MCD diet, except those in the control group (control diet), for 6 weeks. Results: Esculin (20 and 40 mg/kg) inhibited MCD diet-induced hepatic lipid content (triglyceride: 16.95 +/- 0.67 and 14.85 +/- 0.78 vs. 21.21 +/- 1.13 mg/g; total cholesterol: 5.10 +/- 0.34 and 4.08 +/- 0.47 vs. 7.31 +/- 0.58 mg/g), fibrosis, and inflammation (ALT: 379.61 +/- 40.30 and 312.72 +/- 21.45 vs. 559.51 +/- 37.01 U/L; AST: 428.22 +/- 34.29 and 328.23 +/- 23.21 vs. 579.36 +/- 31.93U/L). In vitro, esculin reduced tumour necrosis factor-a, interleukin-6, fibronectin, and collagen 4A1 levels, but had no effect on lipid levels in HepG2 cells induced by free fatty acid. Esculin increased Sirt1 expression levels and decreased NF-kappa B acetylation levels in vivo and in vitro. Interfering with Sirt1 expression attenuated the beneficial effect of esculin on inflammatory and fibrotic factor production in HepG2 cells. Conclusions: These findings demonstrate that esculin ameliorates MCD diet-induced NASH by regulating the Sirt1/ac-NF-kappa B signalling pathway. Esculin could thus be employed as a therapy for NASH.

Automated summary

Esculin has hepatoprotective effects on MCD diet-induced NASH by regulating the Sirt1/ac-NF-κB signaling pathway. It could be employed as a therapy for NASH.