Combined carvacrol and cilostazol ameliorate ethanol-induced liver fibrosis in rats: Possible role of SIRT1/Nrf2/HO-1 pathway

Int Immunopharmacol. 2023 Jan 27;116:109750. doi: 10.1016/j.intimp.2023.109750. Online ahead of print.ABSTRACTCarvacrol is a natural phenolic monoterpenoid, and cilostazol is a selective phosphodiesterase-3 inhibitor with antioxidant, anti-inflammatory and antiapoptotic effects. This experiment aimed to explore the hepatoprotective effects of carvacrol and cilostazol alone and in combination against alcoholic liver fibrosis (ALF), and the underlying mechanisms, using silymarin as a reference anti-fibrotic product. ALF was induced by oral administration of ethanol (1 ml/100 g/day) thrice per week. Silymarin (100 mg/kg), carvacrol (70 mg/kg), cilostazol (50 mg/kg), or carvacrol + cilostazol combination were administered daily and concurrently with ethanol for six weeks. Hepatic changes were evaluated by quantifying serum biomarkers of liver injury, hepatic MDA, GSH and NOx as oxidative stress markers, interleukin (IL)-10 as an anti-inflammatory cytokine, 4-hydroxyproline (4-HYP) as a collagen synthesis indicator, transforming growth factor (TGF)-β1 as a profibrogenic cytokine, α-smooth muscle actin (α-SMA) as a marker of hepatic stellate cells (HSCs) activation, histopathological (necroinflammation and fibrosis) scores and hepatic sirtuin-1 (SIRT1), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) mRNA levels. Our results showed that carvacrol, cilostazol, and their combination significantly ameliorated ethanol-induced hepatic fibrosis manifeste...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research