Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham+Cur group and BDL+Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signal-regulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1α (HIF-1α) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1α and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0·05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P<0·05), indicating return of these parameters towards normalcy. In conclusion, Curcumin showed hepatoprotective activity against BDL-induced liver injury and hepatic insulin resistance by influencing the expression of some genes/proteins involved in these processes, and the results suggest that it can be used as a therapeutic option.
Keywords: BDL biliary duct ligated; DPPH 2; ECM extracellular matrix; ERK1 extracellular signal-regulated kinase 1; FBG fasting blood glucose; HIF-1α hypoxia-inducible factor-1α; HOMA-IR homoeostasis model assessment-estimated insulin resistance; HSC hepatic stellate cells; IR insulin resistance; IRS1 insulin receptor substrate 1; JAK Janus kinase; MDA malondialdehyde; NOX1 dinucleotide phosphate oxidase 1; ROS reactive oxygen species; Rac1 Ras-related C3 botulinum toxin substrate 1; SOCS3 suppressor of cytokine signalling 3; STAT3 signal transducer and activator of transcription 3; Sp1 specific protein 1; TGF-β1 transforming growth factor-β1; iNOS inducible nitric oxide synthase; 2-diphenyl-1-picrylhydrazyl; Curcumin; Insulin receptor substrate 1; Insulin resistance; Liver fibrosis; Suppressor of cytokine signalling 3.