Curcumin and saroglitazar attenuate diet-induced nonalcoholic steatohepatitis by activating the Nrf۲ pathway and suppressing ERK۱/۲ signaling

Objective(s): Non-alcoholic fatty liver disease (NAFLD) is a chronic steatohepatitis disorder. If left untreated, it can progress to hepatocellular carcinoma. Several studies have shown that saroglitazar, a PPARα/γ dual agonist, and curcumin (the principal constituent of turmeric) may be effective in the treatment of NAFLD. This research aimed to study the pharmacological mechanism of these compounds in rats with NAFLD.Materials and Methods: NAFLD was induced in male Wistar rats (aged ۶–۸ weeks) by feeding them a high-fat diet (HFD) for ۶ weeks. Subsequently, the rats were divided into four groups, with Group ۱ continuing on HFD, while groups ۲, ۳, and ۴ received HFD supplemented with saroglitazar, curcumin, and both saroglitazar and curcumin, respectively. We evaluated the expression of Nrf۲, ERK۱/۲, NOX۱,۲,۴, antioxidant enzymes, PPARα, γ, and genes regulating lipid metabolism in the liver. Histopathology of liver tissue was also examined. Furthermore, we analyzed serum levels of lipid profiles and hepatic enzymes.Results: Rats with NAFLD that received treatment involving saroglitazar and curcumin showed a significant decrease in the expression of ERK۱/۲, SREBP۱, PPARγ, pro-inflammatory cytokines, NOXs, and ROS levels. Additionally, the levels of Nrf۲, PPARα, and antioxidant enzymes showed a significant increase. The serum levels of lipid profiles and hepatic enzymes also decreased significantly after drug treatment.Conclusion: Our results confirm that both saroglitazar and curcumin ameliorate NAFLD by regulating the Nrf۲ and ERK۱/۲ signaling pathways. These findings suggest that curcumin could serve as a suitable substitute for saroglitazar, although they appear to have a synergistic effect.

کلیدواژه ها:

Curcumin ، ERK۱/۲ ، NAFLD ، Nrf۲ ، Saroglitazar