Butyrolactone I attenuates inflammation in murine NASH by inhibiting the NF-κB signaling pathway

Abstract

Nonalcoholic steatohepatitis (NASH) is the development of non-alcoholic fatty liver disease (NAFLD) and a key element in the exacerbation of NAFLD. Since there are currently no drugs approved by the U.S. Food and Drug Administration to treat this disease, the search for treatments that can be translated into clinical use is urgent. Butyrolactone I (BLI), isolated from Aspergillus terreus, is an active compound possessing multiple biological activities. However, the effects of BLI on NASH have never been reported. In this study, RAW264.7 cells stimulated by lipopolysaccharide (LPS) were applied to study the anti-inflammatory effect and the underlying mechanisms of BLI in vitro. Following this, mice fed with high-fat and -fructose diet (HFFD) were used to explore the alleviation of NASH by BLIin vivo. We found that BLI attenuated inflammation in LPS-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway and downregulating the expression of iNOS and COX-2. Moreover, results of experiments in vivo demonstrated that BLI reduced serum transaminase levels, decreased hepatic fat accumulation, inhibited inflammation, suppressed oxidative stress, and ameliorated liver fibrosis. For the first time, we investigated the role of BLI in the treatment of murine NASH. We found that BLI alleviates NASH partly by inhibiting the NF-κB pathway of signaling. Given its hepatoprotective effects and non-toxic properties, BLI can be a novel and effective drug for NASH patients.

Keywords: Butyrolactone I; Inflammation; NF-κB signaling pathway; Nonalcoholic steatohepatitis.