Evaluation of the Mechanism of Modified Lingguizhugan Decoction in the Treatment of Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic steatohepatitis (NASH) may develop into cirrhosis and liver cancer, which imposes a great burden to individuals and society. Lingguizhugan decoction is a commonly used dampness dispelling medication in traditional Chinese medicine and is often used to treat those with phlegm and retained fluid from various causes and pathogeneses. The objective of this study was to explore the effect and mechanism of modified Lingguizhugan decoction (MLGZG) on lipid metabolism and the inflammatory response to identify a theoretical basis to promote its clinical application in NASH therapy. After treatment with MLGZG for 8 weeks, the weight of high-fat-diet (HFD)-fed NASH rats was significantly higher than that of rats in the normal group, and the weights in each dose group were significantly lower than those in the model group. The treatment groups (low, medium, and high doses) had different degrees of improvement in the changes in hepatocyte tissue structure, steatosis, and inflammatory infiltration. Compared with that in the normal group, the expression of TNF receptor-associated factor-3 (TRAF-3) and nuclear factor κB (NFκB) in the model group significantly increased to varying degrees. Compared with the NASH group, the treatment groups (low, middle, and high doses) showed modified lipid metabolism gene expression and decreased inflammatory factor expression levels. Modified Lingguizhugan decoction can improve the general condition of rats with nonalcoholic fatty liver disease by reducing the expression levels of TRAF3, NF-κB, the Toll-like receptor 4 (TLR-4) pathway, and related proteins, as well as the expression levels of lipid metabolism genes and cytokines.