Ethyl Acetate Extract of Dracocephalum heterophyllum Benth Ameliorates Nonalcoholic Steatohepatitis and Fibrosis via Regulating Bile Acid Metabolism, Oxidative Stress and Inhibiting Inflammation

Abstract

Dracocephalum heterophyllum Benth is well-known for its ability to alleviate liver heat. In this study, Dracocephalum heterophyllum Benth ethyl acetate extracts were evaluated on mouse models of nonalcoholic steatohepatitis and liver fibrosis. After 6 and 8 weeks of treatment, serum parameters and gene expressions in tissue samples, as well as stained tissue sections, demonstrated that the ethyl acetate extracts were effective in treating these liver diseases. The principal bioactive constituent (rosmarinic acid) was identified and screened by high pressure liquid chromatography-1,1-diphenyl-2-picrylhydrazyl and affinity ultrafiltration-HPLC. The rosmarinic acid was separated from extracts with high purity by medium- and high-pressure liquid chromatography. Finally, the interactions between rosmarinic acid and the key targets of lipid metabolism, oxidative stress and inflammation were verified by molecular docking. Thereby, an indirect regulation of lipid and cholesterol metabolism and inhibition of liver inflammation and liver fibrosis by the studied extract has been observed. This study demonstrated that Dracocephalum heterophyllum Benth ethyl acetate extracts have the potential to treat nonalcoholic steatohepatitis and liver fibrosis, revealing their multi-target and multi-pathway therapeutic characteristics.