Comparative analysis of the synergetic effects of Diwuyanggan prescription on high fat diet-induced non-alcoholic fatty liver disease using untargeted metabolomics

Jinlin Xu; Yuehui Jin; Chengwu Song; Guangya Chen; Qiaoyu Li; Hao Yuan; Sha Wei; Min Yang; Sen Li; Shuna Jin

doi:10.1016/j.heliyon.2023.e22151

Comparative analysis of the synergetic effects of Diwuyanggan prescription on high fat diet-induced non-alcoholic fatty liver disease using untargeted metabolomics

Heliyon. 2023 Nov 10;9(11):e22151. doi: 10.1016/j.heliyon.2023.e22151. eCollection 2023 Nov.

Authors

Jinlin Xu^{1

2}, Yuehui Jin¹, Chengwu Song¹, Guangya Chen², Qiaoyu Li¹, Hao Yuan^{1

2}, Sha Wei³, Min Yang³, Sen Li⁴, Shuna Jin³

Affiliations

¹ School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
² Department of Pharmacy, Ezhou Central Hospital, Ezhou 436000, China.
³ School of Basic Medicine Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China.
⁴ Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide and had no approved pharmacological treatments. Diwuyanggan prescription (DWYG) is a traditional Chinese medicine preparation composed of 5 kinds of herbs, which has been used for treating chronic liver diseases in clinic. Whereas, the synergistic mechanism of this prescription for anti-NAFLD remains unclear. In this study, we aimed to demonstrate the synergetic effect of DWYG by using the disassembled prescriptions and untargeted metabolomics research strategies. The therapeutic effects of the whole prescription of DWYG and the individual herb were divided into six groups according to the strategy of disassembled prescriptions, including DWYG, Artemisia capillaris Thunb. (AC), Curcuma longa L. (CL), Schisandra chinensis Baill. (SC), Rehmannia glutinosa Libosch. (RG) and Glycyrrhiza uralensis Fisch. (GU) groups. The high fat diets-induced NAFLD mice model was constructed to evaluate the efficacy effects of DWYG. An untargeted metabolomics based on the UPLC-QTOF-MS/MS approach was carried out to make clear the synergetic effect on the regulation of metabolites dissecting the united mechanisms. Experimental results on animals revealed that the anti-NAFLD effect of DWYG prescription was better than the individual herb group in reducing liver lipid deposition and restoring the abnormality of lipidemia. In addition, further metabolomics analysis indicated that 23 differential metabolites associated with the progression of NAFLD were identified and 19 of them could be improved by DWYG. Compared with five single herbs, DWYG showed the most extensive regulatory effects on metabolites and their related pathways, which were related to lipid and amino acid metabolisms. Besides, each individual herb in DWYG was found to show different degrees of regulatory effects on NAFLD and metabolic pathways. SC and CL possessed the highest relationship in the regulation of NAFLD. Altogether, these results provided an insight into the synergetic mechanisms of DWYG from the metabolic perspective, and also supported a scientific basis for the rationality of clinical use of this prescription.

Keywords: Combination mechanism; Disassembled prescriptions; Diwuyanggan; LC-MS/MS; Metabolomics; Non-alcoholic fatty liver disease.