Combining Serum Pharmacochemistry and Metabolomics to Characterize the Synergistic Compatibility Principle of Polygonati Rhizoma and Angelicae Sinensis Radix for MAFLD Mitigation

Abstract

Introduction: Jiuzhuan Huangjing Pills (JHP) have been shown to exert therapeutic effects on metabolic dysfunction-associated fatty liver disease (MAFLD), with a stronger intervention effect than single herbs. The purpose of this study was to elucidate the chemical constituents and mechanisms of JHP and its raw materials, Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR), in the treatment of MAFLD.

Methods: Serum pharmacochemistry and metabolomics were performed to examine drug-derived and endogenous components in MAFLD rats. In addition, network pharmacology was used to predict the key active components and targets of JHP, PR, and ASR in MAFLD mitigation, followed by molecular docking. ELISA kits were used to detect the levels of LCAT, GPCPD1, NNMT, NMRK1, ADO, and CSAD in liver tissues, while Western blotting was applied to determine the expression of CYP7A1 and CYP27A1.

Results: A total of 22, 8, and 10 compounds from JHP, PR, and ASR, respectively, were identified in serum. Meanwhile, 15, 5, and 7 compounds from JHP, PR, and ASR, respectively, were detected in rat tissues. Moreover, 157, 131, and 114 differential metabolites involved in 27, 6, and 9 pathways were found to be altered by JHP, PR, and ASR, respectively. JHP, PR, and ASR regulated LCAT and GPCPD1 in glycerophospholipid metabolism. JHP and ASR regulated NNMT and NMRK1 in nicotinic and nicotinamide metabolism. JHP further regulated ADO and CSAD in taurine and hypotaurine metabolism, as well as CYP7A1 and CYP27A1 in primary bile acid biosynthesis. Ten components of JHP acted on 12 targets to regulate 12 pathways in MAFLD treatment. Three components of PR acted on seven targets to regulate four pathways, while five components of ASR acted on five targets to regulate three pathways. The binding energies between these drug-derived compounds and their targets were all less than -5 kcal·mol⁻¹.

Discussion: These findings provide a theoretical foundation for the clinical application of JHP in MAFLD and underscore the value of traditional Chinese medicine formulas in addressing complex metabolic diseases through synergistic regulation. However, the intervention effects of JHP-derived components on MAFLD and their potential mechanisms of action on specific targets and metabolites require further investigation.

Conclusion: Our study found that JHP was associated with more components, targets, and pathways, which may be the mechanisms of JHP synergism.

Keywords: Fatty liver; Jiuzhuan Huangjing pills; distribution.; metabolomics; network pharmacology; pharmacodynamic ingredients.