Anti-Inflammatory Pharmacological Mechanism Mediated by the Conversion of Glycosides to Aglycones in Fangfeng (Saposhnikoviae Radix) in Rheumatoid Arthritis Models Based on Serum Metabolomics, Network Pharmacology, and Molecular Docking

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Abstract
This study aims to explore the anti-inflammatory pharmacological components and anti-inflammatory mechanisms of the alcohol extract of Saposhnikoviae Radix (SR). The components of the alcohol extract of SR were analyzed using the UPLC-MS/MS system. The anti-inflammatory efficacy of the alcohol extract and core components of SR was evaluated using the LPS-induced inflammation model of RAW264.7 cells. The anti-inflammatory mechanism of SR in a mouse model of rheumatoid arthritis was expounded by means of serum metabolomics, network pharmacology, and molecular docking. A total of 12 chromones and 13 coumarins were identified in the alcohol extract of SR. The alcohol extract of SR and its components all had good anti-inflammatory activities. In the mouse model of rheumatoid arthritis, the glycoside compounds of SR were transformed into aglycones, thereby exerting anti-inflammatory effects. Moreover, the alcohol extract of SR alleviated the inflammatory response by up-regulating the expression levels of metabolites such as phenylalanine and tyrosine. Network pharmacology and molecular docking results show that SR could exert an anti-inflammatory effect by regulating AGE-RAGE, PI3K-Akt, TNF, MAPK, and Toll-like signaling pathways. In this study, the anti-inflammatory efficacy and mechanisms of the alcohol extract of SR are explored, with the aim of providing a reference for subsequent research.
Funding Information
  • National Institutes for Food and Drug Control (2023SKLDRS0101, 1020050090116, 2023X10)
  • State Key Laboratory of Drug Regulatory Science (2023SKLDRS0101, 1020050090116, 2023X10)
  • Chinese Medicine Institute of NIFDC (2023SKLDRS0101, 1020050090116, 2023X10)
  • Training Fund for academic leaders of NIFDC (2023SKLDRS0101, 1020050090116, 2023X10)

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