# 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

## TL;DR

This study investigates how the alcohol extract of Saposhnikoviae Radix reduces inflammation in rheumatoid arthritis through the conversion of glycosides to aglycones and specific metabolic pathways.

## Contribution

The novel contribution is the identification of anti-inflammatory mechanisms involving glycoside-to-aglycone conversion and key signaling pathways in rheumatoid arthritis.

## Key findings

- The alcohol extract of SR contains 12 chromones and 13 coumarins with anti-inflammatory activity.
- SR's glycosides convert to aglycones in rheumatoid arthritis models, reducing inflammation.
- SR modulates AGE-RAGE, PI3K-Akt, TNF, MAPK, and Toll-like pathways to exert anti-inflammatory effects.

## 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.