Corrigendum: Investigating the mechanisms of resveratrol in the treatment of gouty arthritis through the integration of network pharmacology and metabolics

Xiaomin Xu Donghua Yu ^* Yu Wang Xin Jiang ^* Fang Lu ^* Shumin Liu ^*

• Heilongjiang University of Chinese Medicine, Harbin, China

Objective: This study aimed to explore the potential regulatory mechanisms of Resveratrol (Res) on Gouty arthritis (GA) by integrating network pharmacology and metabolomics technologies. Method: Network pharmacology was utilized to predict the regulatory mechanisms of Res on GA, and experimental methods including HE staining, ELISA, immunohistochemistry, real-time PCR, and molecular docking were employed to validate the role of the NF-κB signaling pathway in a Monosodium urate (MSU)-induced rat model of GA. In addition, serum metabolomics technology was used to further investigate the mechanism of Res in the treatment of GA. Results: The network pharmacology results demonstrated that Res may exert its therapeutic effects on GA through the NF-κB signaling pathway. Animal experiments revealed that in the MSU-induced rat model of GA, pathological damage, serum biochemical indicators, and levels of inflammatory factors were significantly increased, and the expression of TLR4, MyD88, NF-κB mRNA, and proteins in ankle joint tissues were also significantly elevated, indicating the activation of the NF-κB signaling pathway during acute GA attacks. Intervention with Res significantly reduced the pathological damage, serum biochemical indicators, levels of inflammatory factors, as well as the expression of TLR4, MyD88, and NF-κB proteins in the model rats. Serum metabolomics results showed that Res improved the deviation of serum metabolic trajectories in the GA model rats. Furthermore, 24 shared differential biomarkers involved in 6 related metabolic pathways were identified after Res intervention. Pathway analysis revealed that the most extensively affected metabolic pathways were sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and arachidonic acid metabolism. Integration of network pharmacology and metabolomics revealed that Res could regulate the metabolism of 1-phenylethylamine and subsequently modulate arachidonic acid metabolism to inhibit the NF-κB signaling pathway, thereby achieving therapeutic effects on GA. Conclusion: Therefore, we believe that the mechanism of resveratrol inhibiting the inflammatory response during acute attack of gouty arthritis is to regulate the metabolic pathways such as arachidonic acid by regulating metabolites such as 1-Phenylethylamine, so as to inhibit the NF-κB signaling pathway.