Potential components and action mechanism of Tongzhi Surunjiang Pills against acute gouty arthritis: UPLC-MS/MS, network pharmacology, molecular docking, and transcriptomic analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gouty arthritis (GA) is a disease caused by the malfunction of purine and/or uric acid metabolism. Tongzhi Surunjing Pills (TZSRJP), a traditional Chinese medicine formula derived from the ancient Uyghur book "Karzhibadin Kadeer", is used clinically to treat GA, which still needs more research in its complex regulatory mechanisms.

AIM OF STUDY: The aim of the study was to elucidate the main potential active components of TZSRJP and the mechanism by which it treated GA.

METHODS

We used network pharmacology and molecular docking to predict possible active ingredients and targets, and UPLC-MS to identify the content of key components, followed by transcriptomics to analyze targets of action and also demonstrated our hypothesis in rats.

RESULTS

Network pharmacology showed that TZSRJP Contained 120 active components and 934 potential targets. 9 of major active ingredients, such as gallic acid, colchicine, senoside A, and so on were identified and quantified by UPLC-MS. KEGG predicted the therapeutic effects mainly through NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway; molecular docking showed that its main active ingredients had high affinity with inflammation-related proteins such as NLRP3, IL-1β, and TNF. Transcriptomics also verified that the therapeutic effects were mainly carried out through inflammatory pathways. In vivo experiments verified the efficacy of TZSRJP in the treatment of GA and reduced the expression of proteins and genes related to the NLRP3 pathway. Therefore, TZSRJP alleviates GA development through the NLRP3 pathway, and the main components contain colchicine, gallic acid, and so on.