Gout arthritis (GA) is the most prevalent form of inflammatory arthritis, occurring in approximately 1% to 3% of the population in China. 1,2 GA is characterized by the accumulation of monosodium urate (MSU) crystals in joints and tendons. The standard approach in Western medicine for treating GA involves the use of non-steroidal anti-inflammatory drugs and uric acid (UA) lowering medications. While these drugs have demonstrated anti-inflammatory and analgesic properties, as well as the ability to suppress UA production, they are also associated with adverse effects including liver and kidney damage, as well as gastrointestinal toxicity. 3 There is therefore an urgent need to develop safe and effective therapeutic interventions for the treatment of GA.

In clinical practice, Tibetan medicine bloodletting therapy (Darika) has shown good efficacy in treating gout. 4, 5, 6 Before implementing Tibetan bloodletting therapy, it is customary to consume Tibetan medicine Sanguotang (SGT), which promotes the maturation and expedited recovery of diseased blood. This approach is advantageous as it minimizes harm to healthy blood during the smooth excretion of the diseased blood, addressing both the symptoms and underlying causes of gout. 7 First recorded in the eighth century AD in the “Four Medical Codes”, the Tibetan medicine SGT, comprising Kezi, Yuganzi, and Maokezi, has yielded satisfactory results in clinical application. The SGT formula, commonly used in clinical practice, is often used to treat ailments such as gout, polycythemia vera, and hyperlipidemia. Modern research has shown that the SGT formula mainly contains phenolic acids such as ellagic acid and tannic acid, tannins such as gallic acid, corilagin, helicteric acid, chebulagic acid, and tannic acid, organic acids such as vitamin C, triterpenoids such as oleanolic acid and maslinic acid, flavonoids such as quercetin and kaempferol, and other components. 8,9 Modern pharmacological studies have shown that the SGT formula primarily exhibits pharmacological effects such as antimicrobial, anti-inflammatory, anti-tumor, hypoglycemic, hypolipidemic, radioprotective, and hepatorenal protective effects. 10,11 The water extract of SGT formula can inhibit the expressions of peroxisome proliferator-activated receptor gamma, transcription factor CCAAT enhancer-binding protein alpha, glucose transporter 4, and fatty acid synthase, thereby achieving lipid-lowering effects. Moreover, the SGT is mainly associated with inflammation-related pathways, including IL-7\HIF-1, NF-κB, and TNF signaling pathways. The NF-κB signaling pathway serves as a key indicator of inflammatory response and consists of a series of transcription factors. 12 Activation of the NF-κB pathway can induce the production of inflammatory cytokines, thereby leading to joint damage. 13 Additionally, SGT can enhance local concentrations of PO2, UA, blood viscosity, and inflammatory factor levels, thereby effectively treating gout. 14 Nonetheless, limited research has been conducted on the mechanism of action of SGT for the treatment of GA.

Herein, we conducted a network pharmacology analysis to elucidate the specific mechanism of SGT in the treatment of GA. The main pharmacological components and potential targets of SGT were identified and a “drug-compound-target” network was established. These in vitro findings were validated using animal experiments. The findings of our study will provide both theoretical and experimental support for the rational use and mechanisms of SGT in the clinical treatment of GA.