Acetylshikonin alleviates gouty arthritis by increasing sirtuin1 expression and promoting lymphatic drainage.

BACKGROUND: Gouty arthritis (GA) is a common and painful inflammatory joint disease. Acetylshikonin (Askn), a major bioactive compound extracted from the traditional Chinese medicine Arnebia euchroma, has an unknown therapeutic potential and mechanism of action against GA. This study aimed to investigate the effects and underlying mechanisms of Askn in a mouse model of GA. METHODS: A GA model was established in 6- to 8-week-old male mice by injecting a 3% monosodium urate (MSU) crystal suspension into the hind paw metatarsophalangeal joint. The mice were randomly divided into three groups: the healthy control group, the GA model group, and the Askn-treated group (30 mg/kg, i.p.). Each group consisted of n = 10 mice. The primary endpoint was the degree of paw swelling, which was assessed by a Vernier calliper. Secondary assessments included liver/kidney toxicity (H&E staining and ultrasound), inflammatory factor expression (qRT‒PCR and immunofluorescence), and lymphatic drainage (ICG‒NIR imaging). RESULTS: Paw swelling was significantly lower in Askn-treated mice than in the GA model group. Askn treatment did not induce hepatotoxicity or nephrotoxicity. A significant improvement in the inflammatory pathological condition of the synovial tissues and surrounding soft tissues at the metatarsophalangeal joint was observed in Askn-treated mice. The mRNA expression of IL-1β, TNF-α, IL-6, and iNOS markedly decreased following Askn treatment. Furthermore, Askn significantly enhanced lymphatic drainage, as indicated by ICG signal intensity, and modulated the SIRT1/NLRP3 pathway. CONCLUSION: Askn alleviates GA symptoms by enhancing lymphatic drainage and upregulating SIRT1 expression, which subsequently inhibits NLRP3-mediated inflammation.