Capsaicin Alleviates Ankylosing Spondylitis in Mice: A Study on the NLRP3/Caspase-1/GSDMD Pyroptosis Pathway and Intestinal Barrier Repair

Abstract

Background: Cell pyroptosis and dysbiosis of the gut microbiota are closely related to the pathogenesis of Ankylosing Spondylitis (AS). Capsaicin, an active component in chili peppers, has demonstrated anti-inflammatory and antioxidant potential. This study aims to explore the therapeutic effects of capsaicin on a mouse model of AS and its underlying mechanisms. Methods: The AS mouse model was established and divided into control, AS model, capsaicin-treated, and sulfasalazine (positive control drug) treated groups. Cytokines in serum were detected by Enzyme-Linked Immunosorbent Assays (ELISA). The activation status of pyroptosis-related proteins and the nuclear factor kappa-B (NF-κB) pathway in spinal joint tissues were analyzed by Western blot. The function of the intestinal mucosal barrier was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Additionally, the composition of the gut microbiota was analyzed. Results: Capsaicin inhibited tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-17A in the serum of AS mice and increased IL-10 (p < 0.01). In the spinal joint tissues, capsaicin effectively inhibited pyroptosis-related proteins such as NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD) (p < 0.01), thus reducing cell pyroptosis. Furthermore, capsaicin inhibited the activation of the NF-κB pathway (p < 0.01), improved the function of the intestinal mucosal barrier, increased levels of beneficial probiotics such as Lactobacillus and Bifidobacterium (p < 0.001), and decreased levels of harmful bacteria including Enterococcus faecalis (p < 0.05) and Escherichia coli (p < 0.001). Conclusion: This study confirms that capsaicin alleviates inflammation and pathological damage in AS mice by inhibiting the pyroptosis pathway, repairing the intestinal barrier, and regulating the composition of the gut microbiota.