ArticleFrontiers in endocrinology2026
Capsaicin ameliorates diabetic nephropathy by targeted activation of GPX4 and inhibition of pyroptosis.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Capsaicin (CAP) is the primary pungent alkaloid found in chili peppers. The aim of this study is to screen for candidate therapeutic agents targeting the mitochondrial dysfunction-pyroptosis axis in diabetic nephropathy (DN) and to validate the efficacy and mechanism of action of capsaicin. Methods: Bioinformatics analysis was conducted to identify candidate genes and drugs. The protective effects and underlying mechanisms of CAP were investigated using a high-glucose (HG)-induced HK-2 cell model and a streptozotocin-induced T1DM DN rat model. Experimental techniques included CCK8 assay, flow cytometry (pyroptosis and ROS), JC-1 staining, Western blot analysis, and histopathological staining. GPX4-IN-3 was applied Results: Bioinformatic analysis identified 12 intersecting genes and highlighted CAP as a potential GPX4-targeting compound. Molecular docking demonstrated a high binding affinity of CAP for GPX4 and caspase-9. Conclusion: This study demonstrates that CAP ameliorates diabetic renal injury by targeting GPX4, thereby mitigating mitochondrial dysfunction and subsequent NLRP3-mediated pyroptosis. These findings validate the bioinformatic prediction and reveal a novel mechanism of action for CAP, positioning it as a promising therapeutic candidate for DN.
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