Ginsenoside CK targets NEK7 to suppress inflammasome activation and mitigate diabetes-induced muscle atrophy.

Diabetes-induced skeletal muscle atrophy is closely linked to oxidative stress and chronic inflammation, which severely compromise quality of life. This study aimed to identify effective anti-inflammatory strategies to mitigate muscle degeneration in diabetes. We investigated the molecular mechanism of Ginsenoside CK (Gin), a major bioactive component of ginseng known for its anti-inflammatory properties. Using activity-based protein profiling, we identified never in mitosis A-related kinase 7 (NEK7) as a direct target of Gin. Mechanistically, Gin covalently binds to histidine 262 (H262) of NEK7-an essential residue for NEK7-NLRP3 interaction-thereby disrupting inflammasome formation. In a diabetic mouse model of skeletal muscle atrophy, Gin administration significantly inhibited NEK7-NLRP3 complex formation, reduced interleukin-6 levels, and attenuated muscle atrophy. These findings establish NEK7 as a critical therapeutic target of Gin and suggest that targeting the NEK7-NLRP3 axis may offer a promising strategy for treating inflammation-driven diabetic muscle wasting. Developing novel inhibitors of NEK7-NLRP3 interaction are expected to advance the treatment of inflammation-associated conditions.