Ginsenoside C-K

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.

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related morbidity and mortality worldwide. Despite advancements in conventional therapies, the prognosis for patients with GI malignancies remains suboptimal, often due to therapy resistance and adverse side effects. Consequently, there is a pressing need to explore novel, effective, and safer therapeutic agents. Ginsenosides, the principal active components of Panax ginseng, have garnered attention for their multifaceted biological activities, including anticancer properties. Preclinical studies have demonstrated that ginsenosides such as Rg3, Rh2, and compound K exert anticancer effects by modulating key signaling pathways, inducing apoptosis, inhibiting angiogenesis, and enhancing immune responses in various GI cancer models. Notably, ginsenoside Rg3 has been shown to inhibit tumor growth and metastasis in gastric and colorectal cancer models by suppressing vascular endothelial growth factor (VEGF) expression and modulating the NF-κB pathway. Furthermore, ginsenosides have been reported to enhance the efficacy of conventional chemotherapeutic agents and mitigate their side effects, suggesting a potential role as adjuvant therapies. While these findings are promising, clinical evidence remains limited. Some clinical studies have indicated that ginseng preparations may improve postoperative immunity and survival in gastric cancer patients. However, comprehensive clinical trials are necessary to validate the efficacy and safety of ginsenosides in GI cancer treatment. This review aims to consolidate current knowledge on the anticancer potential of ginsenosides in GI cancers, emphasizing their molecular mechanisms of action and highlighting the need for further clinical investigations to translate these findings into therapeutic applications.