Ribes fasciculatum var. Chinense leaf extract alleviates muscle atrophy caused by chronic inflammatory conditions through suppressing polarization into M1 macrophages

Scope: Ribes fasciculatum Siebold & Zucc. var. chinense Maxim. Leave extract (RFE) has been reported to be non-toxic and suitable for consumption as a food, with documented anti-allergic and anti-obesity effects. Skeletal muscle atrophy in various chronic inflammatory conditions has been a significant concern, yet the role of RFE in ameliorating muscle atrophy remains to be demonstrated. This study aims to investigate the regulation of muscle atrophy by RFE in chronic inflammatory conditions. Methods and results: C2C12 myoblasts were treated with conditioned medium from Raw264.7 macrophages induced with LPS to simulate an inflammatory condition, or with conditioned medium containing RFE. This study found that muscle atrophy is significantly exacerbated in the inflammatory conditions, while RFE markedly improves this condition. RFE was found to recover the diminished differentiation capacity of myoblasts that occurs in chronic inflammatory conditions. Importantly, RFE mediates inhibition of polarization into pro-inflammatory M1 macrophages in Raw264.7 cells. This indicates that afzelin, active compound of RFE, interferes with the binding of LPS to the TLR4/MD2 complex. Conclusion: These results suggest that RFE can improve muscle atrophy in chronic inflammatory states by disrupting the binding of LPS to the TLR4/MD2 complex and inhibiting the polarization of macrophages into M1 phenotype.