Inhibitor of FTO, Rhein, Restrains the Differentiation of Myoblasts and Delays Skeletal Muscle Regeneration.

N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits , a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, and expression increased while m6A levels decreased. After muscle injury, and expression initially rose but later fell, while m6A levels initially dropped and then recovered. Inhibition of by Rhein reduced MyHC and expression, indicating myoblast differentiation suppression. In a mouse model, Rhein decreased MyHC expression and muscle fiber cross-sectional area, delaying muscle regeneration. Rhein's ability to increase RNA m6A modification delays skeletal muscle remodeling post-injury, suggesting a new medicinal application for this plant extract.