Cinchonidine induces muscle weakness by inhibiting insulin-mediated IRS-1-AKT signaling pathway

Sarcopenia is an age-related condition marked by a reduction in muscle mass and strength, and it is associated with impaired muscle regeneration and differentiation. While diseases like cardiovascular and chronic liver disease can induce sarcopenia, there is limited evidence regarding the specific diseases and mechanisms responsible for its development. In skeletal muscle, the loss of muscle mass is accompanied by a decrease in myofilament proteins and the inhibition of muscle differentiation in satellite cells. Bioactive compounds obtained from natural products have been traditionally used as therapeutics for diverse conditions. In this report, we investigated the effect of cinchonidine (CD) extracted from Cinchona tree on muscle differentiation of mouse satellite cells, and myoblast cell lines. CD significantly inhibited muscle differentiation by suppressing myotube formation and gene expression of myogenesis markers. In addition, CD reduced muscle differentiation by blocking phosphorylation of insulin receptor substrate 1 (IRS-1) during insulin-induced signal transduction. Therefore, the results show that CD, an antimalarial agent, inhibited muscle differentiation through the suppression of IRS-1 phosphorylation, suggesting that sarcopenia can be induced by CD.