摘要Duchenne muscular dystrophy(DMD)is a progressive neuromuscular disease caused by a mutation in the gene encoding the dystrophin protein.Catalpol is an iridoid glycoside found in Chinese herbs with anti-inflammatory,anti-oxidant,anti-apoptotic,and hypoglycemic activities that can protect against muscle wasting.In the present study we investigated the effects of catalpol on DMD.Aged Dystrophin-deficient(mdx)mice(12 months old)were treated with catalpol(100,200 mg·kg-1·d-1,ig)for 6 weeks.At the end of the experiment,the mice were sacrificed,and gastrocnemius(GAS),tibialis anterior(TA),extensor digitorum longus(EDL),soleus(SOL)muscles were collected.We found that catalpol administration dose-dependently increased stride length and decreased stride width in Gait test.Wire grip test showed that the time of wire grip and grip strength were increased.We found that catalpol administration dose-dependently alleviated skeletal muscle damage,evidenced by reduced plasma CK and LDH activity as well as increased the weight of skeletal muscles.Catalpol administration had no effect on dystrophin expression,but exerted anti-inflammatory effects.Furthermore,catalpol administration dose-dependently decreased tibialis anterior(TA)muscle fibrosis,and inhibited the expression of TGF-β1,TAK1 and α-SMA.In primary myoblasts from mdx mice,knockdown of TAK1 abolished the inhibitory effects of catalpol on the expression levels of TGF-β1 and α-SMA.In conclusion,catalpol can restore skeletal muscle strength and alleviate skeletal muscle damage in aged mdx mice,thus may provide a novel therapy for DMD.Catalpol attenuates muscle fibrosis by inhibiting the TGF-β1/TAK1 signaling pathway.