Catalpol counteracts the pathology in a mouse model of Duchenne muscular dystrophy by inhibiting the TGF-β1/TAK1 signaling pathway  

作　　者：Deng-qiu Xu Lei Zhao Si-jia Li Xiao-fei Huang Chun-jie Li Li-xin Sun Xi-hua Li Lu-yong Zhang Zhen-zhou Jiang 

机构地区：[1]Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University,Nanjing 210009,China [2]Department of Neurology,Children’s Hospital of Fudan University,Shanghai 200032,China [3]Center for Drug Screening and Pharmacodynamics Evaluation,School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China [4]Key Laboratory of Drug Quality Control and Pharmacovigilance,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Acta Pharmacologica Sinica》2021年第7期1080-1089,共10页中国药理学报（英文版）

基　　金：This work was supported by grants from the Scholar of the 14th Batch of"Six Talents Peak"High-level Talent Selection Program(SWYY-094);the Postgraduate Research Practice Innovation Program of Jiangsu Province(KYCX19-0763);the"Double First-Class"University Project(CPU2018GY33);and the National Natural Science Foundation of China(Nos.81773827 and 81573514 to ZZJ,No.81773995 to LYZ).

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.

关 键 词：Duchenne muscular dystrophy CATALPOL TGF-Β1 TAK1 Α-SMA muscle fibrosis 

分 类 号：R965[医药卫生—药理学]