A Non-Antibiotic Erythromycin Derivative Improves Muscle Endurance by Regulating Endogenous Anti-Fatigue Protein Orosomucoid in Mice

Jiayi Feng,Jingjing Wan，Weidong Zhang,Xia Liu

Clinical and Experimental Pharmacology and Physiology（2024）

Second Mil Med Univ | China Inst Pharmaceut Ind

Cited 0|Views3

Abstract

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti-fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS-01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS-01 could time- and dose-dependently prolong mice forced-swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS-01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared. Therefore, HMS-01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.

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Key words

erythromycin derivatives,glycogen,mitochondria,muscle endurance,orosomucoid (ORM)

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