1. A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid in mice.
- Author
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Feng J, Wan J, Guo P, Sun Y, Chen F, Chen Y, Sun Q, Zhang W, and Liu X
- Subjects
- Animals, Mice, Male, Mice, Inbred C57BL, Erythromycin pharmacology, Erythromycin analogs & derivatives, Muscle Fatigue drug effects, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Glycogen metabolism, Orosomucoid metabolism, Physical Endurance drug effects
- 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., (© 2024 John Wiley & Sons Australia, Ltd.)
- Published
- 2024
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