A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid in mice.
erythromycin derivatives
glycogen
mitochondria
muscle endurance
orosomucoid (ORM)
Journal
Clinical and experimental pharmacology & physiology
ISSN: 1440-1681
Titre abrégé: Clin Exp Pharmacol Physiol
Pays: Australia
ID NLM: 0425076
Informations de publication
Date de publication:
Jul 2024
Jul 2024
Historique:
revised:
15
04
2024
received:
10
11
2023
accepted:
28
04
2024
medline:
31
5
2024
pubmed:
31
5
2024
entrez:
30
5
2024
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38815994
doi: 10.1111/1440-1681.13873
doi:
Substances chimiques
Erythromycin
63937KV33D
Glycogen
9005-79-2
Orosomucoid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13873Subventions
Organisme : National Science and Technology Major Projects of China
ID : 2018ZX09J18110-003-001
Organisme : National Science and Technology Major Projects of China
ID : 2018ZX09711002-003-015
Organisme : National Natural Science Foundation of China
ID : 82273920
Organisme : National Natural Science Foundation of China
ID : 82073842
Organisme : National Natural Science Foundation of China
ID : 82104257
Organisme : National Natural Science Foundation of China
ID : 82073907
Organisme : Shanghai Science and Technology Innovation Action Plan
ID : 21XD1404700
Informations de copyright
© 2024 John Wiley & Sons Australia, Ltd.
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