Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy

Area of Science:

• Biochemistry
• Muscle Biology
• Pharmacology

Background:

• Sarcopenia, the age-related decline in muscle mass and function, lacks approved pharmacological treatments.
• Identifying novel therapeutic agents to combat muscle atrophy is a critical unmet medical need.

Purpose of the Study:

• To screen for drug candidates capable of inhibiting myotube atrophy using a novel promoter assay.
• To evaluate the efficacy of Alverine citrate (AC) as a potential therapeutic for muscle wasting conditions.

Main Methods:

• Development of an atrogin-1/MAFbx promoter assay for high-throughput screening.
• In vitro studies using C2C12 myoblasts to assess AC's effects on myotube diameter and atrophy signals.
• In vivo studies involving oral administration of AC to aged and hindlimb-disused mice.

Main Results:

• Alverine citrate (AC) was identified as a potent inhibitor of myotube atrophy in vitro.
• AC treatment increased myotube diameter and reversed atrophy induced by C26-conditioned medium or dexamethasone.
• AC enhanced myoblast fusion and improved muscle mass and physical performance in aged and disused mouse models.

Conclusions:

• Alverine citrate demonstrates significant potential as a therapeutic agent for muscle weakness.
• AC may serve as a novel treatment strategy for sarcopenia and other muscle wasting conditions.