Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy.

Abstract

Sarcopenia is the age-related loss of muscle mass and function and no pharmacological medication has been approved for its treatment. We established an atrogin-1/MAFbx promoter assay to find drug candidates that inhibit myotube atrophy. Alverine citrate (AC) was identified using high-throughput screening of an existing drug library. AC is an established medicine for stomach and intestinal spasms. AC treatment increased myotube diameter and inhibited atrophy signals induced by either C26-conditioned medium or dexamethasone in cultured C2C12 myoblasts. AC also enhanced myoblast fusion through the upregulation of fusion-related genes during C2C12 myoblast differentiation. Oral administration of AC improves muscle mass and physical performance in aged mice, as well as hindlimb-disused mice. Taken together, our data suggest that AC may be a novel therapeutic candidate for improving muscle weakness, including sarcopenia.

• Authors: Jong Hyeon Yoon, Seung-Min Lee, Younglang Lee, Min Ju Kim, Jae Won Yang, Jeong Yi Choi, Ju Yeon Kwak, Kwang-Pyo Lee, Yong Ryoul Yang, Ki-Sun Kwon
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 586 Pg. 157-162 (01 01 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 34847441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cadherins
• Cav3 protein, mouse
• Caveolin 3
• Cdh2 protein, mouse
• Integrin beta1
• Itgb1 protein, mouse
• Parasympatholytics
• Propylamines
• alverine
• Dexamethasone

Topics

• Aging (genetics, metabolism)
• Animals
• Biomarkers (metabolism)
• Cadherins (genetics, metabolism)
• Caveolin 3 (genetics, metabolism)
• Cell Differentiation (drug effects)
• Cell Line
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Gene Expression
• High-Throughput Screening Assays
• Immobilization
• Integrin beta1 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Muscle Development (genetics)
• Muscle Fibers, Skeletal (drug effects, metabolism, pathology)
• Muscle Strength (drug effects)
• Muscle, Skeletal (drug effects, metabolism, pathology)
• Muscular Atrophy (genetics, metabolism, pathology, prevention & control)
• Myoblasts (drug effects, metabolism, pathology)
• Parasympatholytics (pharmacology)
• Propylamines (pharmacology)
• Sarcopenia (genetics, metabolism, pathology, prevention & control)