Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:586 |
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| Enthalten in: |
Biochemical and biophysical research communications - 586(2022) vom: 01. Jan., Seite 157-162 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoon, Jong Hyeon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.01.2022 Date Revised 12.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2021.11.076 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM333844319 |
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| 520 | |a Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Aging | |
| 650 | 4 | |a Alverine citrate | |
| 650 | 4 | |a Sarcopenia | |
| 650 | 4 | |a Skeletal muscle atrophy | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Cadherins |2 NLM | |
| 650 | 7 | |a Cav3 protein, mouse |2 NLM | |
| 650 | 7 | |a Caveolin 3 |2 NLM | |
| 650 | 7 | |a Cdh2 protein, mouse |2 NLM | |
| 650 | 7 | |a Integrin beta1 |2 NLM | |
| 650 | 7 | |a Itgb1 protein, mouse |2 NLM | |
| 650 | 7 | |a Parasympatholytics |2 NLM | |
| 650 | 7 | |a Propylamines |2 NLM | |
| 650 | 7 | |a alverine |2 NLM | |
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| 650 | 7 | |a Dexamethasone |2 NLM | |
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| 700 | 1 | |a Lee, Seung-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Younglang |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Min Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jae Won |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Jeong Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Kwak, Ju Yeon |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Kwang-Pyo |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yong Ryoul |e verfasserin |4 aut | |
| 700 | 1 | |a Kwon, Ki-Sun |e verfasserin |4 aut | |
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