Diosgenin prevents dexamethasone-induced myotube atrophy in C2C12 cells

Yasukiyo Yoshioka; Shiori Oishi; Keita Onoda; Katsumi Shibata; Noriyuki Miyoshi

doi:10.1016/j.abb.2023.109759

Diosgenin prevents dexamethasone-induced myotube atrophy in C2C12 cells

Arch Biochem Biophys. 2023 Oct 1:747:109759. doi: 10.1016/j.abb.2023.109759. Epub 2023 Sep 16.

Authors

Yasukiyo Yoshioka¹, Shiori Oishi¹, Keita Onoda¹, Katsumi Shibata², Noriyuki Miyoshi³

Affiliations

¹ Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
² Faculty of Clinical Nutrition and Dietetics, Konan Women's University, Kobe, Hyogo, 685-0001, Japan.
³ Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan. Electronic address: miyoshin@u-shizuoka-ken.ac.jp.

PMID: 37722527
DOI: 10.1016/j.abb.2023.109759

Abstract

Several pathophysiological abnormalities, including a sedentary lifestyle, chronic diseases, and oxidative stress, can contribute to muscle atrophy triggered by an imbalance in muscle protein synthesis and degradation. Resolving muscle atrophy is a critical issue as it can reduce the quality of life. Here, one of the promising functional food factors, diosgenin (a steroidal sapogenin) showed strong preventive activities against dexamethasone (Dex)-induced muscle atrophy, as determined by the expression levels and morphology of the myosin heavy chain in C2C12 myotubes. Diosgenin inhibited protein expressions of Dex-induced skeletal muscle-specific ubiquitin ligase, including muscle RING finger 1 (MuRF1) and casitas B-lineage lymphoma protooncogene b (Cbl-b) but not atrogin-1. Diosgenin ameliorated Dex-induced declines of Akt phosphorylation at Ser473 and FoxO3a phosphorylation at Ser253, which probably at least partially contributed to the suppression of MuRF1, Cbl-b, and atrogin-1 gene expression. Additionally, diosgenin inhibited Dex-induced nuclear translocation of the glucocorticoid receptor (GR), diosgenin therefore may competitively inhibit the interaction between Dex and GR. These findings suggest that diosgenin is an effective functional food for preventing glucocorticoid-induced skeletal muscle atrophy.

Keywords: C2C12 myotube cells; Dexamethasone; Diosgenin; Glucocorticoid receptor; Muscle atrophy.