Quercetin glycosides prevent dexamethasone-induced muscle atrophy in mice

Yuta Otsuka,Kahori Egawa,Noriyuki Kanzaki,Takayuki Izumo,Tomohiro Rogi,Hiroshi Shibata

doi:10.1016/j.bbrep.2019.100618

Yuta Otsuka, Kahori Egawa + Show 4 more

Open Access

https://doi.org/10.1016/j.bbrep.2019.100618

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Abstract

Although quercetin has numerous biological benefits, including preventing muscle atrophy due to disuse, no reports have been published to date about the preventive effects and molecular mechanisms underlying drug-induced muscle atrophy. Highly soluble and bioavailable quercetin glycosides (QGs) were used to examine the inhibition of dexamethasone (DEX)-induced muscle atrophy in vivo. Male BALB/cCrSlc mice were treated with or without QGs for 7 days ad libitum, followed by addition of DEX to their drinking water for a further 7 days. The weight of gastrocnemius (GM) adjusted by body weight was significantly decreased on day 7 after DEX treatment. DEX-induced decrease of GM weight was improved by QG co-administration on day 7. The mRNA levels of muscle atrophy-related genes in the gastrocnemius were significantly lowered by QGs on day 1. In particular, the expression of myostatin, a master regulator of muscle mass homeostasis, was suppressed to that of the control level. In murine C2C12 myotubes, quercetin elevated the phosphorylation of Akt, which are downstream of the myostatin pathway, as well as expression of atrogenes. We demonstrated the protective effect of QGs in DEX-induced muscle atrophy, which might depend on the suppression of myostatin signaling.

Highlights

Skeletal muscle is an abundant tissue in the human body
Recent studies show that two muscle-specific E3 ubiquitin ligases, atrogin-1/muscle atrophy F-box and muscle ring finger protein 1 (MuRF-1), the socalled atrogenes [3], play key roles in muscle atrophy caused by immobilization and denervation [4,5], as well as DEX treatment [6]
We demonstrated that oral administration of quercetin glycosides (QGs) prevented DEX-induced muscle atrophy and expression of atrogenes in mice

Summary

Introduction

Skeletal muscle is an abundant tissue in the human body. It is involved in mobility and movement and in glucose and lipid metabolism. Recent studies show that two muscle-specific E3 ubiquitin ligases, atrogin-1/muscle atrophy F-box (atrogin-1) and muscle ring finger protein 1 (MuRF-1), the socalled atrogenes [3], play key roles in muscle atrophy caused by immobilization and denervation [4,5], as well as DEX treatment [6]. Their gene expression and activities are regulated by transcription factors from the class O type forkhead (Foxo) family [4,5,6,7]

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