Ishophloroglucin A, Isolated from Ishige okamurae, Alleviates Dexamethasone-Induced Muscle Atrophy through Muscle Protein Metabolism In Vivo

Abstract

The in vitro capacity of Ishige okamurae extract (IO) to improve impaired muscle function has been previously examined. However, the mechanism underlying IO-mediated muscle protein metabolism and the role of its component, Ishophloroglucin A (IPA), in mice with dexamethasone (Dexa)-induced muscle atrophy remains unknown. In the present study, we evaluated the effect of IO and IPA supplementation on Dexa-induced muscle atrophy by assessing muscle protein metabolism in gastrocnemius and soleus muscles of mice. IO and IPA supplementation improved the Dexa-induced decrease in muscle weight and width, leading to enhanced grip strength. In addition, IO and IPA supplementation regulated impaired protein synthesis (PI3K and Akt) or degradation (muscle-specific ubiquitin ligase muscle RING finger and atrogin-1) by modulating mRNA levels in gastrocnemius and soleus muscles. Additionally, IO and IPA upregulated mRNA levels associated with muscle growth activation (transient receptor potential vanilloid type 4 and adenosine A1 receptor) or inhibition (myostatin and sirtuin 1) in gastrocnemius and soleus muscle tissues of Dexa-induced mice. Collectively, these results suggest that IO and IO-derived IPA can regulate muscle growth through muscle protein metabolism in Dexa-induced muscle atrophy.