Inhibitory effects of curcuminoids on dexamethasone-induced muscle atrophy in differentiation of C2C12 cells

Abstract

Background: Sarcopenia is a disease of progressive loss of muscle mass due to the imbalance of protein synthesis and proteolysis, and tends to emerge with ageing. Currently its treatment consists of non-drug therapies and drug therapies, but some medications can have various side effects. Therefore, it is important to search for effective herbal medicines that can modulate muscle mass. Purpose: In this study, we investigated the inhibition effects of Cu, De, Bis, CRE, CRE-SD, CRE-Bin, and CRE-Ter on dexamethasone-induced muscle atrophy in differentiation of C2C12 cells. Methods: C2C12 cells were cultured and treated with various concentrations of curcuminoids including, Cu, De, Bis, CRE, CRE-SD, CRE-Bin, and CRE-Ter. The inhibitory effects were studied using various methods, including MTT and LDH assays for cell viability and cell cytotoxicity, RT-qPCR for gene expression analysis, and Western blots for protein analysis. In this study, dexamethasone-treated C2C12 myotubes (Dex) are the positive drug control and used as in vitro models of muscle atrophy. Results: The results revealed that treating differentiated C2C12 cells with Cu, CRE, CRE-Bin, and CRE-Ter reduced Atrogin-1 and MuRF-1 expression, whereas CRE-SD reduced only MuRF-1 expression. The Western blot analysis results show that Cu, CRE, CRE-Bin, CRE-Ter, and CRE-SD upregulated the phosphorylation level of Akt, which is an important protein in the mTOR signaling pathway. Conclusion: Our results show that Cu, CRE, CRE-Bin, CRE-SD, and CRE-Ter tend to inhibit muscle atrophy by decreasing expression of Atrogin-1 and MuRF-1 inhibiting protein degradation, and to upregulate Phospho-Akt to stimulate protein synthesis. These results provide corroborating evidence of therapeutic potential to treat sarcopenia patients.

Keywords

• Curcuminoids
• Sarcopenia
• Muscle atrophy
• C2C12 cells
• Atrogin-1
• MuRF1