Evaluation of the effects of ursolic acid/γ‑cyclodextrin or cyclodextrin‑based metal‑organic framework‑1 complexes on reducing cytotoxicity and improving muscle atrophy in C2C12 cells

The present study aimed to evaluate the effects of ursolic acid (UA), a compound found in apple peels and other fruits and known for its biological activities on the improvement of muscle atrophy. The present study also examined γ‑cyclodextrin (γ‑CD) and cyclodextrin‑based metal‑organic framework‑1 (CD‑MOF‑1) complexes for their effects on the proliferation of C2C12 myotube cells, which are derived from mouse skeletal muscle. Cell viability under proliferative and differentiation conditions was assessed using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Cell viability was reduced at 20 µM in intact UA, at 40 µM in UA/γ‑CD, and at 20 µM in UA/CD‑MOF‑1 cells under proliferative conditions. Under differentiation conditions, cell viability was decreased at 20 µM in intact UA, at 40 µM in UA/γ‑CD, and at 10 µM in UA/CD‑MOF‑1. The reduced viability of C2C12 cells under proliferative and differentiation conditions was not observed in UA/γ‑CD concentrations up to and higher than those of intact UA, suggesting that the cytotoxic effect of UA was mitigated. Under both proliferative and differentiation conditions, encapsulation with CD‑MOF‑1 did not reduce the cytotoxic effect of UA, suggesting that UA/CD‑MOF‑1 enhanced the intracellular release of UA. The myotube diameters of the C2C12 cells were measured to evaluate muscle atrophy. The addition of dexamethasone (DEX) decreased the myotube diameter; however, UA + DEX, UA/γ‑CD + DEX, and UA/CD‑MOF‑1 + DEX exhibited no difference compared with the control, suggesting that UA ameliorated muscle atrophy induced by DEX. On the whole, the present study confirms that UA myotubular cells can act even when UA/γ‑CD and UA/CD‑MOF‑1 form inclusion complexes, and that muscle atrophy is sustained in UA myotubular cells.