The presence of glycoside derivatives of 1 alpha,25(OH)(2)D-3 endows plants to gradual release of the free bioactive form of 1 alpha,25(OH)(2)D-3 from its glycoconjugates by endogenous animal tissue glycosidases. This results in increased half-life of the hormone in blood when purified plant fractions are administered for therapeutic purposes. In this work, we evaluated the role 1 alpha,25(OH)(2)D-3-glycosides enriched natural product (Solbone A) from Solanum glaucophyllum leaf extract compared with synthetic 1 alpha,25(OH)(2)D-3 on myogenic differentiation in C2C12 myoblasts. For these, differentiation markers and myogenic parameters were studied in C2C12 myoblasts. Results showed that Solbone A, likewise the synthetic hormone, increased creatine kinase activity at day 2 after differentiation induction (60%, p < 0.05). Solbone A and synthetic 1 alpha,25(OH)(2)D-3 increased vitamin D-3 receptor protein expression at 10 nM (50% and 30%, respectively) and the transcription factor myogenin (80%, p < 0.05). However, tropomyosin expression was not affected by both compounds. In addition, myosin heavy chain (MHC) protein expression was increased 30% at day 2 of differentiation. Solbone A or synthetic 1 alpha,25(OH)(2)D-3 had no effects on myogenin nor MHC cell localization. Cellular mass increased with myogenesis progression, being Solbone A more effective than synthetic 1 alpha,25(OH)(2)D-3. Finally, Solbone A, as well as synthetic 1 alpha,25(OH)(2)D-3, augmented the index fusion of cultured muscle fibers. In conclusion, these results demonstrated that Solbone A exhibit at least equal or greater effects on early myoblast differentiation as synthetic hormone, suggesting that plant glycosides could be an effective, accessible and cheaper substitute for synthetic 1 alpha,25(OH)(2)D-3 to promote muscle growth. (C) 2016 Elsevier Inc. All rights reserved.