Natural diarylheptanoid compounds from Curcuma comosa Roxb. promote differentiation of mouse myoblasts C2C12 cells selectively via ER alpha receptors

Abstract

© 2016, Springer Science+Business Media New York. Diarylheptanoids exhibit numerous biological activities and have been used as traditional medicine in Asian countries. However, their effects on myogenesis are still unknown. This study determined the effects of eight different diarylheptanoid compounds including 1,7-diphenyl-(6E)-6-hepten-3-one (compound 1) and its analogs (compounds 2–8) isolated and purified from Curcuma comosa Roxb. on mouse myoblasts (C2C12 cells) proliferation and differentiation. All compounds (10−9–10−5M) were non-toxic to C2C12 cells, and had no anti-oxidant activity except (3S)-1-(3,4–dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (compound 8), which showed higher activity compared to that of ascorbic acid. Additionally, this compound (10−8M) effectively prevented the toxic effect of H2O2 on C2C12 cells. Proliferation of C2C12 cells was significantly increased by all compounds except compound 1 and (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (compound 4), whereas differentiation of myoblasts was enhanced by all compounds. The effect on proliferation was not blocked by ICI 182,780, but this blocker completely inhibited the effects of diarylheptanoids on differentiation. In addition, silencing the transcription of oestrogen receptor α (ERα), but not estrogen receptor β (ERβ), completely abolished the enhancement of differentiation. Together, the results indicate that diarylheptanoids enhance proliferation of C2C12 cells by a non-estrogenic mechanism, but induce differentiation selectively via ERα. These compounds may have potential for further development as therapeutic agents for treatment of muscle injury and/or diseases.