Ficus lindsayana Leaf Extract Protects C2C12 Mouse Myoblasts Against the Suppressive Effects of Bisphenol-A on Myogenic Differentiation

Recently, toxicological and epidemiological research has provided strong support for the unfavorable effects of bisphenol-A (BPA, 2,2 '-bis(4-hydroxyphenyl) propane) on myogenesis and its underlying mechanisms. Researchers have therefore been looking for new strategies to prevent or mitigate these injurious effects of BPA on the human body. It has been found that plant extracts may act as potential therapeutic agents or functional foods, preventing human diseases caused by BPA. We previously reported that Ficus lindsayana (FL) extract exhibits anti-inflammation activity in macrophages via suppressing the expression of inflammation-related molecules and anti-insulin resistance in inflammation-treated adipocytes. In this study, we investigated whether Ficus lindsayana leaf extract (FLLE) protects C2C12 mouse myoblasts against the suppressive effects of BPA on myogenic differentiation. The viability of BPA-stimulated C2C12 myoblasts was significantly increased when co-treated with FLLE (200 mu g/mL), suggesting that the extract may lessen the inhibitory effects of BPA on cell division. We also found that FLLE significantly increased neo-myotube formation by inducing the fusion of myoblasts into multinucleated myotubes when compared to the BPA-treated control cells, without impacting cell viability. In addition, the levels of myogenin and myocyte enhancer factor 2A (MEF2A), which are crucial markers and regulators of myogenesis, were markedly increased by the addition of FLLE (50 mu g/mL) to the BPA-treated C2C12 cells. This finding suggests that FLLE effectively improved myogenic differentiation in BPA-exposed myoblasts. FLLE treatment (50 mu g/mL) significantly raised total Akt protein levels in the BPA-treated C2C12 cells, enhancing protein phosphorylation. In addition, FLLE (50 mu g/mL) obviously increased the phosphorylation levels of p70S6K and 4E-BP1, key downstream targets of the Akt/mTOR signaling cascade, by elevating total p70S6K and 4E-BP1 levels. These results suggest that FLLE diminishes the decline in myogenic differentiation induced by BPA via the regulation of the myocyte differentiation-related signaling pathway. The information obtained from this study demonstrates the health benefits of this plant, which warrants further investigation as an alternative medicine, functional ingredient, or food supplement that can prevent the negative health effects of BPA or other toxicants.