Pitchakarn Pornsiri, Karinchai Jirarat, Buacheen Pensiri, Imsumran Arisa, Wongnoppavich Ariyaphong, Boonyapranai Kongsak, Ounjaijean Sakaewan
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Research Center for Non-Infectious Diseases and Environmental Health Sciences, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Int J Mol Sci. 2025 Jan 8;26(2):476. doi: 10.3390/ijms26020476.
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 (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 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 µg/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 µg/mL) to the BPA-treated C2C12 cells. This finding suggests that FLLE effectively improved myogenic differentiation in BPA-exposed myoblasts. FLLE treatment (50 µg/mL) significantly raised total Akt protein levels in the BPA-treated C2C12 cells, enhancing protein phosphorylation. In addition, FLLE (50 µg/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.
最近，毒理学和流行病学研究为双酚A（BPA，2,2'-双（4-羟苯基）丙烷）对肌生成的不利影响及其潜在机制提供了有力支持。因此，研究人员一直在寻找新的策略来预防或减轻BPA对人体的这些有害影响。已发现植物提取物可能作为潜在的治疗剂或功能性食品，预防由BPA引起的人类疾病。我们之前报道过，（FL）提取物通过抑制炎症相关分子的表达在巨噬细胞中表现出抗炎活性，并在炎症处理的脂肪细胞中具有抗胰岛素抵抗作用。在本研究中，我们调查了FL叶提取物（FLLE）是否能保护C2C12小鼠成肌细胞免受BPA对肌源性分化的抑制作用。当与FLLE（200µg/mL）共同处理时，BPA刺激的C2C12成肌细胞的活力显著增加，这表明该提取物可能减轻BPA对细胞分裂的抑制作用。我们还发现，与BPA处理的对照细胞相比，FLLE通过诱导成肌细胞融合形成多核肌管，显著增加了新的肌管形成，且不影响细胞活力。此外，通过向BPA处理的C2C12细胞中添加FLLE（50µg/mL），肌生成素和肌细胞增强因子2A（MEF2A）的水平显著增加，它们是肌生成的关键标志物和调节因子。这一发现表明，FLLE有效地改善了BPA暴露的成肌细胞中的肌源性分化。FLLE处理（50µg/mL）显著提高了BPA处理的C2C12细胞中总的Akt蛋白水平，增强了蛋白磷酸化。此外，FLLE（50µg/mL）通过提高总的p70S6K和4E-BP1水平，明显增加了p70S6K和4E-BP1的磷酸化水平，它们是Akt/mTOR信号级联反应的关键下游靶点。这些结果表明，FLLE通过调节与肌细胞分化相关的信号通路，减轻了BPA诱导的肌源性分化的下降。从本研究中获得的信息证明了这种植物对健康的益处，这值得作为一种替代药物、功能性成分或食品补充剂进行进一步研究，以预防BPA或其他毒物对健康的负面影响。
