State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Ophthalmic Res. 2021;64(2):337-344. doi: 10.1159/000508251. Epub 2020 Apr 28.
Paralytic strabismus involves a functional loss of extraocular muscles resulting from muscular or neuronal disorders. Currently, only a limited number of drugs are available for functional repair of extraocular muscles. Here, we investigated the effects of a novel drug, flavonoids sophoranone, on the differentiation of extraocular muscles as assessed in bothin vivo and in vitro models.
The effect of flavonoids sophoranone on C2C12 cells was examinedin vitro as evaluated with use of apoptosis, reactive oxygen species (ROS), and cell viability assays. Then, both in vivo and in vitro effects of this drug were examined on the differentiation of C2C12 and satellite cells within extraocular muscles in rabbits. For these latter experiments, RT-PCR and Western blot assays were used to determine expression levels of markers for myogenic differentiation.
With use of flavonoids sophoranone concentrations ranging from 0 to 10 μM, no effects were observed upon cell apoptosis, ROS, and cell cycle in C2C12 cells. Based on MTT assay results, flavonoids sophoranone was shown to increase C2C12 cell proliferation. Moreover, flavonoids sophoranone promoted the differentiation of C2C12 and satellite cells within extraocular muscles in rabbits, which were verified as based on cell morphology and expression levels of mRNA and protein markers of myogenic differentiation. Finally, flavonoids sophoranone treatment also increased gene expressions of Myh3, Myog, and MCK.
The capacity for flavonoids sophoranone to upgrade the differentiation of both C2C12 and satellite cells within extraocular muscles in rabbits at concentrations producing no adverse effects suggest that this drug may provide a safe and effective means to promote repair of damaged extraocular muscles.
麻痹性斜视涉及眼外肌的功能丧失，由肌肉或神经元疾病引起。目前，只有有限数量的药物可用于眼外肌的功能修复。在这里，我们研究了一种新型药物，槐烷酮类黄酮，在体内和体外模型中对眼外肌分化的影响。
在体外，通过使用细胞凋亡、活性氧（ROS）和细胞活力测定来评估槐烷酮类黄酮对 C2C12 细胞的影响。然后，在体内和体外，研究了该药物对兔眼外肌中 C2C12 和卫星细胞分化的影响。对于这些后续实验，使用 RT-PCR 和 Western blot 分析来确定肌发生分化标志物的表达水平。
使用浓度范围为 0 至 10 μM 的槐烷酮类黄酮，在 C2C12 细胞中观察到对细胞凋亡、ROS 和细胞周期没有影响。基于 MTT 测定结果，槐烷酮类黄酮显示出增加 C2C12 细胞增殖的作用。此外，槐烷酮类黄酮促进了兔眼外肌中 C2C12 和卫星细胞的分化，这可以根据细胞形态和肌发生分化的 mRNA 和蛋白标志物的表达水平来验证。最后，槐烷酮类黄酮处理还增加了 Myh3、Myog 和 MCK 的基因表达。
槐烷酮类黄酮能够在不产生不良反应的浓度下提高兔眼外肌中 C2C12 和卫星细胞的分化能力，这表明该药物可能提供一种安全有效的促进受损眼外肌修复的方法。
