Baicalein modulates mitochondrial function by upregulating mitochondrial uncoupling protein-1 (UCP1) expression in brown adipocytes, cytotoxicity, and computational studies
Baicalein modulates mitochondrial function by upregulating mitochondrial uncoupling protein-1 (UCP1) expression in brown adipocytes, cytotoxicity, and computational studies
复制标题
黄芩素通过上调棕色脂肪细胞中线粒体解偶联蛋白-1 (UCP1) 的表达、细胞毒性和计算研究来调节线粒体功能
DOI：
10.1016/j.ijbiomac.2022.09.285
复制
发表时间：
2022-11-05
影响因子：
8.2
通讯作者：
Song, Yongfeng
中科院分区：
文献类型：
--
作者：
Reyad-ul-Ferdous, Md.;Song, Yongfeng
背景：肥胖、脂肪肝、2型糖尿病和非酒精性脂肪肝（NAFLD）都是由过量食物摄入引起的代谢性疾病。现有的药物分子具有不良的副作用，并引起其他疾病的发展（奥利司他引起血管性水肿和月经不规律；醋酸甲地孕酮引起高血压和失眠）。通过增加脂质消耗和增加非寒战产热，靶向脂肪细胞中线粒体解偶联蛋白-1 （UCP1）的表达可能是一种治疗肥胖或与肥胖相关的代谢紊乱的有利策略。方法：在本研究中，我们使用先前生产的UCP1-A-GFP报告细胞系来寻找新的抗肥胖或代谢综合征的药理化合物，然后我们在细胞分析、细胞毒性、线粒体功能、线粒体DNA定量、线粒体ATP生成和计算机模型中进行了测试。结果：黄芩素通过改变线粒体功能在预防肥胖中起关键作用。黄芩素降低ATP的产生，同时显著增加褐色脂肪细胞中UCP1基因的表达。因此，细胞产热作用增强。黄芩素对HEK293T细胞系无害。通过计算机研究揭示了药物-蛋白相互作用和UCP1结合。因此，我们的研究阐明了黄芩素通过调节线粒体活性在代谢和肥胖相关疾病中的治疗作用（补充图2）。结论：需要在小鼠和人类模型中进行进一步的研究，以了解线粒体调节的全部作用机制。药物开发研究也需要研制出精确的配方。
Background: Obesity, fatty liver, type 2 diabetes, and Non-alcoholic fatty liver disease (NAFLD) are all metabolic diseases caused by excess food consumption. Existing drug molecules had negative side effects and caused other diseases to develop (Orlistat causes angioedema, and menstrual irregularities; megestrol acetate causes hypertension, and insomnia). By enhancing lipid consumption and increasing nonshivering thermogenesis, targeting mitochondrial uncoupling protein-1 (UCP1) expression in adipocytes could be an auspicious treatment strategy against obesity or metabolic disorders associated with obesity.Methods: We used previously produced UCP1-A-GFP reporter cell lines in this investigation to find new pharmacological compounds against obesity or metabolic syndrome, which we then tested in cellular analysis, cytotoxicity, mitochondrial function, mitochondrial DNA quantification, mitochondrial ATP production, and insilico models.Results: Baicalein was discovered to play a critical role in obesity prevention via altering mitochondrial function. Baicalein lowers ATP generation while increasing considerable UCP1 gene expression in brown adipocytes. As a result, cellular thermogenesis is boosted. The HEK293T cell line is harmless by baicalein. The investigation by the in-silico study revealed drug-protein interaction and UCP1 binding. Thus, our research clarifies baicalein's therapeutic role in metabolic and obesity-related illnesses via modulating mitochondrial activity (Supplementary Fig. 2).Conclusions: Further studies are required in both murine and human models to understand the full mechanism of action by mitochondrial modulation. Drug development investigation also requires to development of a precise formulation.