Luo Jinhai, Luo Jincan, Wu Yingzi, Fu Yu, Fang Zhonghao, Han Bincheng, Du Bin, Yang Zifeng, Xu Baojun
Guangdong Provincial Key Laboratory IRADS and Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China.
National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Antioxidants (Basel). 2024 Nov 11;13(11):1380. doi: 10.3390/antiox13111380.
Obesity is a chronic and complex disease defined by the excessive deposition of fat and is highly associated with oxidative stress. Adzuki bean saponins (ABS) showed anti-obesity activity in our previous in vivo study; however, the active saponins of adzuki beans and potential mechanisms are still unclear. This research aims to elucidate the anti-obesity effects of ABS in improving lipid metabolism and oxidative stress, exploring the effective ingredients and potential molecular mechanisms through UHPLC-QE-MS analysis, network pharmacology, bioinformatics, and in vitro experiments both in the 3T3-L1 cell line and HepG2 cell line. The results indicate that ABS can improve intracellular lipid accumulation, adipogenesis, oxidative stress, and mitochondrial damage caused by lipid accumulation including ROS generation, abnormal mitochondrial membrane potential, and ATP disorder. Fifteen saponin components were identified with the UHPLC-QE-MS analysis. The network pharmacology and bioinformatics analyses indicated that the PI3K/Akt signaling pathway is associated with the bioactive effect of ABS. Through Western blotting and immunofluorescence analysis, the anti-obesity effect of ABS is achieved through regulation of the PI3K/Akt/GSK3β/β-catenin signaling pathway and activation of downstream transcription factor c-Myc in the lipid accumulation cell model, and regulation of β-catenin signaling and inhibition of downstream transcription factor C/EBPα in the adipocyte cell model. These results illustrate the biological activity of ABS in improving fat metabolism and oxidative stress by restoring mitochondrial function through β-catenin signaling, the PI3K/Akt/GSK3β/β-catenin signaling pathway, laying the foundation for its further development.
肥胖是一种由脂肪过度沉积定义的慢性复杂疾病，与氧化应激高度相关。在我们之前的体内研究中，赤小豆皂苷（ABS）显示出抗肥胖活性；然而，赤小豆的活性皂苷及其潜在机制仍不清楚。本研究旨在通过超高效液相色谱-四极杆飞行时间质谱（UHPLC-QE-MS）分析、网络药理学、生物信息学以及在3T3-L1细胞系和HepG2细胞系中的体外实验，阐明ABS在改善脂质代谢和氧化应激方面的抗肥胖作用，探索有效成分和潜在分子机制。结果表明，ABS可以改善细胞内脂质积累、脂肪生成、氧化应激以及脂质积累引起的线粒体损伤，包括活性氧生成、线粒体膜电位异常和ATP紊乱。通过UHPLC-QE-MS分析鉴定出15种皂苷成分。网络药理学和生物信息学分析表明，PI3K/Akt信号通路与ABS的生物活性作用相关。通过蛋白质免疫印迹法和免疫荧光分析，在脂质积累细胞模型中，ABS的抗肥胖作用是通过调节PI3K/Akt/GSK3β/β-连环蛋白信号通路并激活下游转录因子c-Myc实现的，在脂肪细胞模型中则是通过调节β-连环蛋白信号并抑制下游转录因子C/EBPα实现的。这些结果说明了ABS通过β-连环蛋白信号、PI3K/Akt/GSK3β/β-连环蛋白信号通路恢复线粒体功能，从而改善脂肪代谢和氧化应激的生物学活性，为其进一步开发奠定了基础。
