Kwon Eun-Bin, Lee Jae-Won, Park Ji-Yoon, Kim Namho, Lee Su Hyeon, Kim Doo-Young, Ahn Sunjoo, Choi Gahyeon, Park Young Bin, Choi Jae-Mun, Ryu Hyung Won, Kim Mun-Ock
Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea.
Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea; Department of Biotechnology, University of Science and Technology, Daejeon 34113, Republic of Korea.
Biomed Pharmacother. 2025 Aug;189:118281. doi: 10.1016/j.biopha.2025.118281. Epub 2025 Jun 18.
Chiisanogenin (CHI), a bioactive compound derived from Eleutherococcus sessiliflorus (Rupr. & Maxim.), has gained attention for its potential therapeutic effects on glucose metabolism. This study aimed to elucidate the mechanisms underlying the blood glucose-lowering effects of CHI through both in vitro and in vivo investigations. In vitro experiments using L6 myotubes demonstrated that CHI enhanced glucose uptake in a dose-dependent manner. CHI promoted glucose transporter type 4 (GLUT4)-dependent glucose uptake through the insulin receptor substrate 1/phosphatidylinositol 3-kinase/protein kinase B (IRS-1/PI3K/Akt) signaling pathway, activating AS160 and facilitating the translocation of GLUT4 storage vesicles to the plasma membrane. Additionally, cell permeability assays using Caco-2 cells demonstrated that CHI possesses high cellular permeability. Mice treated with CHI before oral glucose administration showed a significant reduction in postprandial blood glucose levels compared to the control group. Overall, these results suggest that CHI activates insulin signaling independently of exogenous insulin and mimics insulin-like effects in vivo. Finally, molecular docking analysis was conducted to determine whether CHI interacts with the insulin receptor. The analysis predicted that CHI interacts with the insulin receptor with a binding energy of -6.96 kcal/mol. These findings suggest that CHI exerts a blood glucose-lowering effect, highlighting its potential as a functional material for the development of anti-diabetic functional food ingredient or dietary supplement after US FDA GRAS registration.
刺五加苷（CHI）是一种从无梗五加（Rupr. & Maxim.）中提取的生物活性化合物，因其对葡萄糖代谢的潜在治疗作用而受到关注。本研究旨在通过体外和体内研究阐明CHI降血糖作用的潜在机制。使用L6肌管进行的体外实验表明，CHI以剂量依赖的方式增强葡萄糖摄取。CHI通过胰岛素受体底物1/磷脂酰肌醇3激酶/蛋白激酶B（IRS-1/PI3K/Akt）信号通路促进依赖葡萄糖转运蛋白4（GLUT4）的葡萄糖摄取，激活AS160并促进GLUT4储存囊泡向质膜的转运。此外，使用Caco-2细胞进行的细胞通透性试验表明，CHI具有较高的细胞通透性。与对照组相比，口服葡萄糖前用CHI处理的小鼠餐后血糖水平显著降低。总体而言，这些结果表明，CHI可独立于外源性胰岛素激活胰岛素信号，并在体内模拟胰岛素样作用。最后，进行分子对接分析以确定CHI是否与胰岛素受体相互作用。分析预测，CHI与胰岛素受体相互作用，结合能为-6.96 kcal/mol。这些发现表明，CHI具有降血糖作用，突出了其在美国食品药品监督管理局（FDA）GRAS注册后作为抗糖尿病功能性食品成分或膳食补充剂开发的功能材料的潜力。
