An Yongcheng, Zhao Hongbin, He Changhao, Shi Lu, Su Xiaohua, Zhang Huilin, Huang Yan, Shan Ziyi, Wang Menglu, Du Yuhang, Xie Jiamei, Zhao Yige, Yang Yang, Huang Zhiyun, Wan Anfeng, Zhao Ying, Zhao Baosheng
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
Int Immunopharmacol. 2025 May 27;156:114675. doi: 10.1016/j.intimp.2025.114675. Epub 2025 Apr 25.
Type 2 diabetes mellitus (T2DM), one of the prevalent chronic diseases, significantly impacts individuals and society. Xiasangju (XSJ), a herbal tea formulation, has been commonly used in traditional Chinese medicine. Accumulating evidence suggests that XSJ can alleviate metabolic syndrome by regulating glucose and lipid metabolism, lowering liver index and improving glucose tolerance. In the present study, db/db mice were used to examine the effect of XSJ on treating T2DM, and Western blotting was performed to explore the underlying anti-T2DM pharmacological mechanisms. With AMP-activated protein kinase (AMPK) chosen as the target protein, surface plasmon resonance (SPR)-LC-MS technology was used to identify potential active ingredients of XSJ. To further explore the role of potential active ingredients of XSJ, their effects were investigated in insulin resistance (IR)-HepG2 cells. Our results demonstrate that in diabetic db/db mice, XSJ activated the AMPK pathway, which regulated hepatic glucose metabolism and inhibited oxidative stress caused by hepatic NADPH oxidase 4 (NOX4), thereby ameliorating hepatic IR. By means of SPR-LC-MS experiments, 4-Methylesculetin was identified as an important active ingredient in XSJ. Subsequently, to further elucidate the effects of this ingredient, in IR-HepG2 cells, 4-Methylesculetin was found to mitigate oxidative stress, enhance glucose consumption, and promote glycogen synthesis. This study demonstrated that XSJ improved T2DM and mitigated oxidative stress by activating the AMPK pathway. Specifically, 4-Methylesculetin emerged as a promising therapeutic agent for T2DM.
2型糖尿病（T2DM）是一种常见的慢性疾病，对个人和社会都有重大影响。夏桑菊（XSJ）是一种草药茶配方，在传统中医中常用。越来越多的证据表明，夏桑菊可通过调节糖脂代谢、降低肝脏指数和改善糖耐量来缓解代谢综合征。在本研究中，使用db/db小鼠来研究夏桑菊治疗T2DM的效果，并进行蛋白质印迹法以探索其潜在的抗T2DM药理机制。选择AMP激活的蛋白激酶（AMPK）作为靶蛋白，采用表面等离子体共振（SPR）-液相色谱-质谱联用技术鉴定夏桑菊的潜在活性成分。为了进一步探索夏桑菊潜在活性成分的作用，在胰岛素抵抗（IR）-HepG2细胞中研究了它们的效果。我们的结果表明，在糖尿病db/db小鼠中，夏桑菊激活了AMPK通路，该通路调节肝脏葡萄糖代谢并抑制肝脏NADPH氧化酶4（NOX4）引起的氧化应激，从而改善肝脏IR。通过SPR-LC-MS实验，鉴定出4-甲基七叶亭为夏桑菊中的一种重要活性成分。随后，为了进一步阐明该成分的作用，在IR-HepG2细胞中发现4-甲基七叶亭可减轻氧化应激、增加葡萄糖消耗并促进糖原合成。本研究表明，夏桑菊通过激活AMPK通路改善T2DM并减轻氧化应激。具体而言，4-甲基七叶亭有望成为治疗T2DM的药物。
