Yang Qiyue, Luo Qiwei, Xia Wenrui, Yao Nairong, Wang Fang, Xie Chunguang, Zhang Haiyan, He Yanan
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, PR China.
National Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, PR China.
J Ethnopharmacol. 2025 Jan 31;340:119286. doi: 10.1016/j.jep.2024.119286. Epub 2024 Dec 24.
Yi-guan-jian decoction (YGJ) is a traditional Chinese medicine prescription commonly used for treating syndromes associated with Yin deficiency in the liver and kidney, as well as Qi-obstructed in liver.
YGJ has shown potential alleviating cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the precise mechanisms are not yet fully understood. This study aims to reveal the mechanism by which YGJ alleviates cognitive dysfunction in T2DM.
Various doses of YGJ were administered to T2DM rats with cognitive dysfunction for 8 weeks. The positive control group received a combination of metformin and memantine. Cognitive function was assessed in T2DM rats using the Morris water maze test during treatment. Changes in gut microbiota and bile acids in the intestine were evaluated, and their interactions analyzed. Additionally, this study also evaluated the expressions of inflammatory markers (IL-1β,TNF-α, IL-16, IL-18 and CRP protein), Tau protein, neurotransmitter (5-HT and GABA), and bile acid receptor (FXR, PXR, VDR, and TGR5).
YGJ significantly alleviated insulin resistance and hyperlipidemia, reduce the levels of inflammatory factors in serum and hippocampus, and decreased mortality in T2DM rats. The Morris water maze test indicated that YGJ reduced the escape latency and increased platform crossing frequency, thereby improving cognitive function in T2DM rats. Furthermore, YGJ regulated the abundance of microorganisms associated with bile acid metabolism, including Romboutsia, Bacteroides, Turicibacter, Blautia, and Ruminococcus, thus regulating bile acid metabolism in T2DM rats. Additionally, YGJ also regulated bile acid metabolism by regulating intestinal FXR, PXR, VDR and TRG5 receptors.
YGJ can alleviate glucose homeostasis, insulin sensitivity, lipid metabolism, neuroinflammation, cognitive function, as well as remodel intestinal flora and BA composition in CDT2DM rats, which is a potential complementary and alternative therapy for the prevention and treatment of CDT2DM. These effects may be associated that YGJ regulates the structure of intestinal flora and BA metabolism, and inhibits intestinal BA receptors FXR, PXR, TGR5, and VDR.
一贯煎（YGJ）是一种传统中药方剂，常用于治疗肝肾阴虚以及肝郁气滞相关的证候。
YGJ已显示出缓解2型糖尿病（T2DM）认知功能障碍的潜力。然而，确切机制尚未完全明确。本研究旨在揭示YGJ缓解T2DM认知功能障碍的机制。
将不同剂量的YGJ给予患有认知功能障碍的T2DM大鼠，持续给药8周。阳性对照组给予二甲双胍和美金刚的组合。在治疗期间，使用Morris水迷宫试验评估T2DM大鼠的认知功能。评估肠道微生物群和肠道胆汁酸的变化，并分析它们之间的相互作用。此外，本研究还评估了炎症标志物（IL-1β、TNF-α、IL-16、IL-18和CRP蛋白）、Tau蛋白、神经递质（5-HT和GABA）以及胆汁酸受体（FXR、PXR、VDR和TGR5）的表达。
YGJ显著减轻胰岛素抵抗和高脂血症，降低血清和海马中的炎症因子水平，并降低T2DM大鼠的死亡率。Morris水迷宫试验表明，YGJ缩短了逃避潜伏期并增加了穿越平台的频率，从而改善了T2DM大鼠的认知功能。此外，YGJ调节了与胆汁酸代谢相关的微生物丰度，包括罗姆布茨菌属、拟杆菌属、Turicibacter、布劳特氏菌属和瘤胃球菌属，从而调节T2DM大鼠的胆汁酸代谢。此外，YGJ还通过调节肠道FXR、PXR、VDR和TRG5受体来调节胆汁酸代谢。
YGJ可以改善CDT2DM大鼠的葡萄糖稳态、胰岛素敏感性、脂质代谢、神经炎症、认知功能，以及重塑肠道菌群和胆汁酸组成，是预防和治疗CDT2DM的一种潜在的补充和替代疗法。这些作用可能与YGJ调节肠道菌群结构和胆汁酸代谢，并抑制肠道胆汁酸受体FXR、PXR、TGR5和VDR有关。
