Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang, 712083, China; Department of Pharmacology, Shaanxi University of Chinese Medicine & Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine & Engineering Research Center of Brain Health Industry of Chinese Medicine, Universities of Shaanxi Province, Xianyang, 712046, China.
Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang, 712083, China; Department of Pharmacology, Shaanxi University of Chinese Medicine & Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine & Engineering Research Center of Brain Health Industry of Chinese Medicine, Universities of Shaanxi Province, Xianyang, 712046, China.
J Ethnopharmacol. 2024 Jun 12;327:118045. doi: 10.1016/j.jep.2024.118045. Epub 2024 Mar 11.
Yunvjian (YNJ), a traditional Chinese herbal formula first reported in Jing Yue Quan Shu, is commonly used in the clinical treatment of type 2 diabetes mellitus (T2DM). However, the mechanism by which YNJ affects T2DM remains unclear.
This study aimed to assess the therapeutic effects of YNJ on T2DM and explore the potential mechanism involved.
High-performance liquid chromatography (HPLC) was used to identify the chemical compounds of YNJ. The anti-T2DM effects of YNJ were observed in a high-fat diet/streptozotocin induced rat model. The type 2 diabetic rats were prepared as follows: rats were fed a high-fat diet for four weeks and then intraperitoneally injected with a low dose (30 mg/kg) of streptozotocin. YNJ and the positive control metformin were used in these experiments. Biochemical assays were implemented to determine the fasting blood glucose, glucose tolerance, insulin sensitivity, serum lipid levels, and oxidative stress index of the pancreas. Hematoxylin-eosin (H&E) staining was used to assess histopathological alterations in the pancreas. The mechanism by which YNJ affects T2DM was evaluated in INS-1 cells treated with glucose and high sodium palmitate. YNJ-supplemented serum was used in these experiments. Methyl thiazolyl tetrazolium assays, enzyme-linked immunosorbent assays, Nile red staining, flow cytometric analysis, and Western blotting were used to assess apoptosis, insulin secretion, lipid accumulation, reactive oxygen species production, and protein levels.
Five major compounds were identified in YNJ. In high-fat diet/streptozotocin-induced diabetic rats, YNJ-M notably decreased fasting blood glucose and lipid levels; ameliorated glucose tolerance, insulin sensitivity, and islet morphology; reduced Malondialdehyde levels; and restored superoxide dismutase activity in the pancreatic islets. Furthermore, the effect of YNJ-M was significantly greater than that of YNJ-L, and YNJ-H had little effect on diabetic rats. In vitro experiments revealed that YNJ-supplemented serum (10%, 15%, and 20%) dramatically suppressed apoptosis, mitigated intracellular lipid accumulation and reduced intracellular oxidative stress levels in a dose-dependent manner. Additionally, YNJ-supplemented serum increased the protein expression of Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, and superoxide dismutase 1 and inhibited the protein expression of Kelch-like ECH-associated protein 1.
YNJ ameliorates high-fat diet/streptozotocin induced experimental T2DM. The underlying mechanism involves reducing oxidative stress in pancreatic beta cells. The findings of this study provide scientific justification for the application of the traditional medicine YNJ in treating T2DM.
云堇（YNJ）是一种中药复方，最早见于《景岳全书》，常用于临床治疗 2 型糖尿病（T2DM）。然而，YNJ 影响 T2DM 的机制尚不清楚。
本研究旨在评估 YNJ 对 T2DM 的治疗效果，并探讨其潜在机制。
采用高效液相色谱法（HPLC）鉴定 YNJ 的化学成分。采用高脂饮食/链脲佐菌素诱导的大鼠模型观察 YNJ 的抗 T2DM 作用。将 2 型糖尿病大鼠制备如下：大鼠高脂饮食喂养 4 周，然后腹腔注射低剂量（30mg/kg）链脲佐菌素。YNJ 和阳性对照二甲双胍用于这些实验。进行生化测定以确定空腹血糖、葡萄糖耐量、胰岛素敏感性、血清脂质水平和胰腺氧化应激指数。苏木精-伊红（H&E）染色评估胰腺组织病理学改变。采用葡萄糖和高浓度软脂酸钠处理的 INS-1 细胞评价 YNJ 影响 T2DM 的机制。这些实验中使用了添加 YNJ 的血清。采用噻唑蓝比色法、酶联免疫吸附测定、尼罗红染色、流式细胞术分析和 Western blot 法评估细胞凋亡、胰岛素分泌、脂质积累、活性氧产生和蛋白水平。
YNJ 中鉴定出 5 种主要化合物。在高脂饮食/链脲佐菌素诱导的糖尿病大鼠中，YNJ-M 显著降低空腹血糖和血脂水平；改善葡萄糖耐量、胰岛素敏感性和胰岛形态；降低丙二醛水平；并恢复胰腺胰岛中超氧化物歧化酶的活性。此外，YNJ-M 的作用明显强于 YNJ-L，而 YNJ-H 对糖尿病大鼠几乎没有作用。体外实验表明，YNJ 补充血清（10%、15%和 20%）可显著抑制细胞凋亡，减轻细胞内脂质积累，并以剂量依赖性方式降低细胞内氧化应激水平。此外，YNJ 补充血清增加核因子红细胞 2 相关因子 2、血红素加氧酶-1 和超氧化物歧化酶 1 的蛋白表达，并抑制 Kelch 样 ECH 相关蛋白 1 的蛋白表达。
YNJ 改善了高脂饮食/链脲佐菌素诱导的实验性 2 型糖尿病。其作用机制涉及降低胰腺β细胞的氧化应激。本研究结果为传统药物 YNJ 治疗 2 型糖尿病提供了科学依据。
