Department of Pharmacy, Qinghai University, Xining, Qinghai, 810001, China.
College of Animal Husbandry and Veterinary Science, Qinghai University, 810001, China.
J Ethnopharmacol. 2024 Oct 5;332:118341. doi: 10.1016/j.jep.2024.118341. Epub 2024 May 14.
The extracellular regulated protein kinase (ERK) plays a crucial role in the mitogen-activated protein kinase (MAPK) family, influencing apoptosis, proliferation, and differentiation. It connection to the insulin (INS) signaling cascade and the development of type 2 diabetes mellitus (T2DM) has been established. Rubus irritans Focke, an indispensable herb in Chinese Tibetan medicine for diabetes mellitus treatment, lacks a comprehensive understanding of its effects and pharmacological mechanisms in T2DM.
This study aimed to elucidate the effects of Rubus irritans Focke extract (Rife) on a T2DM rat model, exploring its impact on glycemic and lipid metabolism, histopathological changes, and its potential targeting of the extracellular regulated protein kinase/insulin receptor substrate-1 (ERK/IRS-1) signaling pathway.
A T2DM rat model was induced by streptozotocin (STZ) injection (40 mg/kg) in high-fat diet-fed (HFD) male Wistar rats. Rife and metformin (Met) were administered for 4 weeks, and glycemic, lipid metabolism indices, and histopathological changes were assessed. Protein expression of ERK, IRS-1 in rat liver tissues was examined to evaluate the impact on the ERK/IRS-1 pathway.
Rife reducing hepatic ERK and IRS-1 protein expression in T2DM rats. Untargeted metabolomics identified 13 potential biomarkers and 4 differential metabolic pathways related to glycolipid metabolism disorders.
Rife demonstrated improved glycolipid metabolism in T2DM rats by inhibiting the ERK/IRS-1 related signaling pathway and influencing multiple metabolic pathways. This study provides valuable insights into the potential therapeutic mechanisms of Rife in the context of T2DM.
细胞外调节蛋白激酶（ERK）在丝裂原活化蛋白激酶（MAPK）家族中发挥着关键作用，影响细胞凋亡、增殖和分化。它与胰岛素（INS）信号级联和 2 型糖尿病（T2DM）的发展之间的联系已经建立。悬钩子属植物是藏医治疗糖尿病不可或缺的草药，但对其在 T2DM 中的作用和药理机制仍缺乏全面了解。
本研究旨在阐明悬钩子属植物提取物（Rife）对 T2DM 大鼠模型的影响，探讨其对血糖和脂代谢的影响、组织病理学变化，以及其对细胞外调节蛋白激酶/胰岛素受体底物-1（ERK/IRS-1）信号通路的潜在靶向作用。
采用链脲佐菌素（STZ）（40mg/kg）注射联合高脂饮食（HFD）喂养雄性 Wistar 大鼠诱导 T2DM 大鼠模型。给予 Rife 和二甲双胍（Met）治疗 4 周，评估血糖、脂代谢指标和组织病理学变化。检测大鼠肝组织中 ERK、IRS-1 蛋白表达，评估对 ERK/IRS-1 通路的影响。
Rife 降低 T2DM 大鼠肝组织中 ERK 和 IRS-1 蛋白表达。非靶向代谢组学鉴定出 13 个与糖脂代谢紊乱相关的潜在生物标志物和 4 个差异代谢途径。
Rife 通过抑制 ERK/IRS-1 相关信号通路和影响多种代谢途径，改善 T2DM 大鼠的糖脂代谢。本研究为 Rife 治疗 T2DM 的潜在治疗机制提供了有价值的见解。
