Modulation of glycolipid metabolism in T2DM rats by Rubus irritans Focke extract: Insights from metabolic profiling and ERK/IRS-1 signaling pathway

• Published in: Journal of ethnopharmacology 2024-10, Vol.332, p.118341, Article 118341
• Main Authors: Han, Yongxia, Zhang, Zonghao, Song, Qingyun, Sun, Shengnan, Li, Wenyuan, Yang, Fang, Tong, Li
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Glucolipid metabolism; Glycolipids - pharmacology; Hypoglycemic Agents - pharmacology; Insulin Receptor Substrate Proteins - metabolism; Lipid Metabolism - drug effects; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; MAP Kinase Signaling System - drug effects; Plant Extracts - pharmacology; Rats; Rats, Wistar; Rubus irritans Focke extract; Signal Transduction - drug effects; Streptozocin; T2DM; Untargeted metabolomics
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118341

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. [Display omitted] •Rubus irritans Focke extract ameliorates glycolipid metabolism in T2DM rats.•Metabolomic analysis reveals distinct metabolic profiles influenced by the Rubus irritans Focke extract.•ERK/IRS-1 signaling pathway modulation contributes to improved insulin sensitivity.•First identification of key bioactive components group on prevention of diabetes in Rubus irritans Focke extract.