In Vivo, In Vitro, And Molecular Evidence For The Antidiabetic And Antilipidemic Efficacy Of Salacia Reticulata Through AMPK– SREBP Pathway Regulation

Abstract

Background: Salacia reticulata (SRE) is a well-recognized traditional plant used in the management of diabetes and obesity. Although its antidiabetic activity is established, the combined effects on glucose regulation, lipid metabolism, and oxidative stress remain insufficiently elucidated. AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein-1c (SREBP-1c) are critical regulators of energy balance, and their modulation may explain the therapeutic actions of SRE. This study aimed to evaluate the phytochemical profile, antidiabetic efficacy, and metabolic effects of standardized ethanolic SRE using in vivo and in vitro models.

Methods: The extract was standardized for marker compounds (salacinol, kotalanol) and polyphenols. In vivo, streptozotocin (STZ)-induced diabetic Wistar rats were treated with SRE (200 mg/kg) for 28 days, and outcomes included fasting blood glucose, lipid profile, antioxidant markers, and pancreatic histopathology. Limited molecular analysis was performed by Western blotting of pancreatic tissues to assess AMPK activation and SREBP-1c expression. In vitro, cytocompatibility was evaluated in HepG2 hepatocytes and 3T3-L1 adipocytes (MTT assay). Functional assays included Oil Red O staining and triglyceride quantification in adipocytes, and Nile Red fluorescence in fatty acid–loaded hepatocytes.

Results: SRE retained its bioactive markers and was cytocompatible up to 100 µg/mL in cell culture models. In vivo, SRE significantly reduced fasting blood glucose, improved serum lipid profiles, restored antioxidant balance, and preserved pancreatic β-cell morphology, comparable to metformin. Western blot analysis confirmed activation of AMPK and down-regulation of SREBP-1c in pancreatic tissue. In vitro, SRE inhibited adipogenesis in 3T3-L1 adipocytes and reduced lipid accumulation in FFA-loaded HepG2 cells, indicating its role in suppressing lipogenesis.

Conclusion: SRE exerts potent antidiabetic and antihyperlipidemic effects by activating AMPK and repressing SREBP-1c, resulting in improved glucose regulation, enhanced antioxidant defense, and attenuation of lipid accumulation. These findings provide mechanistic support for the traditional use of S. reticulata and highlight its potential in the management of diabetes, obesity, and associated metabolic disorders.