ArticleApplied biochemistry and biotechnology2025
Multi Targeted Activity of Cocculus hirsutus through Modulation of DPP-IV and PTP-1B Leading to Enhancement of Glucose Uptake and Attenuation of Lipid Accumulation.
Article in Applied biochemistry and biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Multi-targeted therapies are gaining attention in the management of multifactorial diseases due to their poly pharmacology, enhanced potency and reduced toxicity. Metabolic disorders like Type 2 diabetes mellitus (T2DM) and obesity necessitate multi-targeted therapy to improve insulin sensitivity, regulate glucose homeostasis and support weight loss. Medicinal plants rich in bioactive compounds exhibit multi-targetted action with minimal side effects. In the current study, Cocculus hirsutus methanol extract (CME) and its hydromethanolic fraction (HMF) were investigated for their multi-target potential. Significant inhibition of Dipeptidyl peptidase IV (DPP-IV), a key enzyme in glucose metabolism was observed due to CME (54%) and HMF (70%) at 10 µg/ml and 1 µg/ml respectively. Protein Tyrosine Phosphatase 1B (PTP-1B), involved in the regulation of insulin signalling, was also inhibited by CME (67%) and HMF (73%) at 10 µg/ml concentration. An increase in glucose uptake was observed due to CME (62% and 65%) and HMF (63% and 68%) in 3T3-L1 adipocytes and L6 myotubes at 100 ng/ml. Further, investigation of HMF showed a decrease in lipid accumulation by 63% at 1 µg/ml in 3T3-L1 cells. Interestingly, HMF improved insulin sensitivity by upregulating GLUT4 expression (p < 0.05) via the PI3K/AKT pathway in both 3T3-L1 adipocytes and L6 myotubes. An inhibition in lipid accumulation was also observed by suppression of Peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.05), a key regulator of adipogenesis in 3T3-L1 adipocytes. Gas chromatography-mass spectrometry analysis of the HMF showed the major component to be 3-methylmannoside (26.52%).
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