Evaluation of Antihyperglycemic Effect of Pectolinarigenin in Experimentally Induced Type 2 Diabetes Mellitus in Rats

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease of insulin resistance with insufficient insulin secretion, in addition to chronic inflammation and impaired glucose metabolism. Finding new therapeutic uses of drugs that can target multiple pathways will serve an important role in disease management. The possible pharmacological effects of pectolinarigenin merit further investigation for its antidiabetic activity. Aim: Evaluation of the therapeutic impact of pectolinarigenin on the major molecular targets linked to T2DM via computational and experimental techniques. Methods: The interaction of pectolinarigenin with key T2DM targets was explored in silico using molecular docking simulations of Peroxisome Proliferator-Activated Receptor (PPAR), Dipeptidyl Peptidase 4 (DPP4) and Sulphonylurea Receptor 1 (SUR1). Animal Experimental Design: Animals (Sprague-Dawley male rats) were divided into five categories: normal, disease control, reference standard (glibenclamide), and pectolinarigenin at doses of 20 and 50 mg/kg, respectively (oral experiment). Different metabolic and biochemical parameters were measured over five weeks, including serum glucose fasting, insulin sensitivity, oxidative stress, inflammatory markers, lipid profiles, and HbA1c levels. Results: Docking analysis showed significant binding affinities of pectolinarigenin with diverse T2DM-associated targets, indicating its potential for multi-target therapy. Furthermore, treatment with pectolinarigenin improved glucose tolerance, markedly decreased fasting blood glucose levels, and increased insulin sensitivity in vivo compared to the disease control and reference standard groups. Compared to rats who received 50 mg/kg, rats who received 50 mg/kg and rats who lost a significant amount of weight had improved lipid profiles, maintained weight better, and had improved antioxidant defences and inflammation markers, as well as significantly lower HbA1c levels. These findings highlight the compound’s effectiveness for glycemic control and prevention of diabetes-related complications. Conclusion: Pectolinarigenin exhibited significant antidiabetic activity in both computational and experimental strategies, enhancing metabolic markers and alleviating inflammation. These findings underscore its potential as a therapeutic candidate for the treatment of diabetes. Additional research, including clinical trials, is needed to prove its effectiveness in people. Major Findings: Pectolinarigenin markedly enhanced glucose tolerance, insulin sensitivity, lipid profiles and oxidative stress parameters, with the 50 mg/kg dose-related effects being the most evident. This information further describes its potential for use as a novel antidiabetic agent and prevention of diabetes-related complications.