AUTHOR=Saka W. A. , Oyekunle O. S. , Akhigbe T. M. , Oladipo O. O. , Ajayi M. B. , Adekola A. T. , Omole A. I. , Akhigbe R. E. TITLE=Andrographis paniculata improves glucose regulation by enhancing insulin sensitivity and upregulating GLUT 4 expression in Wistar rats JOURNAL=Frontiers in Nutrition VOLUME=Volume 11 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1416641 DOI=10.3389/fnut.2024.1416641 ISSN=2296-861X ABSTRACT=Context: Although the hypoglycaemic effect of Andrographis paniculata (Burm.f.) Nees [Acanthaceae] has been documented, reports on its effect in an apparently healthy state are limited.Objective: This study investigated whether or not A. paniculata exerts hypoglycaemic effect in a non-diabetic state. It also explored the impact of A. paniculata on glycolytic enzymes and GLUT 4 protein expression, as a possible mode of action.Methods: Twenty male Wistar rats were randomly assigned into two groups (n= 10 rats/group).The control rats were vehicle-treated (0.5 ml of distilled water), while the A. paniculata-treated rats had 500 mg/kg of A. paniculata per os once daily for thirty five days. Results: A. paniculata treatment led to improved insulin sensitivity evidenced by increased HOMA-β (88.08±2.13 vs. 120.80±1.52, p < 0.0001), HOMA-S (283.60±8.82 vs. 300.50±9.30, p = 0.0189), and reduced TyG index (4.22±0.04 vs. 3.95±0.07, p < 0.0002) and HOMA-IR (0.32±0.01 vs. 0.25±0.01, p < 0.0001) when compared with the control. It also improved glucose regulation as depicted by reduced fasting blood glucose (3.77±0.10 vs. 3.24±0.11, p < 0.0001) and glycated hemoglobin (HbA1c) (7.69±1.15 vs. 5.95±0.82, p = 0.0245), and atherogenic dyslipidaemia, including AIP (-0.12±0.03 vs. -0.26±0.03, p < 0.0001) and CRI-I (2.70±0.29 vs.1.84±0.27, p < 0.0001). These findings were accompanied by enhanced hepatic and muscular redox state, increased activities of glycolytic enzymes, upregulated GLUT 4 (0.80±0.27 vs. 6.20±0.84, p < 0.0001), and increased circulating nitric oxide (5.45±0.24 vs. 6.79±0.33, p = 0.0002).A. paniculata exerts positive effect on glucose metabolism and utilization by improving insulin sensitivity and upregulating the activities of glycolytic enzymes and GLUT 4 protein expression. This implies that A. paniculata may be beneficial in preventing insulin resistance and incident diabetes. Nonetheless, it should be used with caution to prevent hypoglycaemia in a non-diabetic state.