In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

Diabetes mellitus (DM) is a chronic metabolic condition that can lead to significant complications and a high fatality rate worldwide. Efforts are ramping up to find and develop novel alpha-glucosidase and alpha-amylase inhibitors that are both effective and potentially safe. Traditional methodologies are being replaced with new techniques that are less complicated and less time demanding; yet, both the experimental and computational strategies are viable and complementary in drug discovery and development. As a result, this study was conducted to investigate the in vitro anti-diabetic potential of aqueous acetone Helichrysum petiolare and B.L Burtt extract (AAHPE) using a 2-NBDG, 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-d-glucose uptake assay. In addition, we performed molecular docking of the flavonoid constituents identified and quantified by liquid chromatography-mass spectrometry (LC-MS) from AAHPE with the potential to serve as effective and safe alpha-amylase and alpha-glucosidase inhibitors, which are important in drug discovery and development. The results showed that AAHPE is a potential inhibitor of both alpha-amylase and alpha-glucosidase, with IC50 values of 46.50 & PLUSMN; 6.17 (mu g/mL) and 37.81 & PLUSMN; 5.15 (mu g/mL), respectively. This is demonstrated by a significant increase in the glucose uptake activity percentage in a concentration-dependent manner compared to the control, with the highest AAHPE concentration of 75 mu g/mL of glucose uptake activity being higher than metformin, a standard anti-diabetic drug, in the insulin-resistant HepG2 cell line. The molecular docking results displayed that the constituents strongly bind alpha-amylase and alpha-glucosidase while achieving better binding affinities that ranged from & UDelta;G = -7.2 to -9.6 kcal/mol (compared with acarbose & UDelta;G = -6.1 kcal/mol) for alpha-amylase, and & UDelta;G = -7.3 to -9.0 kcal/mol (compared with acarbose & UDelta;G = -6.3 kcal/mol) for alpha-glucosidase. This study revealed the potential use of the H. petiolare plant extract and its phytochemicals, which could be explored to develop potent and safe alpha-amylase and alpha-glucosidase inhibitors to treat postprandial glycemic levels in diabetic patients.