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

Abstract

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 α-glucosidase and α-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 α-amylase and α-glucosidase inhibitors, which are important in drug discovery and development. The results showed that AAHPE is a potential inhibitor of both α-amylase and α-glucosidase, with IC50 values of 46.50 ± 6.17 (µg/mL) and 37.81 ± 5.15 (µg/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 µg/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 α-amylase and α-glucosidase while achieving better binding affinities that ranged from ΔG = −7.2 to −9.6 kcal/mol (compared with acarbose ΔG = −6.1 kcal/mol) for α-amylase, and ΔG = −7.3 to −9.0 kcal/mol (compared with acarbose ΔG = −6.3 kcal/mol) for α-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 α-amylase and α-glucosidase inhibitors to treat postprandial glycemic levels in diabetic patients.

Reaction Products of β-Aminopropioamidoximes Nitrobenzenesulfochlorination: Linear and Rearranged to Spiropyrazolinium Salts with Antidiabetic Activity

“…Essentially, the regulation of α-amylase and α-glucosidase biological functions (inhibition) is critical to the treatment regimen. This implies that new drug candidates with a potent inhibition of the α-glucosidase and α-amylase would be valuable to drug discovery and development for diabetes mellitus [ 30 ].…”

Helichrysum Genus and Compound Activities in the Management of Diabetes Mellitus

“…In the same study, it was also indicated that the extracts inhibited alpha-amylase and alpha-glucosidase activities in a dose-dependent manner as compared to the respective positive controls. In another study [ 86 ], the aqueous acetone extract of H. petiolare was shown to display an increased glucose uptake in HepG2 cells in a concentration-dependent manner and had moderate inhibitory effects against alpha-amylase and alpha-glucosidase activity compared to the acarbose, the positive control used in the study.…”

Bioactivity Guided Study for the Isolation and Identification of Antidiabetic Compounds from Edible Seaweed—Ulva reticulata

“…In vitro α-amylase and α-glucosidase inhibition study of isolated compounds and its active fraction (F4) was carried out, revealing active fraction (F4) showed the α-amylase (71.67%) and α-glucosidase (38.01%) inhibition at a concentration of 100 µg mL −1 as compared to the individual identified compounds. Carbohydrate-digesting enzymes αamylase and α-glucosidase are associated with postprandial hyperglycemia; as a result, inhibition of these major enzymes helps reduce glucose release and absorption in the small intestine [50].…”