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

Oluwafemi Omoniyi Oguntibeju,Okobi Eko Ekpo,Gail Denise Hughes,Habeebat Adekilekun Oyewusi,Kolajo Adedamola Akinyede

doi:10.3390/molecules27010155

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.

Highlights

Diabetes mellitus (DM) is a complex global public health condition and, after cancer and cardiovascular disease, is the third most common chronic and non-contagious disease [1]
A combined physicochemical, pharmacokinetics, drug-like properties, and molecular docking study was performed for α-amylase and α-glucosidase with anti-diabetic constituents of acetone extract of Helichrysum petiolare (AAHPE) to assess new potential therapeutic drug candidates
liquid chromatography-mass spectrometry (LC-mass spectrometer (MS))/MS analysis revealed phytochemicals or bioactive compounds, of which those with high concentrations were chosen for the molecular docking analysis

Summary

Introduction

Diabetes mellitus (DM) is a complex global public health condition and, after cancer and cardiovascular disease, is the third most common chronic and non-contagious disease [1]. Chronic hyperglycemia produces antioxidant imbalances in the body; treating DM requires exogenous antioxidants, notably flavonoids, which are bioactive components of many medicinal plants. Medicinal plants are the repository of many bioactive compounds; their excellent nutritional values and biological or pharmacological activities are mainly due to flavonoids [4]. Flavonoids are important bioactive plant compounds with a wide range of nutritional and health benefits as well as biological activities, such as anti-atherosclerosis, anti-inflammatory, anti-diabetic, neuroprotective, antioxidant, anti-proliferative, antimicrobial, and hepatoprotective [5,6,7,8,9,10] activities. The biological effects of flavonoids are due to their interactions with various proteins and enzymes, including cytochrome P450, laminin receptor, phospholipase A2, α-amylase, α-glucosidase [4], and many others. Flavonoids influence insulin production, insulin signaling, carbohydrate metabolism/digestion, and glucose absorption in insulin-sensitive tissues through a variety of intracellular signaling pathways [12,13]

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