Department of Medical Bioscience, University of the Western Cape, Bellville, Cape Town 7530, South Africa.
Biochemistry Unit, Department of Science Technology, The Federal Polytechnic P.M.B.5351, Ado Ekiti 360231, Ekiti State, Nigeria.
Molecules. 2021 Dec 28;27(1):155. doi: 10.3390/molecules27010155.
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 and B.L Burtt extract (AAHPE) using a 2-NBDG, 2-(-(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 IC 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 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.
糖尿病（DM）是一种慢性代谢性疾病，可导致全球范围内的严重并发症和高死亡率。目前正在加紧努力寻找和开发既有效又潜在安全的新型α-葡萄糖苷酶和α-淀粉酶抑制剂。传统方法正在被更简单、耗时更少的新技术所取代；然而，实验和计算策略在药物发现和开发中都是可行和互补的。因此，这项研究旨在使用 2-NBDG 和 2-（-（7-硝基苯并-2-氧代-1,3-二唑-4-基）氨基）-2-脱氧-D-葡萄糖摄取测定法，研究水丙酮和 B.L Burtt 提取物（AAHPE）的体外抗糖尿病潜力。此外，我们还对通过液相色谱-质谱（LC-MS）从 AAHPE 中鉴定和定量的黄酮类成分进行了分子对接，这些成分有可能成为有效和安全的α-淀粉酶和α-葡萄糖苷酶抑制剂，这在药物发现和开发中很重要。结果表明，AAHPE 是一种潜在的α-淀粉酶和α-葡萄糖苷酶抑制剂，其 IC 值分别为 46.50±6.17（µg/mL）和 37.81±5.15（µg/mL）。与对照相比，AAHPE 浓度依赖性地显著增加了葡萄糖摄取活性百分比，75µg/mL 的 AAHPE 葡萄糖摄取活性高于胰岛素抵抗 HepG2 细胞系中的标准抗糖尿病药物二甲双胍。分子对接结果显示，这些成分与α-淀粉酶和α-葡萄糖苷酶结合牢固，同时实现了更好的结合亲和力，范围从-7.2 到-9.6 kcal/mol（与阿卡波糖的-6.1 kcal/mol 相比）对于α-淀粉酶，和-7.3 到-9.0 kcal/mol（与阿卡波糖的-6.3 kcal/mol 相比）对于α-葡萄糖苷酶。这项研究揭示了植物提取物及其植物化学物质的潜在用途，这可能有助于开发有效的、安全的α-淀粉酶和α-葡萄糖苷酶抑制剂，以控制糖尿病患者餐后血糖水平。
