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治疗来自M. Bieb的高血糖症:-α-葡萄糖苷酶、抗氧化剂、抗糖尿病及基于分子对接的方法

Treating Hyperglycemia From M. Bieb: - α-Glucosidase, Antioxidant, Antidiabetic and Molecular Docking-Based Approaches.

作者信息

Sadiq Abdul, Rashid Umer, Ahmad Sadiq, Zahoor Mohammad, AlAjmi Mohamed F, Ullah Riaz, Noman Omar M, Ullah Farhat, Ayaz Muhammad, Khan Iftikhar, Islam Zia-Ul, Ali Waqar

机构信息

Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, Pakistan.

Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.

出版信息

Front Chem. 2020 Nov 26;8:558641. doi: 10.3389/fchem.2020.558641. eCollection 2020.

Abstract

Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature of , we have evaluated its antidiabetic and antioxidant potentials. Both and assays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (HO)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract of (Ec.Cr) and its sub-fractions [i.e., -hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC of 437 μg/ml in comparison to the standard acarbose (IC 25 μg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC values recorded for Ec.Chf were 112, 109, and 150 μg/ml against DPPH, ABTS, and HO respectively. Based on the potential of Ec.Chf, this was subjected to the model experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 μg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude that is a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction of into active sites of the homology model of α-glucosidase.

摘要

基于天然的药物被认为是安全、有效且经济的。鉴于刺芹属植物的药用重要性以及其未被探索的特性,我们评估了其抗糖尿病和抗氧化潜力。已进行了α - 葡萄糖苷酶抑制试验和抗氧化试验来测定其抗糖尿病能力。通过使用不同的自由基[即1,1 - 二苯基 - 2 - 苦基肼(DPPH)、2,2 - 联氮 - 双 - (3 - 乙基苯并噻唑啉 - 6 - 磺酸)(ABTS)和过氧化氢(H₂O₂)]来测定抗氧化活性。此外,通过气相色谱 - 质谱联用(GC - MS)分析在活性最高的溶剂馏分中鉴定出了不同的植物成分。此外,还通过高效液相色谱 - 二极管阵列检测器(HPLC - DAD)分析了甲醇提取物和氯仿馏分的比较指纹图谱。本研究采用了刺芹的粗甲醇提取物(Ec.Cr)及其亚馏分[即正己烷(Ec.Hex)、氯仿(Ec.Chf)、乙酸乙酯(Ec.EtAc)和水相(Ec.Aq)]。在α - 葡萄糖苷酶抑制试验中,观察到对该酶的浓度依赖性抑制反应。活性最高的样品是Ec.Chf,与标准阿卡波糖(IC₅₀ 25 μg/ml)相比,其IC₅₀为437 μg/ml。其余样品对α - 葡萄糖苷酶表现出中度抑制作用。在抗氧化试验中,Ec.Chf和Ec.Cr对所有自由基都表现出显著的清除作用。Ec.Chf对DPPH、ABTS和H₂O₂的IC₅₀值分别为112、109和150 μg/ml。基于Ec.Chf的潜力,对其进行了体内模型实验。Ec.Chf在500 μg/Kg时可使血糖水平降低至10.3 mmol/L。对Ec.Chf也进行了GC - MS分析。GC - MS分析证实存在60种化合物。鉴定出的植物成分包括一些先前在抗糖尿病和抗氧化研究中报道过的重要化合物,其中包括百里香酚、生育酚、叶绿醇、橙花叔醇、(I)- 新植二烯、亚麻酸和镰叶芹醇。同样,Ec.Cr和Ec.Chf的HPLC - DAD色谱图显示出各种峰,这进一步证明了重要植物化学物质存在的可能性。简而言之,我们可以得出结论,刺芹是生物活性化合物的潜在来源,可能对糖尿病等疾病以及自由基介导的疾病的管理有益。进行了分子对接以探索刺芹氯仿馏分中所有鉴定出的生物活性化合物在α - 葡萄糖苷酶同源模型活性位点中的可能作用。

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