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沙枣(Elaeagnus umbellata(Thunb.))的植物化学分析及在链脲佐菌素诱导的糖尿病大鼠中的抗糖尿病潜力:药理学和计算方法。

Phytochemical analysis and antidiabetic potential of Elaeagnus umbellata (Thunb.) in streptozotocin-induced diabetic rats: pharmacological and computational approach.

机构信息

Department of Chemistry, University of Malakand, Chakdara Dir (L), Khyber Pakhtunkhwa, Pakistan.

Department of Botany, University of Malakand, Chakdara Dir (L), Khyber Pakhtunkhwa, Pakistan.

出版信息

BMC Complement Altern Med. 2018 Dec 13;18(1):332. doi: 10.1186/s12906-018-2381-8.

Abstract

BACKGROUND

The fruit of Elaeagnus umbellata has high medicinal values and is an excellent source of phytochemicals. This study was aimed to evaluate the antioxidant, enzyme inhibitory and antidiabetic potential of Elaeagnus umbellata.

METHODS

The antioxidant potential of the crude extract and subfractions of E. umbellata fruit were determined using DPPH (2, 20-diphenyl-1-picrylhydrazyl) and ABTS (2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) assays. The enzyme inhibitory potentials of extracts against α-amylase and α-glucosidase enzymes were also determined. The in vivo anti-hyperglycemic effects of the extract in STZ-induced type 2 diabetes were determined using Sprague Dawley adult rats. HPLC system (Agilent 1260) was used for the identification of bioactive compounds present in extracts. Molecular docking was used to identify and compare the interaction between the compounds (active constituents) and standard inhibitor acarbose with the α-amylase and α-glucosidase active sites.

RESULTS

The chloroform, ethyl acetate, and butanol fractions showed significant antioxidant potential with IC values of 40, 45 and 60 μg/mL against DPPH and 57, 70 and 120 μg/mL against ABTS free radicals respectively. The chloroform and ethyl acetate were highly active against α-amylase and α-glucosidase (IC values 58 and 200 μg/ml against α-amylase 60 and 140 μg/ml against α-glucosidase. The crude extract, chloroform, and ethyl acetate fractions were more potent in controlling the hyperglycemia in STZ-induced type 2 diabetes in rats and considerable reduction of glucose level was observed compared to the non-treated group. Furthermore, the extracts were also found useful in controlling the secondary complications associated with type 2 diabetes mellitus which was evident from the observed substantial reduction in the blood level of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, total cholesterol, low-density lipoproteins, and triglycerides. The molecular docking approach indicated the favorable inhibitory interaction between the docked compounds and the active sites of the α-amylase and α-glucosidase. All docked compounds occupied the same binding site as occupied by acarbose.

CONCLUSION

It was concluded that E. umbellata can be used in the treatment of type 2 diabetes and oxidative stress. The extracts were also found to be effective in relieving the secondary complications associated with type 2 diabetes.

摘要

背景

沙棘果具有很高的药用价值,是植物化学物质的极好来源。本研究旨在评估沙棘果的抗氧化、酶抑制和抗糖尿病潜力。

方法

使用 DPPH(2,20-二苯基-1-苦基肼)和 ABTS(2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸)测定沙棘果粗提取物和各馏分的抗氧化潜力。还测定了提取物对α-淀粉酶和α-葡萄糖苷酶的酶抑制潜力。使用 Sprague Dawley 成年大鼠测定提取物在 STZ 诱导的 2 型糖尿病中的体内降血糖作用。使用高效液相色谱系统(Agilent 1260)鉴定提取物中存在的生物活性化合物。使用分子对接来鉴定和比较化合物(活性成分)与标准抑制剂阿卡波糖与α-淀粉酶和α-葡萄糖苷酶活性位点的相互作用。

结果

氯仿、乙酸乙酯和正丁醇馏分对 DPPH 的 IC 值分别为 40、45 和 60μg/mL,对 ABTS 自由基的 IC 值分别为 57、70 和 120μg/mL,表现出显著的抗氧化潜力。氯仿和乙酸乙酯对α-淀粉酶和α-葡萄糖苷酶的活性很高(IC 值分别为 58 和 200μg/ml 对α-淀粉酶,60 和 140μg/ml 对α-葡萄糖苷酶)。与未处理组相比,粗提物、氯仿和乙酸乙酯馏分在控制 STZ 诱导的 2 型糖尿病大鼠高血糖方面更有效,观察到葡萄糖水平显著降低。此外,提取物还可有效控制 2 型糖尿病相关的继发性并发症,这从观察到的血清谷氨酸草酰乙酸转氨酶、血清谷氨酸丙酮酸转氨酶、碱性磷酸酶、总胆固醇、低密度脂蛋白和甘油三酯的血液水平显著降低中可以看出。分子对接方法表明,对接化合物与α-淀粉酶和α-葡萄糖苷酶的活性位点之间存在有利的抑制相互作用。所有对接的化合物都占据了与阿卡波糖相同的结合位点。

结论

综上所述,沙棘果可用于治疗 2 型糖尿病和氧化应激。提取物还可有效缓解 2 型糖尿病相关的继发性并发症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4e8/6293591/a38ac55a9551/12906_2018_2381_Fig1_HTML.jpg

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