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使君子调节葡萄糖代谢、胆碱能活动和 Nrf2 表达,同时抑制糖尿病大鼠的氧化应激和血脂异常。

Dacryodes edulis (G. Don) H.J. Lam modulates glucose metabolism, cholinergic activities and Nrf2 expression, while suppressing oxidative stress and dyslipidemia in diabetic rats.

机构信息

Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, (Westville Campus), Durban, 4000, South Africa; Department of Pharmacology, University of the Free State, Bloemfontein, 9300, South Africa.

Department of Human Anatomy, Federal University of Technology, Akure, Nigeria.

出版信息

J Ethnopharmacol. 2020 Jun 12;255:112744. doi: 10.1016/j.jep.2020.112744. Epub 2020 Mar 9.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Dacryodes edulis L. is an evergreen tree indigenous to western and eastern Africa which is utilized for nutritional and medicinal purposes. Folklorically, different parts of the tree are used in treating and managing diabetes and its complications.

AIMS

The antidiabetic effect of the butanol fraction of D. edulis ethanol extract (BFDE) was studied in fructose-streptozotocin induced type 2 diabetic rats.

METHODS

The ethanol extract was fractionated to yield the hexane, dichloromethane, ethyl acetate, butanol and aqueous fractions. The in vitro antidiabetic activities of the fractions were determined by their ability to inhibit α-glucosidase activity. BDFE was the most active and showed no cytotoxic effect while stimulating glucose uptake in 3T3-L1 adipocytes. Thus, selected for in vivo study. Diabetic rats were grouped into 4. The negative control group was administered water only, another group was treated with metformin (200 mg/kg bodyweight), while the other groups were administered BDFE at 150 and 300 mg/kg bodyweight respectively. Two other groups consisting of normal rats were given water and BFDE (300 mg/kg bodyweight) respectively, with the former serving as normal control. After 6 weeks of intervention, the rats were humanely sacrificed using appropriate anaesthesia.

RESULTS

Treatment with the fraction significantly (p < 0.05) reduced the blood glucose level of the diabetic rats, with concomitant increase in serum insulin secretion. It also caused significant (p < 0.05) elevation of reduced glutathione level, superoxide dismutase, catalase, α-amylase, and ATPase activities, with concomitant depletion in myeloperoxidase activity, NO and MDA levels of the serum and pancreas. The pancreatic morphology and β-cell function were significantly improved in BFDE-treated rats, with restoration of the pancreatic capillary networks. Treatment with BFDE significantly (p < 0.05) inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase, while suppressing the expression of Nrf2. HPLC analysis revealed the presence of gallic acid, vanillic acid, vanillin, and (-)-epicatechin in the fraction.

CONCLUSION

These results portray the antidiabetic and antioxidative properties of BFDE, which may be a synergistic consequence of the identified phenolics.

摘要

民族药理学相关性

非洲西部和东部的一种常绿树木,被称为非洲吊灯树,因其营养和药用价值而被使用。民间传说中,该树的不同部位可用于治疗和管理糖尿病及其并发症。

目的

研究吊灯树乙醇提取物的丁醇部分(BFDE)对果糖-链脲佐菌素诱导的 2 型糖尿病大鼠的抗糖尿病作用。

方法

将乙醇提取物进行分段,得到正己烷、二氯甲烷、乙酸乙酯、丁醇和水相部分。通过抑制α-葡萄糖苷酶活性来测定各部分的体外抗糖尿病活性。BFDE 是最活跃的,没有细胞毒性作用,同时刺激 3T3-L1 脂肪细胞摄取葡萄糖。因此,选择进行体内研究。将糖尿病大鼠分为 4 组。阴性对照组给予水,另一组给予二甲双胍(200mg/kg 体重),而其他两组分别给予 BFDE 150 和 300mg/kg 体重。另外两组正常大鼠分别给予水和 BFDE(300mg/kg 体重),前者作为正常对照。干预 6 周后,用适当的麻醉剂对大鼠进行安乐死。

结果

该部分的治疗显著降低了糖尿病大鼠的血糖水平(p<0.05),同时增加了血清胰岛素分泌。它还导致还原型谷胱甘肽水平、超氧化物歧化酶、过氧化氢酶、α-淀粉酶和 ATP 酶活性显著升高(p<0.05),同时使血清和胰腺中髓过氧化物酶活性、NO 和 MDA 水平显著降低。BFDE 治疗的大鼠胰腺形态和β细胞功能明显改善,恢复了胰腺毛细血管网络。BFDE 治疗显著抑制了糖原磷酸化酶、果糖 1,6-二磷酸酶、葡萄糖 6-磷酸酶和乙酰胆碱酯酶的活性,同时抑制了 Nrf2 的表达。HPLC 分析表明该部分含有没食子酸、香草酸、香草醛和(-)-表儿茶素。

结论

这些结果描绘了 BFDE 的抗糖尿病和抗氧化特性,这可能是鉴定出的酚类物质的协同结果。

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