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犀牛刺素C改善链脲佐菌素-烟酰胺诱导的成年雄性糖尿病大鼠的高血糖、高血脂和胰腺损伤。

Rhinacanthin C ameliorates hyperglycaemia, hyperlipidemia and pancreatic destruction in streptozotocin-nicotinamide induced adult male diabetic rats.

作者信息

Adam Siti Hajar, Giribabu Nelli, Rao Pasupuleti Visweswara, Sayem Abu Sadat Md, Arya Aditya, Panichayupakaranant Pharkphoom, Korla Praveen Kumar, Salleh Naguib

机构信息

Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Faculty of Agro Based Industry, University Malaysia Kelantan, Campus Jeli, Locked Bag No. 100, 17600 Jeli, Kelantan, Malaysia.

出版信息

Eur J Pharmacol. 2016 Jan 15;771:173-90. doi: 10.1016/j.ejphar.2015.12.028. Epub 2015 Dec 17.

Abstract

Effect of Rhinacanthin C on hyperglycaemia, hyperlipidemia and pancreatic dysfunction in diabetes was investigated. In-vitro effect of Rhinacanthin C on glucose uptake was studied in 3T3-L1 cell line. Meanwhile, in-vivo effect of 28-days treatment with 5mg/kg/day or 20mg/kg/day Rhinacanthin C was studied in streptozotocin-nicotinamide induced male diabetic rats. Following completion of treatment, fasting blood glucose (FBG), HbA1c, insulin and lipid profile levels were measured by biochemical assays. Histopathological changes in pancreas were observed by light microscopy while levels of pancreatic oxidative stress were determined by enzymatic assays. Expression of insulin, TNFα, Ikkβ and caspase-3 in pancreas were quantified by immunohistochemistry. Molecular docking was used to identify interactions between Rhinacathin C with SOD or GPx enzymes. Dose-dependent increase in glucose uptake was observed with increasing doses of Rhinacathin C. Plasma FBG, HbA1c and lipid profile except LDL levels and pancreatic malonaldehyde level were reduced but serum insulin and pancreatic anti-oxidative enzymes (SOD, CAT and GPx) levels were increased in diabetic rats receiving Rhinacanthin C treatment. Decreased pancreatic histopathological changes with higher pancreatic insulin and Glut-2 levels but lower TNFα, Ikkβ and caspase-3 levels were observed in diabetic rats receiving Rhinacanthin C (P<0.05 compared to non-treated diabetic rats). In diabetic rats which received Rhinacathin C, changes in the above parameters did not achieve the value in non-diabetic rats. Docking shows Rhinacathin C possesses high degree interactions with SOD and GPx. By possessing these effects, Rhinacanthin C could be used as agent to alleviate pancreatic and other complications in diabetes.

摘要

研究了匙羹藤新苷C对糖尿病患者高血糖、高血脂和胰腺功能障碍的影响。在3T3-L1细胞系中研究了匙羹藤新苷C对葡萄糖摄取的体外作用。同时,在链脲佐菌素-烟酰胺诱导的雄性糖尿病大鼠中研究了每天5mg/kg或20mg/kg匙羹藤新苷C治疗28天的体内作用。治疗结束后,通过生化分析测量空腹血糖(FBG)、糖化血红蛋白(HbA1c)、胰岛素和血脂水平。通过光学显微镜观察胰腺的组织病理学变化,同时通过酶法测定胰腺氧化应激水平。通过免疫组织化学定量胰腺中胰岛素、肿瘤坏死因子α(TNFα)、IκB激酶β(Ikkβ)和半胱天冬酶-3(caspase-3)的表达。采用分子对接技术鉴定匙羹藤新苷C与超氧化物歧化酶(SOD)或谷胱甘肽过氧化物酶(GPx)之间的相互作用。随着匙羹藤新苷C剂量的增加,观察到葡萄糖摄取呈剂量依赖性增加。接受匙羹藤新苷C治疗的糖尿病大鼠血浆FBG、HbA1c和除低密度脂蛋白(LDL)水平外的血脂水平降低,胰腺丙二醛水平降低,但血清胰岛素和胰腺抗氧化酶(SOD、过氧化氢酶(CAT)和GPx)水平升高。在接受匙羹藤新苷C的糖尿病大鼠中,观察到胰腺组织病理学变化减少,胰腺胰岛素和葡萄糖转运蛋白2(Glut-2)水平较高,但TNFα、Ikkβ和caspase-3水平较低(与未治疗的糖尿病大鼠相比,P<0.05)。在接受匙羹藤新苷C的糖尿病大鼠中,上述参数的变化未达到非糖尿病大鼠的值。对接显示匙羹藤新苷C与SOD和GPx具有高度相互作用。通过具有这些作用,匙羹藤新苷C可作为缓解糖尿病胰腺及其他并发症的药物。

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