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

Rhinacanthin C ameliorates hyperglycaemia, hyperlipidemia and pancreatic destruction in streptozotocin-nicotinamide induced adult male diabetic rats
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DOI:
10.1016/j.ejphar.2015.12.028
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发表时间:
2016-01-15
影响因子:
5
通讯作者:
Salleh, Naguib
Salleh, Naguib
中科院分区:
医学2区
文献类型:
--
作者:
Adam, Siti Hajar;Giribabu, Nelli;Salleh, Naguib

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研究了菊黄素C对糖尿病高脂血症、高脂血症及胰腺功能障碍的影响。在3 T3-L1细胞系中研究了Rhinacanthin 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用5 mg/kg/天或20 mg/kg/天的Rhinacanthin C治疗28天的体内效果。治疗完成后,通过生化分析测量空腹血糖(FBG)、HbA 1c、胰岛素和血脂水平。光镜观察胰腺组织学变化,酶法测定胰腺氧化应激水平。免疫组化法检测胰腺组织中胰岛素、TNF α、Ikk β和caspase-3的表达。分子对接用于鉴定Rhinacathin C与SOD或GPx酶之间的相互作用。随着Rhinacathin C剂量的增加,观察到葡萄糖摄取的剂量依赖性增加。Rhinacanthin C治疗后,糖尿病大鼠血浆FBG、HbA 1c、血脂(LDL除外)和胰腺丙二醛水平均降低,而血清胰岛素和胰腺抗氧化酶(SOD、CAT和GPx)水平升高。在接受Rhinacanthin 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Glut-2水平较高,但TNF α、Ikk β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Rhinacathin C的糖尿病大鼠中,上述参数的变化未达到非糖尿病大鼠中的值。对接结果表明,Rhinacathin C与SOD和GPx具有高度的相互作用。通过具有这些作用,Rhinacanthin C可以用作减轻糖尿病胰腺和其他并发症的试剂。(C)2015 Elsevier B. V.版权所有。
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 5 mg/kg/day or 20 mg/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, TNF alpha, Ikk beta 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 TNF alpha, Ikk beta 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. (C) 2015 Elsevier B.V. All rights reserved.