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山矾通过下调高能饮食大鼠模型中的脂肪生成和胰岛素抵抗来增强胰岛素敏感性。

Symplocos cochinchinensis enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in high energy diet rat model.

作者信息

Antu Kalathookunnel Antony, Riya Mariam Philip, Nair Anupama, Mishra Arvind, Srivastava Arvind K, Raghu Kozhiparambil Gopalan

机构信息

Agroprocessing and Natural Products Division, CSIR - National Institute for Interdisciplinary Science and Technology(NIIST), Thiruvananthapuram 695019, Kerala, India.

Division of Biochemistry, CSIR - Central Drug Research Institute(CDRI), Sector 10, Janakipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India.

出版信息

J Ethnopharmacol. 2016 Dec 4;193:500-509. doi: 10.1016/j.jep.2016.09.050. Epub 2016 Sep 27.

DOI:10.1016/j.jep.2016.09.050
PMID:27686268
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model.

MATERIALS AND METHODS

Experimental groups consisted of normal diet (ND), ND+SCE 500mg/kg bwd, HFS+vehicle, HFS+metformin 100mg/kg bwd, HFS+SCE 250/500mg/kg bwd. Initially the animals were kept under HFS diet for 8 weeks, and at the end of 8 week period, animals were found to develop insulin resistance and dyslipidemia. Post-administration of SCE, metformin or vehicle were carried out for 3 weeks. Gene and protein expressions relevant to insulin signalling pathway were analysed.

RESULTS

HFS significantly altered the normal physiology of animals via proteins and genes relevant to metabolism like stearoyl-CoA desaturase (SCD1), sterol regulatory element binding protein 1 (SREBP-1c), fatty acid synthase (FAS), glucose 6 phosphatase (G6Pase), phosphoenol pyruvate carboxykinase (PEPCK), glucose transporter 2 (GLUT2), protein tyrosine phosphatse 1B (PTP1B), peroxisome proliferator activated receptor alpha (PPAR alpha), sirtuin 1 (SIRT1) and glucokinase. SCE administration attenuates the insulin resistance in HFS rat by the down regulation of SCD1 gene expression that modulates SREBP-1c dependent and independent hepatic lipid accumulation.

CONCLUSION

SCE enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in HFS rat model.

摘要

民族药理学相关性

这种植物在印度医学体系中被用于治疗糖尿病。这在治疗糖尿病的阿育吠陀制剂“Nisakathakadi Kashayam”的成分中清晰可见,该植物是此制剂的主要成分之一。研究目的:本研究旨在使用高果糖和饱和脂肪(HFS)喂养的胰岛素抵抗大鼠模型,阐明山矾乙醇提取物(SCE)胰岛素增敏作用的分子机制。

材料与方法

实验组包括正常饮食(ND)组、ND + SCE 500mg/kg体重组、HFS + 赋形剂组、HFS + 二甲双胍100mg/kg体重组、HFS + SCE 250/500mg/kg体重组。最初,动物维持HFS饮食8周,在8周结束时,发现动物出现胰岛素抵抗和血脂异常。给予SCE、二甲双胍或赋形剂3周后,分析与胰岛素信号通路相关的基因和蛋白质表达。

结果

HFS通过与代谢相关的蛋白质和基因,如硬脂酰辅酶A去饱和酶(SCD1)、固醇调节元件结合蛋白1(SREBP - 1c)、脂肪酸合酶(FAS)、葡萄糖6磷酸酶(G6Pase)、磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖转运蛋白2(GLUT2)、蛋白酪氨酸磷酸酶1B(PTP1B)、过氧化物酶体增殖物激活受体α(PPARα)、沉默调节蛋白1(SIRT1)和葡萄糖激酶,显著改变动物的正常生理状态。给予SCE可通过下调调节SREBP - 1c依赖性和非依赖性肝脏脂质积累的SCD1基因表达,减轻HFS大鼠的胰岛素抵抗。

结论

在HFS大鼠模型中,SCE通过下调脂肪生成和胰岛素抵抗来增强胰岛素敏感性。

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