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荜茇多酚提取物通过上调胰岛素分泌和抑制 JNK 信号通路减轻糖尿病大鼠高血糖的作用。

Effect of Caesalpinia bonduc Polyphenol Extract on Alloxan-Induced Diabetic Rats in Attenuating Hyperglycemia by Upregulating Insulin Secretion and Inhibiting JNK Signaling Pathway.

机构信息

Faculty of Pharmaceutical Sciences, The University of Faisalabad, Faisalabad 38000, Pakistan.

Institutes of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad 38000, Pakistan.

出版信息

Oxid Med Cell Longev. 2020 Mar 17;2020:9020219. doi: 10.1155/2020/9020219. eCollection 2020.

Abstract

Caesalpinia bonduc has been used in herbal medicines for the treatment of a wide range of diseases from decades. The present study has explored the remedial potential and underlying mechanism of polyphenol extract of Caesalpinia bonduc in alloxanized diabetic rats. HPLC/MS analysis confirmed the presence of phenolics in considerable concentrations in Caesalpinia bonduc extract. Administration of different doses (250 and 500 mg/kg) of CPP extract to hyperglycemic rats for 8 weeks restored blood and serum glucose, insulin, glycosylated hemoglobin, leptin, amylin, and carbohydrate metabolizing enzymes level towards normal compared to alloxanized diabetic group. The effect of CPP extract on various genes such as Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 in insulin signaling pathway and Traf-4, Traf-6, and Mapk-8 in MAPK downstream JNK cascade was examined through qRT-PCR to access the core molecular mechanism involved in CPP-induced recovery of diabetes. Results have revealed that CPP extract reduced oxidative stress in pancreatic cells by restoring free radical scavenging potential, reducing the mRNA expression of Mapk-8, Traf-4, and Traf-6, and increasing the Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 expression ensuing regeneration of cells and subsequent insulin release from pancreas. The results obtained in this study recommend that CPP extract may be a promising therapeutic restorative agent in the treatment of diabetes mellitus.

摘要

罗望子多酚提取物对四氧嘧啶糖尿病大鼠的治疗作用及机制研究

几十年来,罗望子一直被用于草药医学,以治疗各种疾病。本研究探讨了罗望子多酚提取物对四氧嘧啶糖尿病大鼠的治疗潜力及其潜在机制。HPLC/MS 分析证实罗望子提取物中含有相当浓度的酚类物质。8 周内,不同剂量(250 和 500mg/kg)的 CPP 提取物给药于高血糖大鼠,可使血糖、血清胰岛素、糖化血红蛋白、瘦素、淀粉样蛋白和碳水化合物代谢酶水平恢复正常,与四氧嘧啶糖尿病组相比。通过 qRT-PCR 研究 CPP 提取物对胰岛素信号通路中各种基因(如 Pdx-1、Ins-1、ngn-3、GLUT-4 和 IRS-1)以及 MAPK 下游 JNK 级联中 Traf-4、Traf-6 和 Mapk-8 的影响,以评估 CPP 诱导糖尿病恢复所涉及的核心分子机制。结果表明,CPP 提取物通过恢复自由基清除能力,降低 Mapk-8、Traf-4 和 Traf-6 的 mRNA 表达,增加 Pdx-1、Ins-1、ngn-3、GLUT-4 和 IRS-1 的表达,减少胰腺β细胞的氧化应激,从而促进β细胞的再生和随后胰岛素的释放。本研究结果表明,CPP 提取物可能是治疗糖尿病的一种有前途的治疗恢复剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69a7/7103044/72b11c52b471/OMCL2020-9020219.001.jpg

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