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基于植物的生物活性化合物作为胰高血糖素样肽-1分泌刺激剂的治疗潜力的生化研究

Biochemical Investigation of Therapeutic Potentials of Plant-Based Bioactive Compounds as Stimulators of Glucagon like peptide-1 Secretion.

作者信息

Javed Areeba, Muzammal Ayman, Akash Muhammad Sajid Hamid, Rehman Kanwal

机构信息

Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan.

Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan.

出版信息

Dose Response. 2022 Jul 8;20(3):15593258221114184. doi: 10.1177/15593258221114184. eCollection 2022 Jul-Sep.

Abstract

This study was aimed to investigate the therapeutic potentials of plant-based bioactive compounds; lutein and resveratrol alone and/or in combination with DPP-4 enzyme inhibitor; sitagliptin on the secretion and bioavailability of Glucagon like peptide-1(GLP). For this, experimental rats were divided into seven groups. Group 1 was marked as control, while other six groups received streptozotocin (60 mg/kg I.P.). Later, group 2 was kept disease-control. While group 3 received 10 mg/kg/day sitagliptin (DDP-4i). Group 4 received 40 mg/kg/day lutein (LUT) and group 5 received 30 mg/kg/day resveratrol (RES). While group 6 and 7 were received combination of DPP-4i+LUT and DPP-4i+RES, respectively. Combined administration of DPP-4i+LUT or DPP-4i+RES showed expected therapeutic effects by lowering the fasting blood glucose and maintaining the serum insulin concentrations with improved glucose sensitivity and reduced insulin resistance. Further, co-administration of LUT and RES with DPP-4i revealed beneficial effects on measures of insulin resistance, circulating lipids, glycemic index, oxidative stress, and inflammatory status along with restoration of histological morphology of pancreatic cells and enterocytes that seemed to improve the level of GLP-1. Hence, substantial verdicts of this study showing therapeutic potentials of LUT and RES would surely help to recognize the potential effects in combination with DPP-4i as stimulators of GLP-1 secretion.

摘要

本研究旨在探讨植物源性生物活性化合物叶黄素和白藜芦醇单独及/或与二肽基肽酶-4(DPP-4)酶抑制剂西他列汀联合使用对胰高血糖素样肽-1(GLP)分泌和生物利用度的治疗潜力。为此,将实验大鼠分为七组。第1组标记为对照组,而其他六组接受链脲佐菌素(60mg/kg腹腔注射)。之后,第2组作为疾病对照组。第3组接受10mg/kg/天的西他列汀(DDP-4i)。第4组接受40mg/kg/天的叶黄素(LUT),第5组接受30mg/kg/天的白藜芦醇(RES)。第6组和第7组分别接受DPP-4i+LUT和DPP-4i+RES的联合用药。DPP-4i+LUT或DPP-4i+RES的联合给药通过降低空腹血糖和维持血清胰岛素浓度,显示出预期的治疗效果,同时提高了葡萄糖敏感性并降低了胰岛素抵抗。此外,LUT和RES与DPP-4i的联合给药对胰岛素抵抗、循环脂质、血糖指数、氧化应激和炎症状态的指标显示出有益作用,同时恢复了胰腺细胞和肠上皮细胞的组织形态学,这似乎提高了GLP-1的水平。因此,本研究的大量结论表明LUT和RES的治疗潜力,肯定有助于认识到它们与DPP-4i联合作为GLP-1分泌刺激剂的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f25/9272481/27a43434ce80/10.1177_15593258221114184-fig1.jpg

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