A dipyrrole derivative from Aloe vera inhibits an anti-diabetic drug target Dipeptidyl Peptidase (DPP)-IV in vitro
A dipyrrole derivative from Aloe vera inhibits an anti-diabetic drug target Dipeptidyl Peptidase (DPP)-IV in vitro
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芦荟的二吡咯衍生物在体外抑制抗糖尿病药物靶标二肽基肽酶 (DPP)-IV
DOI：
10.1080/10826068.2019.1710712
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发表时间：
2020
影响因子：
2.9
通讯作者：
Krishnan Venkataraman
中科院分区：
文献类型：
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作者：
C. Prasannaraja;A. S. Kamalanathan;M. Vijayalakshmi;Krishnan Venkataraman
芦荟是一种多肉草本植物，在传统医学中有着悠久的使用历史，包括糖尿病。本实验室前期研究表明，芦荟提取物具有体外抑制糖尿病药物靶点二肽基肽酶（DPP） IV的能力。本研究主要从芦荟提取物中分离出参与抑制DPP-IV酶的水溶性活性小分子，并进一步对其结构进行表征，阐明DPP-IV酶的抑制模式。采用制备型反相高压液相色谱（RP-HPLC）、LH-20 Sephadex凝胶过滤层析、分析型RP-HPLC分离芦荟凝胶乙醇提取物中参与抑制DPP-IV的活性分子。通过波谱分析，预测分离得到的DPP-IV抑制剂的结构为3,6 -二氧基3,3a, 6,6 a-四氢吡咯[3,4 -c]吡咯- 1,4 -二甲酰胺，化学式为C8H6N4O4，分子量为225.175 Da。该分子以非竞争性方式抑制DPP-IV酶，IC50值为8.59±2.61µM， Ki值为4.7±0.038µM。从而确定了DPP-IV的抑制机制和抑制常数。本研究结果提示，芦荟提取物对DPP-IV酶的抑制作用可能是其恢复糖尿病动物胰岛细胞质量的途径之一。
Abstract Aloe vera, a succulent herb, has a long history of use in traditional medicine, including diabetes. Earlier studies from our laboratory demonstrated that the Aloe vera extract has the ability to inhibit the diabetic drug target dipeptidyl peptidase (DPP) IV in vitro. This current study focuses on the isolation of small water soluble active molecule(s) involved in DPP-IV inhibition from Aloe vera extract, and further to characterize its structure and to elucidate the mode of inhibition of the DPP-IV enzyme. Aloe vera gel ethanolic extract was subjected to preparative reverse-phase high-pressure liquid chromatography (RP-HPLC), LH-20 Sephadex gel filtration chromatography, followed by analytical RP-HPLC, to isolate the active molecule involved in DPP-IV inhibition. Based on the spectroscopic studies, the structure of the isolated DPP-IV inhibitor was predicted to be 3, 6-dioxo-3, 3a, 6, 6 a-tetrahydropyrrolo [3, 4-c] pyrrole-1, 4-dicarboxamide with the chemical formula C8H6N4O4, having the molecular weight of 225.175 Da. This molecule inhibited the DPP-IV enzyme in a noncompetitive manner with an IC50 value of 8.59 ± 2.61 µM, with a Ki of 4.7 ± 0.038 µM. Thus, the mechanism of DPP-IV inhibition and the inhibitory constants were determined. The results of our studies suggested that the inhibition of the DPP-IV enzyme as one of the pathways by which the Aloe vera extract may restore the pancreatic islets cell mass in diabetic animal model.