Zhang Hao, Yang Feng-Qing, Gao Jian-Li
Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.
School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China.
Evid Based Complement Alternat Med. 2022 Sep 22;2022:4430050. doi: 10.1155/2022/4430050. eCollection 2022.
With the increase of obesity incidence, the development of antiobesity drugs has aroused extensive interest. In this study, a simple and portable personal glucose meter (PGM) method based on the lipase-mediated reaction combined with molecular docking was developed for the screening of lipase inhibitors. Lipase can catalyse the hydrolysis of 4-acetamidophenyl acetate to form acetaminophen, which can directly trigger the reduction of K[Fe(CN)] to K[Fe(CN)] in the glucose test strips and generate an electrical signal that can be detected by the PGM. When lipase inhibitors exist, the yield of acetaminophen will be reduced and results in a corresponding decrease of the PGM signal. Therefore, the activity of lipase can be measured by the PGM. After optimization of the experimental conditions, the inhibitory activity of fourteen small-molecule compounds and fifteen natural product extracts on lipase were evaluated by the developed PGM method. The results indicate that tannic acid, (-)-epigallocatechin gallate, (-)-epigallocatechin, (-)-epicatechin gallate, and epicatechin have good inhibitory effect on lipase (% of inhibition higher than 40.0%). Besides, the natural product extracts of Galla Chinensis, lemon, and Rhei Radix et Rhizoma have a good inhibitory effect on lipase with % of inhibition of (97.5 ± 0.6)%, (88.1 ± 0.7)%, and (79.1 ± 1.6)%, respectively. Finally, the binding sites and modes of six small-molecule compounds on lipase were investigated by the molecular docking study. The results show that the developed PGM method is an effective approach for the discovery of potential lipase inhibitors.
随着肥胖症发病率的增加，抗肥胖药物的研发引起了广泛关注。在本研究中，开发了一种基于脂肪酶介导反应并结合分子对接的简单便携的个人血糖仪（PGM）方法用于筛选脂肪酶抑制剂。脂肪酶可催化乙酸对乙酰氨基酚水解生成对乙酰氨基酚，其可直接促使葡萄糖测试条中的K[Fe(CN)]还原为K[Fe(CN)]，并产生可被PGM检测到的电信号。当存在脂肪酶抑制剂时，对乙酰氨基酚的产量会降低，导致PGM信号相应减弱。因此，可通过PGM测定脂肪酶的活性。在优化实验条件后，采用所开发的PGM方法评估了14种小分子化合物和15种天然产物提取物对脂肪酶的抑制活性。结果表明，单宁酸、（-）-表没食子儿茶素没食子酸酯、（-）-表没食子儿茶素、（-）-表儿茶素没食子酸酯和表儿茶素对脂肪酶具有良好的抑制作用（抑制率高于40.0%）。此外，五倍子、柠檬和大黄的天然产物提取物对脂肪酶具有良好的抑制作用，抑制率分别为（97.5±0.6）%、（88.1±0.7）%和（79.1±1.6）%。最后，通过分子对接研究考察了6种小分子化合物在脂肪酶上的结合位点和模式。结果表明，所开发的PGM方法是发现潜在脂肪酶抑制剂的有效途径。
