Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources and Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.
Food Funct. 2021 Jun 21;12(12):5650-5657. doi: 10.1039/d0fo03352a.
Chalcones, a class of natural lipase inhibitors, have received substantial attention from researchers in recent years. Although many kinds of chalcones are typically distributed in G. inflata, there is little literature about the anti-lipase activity of G. inflata extracts (GIEs). In the present study, a ligand fishing strategy for fast screening of lipase inhibitors from GIEs was thus proposed. Porcine pancreatic lipase (PPL) was firstly immobilized on carboxyl modified Fe3O4 magnetic nanoparticles (MNPs) to obtain PPL functionalized MNPs (PPL@MNPs), and then the PPL@MNPs were incubated with a bioactive fraction to fish out the ligands. Eight ligands were obtained and identified as one flavone together with seven chalcones. Licochalcone A, licochalcone D and licochalcone E inhibited pancreatic lipase (PL) with IC50 of 4.9, 3.2 and 5.8 μM, respectively. Meanwhile, investigation of the structure-activity relationship also revealed that isopentenyl and hydroxyl substituents at ring A were essential for the noncovalent inhibitory potency of the chalcones.
查耳酮类化合物是一类天然脂肪酶抑制剂，近年来受到研究人员的广泛关注。尽管许多种查耳酮通常分布在膨胀甘草中，但关于膨胀甘草提取物（GIE）的脂肪酶抑制活性的文献却很少。在本研究中，提出了一种配体钓取策略，用于快速筛选 GIEs 中的脂肪酶抑制剂。首先将猪胰脂肪酶（PPL）固定在羧基修饰的 Fe3O4 磁性纳米粒子（MNPs）上，得到 PPL 功能化的 MNPs（PPL@MNPs），然后将 PPL@MNPs 与生物活性部分孵育，以钓出配体。共得到 8 种配体，并鉴定为一种黄酮和 7 种查耳酮。甘草查尔酮 A、甘草查尔酮 D 和甘草查尔酮 E 对胰脂肪酶（PL）的抑制作用的 IC50 值分别为 4.9、3.2 和 5.8 μM。同时，构效关系研究还表明，A 环上的异戊烯基和羟基取代基是查耳酮非共价抑制效力所必需的。
