Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Food Funct. 2021 May 21;12(10):4644-4653. doi: 10.1039/d0fo03366a. Epub 2021 Apr 29.
Chronic diseases, such as obesity, cause great harm to human health. Conventional drugs have promising therapeutic effects but also cause significant side effects. Functional foods are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, screening for active ingredients in natural foods is difficult. In this study, a novel pancreatic lipase inhibitor screening strategy, guided by the drug molecule orlistat, was combined with experimental verification. Twenty compounds from natural foods were evaluated based on the characteristics of orlistat interaction with pancreatic lipase. The characteristics of 13 molecules were comparable to those of orlistat. The pancreatic lipase inhibition rates of curcumin and sinensetin were 82.42 ± 0.50% and 81.07 ± 2.05%, respectively, and their IC values were 0.971 mM and 0.526 mM, respectively; both the inhibition rates as well as IC values were similar to those of orlistat. Curcumin and sinensetin prevented weight gain in mice by 69.17% and 52.29%, respectively, compared to orlistat. Curcumin and sinensetin did not cause significant organ damage in vivo, but significantly reduced the contents of triglycerides and cholesterol in blood and lipids in the liver, protecting liver function. Furthermore, 57 328 molecules in the Chinese Natural Product Database library were screened, and 20 potentially active molecules, found to be highly efficient in our study, were selected. Thus, we successfully established an efficient and accurate strategy for screening active ingredients in natural foods under the guidance of a drug molecule, providing valuable insights for functional food development.
慢性疾病，如肥胖症，对人类健康造成极大危害。传统药物具有良好的治疗效果，但也会引起明显的副作用。功能性食品是药物的极好替代品，因为它们的副作用较少。然而，筛选天然食品中的活性成分是困难的。在这项研究中，我们结合实验验证，采用一种新的胰脂肪酶抑制剂筛选策略，以药物分子奥利司他为指导。根据奥利司他与胰脂肪酶相互作用的特点，评估了 20 种天然食品化合物。13 种分子的特征与奥利司他相似。姜黄素和橙皮素对胰脂肪酶的抑制率分别为 82.42±0.50%和 81.07±2.05%，IC50 值分别为 0.971 mM 和 0.526 mM，抑制率和 IC50 值均与奥利司他相似。与奥利司他相比，姜黄素和橙皮素分别使小鼠体重增加减少了 69.17%和 52.29%。姜黄素和橙皮素在体内不会导致明显的器官损伤，但能显著降低血液中的甘油三酯和胆固醇含量以及肝脏中的脂质含量，保护肝功能。此外，我们从中国天然产物数据库库中筛选了 57328 个分子，选择了 20 个在我们的研究中发现高效的潜在活性分子。因此，我们成功地建立了一种在药物分子指导下筛选天然食品中活性成分的高效、准确策略，为功能性食品的开发提供了有价值的见解。
