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Journal Article Epublish 19 citations

PubMed: 35284458 DOI: 10.3389/fnut.2022.844195

Discovery and Characterization of the Naturally Occurring Inhibitors Against Human Pancreatic Lipase in .

Front Nutr 9:844195

Authors: Xiao-Ya Qin, Xu-Dong Hou, Guang-Hao Zhu, Yuan Xiong, Yun-Qing Song, Liang Zhu, Dong-Fang Zhao, Shou-Ning Jia, Jie Hou, Hui Tang, Guang-Bo Ge

Affiliations

  • Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Pharmacy School of Shihezi University, Xinjiang, China. Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
  • Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Qinghai Hospital of Traditional Chinese Medicine, Xining, China.
  • College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
  • Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Pharmacy School of Shihezi University, Xinjiang, China.

Abstract

Pancreatic lipase (PL) inhibitor therapy has been validated as an efficacious way for preventing and treating obesity and overweight. In the past few decades, porcine PL (pPL) is widely used as the enzyme source for screening the PL inhibitors, which generates a wide range of pPL inhibitors. By contrast, the efficacious inhibitors against human PL (hPL) are rarely reported. This study aims to discover the naturally occurring hPL inhibitors from edible herbal medicines (HMs) and to characterize the inhibitory mechanisms of the newly identified hPL inhibitors. Following the screening of the inhibition potentials of more than 100 HMs against hPL, extract (AGE) displayed the most potent hPL inhibition activity. After that, the major constituents in AGE were identified and purified, while their anti-hPL effects were assayed . The results clearly showed that two abundant constituents in AGE (dihydromyricetin and iso-dihydromyricetin) were moderate hPL inhibitors, while myricetin and quercetin were strong hPL inhibitors [half-maximal inhibitory concentration ( ) values were around 1.5 μM]. Inhibition kinetic analyses demonstrated that myricetin and quercetin potently inhibited hPL-catalyzed near-infrared fluorogenic substrate of human pancreatic lipase (DDAO-ol) hydrolysis in a non-competitive inhibition manner, with values of 2.04 and 2.33 μM, respectively. Molecular dynamics simulations indicated that myricetin and quercetin could stably bind on an allosteric site of hPL. Collectively, this study reveals the key anti-obesity constituents in AGE and elucidates their inhibitory mechanisms against hPL, which offers convincing evidence to support the anti-obesity and lipid-lowering effects of this edible herb.

MeSH

Lipase, Quercetin, Obesity

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