Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay  

作　　者：Li-Juan Ma Xu-Dong Hou Xiao-Ya Qin Rong-Jing He Hao-Nan Yu Qing Hu Xiao-Qing Guan Shou-Ning Jia Jie Hou Tao Lei Guang-Bo Ge 

机构地区：[1]Shanghai Frontiers Science Center of TCM Chemical Biology,Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]Department of Endocrinology,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,200062,China [3]College of Basic Medical Sciences,Dalian Medical University,Dalian,116044,China [4]Qinghai Hospital of Traditional Chinese Medicine,Xining,810099,China

出　　处：《Journal of Pharmaceutical Analysis》2022年第4期683-691,共9页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:82160739,81922070,81973286,and 81973393);Sailing Special Project of Shanghai Rising-Star Program(Grant No.:22YF1441500);Program for Innovative Leading Talents of Qinghai Province(2018&2019);Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202004);Shanghai Science and Technology Innovation Action Plans(Grant Nos.:20S21901500 and 20S21900900);supported by the Shanghai Science and Technology Committee;Project of the National Multidisciplinary Innovation Team of Traditional Chinese Medicine supported by the National Administration of Traditional Chinese Medicine;Key R&D and Transformation Science and Technology Cooperation Project of Qinghai Province(Grant No.:2019-HZ-819);Basic Public Welfare Research Program of Zhejiang Province(Grant No.:LGF22H280012).

摘　　要：Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5e35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 mM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

关 键 词：Human pancreatic lipase Rhodiola crenulata 1 2 3 4 6-Penta-O-Galloyl-β-D-glucopyranose Catechin gallate Inhibitory mechanism 

分 类 号：R373[医药卫生—病原生物学]