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=12.5-35 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 μM,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.

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

Shanghai Frontiers Science Center of TCM Chemical Biology,Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China;Department of Endocrinology,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,200062,China;College of Basic Medical Sciences,Dalian Medical University,Dalian,116044,China;Qinghai Hospital of Traditional Chinese Medicine,Xining,810099,China

药物分析学报（英文）

[1]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-.Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay)[J].药物分析学报（英文）,2022(04):683-691

crenulata,hPL,pIC50

Discovery,human,pancreatic,lipase,inhibitors,from,root,Rhodiola,via,integrating,bioactivity,guided,fractionation,profiling,biochemical,Although,herbal,medicines,HMs,are,widely,used,prevention,treatment,obesity,associated,disorders,key,constituents,exhibiting,anti,their,molecular,mechanisms,poorly,understood,Recently,assessed,inhibitory,potentials,several,against,therapeutic,target,among,which,extract,ERC,showed,most,In,this,study,adopted,integrated,strategy,involving,techniques,assays,identify,Nine,fractions,retention,obtained,using,reverse,phase,liquid,chromatography,strong,while,major,these,bioactive,were,subsequently,identified,quadrupole,flight,mass,spectrometry,LC,TOF,Among,penta,galloyl,glucopyranose,PGG,catechin,gallate,CG,values,respectively,Further,investigations,revealed,that,potently,inhibited,competitive,manner,inhibition,constant,Ki,Collectively,our,integrative,analyses,enabled,efficiently,characterize,well,elucidate,These,findings,provide,convincing,evidence,support,lipid,lowering,properties

0.530748