Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay
- Author:
Ma LI-JUAN
1
;
Hou XU-DONG
;
Qin XIAO-YA
;
He RONG-JING
;
Yu HAO-NAN
;
Hu QING
;
Guan XIAO-QING
;
Jia SHOU-NING
;
Hou JIE
;
Lei TAO
;
Ge GUANG-BO
Author Information
1. 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
- Keywords:
Human pancreatic lipase;
Rhodiola crenulata;
1,2,3,4,6-Penta-O-Galloyl-β-D-glucopyranose;
Catechin gallate;
Inhibitory mechanism
- From:
Journal of Pharmaceutical Analysis
2022;12(4):683-691
- CountryChina
- Language:Chinese
-
Abstract:
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.
