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
,
2
;
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
2. 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.
