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

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

doi:10.1016/j.jpha.2022.04.002

Volume 12 Issue 4

Sep. 2022

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Article Navigation > Journal of Pharmaceutical Analysis > 2022 > 12(4): 683-691

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]. Journal of Pharmaceutical Analysis, 2022, 12(4): 683-691. doi: 10.1016/j.jpha.2022.04.002

Citation:

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]. Journal of Pharmaceutical Analysis, 2022, 12(4): 683-691. doi: 10.1016/j.jpha.2022.04.002

Citation:

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]. Journal of Pharmaceutical Analysis, 2022, 12(4): 683-691. doi: 10.1016/j.jpha.2022.04.002

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

doi: 10.1016/j.jpha.2022.04.002

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

Funds:

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), and Basic Public Welfare Research Program of Zhejiang Province (Grant No.: LGF22H280012). Furthermore, we are grateful to Zhou Yang (Shanghai Standard Technology Co., Ltd., Shanghai, China) for the contribution in the field of MS/MS analysis.

This work was 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 &

Received Date: Sep. 05, 2021
Accepted Date: Apr. 02, 2022
Rev Recd Date: Mar. 20, 2022
Publish Date: Apr. 08, 2022

Abstract

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 (K_i) 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.
- Human pancreatic lipase,
- Rhodiola crenulata,
- 1,2,3,4,6-Penta-O-Galloyl-β-d-glucopyranose,
- Catechin gallate,
- Inhibitory mechanism

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