Dianthrone derivatives from Polygonum multiflorum Thunb: Anti-diabetic activity, structure-activity relationships (SARs), and mode of action

Jian-Bo Yang; Cheng-Shuo Yang; Jiang Li; Guo-Zhu Su; Jin-Ying Tian; Ying Wang; Yue Liu; Feng Wei; Yong Li; Fei Ye; Shuang-Cheng Ma

doi:10.1016/j.bioorg.2023.106491

Dianthrone derivatives from Polygonum multiflorum Thunb: Anti-diabetic activity, structure-activity relationships (SARs), and mode of action

Bioorg Chem. 2023 Jun:135:106491. doi: 10.1016/j.bioorg.2023.106491. Epub 2023 Mar 23.

Authors

Jian-Bo Yang¹, Cheng-Shuo Yang², Jiang Li³, Guo-Zhu Su², Jin-Ying Tian³, Ying Wang⁴, Yue Liu⁵, Feng Wei⁴, Yong Li⁶, Fei Ye⁷, Shuang-Cheng Ma⁸

Affiliations

¹ National Institutes for Food and Drug Control, Beijing 100050, China; Xinjiang Uygur Autonomous Region Institute for Drug Control, Urumqi 830054, China.
² State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
³ Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China; Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
⁴ National Institutes for Food and Drug Control, Beijing 100050, China.
⁵ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
⁶ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: liyong@imm.ac.cn.
⁷ Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China; Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: yefei@imm.ac.cn.
⁸ National Institutes for Food and Drug Control, Beijing 100050, China. Electronic address: masc@nifdc.org.cn.

PMID: 37011521
DOI: 10.1016/j.bioorg.2023.106491

Abstract

PTP1B plays an important role as a key negative regulator of tyrosine phosphorylation associated with insulin receptor signaling in the therapy for diabetes and obesity. In this study, the anti-diabetic activity of dianthrone derivatives from Polygonum multiflorum Thunb., as well as the structure-activity relationships, mechanism, and molecular docking were explored. Among these analogs, trans-emodin dianthrone (compound 1) enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice. By using photoaffinity labeling and mass spectrometry-based proteomics, we discovered that trans-emodin dianthrone (compound 1) may bind to PTP1B allosteric pocket at helix α6/α7, which provides fresh insight into the identification of novel anti-diabetic agents.

Keywords: Anti-diabetic efficacy; Dianthrones; PTP1B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus*
Emodin*
Fallopia multiflora* / chemistry
Fallopia multiflora* / metabolism
Mice
Molecular Docking Simulation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Structure-Activity Relationship

Substances

Emodin
Protein Tyrosine Phosphatase, Non-Receptor Type 1