Dianthrone derivatives from Polygonum multiflorum Thunb: Anti-diabetic activity, structure-activity relationships
Jian-Bo Yang1, Cheng-Shuo Yang2, Jiang Li3
1National Institutes for Food and Drug Control, Beijing 100050, China; Xinjiang Uygur Autonomous Region Institute for Drug Control, Urumqi 830054, China.
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.
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