2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through PPARγ partial agonism.

摘要: Adiponectin is a major adipocytokine secreted from mammalian adipocytes. Relatively low expression of adiponectin associated with various human metabolic diseases and some cancers. Adiponectin-secreting compounds have therapeutic potential for these diseases. Adipogenesis bone marrow-mesenchymal stem cells (hBM-MSCs) has been used as phenotypic assay to find secreting compounds. In phytochemical library screen, 2-formyl-komarovicine, 1-(quinolin-8-yl)-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carbaldehyde, isolated Nitraria komarovii was identified adiponectin-secreting compound. To validate the results impure phytochemical, we synthesized 2-formyl-komarovicine. The synthetic 2-formyl-komarovicine significantly promoted production during adipogenesis in hBM-MSCs. target identification experiment, bound peroxisome proliferator-activated receptor γ (PPARγ) concentration-dependent manner. Notably, competitively inhibited adiponectin-promoting activity full PPARγ agonist, troglitazone, hBM-MSCs, which pharmacological feature partial agonist. ligand-docking model showed that interacted hydrophobic pocket ligand-binding domain, but lacked an interaction stabilize helix H12, one binding themes agonists. We concluded provides novel pharmacophore agonists increase production.