Depsidone and xanthones from Garcinia xanthochymus with hypoglycemic activity and the mechanism of promoting glucose uptake in L6 myotubes. Issue 24 (15th December 2017)

• Record Type: Journal Article
• Authors: Li, Yunfang; Zhao, Ping; Chen, Yu; Fu, Yanze; Shi, Kuan; Liu, Liu; Liu, Hui; Xiong, Mingrui; Liu, Qing-Hua; Yang, Guangzhong; Xiao, Yuxiu
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 24(2017)
• Page Start: 6605
• Page End: 6613
• Publication Date: 2017-12-15
• Subjects: GLUT4 glucose transporter type 4 -- PI3K phosphatidylinositol-3 kinase -- PKB/Akt serine/threonine kinase protein kinase B -- AMPK AMP-activated protein kinase -- DM diabetes mellitus -- T2DM type 2 diabetes mellitus -- DMEM Dulbecco's modified Eagle's medium -- FBS fetal bovine serum -- GSK3β glycogen synthase kinases 3β -- ACC acetyl-CoA carboxylase α -- TMS tetramethylsilane -- CC column chromatography -- PIP2 phosphatidylinositol-4, 5-bisphosphate -- PIP3 phosphatidylinositol-3, 4, 5-triphosphate -- TBST tris-Tween-buffered saline -- HPLC high-performance liquid chromatography -- NMR nuclear magnetic resonance spectroscopy -- MS mass spectroscopy -- UV ultra-violet spectroscopy -- MTT methyl thiazolyl tetrazolium; Garcinia xanthochymus -- Xanthones -- L6 myotubes -- Anti-diabetic activity -- Signaling pathway -- Mechanism; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.10.043
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Garcinia xanthochymus is a widely used folk medicine in southwestern China. Previous studies indicated it possesses potential anti-diabetic activities both in vitro (Fu et al., 2014; Nguyen et al., 2017) and in vivo (Shivanand et al., 2017). To discover bioactive ingredients from it and unveil their mechanism of action against diabetes, the present study was designed to isolate constituents from extract of G. xanthochymus, determine their structures, screen their activities and investigate mechanism of action of the active substances. Twenty compounds including a new depsidone named garciniadepsidone A (20 ) and 19 known xanthones were obtained. All of them were screened to discover the active compounds with anti-diabetic activities. Finally, three xanthones including 12 b -hydroxy-des- d -garcigerrin (5 ), 1, 2, 5, 6-tretrahydroxy-4-(1, 1-dimethyl-2-propenyl)-7-(3-methyl-2-butenyl) xanthone (13 ) and 1, 5, 6-trihydroxy-7, 8-di(3-methyl-2-butenyl)-6′, 6′-dimethylpyrano (2′, 3′:3, 4) xanthone (18 ) were found to be able to significantly stimulate the glucose uptake in the skeleton muscle cells. The effects of the three compounds were comparable to those of insulin and metformin. Based on molecular mechanistic study, it was found that both of compound5 and13 promoted glucose uptake by activating phosphatidylinositol-3 kinase (PI3K)/the serine/threonine kinase protein kinase B (PKB/Akt) signaling pathway and AMP-activated protein kinase (AMPK) signaling pathway, resulting in the translocation of GLUT4 in L6 myotubes without affecting the expression of GLUT4. Compound5 and13 have great potential to be developed as promising leads to target diabetes.