Molecular action mechanism against apoptosis by aqueous extract from guava budding leaves elucidated with human umbilical vein endothelial cell (HUVEC) model.
Chronic cardiovascular and neurodegenerative complications induced by hyperglycemia have been considered to be associated most relevantly with endothelial cell damages (ECD). The protective effects of the aqueous extract of Psidium guajava L. budding leaves (PE) on the ECD in human umbilical vein endothelial cell (HUVEC) model were investigated. Results revealed that glyoxal (GO) and methylglyoxal (MGO) resulting from the glycative and autoxidative reactions of the high blood sugar glucose (G) evoked a huge production of ROS and NO, which in turn increased the production of peroxynitrite, combined with the activation of the nuclear factor kappaB (NFkappaB), leading to cell apoptosis. High plasma glucose activated p38-MAPK, and high GO increased the expressions of p38-MAPK and JNK-MAPK, whereas high MGO levels induced the activity of ERK-MAPK. Glucose and dicarbonyl compounds were all found to be good inducers of intracellular PKCs, which together with MAPK acted as the upstream triggering factor to activate NFkappaB. Conclusively, high plasma glucose together with dicarbonyl compounds can trigger the signaling pathways of MAPK and PKC and induce cell apoptosis through ROS and peroxynitrite stimulation and finally by NFkappaB activation. Such effects of PE were ascribed to its high plant polyphenolic (PPP) contents, the latter being potent ROS inhibitors capable of blocking the glycation of proteins, which otherwise could have brought forth severe detrimental effects to the cells.
Hsieh
Chiu-Lan
CL
Department of Food and Nutrition, Research Institute of Biotechnology, Hungkuang University, 34 Chung-Chie Road, Shalu County, Taichung Hsien, Taiwan. clhsieh@sunrise.hk.edu.tw
Huang
Chien-Ning
CN
Lin
Yuh-Charn
YC
Peng
Robert Y
RY
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D031647:Psidium / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D014471:Umbilical Veins
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases