Antiatherogenic effect of Pistacia lentiscus via GSH restoration and downregulation of CD36 mRNA expression.
Pistacia lentiscus var. Chia (Anacardiaceae) grows almost exclusively on Chios Island, Greece, and gives a resinous exudate resin used for culinary purposes by Mediterranean people. We investigated the molecular mechanisms through which total polar extract of the resin inhibits oxidized low-density lipoprotein (oxLDL) cytotoxic effect on peripheral blood mononuclear cell (PBMC). Cells exposed to oxLDL underwent apoptosis and necrosis, dependent on the duration of exposure. When culturing cells with oxLDL and the polar extract concurrently, we observed inhibition of both the phenomena. Because under oxidative stress the pro-oxidant systems outbalance the antioxidant, potentially producing oxidative damage and ultimately leading to cell death, we measured the levels of intracellular antioxidant glutathione (GSH). Additionally, we measured CD36 expression, a class B scavenger receptor, on CD14-positive cells, as CD36 has been identified as the oxLDL receptor in macrophages and may play a pivotal role in atherosclerotic foam cell formation. oxLDL decreased GSH levels and upregulated CD36 expression. P. lentiscus extract restored GSH levels and downregulated CD36 expression, even at the mRNA level. In order to find out the biologically drastic constituents of the resin's polar extract, fractions derived from RP-HPLC analysis were examined for their antioxidant effect on oxidatively stressed PBMC. The triterpenoid fraction revealed remarkable increase in intracellular GSH. We suggest GSH restoration and downregulation of CD36 mRNA expression as the pathways via which P. lentiscus triterpenes exert antioxidant/antiatherogenic effect. Additionally, our results provide strong evidence of the resin's antiatherogenic effect; therefore it is credited with beneficial health aspects.
Dedoussis
George V Z
GV
Department of Science of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, 17 671 Kallithea, Athens, Greece. dedousi@hua.gr
Kaliora
Andriana C
AC
Psarras
Stellios
S
Chiou
Antonia
A
Mylona
Anastasia
A
Papadopoulos
Nikolaos G
NG
Andrikopoulos
Nikolaos K
NK
D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000517:prevention & control*; D018955:CD36 Antigens / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D027927:Pistacia; D028321:Plant Preparations / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity
D000975:Antioxidants; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D028321:Plant Preparations; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D005978:Glutathione