Zerumbone suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells.
Unregulated uptake of oxidized low-density lipoproteins (ox-LDL) via macrophage scavenger receptors (SRs), such as lectin-like ox-LDL receptor-1 (LOX-1), is a key event in atherosclerosis. In the present study, we used differentiated Caco-2 cells as a model of the human small intestine to evaluate the suppressive effects of 16 traditional food items selected from Okinawa on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced LOX-1 mRNA expression in THP-1 human monocyte-like cells. Three Zingiberaceae plants, Curcuma aromatica Salisbury, Curcuma longa L., and Zingiber zerumbet Smith, markedly suppressed that expression. When added to the apical sides of Caco-2 monolayers, zerumbone, a sesquiterpene from Z. zerumbet Smith, was found to permeate into the basolateral medium as an intact structure in a time-dependent manner. alpha-Humulene, a structural analog of zerumbone lacking the alpha,beta-unsaturated carbonyl group, did not suppress LOX-1 mRNA expression, indicating that its electrophilic moiety might play pivotal roles in its activities. Further, zerumbone attenuated the expression of SR-A, SR-PSOX, and CD36, but not that of CD68 or CLA-1, leading to a blockade of DiI-acLDL uptake, while it also inhibited the transcriptional activities of activator protein-1 and nuclear factor-kappaB. Together, our results indicate that zerumbone is a potential phytochemical for regulating atherosclerosis with reasonable action mechanisms.
Eguchi
Ai
A
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Kaneko
Yuki
Y
Murakami
Akira
A
Ohigashi
Hajime
H
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D008078:Cholesterol, LDL / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D000081222:Monocyclic Sesquiterpenes; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051116:Receptors, Scavenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors
D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D000081222:Monocyclic Sesquiterpenes; D016328:NF-kappa B; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; C403304:zerumbone; C042686:humulene; D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human; D013755:Tetradecanoylphorbol Acetate