1-Phenyl-6,7-dihydroxy-isochroman suppresses lipopolysaccharide-induced pro-inflammatory mediator production in human monocytes.
Extra-virgin olive oil is an integral ingredient of the Mediterranean diet, and it has been suggested that its high consumption has beneficial effects on human health. Its protective effect, in particular against the development of CVD, has been related not only to the high content of oleic acid, but also to the antioxidant and anti-inflammatory properties of polyphenols. In order to verify the anti-inflammatory and anti-atherogenic properties of hydroxy-isochromans, a class of ortho-diphenols present in extra-virgin olive oil, we investigated the potential ability of 1-phenyl-6,7-dihydroxy-isochroman (L137) to modulate the production of key inflammatory mediators by human monocytes, by evaluating its in vitro effects on prostanoid (thromboxane A(2) and PGE(2)) and cytokine (TNF-α) production. Its effect on the protein expression of the inducible form of cyclo-oxygenase-2 (COX-2), a pro-inflammatory enzyme responsible for elevated prostanoid levels, was also explored. The results showed that L137 significantly inhibited both prostanoid and TNF-α production in lipopolysaccharide-primed human monocytes in a dose-dependent manner, by inhibiting the COX activity of COX-2. We also demonstrated that the effects of the isochroman are mediated, at least partly, through the suppression of NF-κB activation leading to the down-regulation of the synthesis of COX-2.
Department of Physiology and Pharmacology Vittorio Erspamer, Sapienza University of Rome, P. le Aldo Moro 5, 00185, Rome, Italy.
Giuliana
G
Trefiletti
Anna Rita
AR
Togna
Valentina
V
Latina
Carolina
C
Marra
Marcella
M
Guiso
Giuseppina I
GI
Togna
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D015415:Biomarkers; D002839:Chromans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000069463:Olive Oil; D010938:Plant Oils / Q000737:chemistry; D013929:Thromboxane B2 / Q000235:genetics / Q000378:metabolism
C477354:1-phenyl-6,7-dihydroxy-isochroman; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D002839:Chromans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000069463:Olive Oil; D010938:Plant Oils; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D001241:Aspirin