title: Artichoke, cynarin and cyanidin downregulate the expression of inducible nitric oxide synthase in human coronary smooth muscle cells.
abstract: Artichoke (Cynara scolymus L.) is one of the world's oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was concentration- and time-dependently inhibited by an artichoke leaf extract (1-100 µg/mL, 6 h or 24 h). Consistently, the artichoke leaf extract also reduced cytokine-induced iNOS promoter activation and iNOS protein expression. In addition, treatment of HCASMC with four well-known artichoke compounds (cynarin > cyanidin > luteolin ≈ cynaroside) led to a downregulation iNOS mRNA and protein expression, with cynarin being the most potent one. In conclusion, artichoke contains both eNOS-upregulating and iNOS-downregulating compounds. Such compounds may contribute to the beneficial effects of artichoke and may per se have therapeutic potentials.
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Ning
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pautz
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Wollscheid
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Reifenberg
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Förstermann
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany. huigeli@uni-mainz.de.
authors.forename: Huige
authors.initials: H
authors.lastname: Li
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology*; D003331:Coronary Vessels; D031943:Cynara scolymus / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011401:Promoter Regions, Genetic
chemical_list: D000872:Anthocyanins; D002934:Cinnamates; D010936:Plant Extracts; C017154:cyanidin; C100257:cynarine; D052247:Nitric Oxide Synthase Type II