Flavonoids and nitric oxide synthase

• Autorzy: Olszanecki R. , Gebska A. , Kozlovski V.I. , Gryglewski R.J.
• Języki publikacji: EN

Abstrakty

EN

Induction of NOS-2 in macrophages and smooth muscles within vascular wall with concomittant suppression of endothelial NOS-3 activity is considered to be a hallmark of vascular inflammation that triggers atherogenesis. Accordingly, drugs designed to reverse these changes should not only support vaning function of NOS-3 but also suppress proinflammatory NO production by NOS-2. It means that using selective inhibitors of induction of NOS-2 (they spare ex definitione constitutive activity of NOS-3) is a more rational approach than using isselectivel. inhibitors of activity of previously induced NOS-2. First of all, those drugs are never sufficiently selective. In our work we tried to identify inhibitors of NOS-2 induction within the group of flavonoids, known stimulators of NOS-3 with putative antiatherogenic effects. Representatives of four main groups of flavonoids: flavonols (kaempferol, quercetin, rutin), flavones (apigenin, primuletin), flavanols (catechine) and flavanones (hesperetin, hesperidin, naringenin) were tried on NOS-2 induction and activity in the in vitro model of LPS-treated macrophages (cell line J774.2). While none of these compounds inhibited activity of NOS-2, all with unexpectedly scattered potencies inhibited induction of NOS-2 protein in LPS-treated J774.2 cells, as evidenced by Western blotting technique. Subsequently, RT-PCR and Northern blotting methods revealed that so far the most potent compounds, kaempferol and apigenin, at micromolar concentrations did inhibit NOS-2 induction at the level of NOS-2 gene transcription. We conclude that some of flavonoids are potent inhibitors of NOS-2 induction. At the same time they may increase endothelial NOS-3 activity. Could these flavonoids become natural parents of future drugs, which will be used for reversal of inflammatory component of atherothrombosis?

Słowa kluczowe

EN

flavonoids; nitric oxide synthase; macrophage; vascular wall; L-arginine; smooth muscle

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2002
• Tom: 53
• Numer: 4,1
• Opis fizyczny: p.571-584,fig.

Twórcy

autor

Olszanecki R.

• Jagiellonian University Medical College, 16 Grzegorzecka str., 31-531 Krakow, Poland

autor

Gebska A.

autor

Kozlovski V.I.

autor

Gryglewski R.J.