Inducible Nitric Oxide Synthase (iNOS) : Dichotomous Impact
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From:
Inducible nitric oxide synthase: what difference does it make?"The [iNOS} dichotomy is sometimes manifest at different times or sites in the same experimental setting."
"In both infection and inflammation, iNOS appears to act both as a direct effector and as a regulator of other effectors."
"..the cytotoxic and proinflammatory potential of iNOS advances the case for its therapeutic inhibition in those of the diseases discussed above that are not thought to be infectious in etiology, such as Alzheimer’s disease, hemorrhagic shock/resuscitation, late-phase vasoocclusive stroke, inflammatory bowel disease, and rheumatoid and osteoarthritis, or in those infectious diseases where the inflammatory effect of iNOS appears to outweigh its antimicrobial effect, such as influenza pneumonia. However, the antiinflammatory role of iNOS emphasizes the possibility of adverse consequences attendant on its inhibition."
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Ethanol extract of propolis (EEP) inhibits nitric oxide synthase gene expression and enzyme activity
I long hoped there would be anything else but MBlue + Red Light to inhibit NO. And voilà: it's the caffeic acid phenethyl ester (CAPE), which is "identified as a major peak in the chromatogram of EEP".
From the abstract:
"EEP inhibited the iNOS promoter activity induced by LPS plus IFN-g through the NF-kB sites of the iNOS promoter. In addition, EEP directly interfered with the catalytic activity of murine recombinant iNOS enzyme. These results suggest that EEP may exert its anti-inflammatory effect by inhibiting the iNOS gene expression via action on the NF-kB sites in the iNOS promoter AND by directly inhibiting the catalytic activity of iNOS."
[emphasis mine.]
Preparation of extract from the paper:
Coarsely powdered propolis (100 g) was extracted with 10 volumes of 95% ethanol for 2 weeks. The ethanol extract was filtered, evaporated, and lyophilized to give the dry ethanol extract (33.3 g).
In Anti-inflammatory Effect of Propolis through Inhibition of Nitric Oxide Production on Carrageenin-Induced Mouse Paw Edema, even smaller amounts of extract were successfully used:
Because lyophilized ethanol extract of propolis used in the present study is equivalent to 18.5 mg propolis per 100 ml, 16) 1: 1000 and 1: 100 dilutions of propolis correspond to 1.85 and 18.5 mg/kg, respectively. Therefore, the propolis used in the present study was 5.4—54 times more potent than that reported by Borrelli et al. ... though there was a difference between mouse and rat.
