Effects of Kaempferol and Myricetin on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Rats

Abstract

When administered as drugs or consumed as food components, polyphenolic compounds synthesized in plants interfere with intracellular signal transduction pathways, including pathways of nitric oxide synthase expression. However, effects of these compounds in vivo do not always correlate with nitric oxide synthase-inhibiting activities revealed in experiments with cultured cells. The initial goal of this work was to compare effects of flavonoids kaempferol and myricetin on inducible nitric oxide synthase mRNA and protein expression monitored by real-time RT-PCR and immunohistochemistry and to evaluate the impact of these effects on nitric oxide production in rat organs measured by means of electron paramagnetic resonance spectroscopy. Kaempferol and myricetin attenuated the lipopolysaccharide-induced outburst of inducible nitric oxide synthase gene expression; kaempferol also significantly decreased the lipopolysaccharide-induced outburst of inducible nitric oxide synthase protein expression in the liver. Myricetin decreased nitric oxide production in intact rat liver. Kaempferol did not decrease nitric oxide production neither in intact rats nor in the lipopolysaccharide-treated animals. Kaempferol even enhanced the lipopolysaccharide-induced increase of nitric oxide production in blood. Myricetin did not interfere with lipopolysaccharide effects. As both kaempferol and myricetin are known as inhibitors of inducible nitric oxide synthase expression, our results suggest that modifications of nitric oxide level in tissues by these compounds cannot be predicted from data about its effects on nitric oxide synthase expression or activity.

The Effect of Mahkota Dewa (Phaleria Macrocarpa) (Scheff.) Fruit Pericarp Extract on Inos in Mice Colon Intermittently-Induced by Dextran Sodium Sulfate

“…Anti-inflammatory activity of P. macrocarpa pericarp extract also proven through decreasing of iNOS expression in mice colon, this results in line with Rostoka et al [22] and Choi et al [23] whom study flavonoid isolates, state that kaempferol, myricetin and rutin lowering iNOS protein expression in the livers of mice, and myricetin lowering nitric oxide production in rat liver. Besides kaempferol, myricetin and rutin, naringin also can inhibit the activation of iNOS enzyme and activation of NF-κB through barriers to degrades IκB and translocation of p65, a subunit of the protein NF-κB which undergo translocation into the cell nucleus when NF-κB regardless of IκB [24].…”

Myricetin Protects Against Cytokine-Induced Cell Death in RIN-m5f β Cells

“…On the other hand, an in vivo study indicated that myricetin could attenuate the lipopolysaccharide-induced outburst of iNOS gene expression and decrease NO production in intact rat liver. 29 Our results also provided evidence that myricetin could reduce cytokine-induced NO formation. Thus, we conclude that myricetin might reduce NO production through the inhibition of NF-jB-dependent iNOS expression in this study.…”

Herbal medicinal products target defined biochemical and molecular mediators of inflammatory autoimmune arthritis

“…The functions of NOS are summarized in Table 1. Decreased production of NO via suppressing or inhibiting NOS reduces arthritic symptoms and affords protection against the loss of body weight 17, 97. Anti-oxidants that are present in a number of plant extracts scavenge NO and other free radicals.…”

“…The in vivo testing was performed using well-established experimental models of human RA (e.g., adjuvant-induced arthritis (AA) 4–7, collagen-induced arthritis (CIA) 8, 9 and streptococcal cell wall-induced arthritis 10–12), whereas the in vitro testing was based on cultures of defined cell types (e.g., macrophages, chondrocytes and fibroblasts) 13–16. For the in vivo studies, the plant products were tested either as an extract (e.g., water-extract and alcoholic extract) 5, 17–19 or as a purified bioactive compound (e.g., triptolide, curcumin, epigallocatechin-3-gallate (EGCG) and acetyl-11-keto-beta-boswellic acid (AKBA) 12, 13, 15, 20) (Fig. 2).…”