Genistein and Gut Inflammation: Role of Nitric Oxide

Abstract

Genistein, a principal soy isoflavone, has been identified as a protein kinase inhibitor that possesses immunosuppressive and anti-inflammatory properties. The aim of the study was to determine if genistein modified chronic ileitis in guinea pigs induced by the hapten trinitrobenzene sulfonic acid (TNBS), and the activity index of cultured macrophages (RAW 264.7 cells) stimulated with lipopolysaccharide (LPS). Genistein at low doses (0.1 mg/kg, s.c.) had mild anti-inflammatory effects in TNBS ileitis. Therapeutic benefit included a reduction in nitric oxide production, granulocyte infiltration and improved mucosal architecture. Genistein, at low doses, also appeared to attenuate immunohistochemical staining for inducible nitric oxide synthase (iNOS) and nitrotyrosine. The beneficial effects of genistein were not apparent at doses above 0.1 mg/kg. We found that genistein also inhibited LPS-induced nitrite production by cultured macrophages and protected against LPS-induced necrosis despite its ability to cause apoptosis. These results indicate that genistein displayed mild anti-inflammatory properties which may, in part, involve an attenuation of nitric oxide release via inducible nitric oxide synthase, and the formation of peroxynitrite.

Anti-inflammatory Plant Flavonoids and Cellular Action Mechanisms

“…Flavone and several other amino-substituted flavones were reported to inhibit NO production (44). Genistein was proved to inhibit LPS-induced NO production in macrophages (45). Several flavonoid derivatives including apigenin, quercetin, and morin also inhibited NO production from LPS / interferon (IFN)-g-activated C6-astrocytes (46).…”

Suppression of arachidonic acid metabolism and nitric oxide formation by kudzu isoflavones in murine macrophages

“…Epigallocatechin gallate (EGCG), apigenin, theaflavin-3,39-digallate, carnosol, citral, curcumin, quercetin, resveratrol, and procyanidins have been recently reported to inhibit the production of peroxynitrite radicals and nitrite [15,16,[24][25][26][27][28]. Genistein has been shown to inhibit LPSinduced nitrite production probably through suppressing iNOS activity and/or iNOS gene expression [29,30].…”

Suppressive Effects of Genistein on Oxidative Stress and NFκB Activation in RAW 264.7 Macrophages

“…[11][12][13][14] This evidence suggests a role of oxidative stress in the intracellular signaling of LPS to activate NFkB. Genistein, a component of iso‰avones rich in legumes, has been identiˆed as a protein kinase inhibitor 15) and reported to have various bioactivities, such as scavenging free radicals to prevent ROS-mediated DNA damage, 16,17) suppression of NO production, 8,18) antioxidative protein expression, 19,20) a neuroprotective eŠect, 21) and an anti-photocarcinogenic eŠect 22) in various cell lines and animal studies. However, little information is available about the eŠects of genistein on the oxidative stress and NFkB activation in LPS-stimulated murine macrophages.…”