Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia

Department of Pharmacology, Faculty of Science, Mahidol University, Rama VI Road, Phayathai, Bangkok 10400, Thailand.
International immunopharmacology (Impact Factor: 2.71). 08/2013; 17(2). DOI: 10.1016/j.intimp.2013.07.013
Source: PubMed

ABSTRACT Microglial activation has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and HIV encephalopathy. Phytoestrogens have been shown to be neuroprotective in neurotoxicity models; however, their effect on microglia has not been well established. In the current study, we report that the soy phytoestrogens, genistein, daidzein, and coumestrol, decreased nitric oxide (NO) production induced by lipopolysaccharide (LPS) in the rat microglial cell line (HAPI). The levels of inducible NO synthase (iNOS) mRNA and protein expression were also reduced. Transcription factors known to govern iNOS expression including interferon regulatory factor-1 (IRF-1) and phosphorylated STAT1 were down regulated. These observations explain, at least in part, the inhibitory effect of phytoestrogens on NO production. The levels of monocyte chemoattractant protein-1 and interleukin-6 mRNA, proinflammatory chemokine and cytokine associated with various neurological disorders, were also reduced following LPS stimulation when HAPI cells were pretreated with phytoestrogens. Hence, genistein, daidzein, and coumestrol could serve as anti-inflammatory agents and may have beneficial effects in the treatment of neurodegenerative diseases.

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    • "Dietary habits, including intake of soy, have been suggested to reduce the risk of developing MS, based on a cross-sectional study, in which the prevalence of MS was lower in lacto-vegetarians as compared to people on a high animal fat diet (Razeghi Jahromi et al., 2014). Phytoestrogenes, such as genistein, daidzein and coumestrol may partly contribute to these effects owing to their anti-inflammatory properties, such as reduction of nitric oxide (NO) and pro-inflammatory cytokines and reduction of microglial activation (Jantaratnotai et al., 2013). In MOG35–55 induced EAE in C57BL/6 mice daily subcutaneous injections of 200 mg/kg genistein starting 14 days after EAE induction attenuated clinical EAE scores and reduced the body weight loss as compared to the vehicle group. "
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