Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia
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. "
ABSTRACT: The association between vitamin D and multiple sclerosis has (re)-opened new interest in nutrition and natural compounds in the prevention and treatment of this neuroinflammatory disease. The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy, sodium chloride and trace elements, and fat soluble vitamins including D, A and E were all considered as disease-modifying nutraceuticals. Studies in experimental autoimmune encephalomyelitis mice suggest that poly-unsaturated fatty acids and their 'inflammation-resolving' metabolites and the gut microflora may reduce auto-aggressive immune cells and reduce progression or risk of relapse, and infection with whipworm eggs may positively change the gut-brain communication. Encouraged by the recent interest in multiple sclerosis-nutrition nature's pharmacy has been searched for novel compounds with anti-inflammatory, immune-modifying and antioxidative properties, the most interesting being the scorpion toxins that inhibit specific potassium channels of T cells and antioxidative compounds including the green tea flavonoid epigallocatechin-3-gallate, curcumin and the mustard oil glycoside from e.g. broccoli, sulforaphane. They mostly also inhibit pro-inflammatory signaling through NF-κB or toll-like receptors and stabilize the blood brain barrier. Disease modifying functions may also complement analgesic and anti-spastic effects of cannabis, its constituents, and of 'endocannabinoid enhancing' drugs or nutricals like inhibitors of fatty acid amide hydrolase. Nutricals will not solve multiple sclerosis therapeutic challenges but possibly support pharmacological interventions or unearth novel structures. Copyright © 2014. Published by Elsevier Inc.Pharmacology [?] Therapeutics 11/2014; 148. DOI:10.1016/j.pharmthera.2014.11.015 · 7.75 Impact Factor
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ABSTRACT: Introduction and objectives: This systematic review was undertaken to determine the extent to which adult subjects representing sex (female), race (non-White) and age (>50) categories are included in clinical studies of HIV curative interventions and thus, by extension, the potential for data to be analyzed that may shed light on the influence of such demographic variables on safety and/or efficacy. Methods: English-language publications retrieved from PubMed and from references of retrieved papers describing clinical studies of curative interventions were read and demographic, recruitment year and intervention-type details were noted. Variables of interest included participation by sex, age and race; changes in participation rates by recruitment year; differences in participation by intervention type. Results: Of 151 publications, 23% reported full demographic data of study enrollees, and only 6% reported conducting efficacy analyses by demographic variables. Included studies recruited participants from 1991-2011. No study conducted safety analyses by demographic variables. The representation of women, older people and non-Whites did not reflect national or international burdens of HIV infection. Participation of demographic subgroups differed by intervention type and study location. Rates of participation of demographic groups of interest did not vary with time. Limited data suggest efficacy, particularly of early therapy initiation followed by treatment interruption, may vary by demographic variables, in this case sex. Conclusion: More data are needed to determine associations between demographic characteristics and safety/efficacy of curative interventions. Studies should be powered to conduct such analyses and cure-relevant measures should be standardized.AIDS Research and Human Retroviruses 10/2014; 31(1). DOI:10.1089/AID.2014.0205 · 2.46 Impact Factor
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ABSTRACT: The antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. It has been reported that this isoflavone is able to inhibit herpes simplex virus (HSV) replication, which is associated with skin and epithelial mucosa infections. The treatment of these infections with antiherpes drugs has resulted in the emergence of resistant viral strains. Based on this evidence, the aim of this study was to investigate the anti-HSV effects of soybean isoflavonoids: daidzein, genistein, glycitein, and coumestrol. Genistein and coumestrol inhibited HSV-1 (KOS and 29R strains, which are acyclovir sensitive and acyclovir resistant, respectively) and HSV-2 (333 strain) replication, whereas no antiviral effects were detected for daidzein and glycitein. The mechanisms of action were evaluated by different methodological strategies. Coumestrol affected the early stages of viral infection, and both compounds were able to reduce HSV-1 protein expression, as well as HSV-2 cell-to-cell spread.Archives of Virology 07/2015; 160. DOI:10.1007/s00705-015-2514-z · 2.28 Impact Factor