Home | About | Quick Start | FAQ
Beta Version 0.1
DHARA is an online index of articles on Ayurveda published in research journals worldwide. Users Online: 20
  Enter Keyword Below :
      
Advanced

The Journal of Pharmacology and Experimental Therapeutics 2007 Mar ; (3) :0
Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide-stimulated microglial cells.
Park JS,   Woo MS,   Kim DH,   Hyun JW,   Kim WK,   Lee JC,   Kim HS  

Abstract
The microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory cytokines and nitric oxide (NO). We found that three types of isoflavones and their metabolites that are transformed by the human intestinal microflora suppress lipopolysaccharide (LPS)-induced release of NO and tumor necrosis factor (TNF)-alpha in primary cultured microglia and BV2 microglial cell lines. The inhibitory effect of the isoflavone metabolites (aglycon form) was more potent than that of isoflavones (glycoside form). The RNase protection assay showed that the isoflavone metabolites regulated inducible nitric oxide synthase (iNOS) and the cytokines at either the transcriptional or post-transcriptional level. A further molecular mechanism study was performed for irisolidone, a metabolite of kakkalide, which had the most potent anti-inflammatory effect among the six isoflavones tested. Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.

DHARA ID: D030563 Pubmed ID: 17194798


Access to Full Paper Not Available
Copyright | Disclaimer | Feedback | Updates | Contact
Developed and maintained by AVP Research Foundation (Formerly AVT Institute for Advanced Research), 136/137, Trichy Road, Ramanathapuram, Coimbatore - 641045, Tamil Nadu, India
Funded by Central Council for Research in Ayurvedic Sciences, Dept. of AYUSH, Ministry of Health and Family Welfare, Government of India, New Delhi