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Science Forum Index » Life Extension Forum » Effect of Ashwagandha on activation of NF-kappaB...
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| rs1000b at (no spam) yahoo.com... |
 Posted: Sat Jun 07, 2008 11:44 am |
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Mol Cancer Ther. 2006 Jun;5(6):1434-45.
Withanolides potentiate apoptosis, inhibit invasion, and abolish
osteoclastogenesis through suppression of nuclear factor-kappaB (NF-
kappaB) activation and NF-kappaB-regulated gene expression.
Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal
BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics,
The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe
Boulevard, Houston, TX 77030, USA.
The plant Withania somnifera Dunal (Ashwagandha), also known as Indian
ginseng, is widely used in the Ayurvedic system of medicine to treat
tumors, inflammation, arthritis, asthma, and hypertension. Chemical
investigation of the roots and leaves of this plant has yielded
bioactive withanolides. Earlier studies showed that withanolides
inhibit cyclooxygenase enzymes, lipid peroxidation, and proliferation
of tumor cells. Because several genes that regulate cellular
proliferation, carcinogenesis, metastasis, and inflammation are
regulated by activation of nuclear factor-kappaB (NF-kappaB), we
hypothesized that the activity of withanolides is mediated through
modulation of NF-kappaB activation. For this report, we investigated
the effect of the withanolide on NF-kappaB and NF-kappaB-regulated
gene expression activated by various carcinogens. We found that
withanolides suppressed NF-kappaB activation induced by a variety of
inflammatory and carcinogenic agents, including tumor necrosis factor
(TNF), interleukin-1beta, doxorubicin, and cigarette smoke condensate.
Suppression was not cell type specific, as both inducible and
constitutive NF-kappaB activation was blocked by withanolides. The
suppression occurred through the inhibition of inhibitory subunit of
IkappaB alpha kinase activation, IkappaB alpha phosphorylation,
IkappaB alpha degradation, p65 phosphorylation, and subsequent p65
nuclear translocation. NF-kappaB-dependent reporter gene expression
activated by TNF, TNF receptor (TNFR) 1, TNFR-associated death domain,
TNFR-associated factor 2, and IkappaB alpha kinase was also
suppressed. Consequently, withanolide suppressed the expression of TNF-
induced NF-kappaB-regulated antiapoptotic (inhibitor of apoptosis
protein 1, Bfl-1/A1, and FADD-like interleukin-1beta-converting enzyme-
inhibitory protein) and metastatic (cyclooxygenase-2 and intercellular
adhesion molecule-1) gene products, enhanced the apoptosis induced by
TNF and chemotherapeutic agents, and suppressed cellular TNF-induced
invasion and receptor activator of NF-kappaB ligand-induced
osteoclastogenesis. Overall, our results indicate that withanolides
inhibit activation of NF-kappaB and NF-kappaB-regulated gene
expression, which may explain the ability of withanolides to enhance
apoptosis and inhibit invasion and osteoclastogenesis.
PMID: 16818501 [PubMed - indexed for MEDLINE] |
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