Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Molecular Mechanisms of Genistein in the Prevention of Inflammatory Cytokine (TNF

Award Number: R15AT005372
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2010
PERIOD OF PERFORMANCE END DATE: 03/31/2015

Group Awards By:

View Award Description

Molecular Mechanisms of Genistein in the Prevention of Inflammatory Cytokine (TNF - DESCRIPTION (provided by applicant): The long-range goal of this research is to identify bioactive components and develop novel nutraceuticals that may improve vascular function and therefore decrease the morbidity and mortality related to vascular dysfunction and related complications. Vascular inflammation and its subsequent endothelial dysfunction play a fundamental role in the initiation and progression of atherosclerosis. It is believed that tumor necrosis factor (TNF)-alpha is critically involved in the pathogenesis of atherosclerosis. Studies show that genistein may have vascular protective effects. However, the molecular mechanism of genistein action is not well understood. The main objective of this study is to evaluate the cellular mechanism of action of genistein in its protective effect on (TNF)-alpha-induced vascular dysfunction. We have collected preliminary data, which suggest a potential anti-inflammatory action of genistein against vascular dysfunction: 1) genistein, at physiological concentrations, significantly inhibited TNF-alpha-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVECs), 2) genistein significantly suppressed TNF-alpha-induced production of monocyte chemoattractant protein -1 (MCP-1) and interleukin-8 (IL-8), two chemokines that are the key factors in the firm adhesion of monocytes to activated endothelial cells, (3) TNF-alpha significantly increased NF-KB binding activity indicating that activation of the transcription factor NF-kB might be critical for the TNF-alpha-induced inflammatory response. We have recently demonstrated that genistein directly activates the cAMP/protein kinase A (PKA) signaling in endothelial cells, which is not related to any known genistein action such as inhibition of tyrosine kinase or binding to estrogen receptors. Our working hypothesis is that genistein, at physiological concentrations, suppresses TNF-alpha-induced recruit of monocytes to endothelial cells via activation of the cAMP/PKA signaling (involving modulation of plasma membrane associated G-proteins) that subsequently inhibits NF-kB activity and its regulated chemokine and adhesion molecular expression. Accordingly, the specific aims of this application are: 1) to determine whether genistein inhibits TNF-alpha-induced expression of adhesion molecules, markers of vascular inflammation and NF-kB in HUVECs, 2) to determine whether the effects of genistein on TNF- alpha-induced monocyte adhesion to endothelial cells, expression of chemokine, adhesion molecules as well as NF-KB activation is mediated through the cAMP/PKA pathway, and whether stimulation of cAMP/PKA cascade by genistein is mediated through G proteins, 3) to investigate whether dietary intake of genistein protects against TNF-alpha-induced vascular inflammation in mice. Fulfillment of the above aims will establish the cellular and molecular mechanisms of action of genistein in its protective effect against vascular dysfunction. PUBLIC HEALTH RELEVANCE: Atherosclerotic vascular disease is a major cause of morbidity and mortality in the industrial world. Our preliminary data indicate genistein, a soybean compound, is a promising agent to protect against vascular dysfunction caused by the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. The elucidation of the molecular mechanism(s) of action of genistein will provide clinically related strategies in protecting against atherosclerotic vascular disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2010	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	70 BOX, 26173	GREENSBORO	NC	27402	GUILFORD	USA	Research and Training in Complementary and Integrative Health	000	2	2/13/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $10,640 )
2012	2010	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	70 BOX, 26173	GREENSBORO	NC	27402	GUILFORD	USA	Research and Training in Complementary and Integrative Health	000	2	3/30/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$10,052
2012	2010	EDWARD VIA VA COLLEGE OF OSTEOPATHIC MEDICINE	2265 KRAFT DRIVE	BLACKSBURG	VA	24060	MONTGOMERY	USA	Research and Training in Complementary and Integrative Health	001	1	3/30/2012	NEW	$588
														Subtotal = $10,640

Issue Date FY: 2011 ( Subtotal = -$10,640 )
2011	2010	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	70 BOX, 26173	GREENSBORO	NC	27402	GUILFORD	USA	Research and Training in Complementary and Integrative Health	001	2	9/28/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$165,971
2011	2010	EDWARD VIA VA COLLEGE OF OSTEOPATHIC MEDICINE	2265 KRAFT DRIVE	BLACKSBURG	VA	24060	MONTGOMERY	USA	Research and Training in Complementary and Integrative Health	000	1	9/27/2011	NEW	-$176,611
														Subtotal = -$10,640

Issue Date FY: 2010 ( Subtotal = $229,050 )
2010	2010	EDWARD VIA VA COLLEGE OF OSTEOPATHIC MEDICINE	2265 KRAFT DRIVE	BLACKSBURG	VA	24060	MONTGOMERY	USA	Research and Training in Complementary and Integrative Health	001	1	3/5/2010	NEW	$0
2010	2010	EDWARD VIA VA COLLEGE OF OSTEOPATHIC MEDICINE	2265 KRAFT DRIVE	BLACKSBURG	VA	24060	MONTGOMERY	USA	Research and Training in Complementary and Integrative Health	000	1	2/23/2010	NEW	$229,050
														Subtotal = $229,050

Grand Total All Awards = $229,050

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular Mechanisms of Genistein in the Prevention of Inflammatory Cytokine (TNF

Award Number: R15AT005372

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2010

PERIOD OF PERFORMANCE END DATE: 03/31/2015

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer