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Dietary Supplements and Inflammation Phase-2: Isoxanthohumol as a treatment for estrogen-deficient-induced visceral hyperalgesia.

Award Number: P20GM103641
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Dietary Supplements and Inflammation Phase-2: Isoxanthohumol as a treatment for estrogen-deficient-induced visceral hyperalgesia. - PROJECT SUMMARY Chronic visceral pain is one of the most common clinical manifestations in such conditions as irritable bowel syndrome, chronic pelvic pain, pancreatitis, and interstitial cystitis. This condition is debilitating and dramatically decreases quality of life. Women are more likely to exhibit visceral pain during the low estrogen phase of the menstrual cycle and the estrogen-deficient menopause state. This clinical observation is recapitulated in animal models as visceral hypersensitivity is exacerbated during the low estrogen phase of the estrous cycle5. Furthermore, ovariectomized, estrogen-deficient mice present more visceral, mechanical, and thermal hyperalgesia than do gonadally intact, estrogen-sufficient, mice. This exacerbation of hyperalgesia exhibited by ovariectomized mice is nullified upon estrogen supplementation. However, the exact molecular mechanism(s) responsible for the protective effect of estrogen therapy on pain modulation remains unresolved. Additionally, estrogen replacement therapy is not a viable option for a number of women due to the potential negative health risks associated with its use if it is initiated after menopause. Therefore, understanding the mechanism(s) by which estrogen protects against visceral pain and developing new therapies to combat this debilitating condition is of significant clinical importance. Studies have revealed that administration of estrogen and phytoestrogen compounds in animals and humans augments microbial diversity which is a key component of a healthy and resilient gut microbiome. Pre-clinical studies have shown that sex differences exist across the lifespan in the gut-microbiome axis and it was recently revealed that estrogen-deficient-induced visceral hypersensitivity is microbiota-dependent. However, a greater understanding of the microbial composition and/or microbial metabolites that regulate this effect is lacking. To investigate the mechanisms by which estrogen and phytoestrogens mediate their anti-nociceptive effects, we propose to use isoxanthohumol (IXO), a natural phytoestrogen prenylflavonoid found in hops (Humulus lupulus L.), in conjunction with visceral hypersensitivity assessment, gut microbial sequencing, and fecal transplants to test the hypothesis that IXO and estrogen mitigate hypersensitivity via changes in the gut microbiome composition. This research will lay the foundation for understanding the mechanism by which estrogen and a new, natural therapy, IXO, reduces visceral hypersensitivity resulting from estrogen deficiency. Furthermore, the proposed research is within the scope of the parent grant as it investigates the use of a dietary compound to treat a debilitating condition. Additionally, this proposal falls in line with the mission of NCCIH to treat the pain management crisis through complementary and integrative management of pain.


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: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	10	5/23/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	10	5/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $294,004 )
2023	2023	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	10	9/1/2023	SUPPLEMENT FOR EXPANSION	$294,004
2023	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	10	8/1/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	10	11/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $294,004

Issue Date FY: 2022 ( Subtotal = $1,949,670 )
2022	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	10	7/22/2022	NON-COMPETING CONTINUATION	$1,949,670
2022	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	9	1/21/2022	NON-COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	9	12/6/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,949,670

Issue Date FY: 2021 ( Subtotal = $2,360,232 )
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	9	9/1/2021	SUPPLEMENT FOR EXPANSION	$137,937
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	9	9/9/2021	SUPPLEMENT FOR EXPANSION	$250,000
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	9	6/14/2021	NON-COMPETING CONTINUATION	$1,972,295
														Subtotal = $2,360,232

Issue Date FY: 2020 ( Subtotal = $1,994,479 )
2020	2020	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	8	8/3/2020	NON-COMPETING CONTINUATION	$1,994,479
2020	2020	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	8	9/28/2020	NON-COMPETING CONTINUATION	$0
2020	2019	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	7	2/14/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,994,479

Issue Date FY: 2019 ( Subtotal = $2,016,232 )
2019	2019	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	005	7	9/10/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	004	7	5/30/2019	NON-COMPETING CONTINUATION	$2,016,232
2019	2018	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	003	6	2/22/2019	COMPETING CONTINUATION	$62,507
2019	2016	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	5	2/22/2019	EXTENSION WITH OR WITHOUT FUNDS	-$62,507
2019	2016	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	5	2/22/2019	EXTENSION WITH OR WITHOUT FUNDS	$1,146
2019	2015	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	4	2/22/2019	NON-COMPETING CONTINUATION	-$1,146
														Subtotal = $2,016,232

Issue Date FY: 2018 ( Subtotal = $2,037,552 )
2018	2018	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	002	6	8/21/2018	COMPETING CONTINUATION	$2,037,552
2018	2016	UNIVERSITY OF SOUTH CAROLINA	1400 WHEAT ST	COLUMBIA	SC	29210	RICHLAND	USA	Biomedical Research and Research Training	000	5	5/4/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
2018	2016	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	5	8/20/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $2,037,552

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	UNIVERSITY OF SOUTH CAROLINA	1400 WHEAT ST	COLUMBIA	SC	29210	RICHLAND	USA	Biomedical Research and Research Training	001	5	12/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$91,591
2017	2015	UNIVERSITY OF SOUTH CAROLINA	1400 WHEAT ST	COLUMBIA	SC	29210	RICHLAND	USA	Biomedical Research and Research Training	000	4	12/22/2016	NON-COMPETING CONTINUATION	-$91,591
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $2,030,749 )
2016	2016	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	5	6/27/2016	EXTENSION WITH OR WITHOUT FUNDS	$2,030,749
														Subtotal = $2,030,749

Issue Date FY: 2015 ( Subtotal = $2,031,538 )
2015	2015	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	4	6/16/2015	NON-COMPETING CONTINUATION	$2,031,538
														Subtotal = $2,031,538

Issue Date FY: 2014 ( Subtotal = $2,032,289 )
2014	2014	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	3	5/27/2014	NON-COMPETING CONTINUATION	$2,032,289
														Subtotal = $2,032,289

Issue Date FY: 2013 ( Subtotal = $1,961,849 )
2013	2013	UNIVERSITY OF SOUTH CAROLINA	516 1/2 SOUTH MAIN STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	001	2	9/12/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,961,849
2013	2012	SOUTH CAROLINA RESEARCH FOUNDATION	901 SUMTER STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	1	11/2/2012	NEW	$0
														Subtotal = $1,961,849

Issue Date FY: 2012 ( Subtotal = $2,005,567 )
2012	2012	SOUTH CAROLINA RESEARCH FOUNDATION	901 SUMTER STREET	COLUMBIA	SC	29208	RICHLAND	USA	Biomedical Research and Research Training	000	1	8/15/2012	NEW	$2,005,567
														Subtotal = $2,005,567

Grand Total All Awards = $20,714,161

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Dietary Supplements and Inflammation Phase-2: Isoxanthohumol as a treatment for estrogen-deficient-induced visceral hyperalgesia.

Award Number: P20GM103641

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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