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Article ; Online: Isothiocyanates: Translating the Power of Plants to People.

Palliyaguru, Dushani L / Yuan, Jian-Min / Kensler, Thomas W / Fahey, Jed W

2018 Volume 62, Issue 18, Page(s) e1700965

Abstract: Isothiocyanates from cruciferous vegetables have been studied extensively in cells and in animals for their disease preventive and therapeutic effects. However, translating their utility to human populations has been both limited and challenging. Herein, ...

Abstract	Isothiocyanates from cruciferous vegetables have been studied extensively in cells and in animals for their disease preventive and therapeutic effects. However, translating their utility to human populations has been both limited and challenging. Herein, clinical trials employing two isothiocyanates, sulforaphane (SFN; 1-isothiocyanato-4-(methylsulfinyl) butane) and phenethyl isothiocyanate (PEITC; 2-isothiocyanatoethylbenzene) that are isolated principally from broccoli and watercress, respectively, are summarized and discussed. Both of these compounds have been used in small human clinical trials, either within food matrices or as single agents, against a variety of diseases ranging from cancer to autism. Results suggest an opportunity to incorporate them, or more likely preparations derived from their source plants, into larger human disease mitigation efforts. The context for the applications of these compounds and plants in evidence-based food and nutritional policy is also evaluated.
MeSH term(s)	Brassica/chemistry ; Cardiovascular Diseases/drug therapy ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2/drug therapy ; Humans ; Isothiocyanates/chemistry ; Isothiocyanates/pharmacology ; Neoplasms/drug therapy ; Skin Diseases/drug therapy ; Sulfoxides ; Treatment Outcome ; Vegetables/chemistry
Chemical Substances	Isothiocyanates ; Sulfoxides ; phenethyl isothiocyanate (6U7TFK75KV) ; sulforaphane (GA49J4310U)
Language	English
Publishing date	2018-03-26
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201700965
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Withania somnifera: From prevention to treatment of cancer.

Palliyaguru, Dushani L / Singh, Shivendra V / Kensler, Thomas W

Molecular nutrition & food research

2016 Volume 60, Issue 6, Page(s) 1342–1353

Abstract: The identification of bioactive molecules that have potential to interrupt carcinogenesis continues to garner research interest. In particular, molecules that have dietary origin are most attractive because of their safety, cost-effectiveness and ... ...

Abstract	The identification of bioactive molecules that have potential to interrupt carcinogenesis continues to garner research interest. In particular, molecules that have dietary origin are most attractive because of their safety, cost-effectiveness and feasibility of oral administration. Nutraceuticals have played an important role in the overall well-being of humans for many years, with or without rigorous evidence backing their health claims. Traditional medicine systems around the world have utilized plants that have medicinal properties for millennia, providing an opportunity for modern day researchers to assess their efficacies against ailments such as cancer. Withania somnifera (WS) is a plant that has been used in Ayurveda (an ancient form of medicine in Asia) and in the recent past, has been demonstrated to have anti-tumorigenic properties in experimental models. While scientific research performed on WS has exploded in the past decade, much regarding the mode of action and molecular targets involved remains unknown. In this review, we discuss the traditional uses of the plant, the experimental evidence supporting its chemopreventive potential as well as roadblocks that need to be overcome in order for WS to be evaluated as a chemopreventive agent in humans.
Language	English
Publishing date	2016-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201500756
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Frailty index as a biomarker of lifespan and healthspan: Focus on pharmacological interventions.

Palliyaguru, Dushani L / Moats, Jacqueline M / Di Germanio, Clara / Bernier, Michel / de Cabo, Rafael

Mechanisms of ageing and development

2019 Volume 180, Page(s) 42–48

Abstract: Although survival has been the focus of aging research for many years, the field is rapidly evolving towards incorporating healthspan and health indices in studies that explore aging-related outcomes. Frailty is one such measure that is tightly ... ...

Abstract	Although survival has been the focus of aging research for many years, the field is rapidly evolving towards incorporating healthspan and health indices in studies that explore aging-related outcomes. Frailty is one such measure that is tightly correlated with human aging. Several frailty measures have been developed that focus on phenotypes of aging, including physical, cognitive and metabolic health that define healthspan. The extent at which cumulative deficits associated with frailty predict functional characteristics of healthy aging and longevity is currently unknown. A growing consensus for the use of animal models has emerged to evaluate a composite measure of frailty that provides a translational basis to understanding human frailty. In this review, we will focus on the impact of several anti-aging interventions, some of which have been characterized as caloric restriction (CR) mimetics such as metformin, rapamycin, and resveratrol as well as more novel approaches that are emerging in the field - nicotinamide adenine dinucleotide precursors, small molecule activators of sirtuins, and senolytics - on a number of frailty measurements associated with aging-related outcomes in mice and discuss the translatability of such measures to human frailty.
MeSH term(s)	Animals ; Caloric Restriction ; Frailty/metabolism ; Frailty/pathology ; Frailty/therapy ; Humans ; Longevity/drug effects ; Metformin/therapeutic use ; Resveratrol/therapeutic use ; Sirolimus/therapeutic use
Chemical Substances	Metformin (9100L32L2N) ; Resveratrol (Q369O8926L) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2019-03-26
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	183915-9
ISSN	1872-6216 ; 0047-6374
ISSN (online)	1872-6216
ISSN	0047-6374
DOI	10.1016/j.mad.2019.03.005
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Article ; Online: Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane.

Yang, Li / Palliyaguru, Dushani L / Kensler, Thomas W

Seminars in oncology

2015 Volume 43, Issue 1, Page(s) 146–153

Abstract: With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-( ... ...

Abstract	With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, preclinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2-Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention.
MeSH term(s)	Animals ; Anticarcinogenic Agents/metabolism ; Anticarcinogenic Agents/pharmacokinetics ; Anticarcinogenic Agents/pharmacology ; Brassica ; Chemoprevention ; Glucosinolates/metabolism ; Glucosinolates/pharmacology ; Humans ; Imidoesters/metabolism ; Imidoesters/pharmacology ; Isothiocyanates/metabolism ; Isothiocyanates/pharmacokinetics ; Isothiocyanates/pharmacology ; NF-E2-Related Factor 2/antagonists & inhibitors ; Neoplasms/epidemiology ; Neoplasms/metabolism ; Neoplasms/prevention & control ; Signal Transduction/drug effects ; Vegetables
Chemical Substances	Anticarcinogenic Agents ; Glucosinolates ; Imidoesters ; Isothiocyanates ; NF-E2-Related Factor 2 ; sulforaphane (GA49J4310U) ; glucoraphanin (Q86A197713)
Language	English
Publishing date	2015-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	189220-4
ISSN	1532-8708 ; 0093-7754
ISSN (online)	1532-8708
ISSN	0093-7754
DOI	10.1053/j.seminoncol.2015.09.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1348: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Isothiocyanates: Translating the Power of Plants to People

Palliyaguru, Dushani L / Yuan, Jian‐Min / Kensler, Thomas W / Fahey, Jed W

Molecular nutrition & food research. 2018 Sept., v. 62, no. 18

2018

Abstract	Isothiocyanates from cruciferous vegetables have been studied extensively in cells and in animals for their disease preventive and therapeutic effects. However, translating their utility to human populations has been both limited and challenging. Herein, clinical trials employing two isothiocyanates, sulforaphane (SFN; 1‐isothiocyanato‐4‐(methylsulfinyl) butane) and phenethyl isothiocyanate (PEITC; 2‐isothiocyanatoethylbenzene) that are isolated principally from broccoli and watercress, respectively, are summarized and discussed. Both of these compounds have been used in small human clinical trials, either within food matrices or as single agents, against a variety of diseases ranging from cancer to autism. Results suggest an opportunity to incorporate them, or more likely preparations derived from their source plants, into larger human disease mitigation efforts. The context for the applications of these compounds and plants in evidence‐based food and nutritional policy is also evaluated.
Keywords	Brassicaceae ; autism ; broccoli ; butanes ; clinical trials ; food matrix ; human diseases ; human population ; neoplasms ; nutrition policy ; sulforaphane ; therapeutics ; watercress
Language	English
Dates of publication	2018-09
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201700965
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Perinatal diet influences health and survival in a mouse model of leukemia.

Palliyaguru, Dushani L / Rudderow, Annamaria L / Sossong, Alex M / Lewis, Kaitlyn N / Younts, Caitlin / Pearson, Kevin J / Bernier, Michel / de Cabo, Rafael

GeroScience

2020 Volume 42, Issue 4, Page(s) 1147–1155

Abstract: The goal of the current study was to determine the role of maternal diet in the perinatal period on the health and survival of the offspring. AKR/J mice, a model described to be susceptible to leukemia development, was used where females were maintained ... ...

Abstract	The goal of the current study was to determine the role of maternal diet in the perinatal period on the health and survival of the offspring. AKR/J mice, a model described to be susceptible to leukemia development, was used where females were maintained on either standard diet (SD), high sucrose diet, Western diet, or calorie restriction (CR) as they were mated with SD-fed males. Body weights, pregnancy rates, litter size, and litter survival were used as markers of successful pregnancy and pup health. Data indicated that maternal diet had significant effects on litter size, early pup survival, and early pup body weights. As pups matured, the makeup of their respective maternal diet was a predictor of adult metabolic health and survival. Overall, these results suggest that perinatal maternal diet is an important determinant of the health and survival of the offspring and that these effects continue well into adulthood, strongly correlating with lifespan.
MeSH term(s)	Animals ; Body Weight ; Diet ; Female ; Leukemia ; Male ; Mice ; Pregnancy ; Reproduction
Language	English
Publishing date	2020-05-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-020-00199-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1502: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Sulforaphane Diminishes the Formation of Mammary Tumors in Rats Exposed to 17β-Estradiol

Palliyaguru, Dushani L / Yang, Li / Chartoumpekis, Dionysios V / Wendell, Stacy G / Fazzari, Marco / Skoko, John J / Liao, Yong / Oesterreich, Steffi / Michalopoulos, George K / Kensler, Thomas W

Nutrients. 2020 July 30, v. 12, no. 8

2020

Abstract: Elevated levels of estrogen are a risk factor for breast cancer. In addition to inducing DNA damage, estrogens can enhance cell proliferation as well as modulate fatty acid metabolism that collectively contributes to mammary tumorigenesis. Sulforaphane ( ... ...

Abstract	Elevated levels of estrogen are a risk factor for breast cancer. In addition to inducing DNA damage, estrogens can enhance cell proliferation as well as modulate fatty acid metabolism that collectively contributes to mammary tumorigenesis. Sulforaphane (SFN) is an isothiocyanate derived from broccoli that is currently under evaluation in multiple clinical trials for prevention of several diseases, including cancer. Previous studies showed that SFN suppressed DNA damage and lipogenesis pathways. Therefore, we hypothesized that administering SFN to animals that are co-exposed to 17β-estradiol (E2) would prevent mammary tumor formation. In our study, 4–6 week old female August Copenhagen Irish rats were implanted with slow-release E2 pellets (3 mg x 3 times) and gavaged 3x/week with either vehicle or 100 μmol/kg SFN for 56 weeks. SFN-treated rats were protected significantly against mammary tumor formation compared to vehicle controls. Mammary glands of SFN-treated rats showed decreased DNA damage while serum free fatty acids and triglyceride species were 1.5 to 2-fold lower in SFN-treated rats. Further characterization also showed that SFN diminished expression of enzymes involved in mammary gland lipogenesis. This study indicated that SFN protects against breast cancer development through multiple potential mechanisms in a clinically relevant hormonal carcinogenesis model.
Keywords	DNA damage ; blood serum ; breast neoplasms ; broccoli ; carcinogenesis ; cell proliferation ; estrogens ; fatty acid metabolism ; females ; lipogenesis ; mammary glands ; mammary neoplasms (animal) ; models ; risk factors ; sulforaphane ; triacylglycerols
Language	English
Dates of publication	2020-0730
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12082282
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Spontaneous chordoma: a case report on a female UM-HET3 mouse from the SLAM study.

Duregon, Eleonora / Vieira Ligo Teixeira, Camila / Palliyaguru, Dushani L / Rudderow, Annamaria L / Hoffmann, Victoria / Bernier, Michel / Price, Nathan L / Camandola, Simonetta / de Cabo, Rafael

Aging pathobiology and therapeutics

2021 Volume 2, Issue 4, Page(s) 219–222

Abstract: A female UM-HET3 mouse from the Study of Longitudinal Aging in Mice (SLAM) was euthanized at 164 weeks of age due to hind limb weakness. Necropsy and histological analysis revealed that the most probable cause of the clinical finding was the compression ... ...

Abstract	A female UM-HET3 mouse from the Study of Longitudinal Aging in Mice (SLAM) was euthanized at 164 weeks of age due to hind limb weakness. Necropsy and histological analysis revealed that the most probable cause of the clinical finding was the compression of the thoracolumbar segment of the spinal cord by herniated intervertebral disks. In addition, a spontaneous chordoma was incidentally found in the coccygeal bones. Given the rarity of this type of tumor, bio-clinical annotations acquired throughout lifespan, detailed histopathological assessment, and comparative clinical-pathological correlations for this mouse are presented and discussed.
Language	English
Publishing date	2021-03-03
Document type	Journal Article
ISSN	2690-1803
ISSN (online)	2690-1803
DOI	10.31491/apt.2020.12.043
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Withania somnifera: From prevention to treatment of cancer

Palliyaguru, Dushani L / Singh, Shivendra V / Kensler, Thomas W

Molecular nutrition & food research. 2016 June, v. 60, no. 6

2016

Abstract	The identification of bioactive molecules that have potential to interrupt carcinogenesis continues to garner research interest. In particular, molecules that have dietary origin are most attractive because of their safety, cost‐effectiveness and feasibility of oral administration. Nutraceuticals have played an important role in the overall well‐being of humans for many years, with or without rigorous evidence backing their health claims. Traditional medicine systems around the world have utilized plants that have medicinal properties for millennia, providing an opportunity for modern day researchers to assess their efficacies against ailments such as cancer. Withania somnifera (WS) is a plant that has been used in Ayurveda (an ancient form of medicine in Asia) and in the recent past, has been demonstrated to have anti‐tumorigenic properties in experimental models. While scientific research performed on WS has exploded in the past decade, much regarding the mode of action and molecular targets involved remains unknown. In this review, we discuss the traditional uses of the plant, the experimental evidence supporting its chemopreventive potential as well as roadblocks that need to be overcome in order for WS to be evaluated as a chemopreventive agent in humans.
Keywords	Ayurvedic medicine ; Withania somnifera ; carcinogenesis ; chemoprevention ; cost effectiveness ; functional foods ; health claims ; humans ; mechanism of action ; medicinal properties ; models ; neoplasms ; oral administration ; Asia
Language	English
Dates of publication	2016-06
Size	p. 1342-1353.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201500756
Database	NAL-Catalogue (AGRICOLA)

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Article: Evaluation of 2‐Thiothiazolidine‐4‐Carboxylic Acid, a Common Metabolite of Isothiocyanates, as a Potential Biomarker of Cruciferous Vegetable Intake

Palliyaguru, Dushani L / Salvatore, Sonia R / Schopfer, Francisco J / Cheng, Xuemei / Zhou, Jingyang / Kensler, Thomas W / Wendell, Stacy G

Molecular nutrition & food research. 2019 Feb., v. 63, no. 3

2019

Abstract: SCOPE: Cruciferous vegetable consumption is associated with favorable health outcomes. Bioactive compounds arising in these, especially isothiocyanates, exert effects that contribute to prevention of disease, in large part through the attenuation of ... ...

Abstract	SCOPE: Cruciferous vegetable consumption is associated with favorable health outcomes. Bioactive compounds arising in these, especially isothiocyanates, exert effects that contribute to prevention of disease, in large part through the attenuation of inflammation and oxidative stress. However, much about isothiocyanate metabolites and their role as biomarkers of crucifer intake remain unknown. METHODS AND RESULTS: The utility and limitations of 2‐thiothiazolidine‐4‐carboxylic acid (TTCA) as a urinary biomarker of broccoli beverage intake are tested in a randomized crossover clinical trial where 50 participants consumed either a glucoraphanin‐rich (GRR) or sulforaphane‐rich (SFR) beverage. Compared to run‐in and wash‐out periods, significantly higher urinary TTCA is observed after broccoli beverage consumption. Measurements also show that TTCA is present in beverage powders and in all tested cruciferous vegetables. GRR results in excretion of ≈87% of the ingested TTCA while SFR results in excretion of ≈176%. Elevated urinary TTCA is observed in rats administered 100 μmol kg–1 SFN. Unlike SFN, TTCA does not activate Nrf2‐mediated cytoprotective signaling. CONCLUSION: Collectively, TTCA appears to be a common isothiocyanate‐derived metabolite that has the capacity to be utilized as a biomarker of cruciferous vegetables that would be beneficial for objective and quantitative tracking of intake in studies.
Keywords	Brassicaceae ; beverages ; bioactive compounds ; biomarkers ; broccoli ; carboxylic acids ; clinical trials ; disease prevention ; excretion ; inflammation ; isothiocyanates ; metabolites ; oxidative stress ; powders ; rats ; vegetable consumption
Language	English
Dates of publication	2019-02
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201801029
Database	NAL-Catalogue (AGRICOLA)

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