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Anti-inflammatory, epigenetic regulatory role of phytochemicals and pkpd modeling of pharmacological effects
Descriptive
TitleInfo
Title
Anti-inflammatory, epigenetic regulatory role of phytochemicals and pkpd modeling of pharmacological effects
Name
(type = personal)
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Boyanapalli
NamePart
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Sarandeep S S
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Sarandeep S S Boyanapalli
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author
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Kong
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Ah-Ng Tony
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Ah-Ng Tony Kong
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Advisory Committee
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chair
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Hatefi
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Arasha
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Arasha Hatefi
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Advisory Committee
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internal member
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(type = personal)
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(type = family)
Androulakis
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Ioannis P
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Ioannis P Androulakis
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Advisory Committee
Role
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internal member
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(type = family)
Verzi
NamePart
(type = given)
Michael
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Michael Verzi
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Advisory Committee
Role
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(authority = RULIB)
outside member
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
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Text
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theses
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2016
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2016-05
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2016
Place
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xx
Language
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eng
Abstract
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Chronic inflammation is considered to play an important factor in neoplastic progression via the induction of reactive oxygen, reactive nitrogen species and induction of growth promoting cytokines. Thus, it is very important to develop new drugs that can inhibit inflammation and prevent cancer formation or progression. Dietary phytochemicals are derived from natural sources and are found commonly in the fruits and vegetables consumed regularly as part of the diet. Understanding the mechanism by which the natural compounds inhibit inflammation and prevent cancers is very important and could pave way to developing new targets and drugs for chemoprevention. During my dissertation, I have studied the anti-inflammatory properties of phytochemicals like Curcumin, Phenethylisothiocyanate (PEITC) and Ursolic acid (UA). The importance of Nrf2, a transcription factor in attenuating inflammation was studied using macrophages from Nrf2 (+/+) and Nrf2 (-/-) mice. The results showed that Nrf2 plays a major role in the anti-inflammatory effects of Curcumin and PEITC as seen from the differences between Nrf2 (+/+) and Nrf2 (-/-) mice macrophages. The anti-inflammatory effect of Curcumin was further evaluated iii in rats. The results showed that Curcumin suppressed lipopolysaccharide (LPS) induced inflammation as well as some epigenetic modifying genes like DNA methyltransferases and Histone deacetylases. The pharmacological response was modeled using an indirect response approach.The epigenetic modulatory role of PEITC was tested in LNCaP (androgne sensitive human prostate adenocarcinoma) cells, the results revealed that PEITC inhibits DNA methylation and increased transcription of RASSF1A, a tumor suppressor gene and in turn promotes apoptosis. Ursolic acid (UA), a pentacyclic triterpenoid was studied for its anti-inflammatory and epigeneitc modulatory role in PTEN-CaP2 cells (Prostate specific PTEN null epithelial cell line). UA suppressed LPS induced inflammatory cytokines as well as inhibited HDAC protein expression along with increasing the expression of Nrf2 a master regulator of anti-oxidate stress response pathway and NQO1. Collectively, the results demonstrated the anti-inflammatory and epigenetic modulatory potential of phytochemicals in vitro and in vivo.
Subject
(authority = RUETD)
Topic
Pharmaceutical Science
Subject
(authority = ETD-LCSH)
Topic
Phytochemicals
Subject
(authority = ETD-LCSH)
Topic
Inflammation
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
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ETD_7147
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (xviii, 143 p. : ill.)
Note
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Ph.D.
Note
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Includes bibliographical references
Note
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by Sarandeep S S Boyanapalli
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TitleInfo
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
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doi:10.7282/T32N54FN
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Boyanapalli
GivenName
Sarandeep
MiddleName
S S
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Copyright Holder
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Permission or license
DateTime
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2016-04-09 11:22:49
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Name
Sarandeep Boyanapalli
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Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
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License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2016-07-26T10:06:01
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