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Pharmacological characterization of brassinosteroids for anabolic and cosmetic applications
Descriptive
TitleInfo
Title
Pharmacological characterization of brassinosteroids for anabolic and cosmetic applications
Name
(type = personal)
NamePart
(type = family)
Esposito
NamePart
(type = given)
Debora Araujo
NamePart
(type = date)
1982-
DisplayForm
Debora Esposito
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
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(type = family)
Raskin
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(type = given)
Ilya
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Ilya Raskin
Affiliation
Advisory Committee
Role
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chair
Name
(type = personal)
NamePart
(type = family)
Gianfagna
NamePart
(type = given)
Thomas
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Thomas Gianfagna
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Huang
NamePart
(type = given)
Bingru
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Bingru Huang
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Shapses
NamePart
(type = given)
Sue
DisplayForm
Sue Shapses
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = personal)
NamePart
(type = family)
Cohick
NamePart
(type = given)
Wendie
DisplayForm
Wendie Cohick
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
TypeOfResource
Text
Genre
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theses
OriginInfo
DateCreated
(qualifier = exact)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-01
CopyrightDate
(qualifier = exact)
2012
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Brassinosteroids (BR) are plant-specific polyhydroxylated derivatives of 5α- cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with unknown function in mammals. This research project was designed to conduct a pharmacological characterization of brassinosteroids in cell culture and small animal models in order to: (1) Elucidate the putative anabolic effect of BR in mammals (2) Establish a structure-activity relationship between BR and their effects on protein synthesis and (3) Measure the effects of BR on glucose metabolism and wound healing. 28-Homobrassinolide (HB) stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 = 4 μM) mediated in part by PI3K/Akt. Oral administration of HB to healthy rats increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass. Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity. Moreover, HB showed no direct binding to the androgen receptor in vitro. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side effects. Next, we synthesized a set of HB analogues and studied their anabolic efficacy in the L6 rat skeletal muscle cells. All anabolic brassinosteroids tested in this study selectively activated the PI3K/Akt signaling pathway as seen by increased Akt phosphorylation in vitro. In C57BL/6J high fat diet-induced obese mice, acute oral administration of 50- 300 mg/kg HB to obese mice resulted in a dose-dependent decrease in fasting blood glucose. Daily chronic administration of HB (50 mg/kg for 8 weeks) ameliorated hyperglycemia and improved oral glucose tolerance associated with obesity without significantly affecting body weight or body composition. Akt is also a key signaling integrator suppressed in slow healing wounds. When C57BL/6J mice were given a dermal wound, topical application of brassinosteroids significantly reduced wound size after 10 days of treatment. Our data suggest that topical brassinosteroids accelerate the wound-healing process in part by shortening the early inflammatory phase and enhancing migration and wound repair by stimulating the PI3K/Akt pathway. Targeting this specific signaling pathway with brassinosteroids may represent a promising approach to the therapy of physical performance, glucose metabolism, and delayed wound healing.
Subject
(authority = RUETD)
Topic
Plant Biology
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_3790
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiii, 171 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Debora Araujo Esposito
Subject
(authority = ETD-LCSH)
Topic
Brassinosteroids--Research
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064080
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3M61J9S
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Esposito
GivenName
Debora
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2012-01-05 20:48:51
AssociatedEntity
Name
Debora Esposito
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
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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19814400
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application/pdf
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