In vivo Modulation of Redox and Nitric Oxide Signaling by Lamiaceae phytochemicals
Date
2010-08
Authors
DeLeon, Robert Corey
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Abstract
Cells are constantly exposed to free radicals as part of normal metabolic
processes. However, in certain conditions the homeostatic balance that exists between
free radicals and cellular antioxidants can be altered, resulting in oxidative stress. In this
state, excess free radicals can damage surrounding macromolecules and subsequently
inhibit normal cell function which can lead to the progression of many chronic diseases.
Plant secondary metabolites are biologically active molecules known to effectively
manage adverse health conditions associated with oxidative stress. In fact,
epidemiological data has shown that diets rich in plant foods are inversely related to risk
for chronic disease. Herbs and spices generally are concentrated sources of a variety of plant secondary metabolites including phenolic compounds, carotenoids, saponins, and
alkaloids. These phytochemicals have chemical structures and electrochemical properties
that are capable of modulating the mtracellular redox environment by stabilizing free
radicals and by increasing the activity and/or expression of important antioxidant
enzymes. The Lamiaceae herb family is large group containing approximately 3200
species grown worldwide for medicinal and culinary purposes. Research has previously
shown these herbs to have antibacterial, antiviral, antioxidant, and anti-cancer properties
which are largely contributed to their phytochemical profiles. The recent evaluations of
these plant's secondary metabolites and their biological functions have importance as
therapeutic agents for various health implications However, the mechanism of action by
which this occurs in vivo is not very well understood. Therefore, the objectives of this
study were to determine the biochemical, physiological, and molecular effects of plant
secondary metabolites from Lamiaceae herbs on redox and nitric oxide signaling in vivo
in Lumbricus terrestris. We have adapated and developed L. terrestrzs as a model system
to study oxidative stress (Hutton et al., 2009). In the current study, the effect of dietary
Lamiaceae herbs on modulating redox/nitric oxide (NO) signaling and sperm quality in
the oxidation prone environment of semmal vesicles was determined. Animals fed ad
bbitum on Lumbricus growth medium (LGM) supplemented with 0% ( control), 0.1 % or
0.5% (w/v) of different herbs. Additionally, the effects of different combinations of
Lamiaceae herbs on modulating redox/nitric oxide signaling in L. terrestris were
conducted. In this objective, the standard LGM was supplemented with two different
Lamiaceae herbs, each at a concentration of 0.05% (w/v). Also, the modulatory effects of
Lamiaceae herbs on a peroxide induced oxidative stress were studied. The seminal vesicles of the animal were dissected out on day 2 and day 6, and gently disrupted. Levels
of malondialdehyde (MDA), DNA fragmentation (DNAF), glutathione (GSH),
nitrates/nitrites (NOx), superoxide dismutase (SOD), catalase (CAT) were determined
using standard assays. Sperm maturity and deformation (DFO) was quantified
microscopically. Data analysis suggests modulation of redox response via protein kinase
C, ARE-Nrf2 and AP-2 mediated expression of SOD, glutathione peroxidase and Nitric
oxide synthase. Additionally, to understand the mechanism of redox modulation by
Lamiaceae herbs we used transgenic strains of Caenorhabdztzs elegans with
transcriptional reporter (GFP) constructs of relevant genes. The C. elegans model
confirmed the observations in L. terrestrzs. All herbs had differential effects on
expression of different genes considered for this study, perhaps due to different bioactive
constituents.
Description
Keywords
Lamiaceae, Phytochemicals, Oxidation, Nitric oxide, Reduction reaction
Citation
DeLeon, R. C. (2010). <i>In vivo modulation of redox and nitric oxide signaling by Lamiaceae phytochemicals</i> (Unpublished thesis). Texas State University-San Marcos, San Marcos, Texas.