In vivo Modulation of Redox and Nitric Oxide Signaling by Lamiaceae phytochemicals




DeLeon, Robert Corey

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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 intracellular 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 adapted and developed L. terrestris 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 seminal vesicles was determined. Animals fed ad libitum 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 Caenorhabditis elegans with transcriptional reporter (GFP) constructs of relevant genes. The C. elegans model confirmed the observations in L. terrestris. All herbs had differential effects on expression of different genes considered for this study, perhaps due to different bioactive constituents.



lamiaceae, phytochemicals, oxidation, nitric oxide, reduction reaction


DeLeon, R. C. (2010). In vivo modulation of redox and nitric oxide signaling by Lamiaceae phytochemicals (Unpublished thesis). Texas State University-San Marcos, San Marcos, Texas.


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