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Carnosol, a dietary diterpene from rosemary (Rosmarinus officinalis) activates Nrf2 leading to sestrin 2 induction in colon cells.

ABSTRACT: Background:Rosemary is abundant with phytochemicals and has recently been approved as an antioxidant food preservative in the European Union. The safety of rosemary is well established, however, the benefits on gastrointestinal health are less known. Our overall hypothesis is that the phytochemicals in rosemary including carnosol have the potential to promote gastrointestinal health by activation of the antioxidant sestrin-2 when consumed in our diet. Methods:Colon cells HCT116 and SW480 were treated with carnosol and evaluated by MTT, immunofluorescence, ELISA, and Western blot analysis to understand the modulation of the PERK/Nrf2/Sestrin-2 pathway. Results:Carnosol was found to modulate PERK and increase the concentration of nuclear Nrf2. Furthermore, a downstream marker of Nrf2 expression, Sestrin-2 was shown to be upregulated. Conclusion:Based on these observations carnosol modulates the PERK and Nrf2 pathways along with increased expression of sestrin-2, a known stress inducible antioxidant.

SUBMITTER: Yan M

PROVIDER: S-EPMC6453141 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Carnosol, a dietary diterpene from rosemary (<i>Rosmarinus officinalis</i>) activates Nrf2 leading to sestrin 2 induction in colon cells.

Yan Miao M Vemu Bhaskar B Veenstra Jacob J Petiwala Sakina M SM Johnson Jeremy J JJ

Integrative molecular medicine 20180815 4

<h4>Background</h4>Rosemary is abundant with phytochemicals and has recently been approved as an antioxidant food preservative in the European Union. The safety of rosemary is well established, however, the benefits on gastrointestinal health are less known. Our overall hypothesis is that the phytochemicals in rosemary including carnosol have the potential to promote gastrointestinal health by activation of the antioxidant sestrin-2 when consumed in our diet.<h4>Methods</h4>Colon cells HCT116 an ...[more]

PMID: 30972223

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Project description:BackgroundNatural antioxidant products are increasingly being used to treat various pathological liver conditions considering the role of oxidative stress in their pathogenesis. Rosemary essential oil has already being used as a preservative in food industry due to its antioxidant and antimicrobial activities, but it was shown to possess additional health benefits. The aim of our study was to evaluate the protective effect of rosemary essential oil on carbon tetrachloride - induced liver injury in rats and to explore whether its mechanism of action is associated with modulation of hepatic oxidative status.MethodsChemical composition of isolated rosemary essential oil was determined by gas chromatography and mass spectrometry. Antioxidant activity was determined in vitro using DPPH assay. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods.ResultsIn this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8-cineole (43.77%), camphor (12.53%), and α-pinene (11.51%). Investigated essential oil was found to exert hepatoprotective effects in the doses of 5 mg/kg and 10 mg/kg by diminishing AST and ALT activities up to 2-fold in serum of rats with carbon tetrachloride-induced acute liver damage. Rosemary essential oil prevented carbon tetrachloride-induced increase of lipid peroxidation in liver homogenates. Furthermore, pre-treatment with studied essential oil during 7 days significantly reversed the activities of antioxidant enzymes catalase, peroxidase, glutathione peroxidase and glutathione reductase in liver homogenates, especially in the dose of 10 mg/kg.ConclusionsOur results demonstrate that rosemary essential oil, beside exhibiting free radical scavenging activity determined by DPPH assay, mediates its hepatoprotective effects also through activation of physiological defense mechanisms.

Project description:It is unclear whether light affects the structure and activity of exogenous secretory tissues like glandular hairs. Therefore, transmission electron microscopy was first used to study plastid differentiation in glandular hairs and leaves of light-grown rosemary (Rosmarinus officinalis "Arp") plants kept for 2 weeks under ambient light conditions. During our detailed analyses, among others, we found leucoplasts with tubuloreticular membrane structures resembling prolamellar bodies in stalk cell plastids of peltate glandular hairs. To study the effect of darkness on plastid differentiation, we then dark-forced adult, light-grown rosemary plants for 2 weeks and observed occasionally the development of new shoots with elongated internodes and pale leaves on them. Absorption and fluorescence spectroscopic analyses of the chlorophyllous pigment contents, the native arrangement of the pigment-protein complexes and photosynthetic activity confirmed that the first and second pairs of leaf primordia of dark-forced shoots were partially etiolated (contained low amounts of protochlorophyll/ide and residual chlorophylls, had etio-chloroplasts with prolamellar bodies and low grana, and impaired photosynthesis). Darkness did not influence plastid structure in fifth leaves or secretory tissues (except for head cells of peltate glandular hairs in which rarely tubuloreticular membranes appeared). The mesophyll cells of cotyledons of 2-week-old dark-germinated rosemary seedlings contained etioplasts with highly regular prolamellar bodies similar to those in mesophyll etio-chloroplasts of leaves and clearly differing from tubuloreticular membranes of secretory cells. Analyses of the essential oil composition obtained after solid phase microextraction and gas chromatography-mass spectroscopy showed that in addition to light, the age of the studied organ (i.e., first leaf primordia and leaf tip vs. fifth, fully developed green leaves) and the type of the organ (cotyledon vs. leaves) also strongly influenced the essential oil composition. Therefore, light conditions and developmental stage are both important factors to be considered in case of potential therapeutic, culinary or aromatic uses of rosemary leaves and their essential oils.

Dataset Information

Carnosol, a dietary diterpene from rosemary (Rosmarinus officinalis) activates Nrf2 leading to sestrin 2 induction in colon cells.

Publications

Carnosol, a dietary diterpene from rosemary (<i>Rosmarinus officinalis</i>) activates Nrf2 leading to sestrin 2 induction in colon cells.

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