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Published on: July 7, 2014
Protective effects of saffron and its active components against oxidative stress and apoptosis in endothelial cells
Niloufar Rahiman1, Maryam Akaberi2, Amirhossein Sahebkar3
1Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
In this study, we investigated the role of mitogen-activated protein kinase (MAPK) signaling pathways in mediation of the protective effects of saffron extract, saffron essential oil, safranal and crocin on bovine aortic endothelial cells against oxidative injury. The viability of cells in response to H2O2-induced toxicity (0.4, 2 and 10 mM) was measured using resazurin assay in the presence or absence of saffron extract (2-40 μg/ml), saffron oil (2-40 μg/ml), safranal (2-40 μM) and crocin (2-40 μM). Dichlorodihydrofluorescin diacetate was used as an indicator for the amount of reactive oxygen species (ROS) in cells at the same concentrations of samples as the former test. In addition, propidium iodide staining of the fragmented DNA was performed to measure the level of apoptotic cells by the application of 2-10 μM of crocin and safranal. Finally, the proteins involved in apoptosis were detected using western blotting at the concentration of 0, 2, 10 μM for crocin and safranal. The results indicated that all tested moieties improved viability and reduced ROS production in H2O2-treated cells (p < 0.001 compared to H2O2). In addition, a significant decrease in apoptosis (3-35%) was observed in the cells that were treated with crocin and safranal. The observed protective effects of crocin and safranal were associated with the activation of SAPK/JNK and inhibition of ERK ½ that are related to MAPK pathways. The antioxidant and anti-apoptotic activities of saffron and its ingredients in endothelial cells are mediated via MAPK signaling pathways and might be of therapeutic potential for endothelial dysfunctionalities.
Insights
Saffron compounds, including safranal and crocin, protect bovine aortic endothelial cells from oxidative stress by reducing reactive oxygen species and apoptosis. These effects are mediated by mitogen-activated protein kinase (MAPK) pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Oxidative stress is a major contributor to endothelial dysfunction.
- Saffron and its constituents possess known antioxidant properties.
- Mitogen-activated protein kinase (MAPK) pathways play critical roles in cellular responses to stress.
Purpose of the Study:
- To investigate the protective mechanisms of saffron extract, essential oil, safranal, and crocin against oxidative injury in bovine aortic endothelial cells.
- To elucidate the role of MAPK signaling pathways in mediating these protective effects.
Main Methods:
- Cell viability was assessed using resazurin assay following hydrogen peroxide (H2O2) exposure.
- Reactive oxygen species (ROS) production was measured using dichlorodihydrofluorescin diacetate.
- Apoptosis was quantified via propidium iodide staining and DNA fragmentation analysis.
- Western blotting was employed to detect apoptosis-related proteins and MAPK pathway activation (SAPK/JNK, ERK1/2).
Main Results:
- Saffron extract, saffron oil, safranal, and crocin significantly improved cell viability and reduced ROS levels in H2O2-treated cells.
- Crocin and safranal demonstrated a dose-dependent decrease in apoptosis.
- The protective effects of crocin and safranal were linked to the activation of SAPK/JNK and inhibition of ERK1/2 within the MAPK pathways.
Conclusions:
- Saffron and its active compounds, safranal and crocin, exhibit significant antioxidant and anti-apoptotic properties in endothelial cells.
- These protective effects are mediated through the modulation of MAPK signaling pathways.
- Saffron constituents hold therapeutic potential for managing endothelial dysfunction.
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