Evaluation Of Neuroprotective Effects Of Rhus Coriaria L. Ethanol Extract
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Date
2015-04
Authors
KHALILPOUR, SABA
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Abstract
Neurodegeneration can be initiated by severe acute traumatic injuries or chronic intermittent and progressive insults from ischemia and hypoxia generating oxidative stress and neuroinflammation, strongly implicated in Alzheimer’s diseases, as well as optic neuropathies. Neuroprotection aims to prevent, retard or reverse neuronal damage as a result of the underlying pathophysiological state. Rhus coriaria L. is a medicinal herb with extensive range of applications in Middle Eastern folk medicine. The present work investigates the neuroprotective properties of Rhus coriaria L. extract in vitro and in vivo.
Chloroform, n-hexane, 98% ethanol and water extracts of the Rhus coriaria L. fruit were prepared via maceration technique and tested for its neurotoxic properties on Retinal Ganglion Cells (RGC-5). Ethanol and water extracts were non-toxic and selected for further neuroprotective studies (IC50 of 249.99 ± 0.17 μg/mL and 166.17 ± 0.37 μg/mL respectively). In vitro ischemia studies revealed ethanol extract (ERC) at 5μg/mL was most effective in rescuing RGC-5 cells from the detrimental effect of serum deprivation by significantly maintaining viability, decreasing apoptotic markers caspases 3/7, 8 and 9 and significantly reducing the number of Hoechst positive apoptotic RGC-5 cells. ERC’s role in attenuating oxidative stress conditions was evaluated by testing its antioxidant capacities using DPPH, ABTS, and β-carotene bleaching tests and its ability to increase glutathione
(GSH) and glutathione-S-transferase (GST) levels. The IC50 of radical scavenging activities were 6.79 ± 0.00 μg/mL, 10.94 ± 0.09 μg/mL and 6.25 ± 0.06 μg/mL respectively. In addition ERC significantly increased the levels of GSH and GST. Screening with GC-MS revealed high amounts of phenolics and flavonoids supporting its potent antioxidant property. In SD-Rat aortic ring assay (RARA), ERC extract at 100 μg/mL inhibited 93.01 ± 0.14 % of blood vessel formation and significantly decreased the activity of the hypoxia induced factor, VEGF concentration in HUVECs lysates from 240.89 ± 0.00 pg/mL to 68.35 ± 9.59 pg/mL. ERC was cytotoxic to HUVECs in proliferation assay with IC50 = 1.81 ± 0.00 μg/mL. In albino Balb/c mice ischemic optic neuropathy, ProSense 750 was used to probe the activation of the inflammatory mediator cathepsin and its activity monitored using the Fluorescence Molecular Tomography (FMT) in vivo imaging system. ERC treated mice (400 mg/kg) had 84.87% reduction of ischemia induced neuroinflammation. ERC therefore exhibits its neuroprotective activities by modulating caspase dependent apoptosis in in vitro model of ischemia, VEGF dependent angiogenic response by its action on endothelial cells, enhancing radical scavenging properties in simulated oxidative stress conditions and inhibiting ischemia induced neuroinflammatory mediator cathepsin in the optic nerve.
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Evaluation Of Neuroprotective , Effects Of Rhus Coriaria L. Ethanol Extract