Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo

Background: Brain ischemia initiates several metabolic events leading to neuronal death. These events mediate large amount of damage that arises after some neurodegenerative disorders as well as transient brain ischemia. Melissa officinalis is considered as a helpful herbal plant in the prevention of various neurological diseases like Alzheimer that is related with oxidative stress. Methods: We examined the effect of Melissa officinalis on hypoxia induced neuronal death in a cortical neuronal culture system as in vitro model and transient hippocampal ischemia as in vivo model. Transient hippocampal ischemia was induced in male rats by tow vessel-occlusion for 20 min. After reperfusion, the histopathological changes and the levels inflammation, oxidative stress status, and caspase-3 activity in hippocampus were measured. Results: Cytotoxicity assays showed a significant protection of a 10 mu g/ml dose of Melissa against hypoxia in cultured neurons which was confirmed by a conventional staining (P<0.05). Melissa treatment decrease caspase3 activity (P<0.05) and TUNEL-positive cells significantly (P<0.01). Melissa oil has also inhibited malon dialdehyde level and attenuated decrease of Antioxidant Capacity in the hippocampus. Pro-inflammatory cytokines TNF-alpha, IL-1 beta and HIF-1 alpha mRNA levels were highly increased after ischemia and treatment with Melissa significantly suppressed HIF-1 alpha gene expression (P<0.05). Discussion: Results showed that Melissa officinalis could be considered as a protective agent in various neurological diseases associated with ischemic brain injury.