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

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.Cytotoxicity assays showed a significant protection of a 10 μg/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-α, IL-1β and HIF-1α mRNA levels were highly increased after ischemia and treatment with Melissa significantly suppressed HIF-1α gene expression (P<0.05).Results showed that Melissa officinalis could be considered as a protective agent in various neurological diseases associated with ischemic brain injury.Ischemic brain injury often causes irreversible neural damage. The cascade of events leading to neuronal injury and death in ischemia includes excitotoxicity, inflammation, edema, apoptosis, and necrosis [1]. In humans and experimental animals subjected to ischemia, selective and delayed neuronal death occurs in pyramidal neurons of the hippocampal CA1 region [2]. Several studies have indicated that early and late neuronal death occurring in the neurons of cortex and hippocampus after ischemia could be both apoptotic and necrotic cell death [3]. A special kind of cell death occurs some days after the initial ischemic insult, a phenomenon termed delayed neuronal death (DND) [4].It is demonstrated that hypoxia-inducible factor-1α (HIF-1α), interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α) expression increase