Ischemic stroke remains a leading cause of death and acquired disability worldwide in adults. In
Georgia, illnesses of blood circulation system is 15.5% from all diseases registered in the country and 8.6% of
new cases. Hypertensive, ischemic and cerebrovascular diseases are characterized by high morbidity and
mortality in this group of illnesses. In 2000-2016, Georgia has a tendency to increase the prevalence of blood
circulation diseases. Ischemic stroke is caused by a reduction in the blood supply to apart of the brain, resulting
in fatal brain damage. Ischemic preconditioning is a phenomenon whereby brief episode(s) of sublethal
ischemia protect the heart against sustained ischemia-reperfusion injury. Pharmacological preconditioning is a
promising approach for treating cerebral ischemia. Chemical agents that have intriguing safety and stability
profile and show neuroprotective effects are the more promising candidates for pharmacologic preconditioning,
especially those from plants. In this regard, a lot of attention attracts the study of some plant derived
polyphenolic compounds effect on mitochondrial bioenergetical processes and their neuroprotective potential.
Nobiletin is an O-methylated flavonoid that has anticancer, antiviral, neuroprotective, anti-inflammatory
activities and depending on the cell types exhibits both pro- or anti-apoptotic properties. Our previous results
has shown that nobiletin causes transient hyperpolarization of mitochondrial membrane which is accompanied
by a temporary increase in the production of peroxides that is observed at 5 minutes of pre-incubation of
nobiletin with mitochondria. Further prolongation of incubation led to the depolarization and decreased the
production of peroxide. Apparently, transient hyperpolarization and peroxide spikes cause the reprogramming
of mitochondrial function underlying the phenomenon, like “ischemic pre-conditions”. According to this our
research goal is to investigate nobiletin’s significance in development of ischemic pre-conditioning, and
identification of a molecular mechanisms which are involved in this phenomen.