Development and design of agents derived from natural sources with neuroprotective properties have received considerable attention. In the literature, it has been stated that these polyphenolic molecules have low adverse impacts and high efficacy when used in pathological conditions. Dietary flavonoids as a subgroup of polyphenols are bioactive products, extracted from several types of vegetables and fruits. Luteolin (3',4',5,7-tetrahydroxyflavone, LUT) is a widespread flavone known to have antioxidant and cytoprotective properties related to nuclear factor erythroid 2-related factor 2-(Nrf2) pathway. Extensive in vitro and in vivo investigations have indicated that LUT exhibits beneficial neuroprotective properties via different mechanisms. However, its psychopharmacological mechanisms are presently investigated in fewer studies. Therefore, we aimed to evaluate the neuroprotective impacts of LUT against central nervous system (CNS) disorders by reviewing available literature. Herein, we also reviewed the studies to understand the underlying mechanisms of LUT for curing CNS disorders.

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.