Gossypetin- based therapeutics for cognitive dysfunction in chronic unpredictable stress- exposed mice.

Chronic unpredictable stress (CUS) is a promising model for induction of cognition impairment. Stress induced memory dysfunction is linked to the activation of kynurenine (KYN) pathway. This pathway indicates that, chronic stress primarily promotes the release of excessive cortisol from the adrenal gland, which tends to activate microglia and further increases kynurenine and its downstream pathway, resulting in excessive quinolinic acid (QA), which further impairs brain derived neurotrophic factor (BDNF) levels and leads to neurodegeneration. Prior studies already established anti-oxidant and anti-depressant activity of gossypetin. This research study was mainly conducted to elaborate neuroprotective activity of gossypetin against CUS-induced cognition impairment via acting on kynurenine pathway. In this study, Swiss albino mice were exposed to various stressors for five weeks and then administered with gossypetin (5, 10 and 20 mg/kg, i.p.) from the 4th to the 7th week (from day 22 to 49). Several behavioral tests were carried out between days 36 to 49 (6th and 7th week) and further corticosterone, neurotransmitters, oxidative stress, and brain-derived neurotrophic factor (BDNF) levels were measured. Results state that CUS exposed mice showed significant improvement in the behavioral pattern after gossypetin treatment. Corticosterone levels and oxidative stress was also found to be significantly decreased in gossypetin (10 and 20 mg/kg, i.p.) treated mice when compared with CUS exposed mice. Whereas, serotonin, norepinephrine and BDNF levels were also found to be increased after gossypetin treatment. Hence, gossypetin can be considered as a neuroprotective agent against cognition impairment caused by chronic unpredictable stress.