Abstract
OBJECTIVE: To investigate the involvement of oxidative and apoptotic mechanisms in the possible neuroprotective effect of Kaempferide (KPD) and Norbergenin (NRG) against AlCl(3)-induced cognitive shutdown in rats. INTRODUCTION: Aluminium chloride (AlCl(3)) is widely known as a neurotoxic agent that induces memory and cognitive shutdown via induction of oxidative stress and apoptosis. KPD is an O-methylated flavonol that possesses anti-oxidant, anti-inflammatory, anti-dementia and anti-depression properties, whereas NRG, a demethylated compound derived from bergenin, possesses an anti-oxidant property and has neuroprotective effects. Both alleviate D-galactose-induced neurotoxicity in rats. METHODS: Eighty-four male Wistar rats were randomly divided into two experimental models: prophylactic (pre-treatment with donepezil, KPD or NRG; n = 42) and curative (post-treatment with donepezil, KPD, or NRG; n = 42). In each of these models, the animals were divided into seven groups (n = 6 per group): group 1 (normal saline), group 2 (200 mg/kg AlCl(3)), group 3 (donepezil + AlCl(3)), group 4 (5 mg/kg KPD + AlCl(3)), group 5 (10 mg/kg KPD + AlCl(3)), group 6 (5 mg/kg NRG + AlCl(3)) and group 7 (10 mg/kg NRG + AlCl(3))Results:Kaempferide and Norbergenin averted the increase in TBARS, NO and AChE, and decrease in the number of crossings, time spent and distance moved in the target quadrant, latency of fall, speed, paw withdrawal threshold (PWT), SOD, CAT, GPx, GR and GSH induced by AlCl(3). These agents also averted the upregulation of Aβ(1-41), p-Tau, caspase-3, Bax and downregulation of Akt, p-CREB, SOD1 and BCl-2 induced by AlCl(3)Conclusion:The neuroprotective effects of KPD and NRG against AlCl(3)-induced Aβ accumulation and cognitive shutdown are mediated via suppression of oxidative stress and apoptosis.