ABSTRACT:
Plumbagin is a low molecular weight lipophilic phytochemical, emerged as a novel antioxidant and neuroprotective agent. Although, neuroprotective effects of plumbagin have been studied in the Parkinson's disease, its efficacy is largely unknown in the other neurodegenerative disorders including Alzheimer's disease (AD). Herein we established the effect of plumbagin (0.1, 0.3 and 0.5 mg/kg. intraperitoneal (ip)] on learning and memory in AD-like condition in mice by using Morris water maze (MWM). AD-like mouse model was developed by intracerebroventricular (icv) administration of single dose of streptozotocin (3 mg/kg). In addition, nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway inhibitor, trigonelline (3, 10, 30 mg/kg, ip) has been administered to study the underlying mechanism in normal mice. Present results revealed a bell shaped efficacy of plumbagin in mice. While plumbagin at 0.3 mg/kg dose significantly lowered the escape latency, 0.1 or 0.5 mg/kg, both, did not affect the escape latency significantly as compare to saline treated mice, thus considered as ineffective. Further, administration of trigonelline dose-dependently (at 10 and 30 mg/kg, ip) increased the escape latency, suggesting memory impairment. Moreover pre- treatment of trigonelline blocked the nootropic effect of plumbagin in MWM. We conclude that plumbagin produce memory enhancing effect on AD-like condition in mice, perhaps via Nrf2/ARE pathway.