Neuroprotective Effects of Higenamine Against the Alzheimer’s Disease Via Amelioration of Cognitive Impairment, A β Burden, Apoptosis and Regulation of Akt/GSK3β Signaling Pathway

Abstract

The present investigation was envisaged to elucidate the neuroprotective effect of Higenamine (HGN) against aluminum chloride (AlCl ₃) triggered experimental Alzheimer’s disease (AD) rat model. Thirty-six male albino Wister rats were randomized and divided in 6 groups and subjected to experimentation for 6 weeks. Control group, AlCl ₃ (100 mg/kg orally), HGN (50 mg/kg orally), HGN25, HGN50, HGN75 (HGN 25, 50 and 75 mg/kg respectively and AlCl ₃ 100 mg/kg orally). After completion of 42 days protocol, the animals were subjected to passive avoidance test. The animals were then anesthetized by intramuscularly injecting ketamine hydrochloride (24 mg/kg body weight) and euthanized by cervical amputation. Cortical and hippocampal tissues were carefully removed and were employed for quantification of aluminum and acetylcholinesterase. The tissues were quantified using Western blotting and detection kits for APP, Aβ _1-42, β and γ secretases, Bax, Bad, caspases-9, cyto-c, pAkt and pGSK-3β, and oxidative markers. HGN significantly protected AlCl ₃ induced memory and learning impairments, Al overload, AChE hyperactivity, amyloid β (Aβ) burden and apoptosis in brain tissues via activating Akt/GSK3β pathway. HGN attenuated oxidative damage induced by Al by modulation of oxidative markers. Our findings advocate the neuroprotective effect of HGN in AlCl ₃ induced AD rat model.