Neuroprotective potential of Honokiol in ICV-STZ induced neuroinflammation, Aβ (1-42) and NF-kB expression in experimental model of rats

Abstract

Alzheimer's disease (AD) is a most common and prevalent age related insidious neurological condition characterised by formation of Aβ _(1-42) plaques and NFT in the hippocampus. Major symptoms of AD include memory and cognitive loss caused by neuroinflammation, Aβ _(1-42) plaques, and NFT accumulation in the brain. Intracerebroventricular administration of STZ up-regulates the level of Aβ _(1-42) plaques, and NFT by activating NF-kB pathway. All animals were trained for behaviour analysis before infusion of ICV-STZ bilaterally, at a dose of 3 mg/kg; icv. The stereotaxic surgery was performed in target region with coordinates -2 mm [AP], 1.6 mm [MR], and1.5 mm [DV]. On day 1 and day 3 after surgery HS (hamilton syringe) was used to infuse STZ at the target region of brain. Morris Water Maze (MWM), and Elevated Plus Maze (EPM) tests were performed to check spatial and learning memory in all groups. ICV-STZ infusion produced memory impairment by increasing the activity of AchE, oxidative markers (LPO, GSH, and nitrite), neurotransmitters levels (AchE, GABA, and glutamate), and release of neuroinflammatory markers (NF-kB, IL-6, and IL-1β). The treatment with Honokiol (Bioactive polyphenolic compound) significantly ameliorated the behavioural changes at a dose of 5, and 10 mg/kg; i.p on day 7, 14, and 21. After behavioural analysis rats were sacrificed on day 22, and the hippocampus tissue was collected to investigate the biochemical, neuroinflammatory, neurotransmitters, histopathological, and immunohistopathological changes. Here, we have found Honokiol significantly down regulates the Aβ plaques via NF-kB inhibition and also reduced neuroinflammation in the brain of rats. Further inhibits the NF-kB expression confirmed for immunohistochemistry analysis. It was observed that Honokiol (5, and 10 mg/kg; i.p) dose-dependently ameliorated AchE level restored neurotransmitters concentrations in hippocampal region, and prevented neuronal loss confirmed from histopathology studies. We concluded that Honokiol drastically produced protective effect in AD model via antioxidant, reducing inflammation, AchE level, restoration of neurofibrillary tangles and preventing NF-kB as well as histopathological changes.

Keywords: Alzheimer’s disease; Aβ-Plaques; Honokiol; ICV-STZ; NF-kB; Neuroinflammation.