V. Mani, Siti Murnirah Jaafar, Nur Syamimi Mohd Azahan
Jul 1, 2017
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1
Influential Citations
16
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Quality indicators
Journal
Life Sciences
Abstract
Aim: The present study is aimed to investigate the ability of ciproxifan, a histamine H3 receptor antagonist to inhibit &bgr;‐amyloid (A&bgr;)‐induced neurotoxicity in SK‐N‐SH cells and APP transgenic mouse model. Materials and methods: In vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in A&bgr;25–35 ‐ induced SK‐N‐SH cells. For the in vivo study, ciproxifan (1 and 3 mg/kg, i.p.) was administrated to transgenic mice for 15 days and behaviour was assessed using the radial arm maze (RAM). Brain tissues were collected to measure A&bgr; levels (A&bgr;1–40 and A&bgr;1–42), acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO), antioxidant activities, cyclooxygenases (COX) and cytokines (IL‐1&agr;, IL‐1&bgr; and IL‐6), while plasma was collected to measure TGF‐1&bgr;. Results: The in vitro studies demonstrated neuroprotective effect of ciproxifan by increasing cell viability and inhibiting reactive oxygen species (ROS) in A&bgr;25–35‐induced SK‐N‐SH cells. Ciproxifan significantly improved the behavioural parameters in RAM. Ciproxifan however, did not alter the A&bgr; levels in APP transgenic mice. Ciproxifan increased ACh and showed anti‐oxidant properties by reducing NO and LPO levels as well as enhancing antioxidant levels. The neuroinflammatory analysis showed that ciproxifan reduced both COX‐1 and COX‐2 activities, decreased the level of pro‐inflammatory cytokines IL‐1&agr;, IL‐1&bgr; and IL‐6 and increased the level of anti‐inflammatory cytokine TGF‐1&bgr;. Conclusion: This present study provides scientific evidence of the use of ciproxifan via antioxidant and cholinergic pathways in the management of AD. Graphical abstract: Figure. No caption available. HighlightsCiproxifan enhanced spatial memory and reduced reference as well as working memory error in APP transgenic mouse.Ciproxifan did not change the levels of A&bgr;1‐40 and A&bgr;1‐42 in APP transgenic mouse brain.Ciproxifan improved brain cholinergic activities in mouse brain.Ciproxifan reduced oxidative stress induced by amyloid plaques.Ciproxifan attenuated the amyloid‐induced neuroinflammation.