Elucidating the mechanisms of lipopolysaccharide-induced cognitive impairment in rats treated with tualang honey and its methanolic extraction
Year: 2020
Type: dissertation
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by \nprogressive loss of cognitive functions. The search for cognitive enhancers from \nnatural products derivative has gained much attention. As a natural antioxidant \nsource, Tualang honey (TH) produced by wild bees (Apis dorsata) is expected to \nhave a positive influence on human health, including cognitive function. Four types \nof honey such as raw TH, irradiated TH, TH methanolic (MTH) and ethyl acetate \nextract were tested in the preliminary study and it was found that MTH exhibited the \nhighest antioxidant potentials. Therefore, this study aimed to elucidate the \nmechanism of TH and MTH on lipopolysaccharide (LPS)-induced cognitive \nimpairment in rats, and compare with memantine, one of the standard drugs used in \nthe management of AD. A total of 100 male Sprague Dawley rats were randomly \ndivided into 5 groups: (i) control, (ii) untreated LPS, (iii) LPS treated with 200 \nmg/kg TH, (iv) LPS treated with 150 mg/kg MTH and (v) LPS treated with 10 mg/kg \nmemantine. All treatments were administered intraperitoneally once daily for 14 \ndays. LPS was injected into the rats at Day 4 of the treatments to create \nneuroinflammatory responses that cause cognitive dysfunctions. Spatial and \nrecognition memory functions were assessed using Morris water maze (MWM) and \nnovel object recognition (NOR) tests. Twenty four hours after completing \nbehavioural tests, all rats were sacrificed and hippocampal tissues were removed. \nLocalization and expression of inflammatory markers in the hippocampal tissue were \ndetermined by immunohistochemistry analysis and Western blot. The levels of \nantioxidant enzymes, oxidative damage and amyloid deposition in rats’ hippocampal \nhomogenates were determined by commercially available ELISA kits. Nissl staining \nof hippocampal slices was employed to determine neuronal count. The \nadministration of LPS to rats resulted in spatial and recognition memory impairment. \nLPS also caused a significant increase in neuroinflammation as evidenced by the \nincrease in COX-2, iNOS and TNF-α expression in hippocampal tissues. There was a \nmarked reduction in the levels of antioxidant enzymes such as CAT, GPx, GR and \nSOD with the concomitant increase in MDA level and amyloid deposition following \nLPS administration. LPS also caused reduction in the number of Nissl positive \nneurons in all hippocampal regions. TH and MTH treatments for 14 days \nsignificantly improved spatial and recognition memory. Besides, TH and MTH were \nable to reduce neuroinflammation, oxidative stress, amyloid deposition as well as \nimprove Nissl positive neuronal count in the hippocampus. The neuroprotective \neffects of TH and MTH were found to be comparable with memantine. In \nconclusion, this study showed that both TH and MTH could prevent LPS-induced \nspatial and recognition memory impairment via its anti-inflammatory, antioxidant \nand anti-amyloidogenic properties. Both TH and MTH have the potential to be used \nas alternative therapy to protect against memory decline in AD patients.
Author: Wan Muhammad Hilmi Wan Yaacob
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Universiti Sains Malaysia
OpenAlex ID: W3184433599