The potential neuroprotective effect of Manuka Honey in Sprague-Dawley rats with Lipopolysaccharide induced neuronal injury

Abstract

Alzheimer’s type dementia is the most common form of dementia and is a large contributor to mortality in the aging and geriatric populations. It is associated with amyloid plaque formation, neurofibrillary tangles, neuro-inflammation and memory loss. There appears to be a causal link between the neuro-inflammation and other pathological processes associated with the development of Alzheimer’s type dementia and gastrointestinal presence of lipopolysaccharide (LPS), a component of the outer cellular membrane of Gram-negative bacteria. In addition to this, there is sufficient evidence suggesting honey as a possible treatment or preventative measure against inflammation and, therefore, against the neuro-inflammation associated with LPS and Alzheimer’s type dementia. In the current study, LPS derived from Escherichia coli (E. coli) was chosen based on the increased prevalence of E. coli infections in South Africa, and Manuka honey was chosen as a treatment against LPS due to its proven therapeutic use and wide use in scientific study. Thus, the aim of this study was to investigate the possible effects of systemic LPS administration on the behaviour and the hippocampal region of the brain as well as investigate the possible protective effect of Manuka honey in a Sprague-Dawley model. This model was successfully implemented using a sample size of 40 over a thirteen-day period after which the animals were terminated, perfused and the intact brain removed and processed for light- and transmission electron microscopy. In addition to this, antemortem studies were conducted to assess the overall health status and possible memory decline of the test subjects. The daily LPS administration of 0.01 mg per kilogram animal weight resulted in no significant weight loss or gain among the animals. In addition to this, no sickness behaviour was observed throughout the thirteen-day period. The LPS administration had no significant effect on the brain to weight ratio or antemortem behavioural studies. Additionally, the daily exposure to 0.5 mL of honey per kilogram animal weight resulted in no significant weight changes or sickness related behaviours among the animals. The morphology analysis of the hippocampal tissue demonstrated some altered metabolic activity and amyloid formation in the LPS exposed groups. The ultrastructural analysis indicated a decreased mitochondrial membrane integrity and enlarged rough endoplasmic reticulum in both exposed groups with these changes observed to a lesser extent in the honey exposed group. In conclusion, this study suggests that LPS and honey exposure alone and in combination does produce some level of response in the dorsal hippocampal region of the Sprague Dawley rat brain. The response to LPS was not sufficient enough to produce statistically significant differences in behaviour amongst the groups; however, it was sufficient to produce differences in histological studies. This may be due to an insufficient exposure period or exposure concentration.