Investigating the effects of centella asiatica on neuroinflammation in beta‐amyloid overexpressing mice

Abstract Background Centella asiatica is a medicinal plant traditionally used for promoting brain health and improving cognition. Our lab has shown that a water extract of Centella asiatica (CAW), can enhance mitochondrial function, promote antioxidant response, and improve cognitive deficits in mouse models of aging and Alzheimer’s disease (AD). Because neuroinflammation is also prevalent in the AD brain and there is growing evidence that the interplay between oxidative stress, mitochondrial dysfunction, and neuroinflammation play a central role in the progression of AD, here we explore the effects of oral CAW treatment on neuroinflammation in the 5xFAD mouse model of beta‐amyloid accumulation. Methods Eight to nine month old male and female 5xFAD mice were treated with 0 or 1000 mg/kg/day of CAW administered in their drinking water or integrated into their diet (AIN‐93M rodent diet) for a total of 5 weeks, after which brain samples were collected. Microglial and astrocytic activation as well as beta‐amyloid pathology is currently being assessed by immunohistochemistry (IHC). Expression of pro‐ and anti‐inflammatory cytokines is also being determined by qPCR in brain samples from these treated animals. Results Preliminary IHC results suggest that CAW administered in the diet reduces the heightened microglial activation found in 5xFAD mice. Our ongoing analysis will determine if there are also effects on astrocytic activation and beta‐amyloid pathology, and whether these effects vary if the CAW is administered in the drinking water rather than the diet. Additionally, gene expression assessments are currently underway on these samples to evaluate the effects of CAW on the expression of pro‐ and anti‐inflammatory cytokines. Conclusion Initial data suggests an anti‐inflammatory effect of the CAW extract. Results will continue to be collected over the next few months, further clarifying our preliminary results as well as generating data for the potential mechanisms or cell types that may mediate the effect of CAW on neuroinflammation. Moreover, we will learn whether the mode of administration, in the diet versus the drinking water, has an effect on the response to CAW, which would have important implications for future experimental design as well as the development of CAW for clinical use.