Bornyl Acetate and Menthol Provide Neuroprotection Against Lipopolysaccharide-Induced Alzheimer’s Disease-Like Condition in C57BL/6 Mice by Downregulating NARC-1 Lipid Antagonist

Alzheimer’s disease (AD) is a progressive neurological illness that causes Aβ deposition and cognitive impairments. Anticholinesterase
and anti-depressant drugs are used as medications; however, their side effects spotlight the need for alternate
treatments. Bornyl acetate and menthol are monoterpenes with bioactive potential investigated against inflammation induced
by lipopolysaccharide (LPS) in C57BL/6 mice. In our study, we analysed various behavioural changes along with memory
activities as well as assessed neuronal damage, acetylcholinesterase activity, amyloid deposition, mitochondrial membrane
integrity, calcium deposition and oxidation derivatives. In addition, we also examined gene and protein expression associated
with lipid dysfunction in neuroinflammation. Our findings revealed that monoterpenes such as bornyl acetate and menthol
potentially improved LPS-induced behaviour changes and cognitive activities. In addition, these compounds have the potential
effects against amyloid plaque formation, calcium build-up, mitochondrial membrane damage and oxidative markers
(malondialdehyde, protein carbonyls and advanced glycation end products) in the LPS-injected C57BL/6 mice. Treatment
with bornyl acetate and menthol also inhibited neural apoptosis-regulated convertase (NARC-1)/proprotein convertase subtilisin/
kexin type 9 (PCSK-9) by upregulating low-density lipoprotein receptor-related protein (LRP)-1 protein expression.
Cholesterol oxidation genes, including 11β-hydroxysteroid dehydrogenase 1 & 2, as well as proinflammatory microglial,
apoptotic and amyloidogenic protein and gene expression, were decreased respectively when treated with monoterpenes while
promoting the upregulation of anti-inflammatory. Based on the results, we concluded that these compounds can potentially
target and prevent neuroinflammation, including Alzheimer’s disease.