Krishnan_2025_Mol.Neurobiol_63_262

Alzheimer's disease (AD) is a progressive neurological illness that causes Abeta deposition and cognitive impairments. Anti-cholinesterase 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 11beta-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.