Sabinene Inhibits Lipopolysaccharide-Induced Memory Decline by Enhancing Cholinergic Function, Decreasing Molybdenum Enzymes, and Suppressing Oxidative Stress and Neuroinflammation.

Abstract

Memory decline is a common hallmark signal of neurodegenerative diseases marked by elevated neuroinflammatory cytokines, oxidative damage and cholinergic insufficiency in cortical regions. Studies indicate that inhibiting these cytokines and associated markers may enhance memory and provide neuroprotection. This study investigates the effects of sabinene, a neuroprotective monoterpene found in essential oils with neuroprotective and antioxidant properties, on lipopolysaccharide (LPS)-induced neuroinflammation, oxidative stress and learning/memory impairment in mice. In this study, mice in groups 1 and 2 received normal saline, while groups 3-5 were pretreated with sabinene (5, 10, and 20 mg/kg). Group 6 received donepezil (1 mg/kg) orally. Groups 2-6 were additionally injected with LPS (0.5 mg/kg, i.p.) 30 min post-treatment for 7 days. Behavioral consequences indicating spatial and non-spatial deficits were assessed through Y-maze and novel-object recognition tests, along with locomotor functions conducted. Biochemical markers of neuroinflammation (TNF-α, IL-6), oxidative stress (glutathione, peroxidase, malondialdehyde, nitrite), cholinergic function, and molybdenum enzymes were analyzed in the prefrontal-cortex (PFC) and hippocampus. Sabinene treatment mitigated LPS-induced memory impairments and reduced motor activity. It also significantly decreased acetylcholinesterase activity and malondialdehyde levels in the hippocampus and PFC while increasing glutathione and glutathione peroxidase levels, respectively. Moreover, sabinene reduced LPS-induced molybdenum enzyme elevation in the PFC. Compared to LPS, sabinene significantly lowered TNF-α and IL-6 levels in the PFC and hippocampus while protecting neuronal cell damage in the PFC. Overall, sabinene enhances memory function in LPS-treated mice by reducing oxidative stress and neuroinflammation while improving cholinergic activity and molybdenum enzymes in the cortical regions of mice brains.