From Ancient Remedies to Modern Neuroscience: The Potential of Citrus Medica Linn. Essential Oil for Cognitive Health

Citrus medica Linn. essential oil (CMEO) is gaining recognition as a potential neurotherapeutic agent that effectively connects traditional herbal practices with modern neuroscience. Enriched with active compounds such as limonene, citral, and β-pinene, CMEO exhibits a broad spectrum of neuroprotective actions. These include the inhibition of amyloid-β aggregation, prevention of tau protein hyperphosphorylation, and mitigation of neuroinflammatory and oxidative stress pathways hallmarks of Alzheimer’s and Parkinson’s diseases. Due to its lipophilic nature, CMEO components readily cross the blood-brain barrier, and its efficacy is further enhanced through intranasal delivery, enabling direct transport to the brain. Preclinical data indicate that CMEO supports cognitive function by enhancing cholinergic activity, regulating glutamatergic transmission, and stimulating neurogenesis via upregulation of brain-derived neurotrophic factor (BDNF). Additionally, CMEO possesses antiviral and antimicrobial properties, with computational studies suggesting limonene may inhibit SARS-CoV-2 protease and experimental findings showing efficacy against biofilm-producing bacteria such as Staphylococcus aureus. Novel formulations like nano-emulsions and nasal sprays offer promising strategies to improve their bioavailability. While in vitro and animal studies validate its pharmacological potential, clinical trials are essential to confirm its therapeutic value and safety profile. As the prevalence of neurodegenerative diseases continues to grow, CMEO stands out as a versatile, natural compound with the potential to fill critical gaps in neuroprotective and cognitive health interventions.