Therapeutic Prospects of Citrus limon and Its Bioactive Constituents in Alzheimer’s Disease | ||
| Bulletin of Pharmaceutical Sciences Assiut University | ||
| Articles in Press, Accepted Manuscript, Available Online from 24 September 2025 | ||
| Document Type: Review Article | ||
| DOI: 10.21608/bfsa.2025.406934.2656 | ||
| Authors | ||
| Yousef Sharaf1; Jilan A. Nazeam* 2; Samir Osman2; Hala Elhefnawy3 | ||
| 1Oncology Pharmacy, National Cancer Institute, Cairo University, Cairo, Egypt | ||
| 2Pharmacognosy Department, Faculty of Pharmacy, October 6 University, Giza, Egypt | ||
| 3Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt | ||
| Abstract | ||
| Alzheimer’s disease (AD), the leading cause of dementia worldwide, remains a formidable therapeutic challenge owing to the limited efficacy of existing pharmacological interventions. This review critically examines the neuroprotective potential of Citrus limon (lemon) and its phytoconstituents derived from juice, peel, pulp, seeds, leaves, and essential oil. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between January 2000 and June 2024, using search terms encompassing Citrus limon, Alzheimer’s disease, key phytochemicals, and mechanistic pathways. Major bioactive classes include flavonoids (hesperidin, eriocitrin, naringin, diosmin), polymethoxylated flavones, phenolic acids, coumarins (e.g., aurapten), alkaloids, terpenoids, limonoids, and essential micronutrients. These constituents exhibit pleiotropic actions, including antioxidant defense via Nrf2 activation, anti-inflammatory modulation via NF-κB, cholinesterase inhibition, and anti-amyloidogenic effects. Preclinical evidence demonstrates their ability to enhance mitochondrial function, improve cognitive performance, and protect against Aβ-induced neurotoxicity, while lemon essential oil has shown anxiolytic and cognitive benefits. Network pharmacology analyses further support multitarget mechanisms involving oxidative stress, neurotransmitter regulation, and apoptosis. Although clinical and epidemiological data suggest cognitive benefits of citrus flavonoids and lemon oil aromatherapy, translation remains limited by small cohorts, lack of standardized preparations, and insufficient biomarker validation. Future research should focus on large-scale, biomarker-driven clinical trials, dose–response studies, and advanced delivery systems such as nanoformulations to enhance therapeutic efficacy. Therefore, C. limon represent a promising, cost-effective, and sustainable adjunct in the prevention and management of AD. | ||
| Keywords | ||
| Citrus limon; Alzheimer’s disease; hesperidin; limonene; oxidative stress | ||
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