Exploring the Neuroprotective Potentials of Flavonoid Metabolites in Syzygium aromaticum: A Review with in-silico Insight to Therapeutic Potential

Ekom Monday Etukudo,1 Ibe Michael Usman,1 Augustine Oviosun,1 Vivian Onyinye Ojiakor,1 Wusa Makena,1 Elna Owembabazi,1 Patrick Maduabuchi Aja,2 Bives Mutume Nzanzu Vivalya,3 Victor Bassey Archibong,4 Emeka Anyanwu1 1Human Anatomy Department, Kampala International University, Bushenyi, Uganda; 2Biochemistry Department, Kampala International University, Bushenyi, Uganda; 3Psychiatry Department, Kampala International University, Bushenyi, Uganda; 4Human Anatomy Department, University of Rwanda, Huye, RwandaCorrespondence: Ibe Michael Usman, Email [email protected]: The worldwide occurrence of neurodegenerative diseases in Alzheimer’s and Parkinson’s patients is increasing owing to multiple disease mechanisms, including oxidative stress, neuroinflammation, mitochondrial dysfunction, and excitotoxicity. Syzygium aromaticum (clove) flavonoid metabolites show strong neuroprotective potential because they act as antioxidants, reduce inflammation and lipid peroxidation, and prevent apoptosis. The key S. aromaticum flavonoid metabolites, quercetin, kaempferol, kumatakenin, myricetin, ombuin 3-O-β-d-glucopyranoside, and tamarixetin 3-O-β-d-glucopyranoside, bind to various brain receptors implicated in disease propagation pathways and induce changes that support neuronal survival and decrease cognitive impairment. In vitro, in vivo, and molecular docking studies were reviewed. The SwissADME and ADMETlab 3.0 web servers demonstrated that these metabolites have favorable drug-like properties and absorption characteristics that follow Lipinski’s Rule of Five, GSK, and Pfizer rules. The metabolites showed good gastrointestinal absorption and desirable physicochemical properties, suggesting safe oral use. The toxicological profile prediction generated from the pkCSM and ADMETlab 3.0 web servers indicated minimal liver, kidney, and brain damage risks; however, ombuin 3-O-β-d-glucopyranoside exhibited weak cardiac toxicity through hERG II blocking, whereas pachypodol requires additional research on long-term toxicity effects. The data from the reviewed studies indicate that S. aromaticum flavonoid metabolites show great promise as therapeutic agents for neurodegenerative diseases caused by oxidative stress, inflammation, apoptosis, and lipid peroxidation. Evidence suggests that their safety and effectiveness are positive, despite minimal risks. Further studies should focus on nanocarrier utilization to improve their Blood-Brain Barrier permeability and enhance therapeutic potential. Experimenting on primates before translating them to human clinical trials will be crucial.Keywords: Syzygium aromaticum, metabolites, flavonoids, neuroprotective, therapeutic, botanical drugs, antioxidant, anti-inflammatory