Exploring the mechanism of sunflower seed oil against Alzheimer’s disease through experimental and network pharmacology studies

Abstract: OBJECTIVES: With the prevalence of Alzheimer’s disease (AD) increasing exponentially, there has been a shift in the focus of drug discovery for AD from treating the symptoms to preventing the development of the disease. Several natural compounds are extensively studied as neuroprotectives in preventing disease progression. Helianthus annuus seed oil (HA) is widely used as cooking oil and is abundant in antioxidant activity. Therefore, we evaluated the effect of HA in mice model of scopolamine-induced amnesia and explored the potential underlying mechanisms. METHODS: Twenty-four male mice were administered orally with either distilled water (control and scopolamine groups) or treatment groups (HA 100 and HA 200 mg/kg) for 8 consecutive days. All groups, except the control group, received an intraperitoneal injection of scopolamine at a dose of 1 mg/kg. Subsequently, novel object recognition task for cognition assessment and open field tests for locomotory activity were performed. In addition, network analysis was performed to identify the key bioactives and targets of HA against AD. Further, the binding affinity of HA bioactives to the key targets was verified by molecular docking analysis. RESULTS: HA (100 mg/kg and 200 mg/kg) significantly ameliorated recognition memory compared to the scopolamine group, suggesting the protective effect of HA against cognitive impairment. Network analysis indicated that the key bioactives of HA, chlorogenic acid, and oleic acid act through multiple targets and pathways, particularly the mitogen-activated protein kinase (MAPK) pathway, to ameliorate AD symptoms. Importantly, chlorogenic acid showed good binding affinity with MAPKs, TP53, and EP300. CONCLUSION: HA has therapeutic benefits in AD acting through the MAPK pathway. However, further studies need to be done to confirm the results derived and translate the potential use of HA as a dietary supplement for preventing AD.