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Abstract Alzheimer{u2019}s disease (AD) is characterized by the progressive loss of brain function that increases with chronological aging considering three hypotheses for pathogenesis; the cholinergic hypothesis, the amyloid hypothesis and the tau hypothesis. Genus salvia is reported for various neuro-therapeutic activities. In this study, the effect of salvia splendens against AD was investigated. Aim of the work: Evaluation of anti AD activity of Salvia splendens. Isolation and identification of the major active compounds. HPLC standardization of the active fraction. Results: Screening the different extracts of salvia splendens for their in vitro antioxidant and acetyl cholinesterase (AchE) inhibitory activity led us to identify petroleum ether and n-butanol fractions as the most potent fractions and further investigation for their efficacy in vivo proved their potential against AD. Bioactivity-directed fractionation of both fractions led to the isolation of four flavanoid aglycones, three phenolic acids and two sterols. AchE inhibitory activity of these compounds was evaluated in vitro where rosmarinic and caffeic acid showed highest inhibitory activity. The most active fraction (n-butanol) was HPLC standardized to contain not less than 0.0254 % (w/w) of rosmarinic acid and 0.0129% (w/w) of caffeic acid. Conclusion and Recommendation: Salvia splendens may have supportive role in controlling AD due to sterols isolated or terpenes and unsaturated fatty acids identified in its pet. ether fraction by GC/MS analysis and phenolic compounds isolated from its n-butanol fraction |