Neuroprotective effect of Salvia splendens extract and its constituents against AlCl3-induced Alzheimer's disease in rats

Salvia splendensis a species of the genusSalviathat is known for its neuro-therapeutic properties. The present study aimed to investigate the effect of two fractions from the methanolic extract of the aerial parts ofS. splendenscultivated in Egypt, the petroleum ether-soluble (PES) andn-butanol-soluble (BS) fractions, against AlCl3-induced Alzheimer's disease (AD) in rats. Rats treated with AlCl3(100 mg/kg b.wt.p.o.) for 4 weeks developed behavioral, biochemical and histological changes similar to that of AD. Behavioral deficits were assessed by T-maze test and percentage changes in oxidative stress and AD markers in brain. Extent of DNA damage and histopathological changes were also evaluated. Results revealed that both fractions; PES and BS (at dose of 500 mg/kg b.wt), significantly attenuated AlCl3-induced behavioral impairment in rats. This effect was accompanied by acetylcholinesterase (AChE) activity inhibition (53.18% and 68.66%, respectively), and A beta deposition reduction (33.3% and 34.3%, respectively). Both fractions markedly decreased oxidative stress markers level (lipid peroxide, protein carbonyl, reduced glutathione and nitric oxide), and inhibited catalase and caspase-3 activities. Also, the content of noradrenaline, adrenaline, 5-HT and dopamine were significantly increased. The fractions preserved the histo-architecture pattern of the hippocampus and cortex from the AlCl3-induced damage. Bioactivity-guided fractionation led to the isolation of two sterols; beta-sitosterol and beta-sitosterolpalmitate from PES fraction, and 6 phenolic compounds (acacetin, chrysoeriol, apigenin, luteolin, rosmarinic acid and caffeic acid) from BS fraction. Rosmarinic acid and caffeic acid significantly inhibited AChE in vitro (IC(50)values of 0.398 mg/mL and 0.327 mg/mL, respectively) compared to physostigmine (IC(50)0.227 mg/mL). The BS fraction is standardized (HPLC-DAD) to contain not less than 0.0254% (w/w)of rosmarinic acid and 0.0129% (w/w) of caffeic acid. These findings suggest thatS. splendensis beneficial in attenuating AlCl3-induced neurotoxicity in rats.