The Salvia genus comprises about 900 species. Salvia officinalis is a perennial evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flower, native to the Mediterranean area, and is cultivated in different European countries. Sage possesses well-known carminative, antispasmodic, antiseptic, astringent, and antihydrotic properties (1,2). According to folk medicine, Salvias herbal preparations are agents that can enhance memory and improve cognitive functions (3). During last decades, several experimental studies explored the potential of medicinal plants in the management of memory disorders and to fight the age-related memory decline (4,5). Among these plants, the pharmacological actions of S. officinalis on healthy subjects and on patients suffering of cognitive decline have been studied (6,7).
S. officinalis contains monoterpenes with a broad range of carbon skeletons, including acyclic, monocyclic, and bicyclic compounds (e.g., thujone, 1,8-cineole, camphor), diterpenes (e.g., carnosic acid), triterpenes (e.g., oleanoic and ursolic acids), and phenolic compounds such as rosmarinic acid (8,9).
Several Salvia species and their isolated constituents possess significant antioxidant and anti-inflammatory activities (10). Extracts of Salvia have been reported to have cholinergic activities relevant to the treatment of Alzheimer’s disease. Inhibition of butyrylcholinesterase was also shown by individual constituents, such as 3-carene and beta-pinene (11). It was shown that administration of extracts of S. officinalis or S. lavandulae folia potentiate memory retention and also interact with muscarinic and nicotinic cholinergic systems that are involved in the cognitive and memory processes (12).
Based on in vitro and in vivo data, S. officinalis herbal preparations were selected for clinical trials to evaluate the potential beneficial actions on cognitive performance in healthy volunteers and in patients with cognitive impairment such as Alzheimer’s disease.
In a randomized, double-blind, placebo-controlled, crossover clinical trial, 30 young healthy volunteers (mean age 24 years) received a single dose of 300 mg or a single dose of 600 mg of dried S. officinalis leaves preparation or placebo, each one in three different days each one separated by 7-day intervals. Participants at pre-dose time and at 1 and 4 hours post-dose underwent mood assessment, evaluated by Bond–Lader mood scales and the State-Trait Anxiety Inventory (STAI) before and after a 20-min performance on the Defined Intensity Stress Simulator (DISS) computerized multitasking battery. DISS is an experimental test consisting of a set of four cognitive and psychomotor tasks presented on a screen layout producing increases in self-ratings of negative mood, arousal, and stress-related physiological responses. Evaluation of the cumulative score reflects accuracy and speed of response to DISS. Both doses of S. officinalis leaves preparation led to postdose improved ratings of mood before performing on the DISS in the absence of stress. The lower dose reduced anxiety while the higher dose increased “alertness,” “calmness,” and “contentedness” on the Bond–Lader scales. However, the lower dose effect of anxiety reduction was abolished by DISS. The higher dose exerted an improvement at task performance on the DISS battery at both postdose sessions, but after the lower dose, task performance was decreased. On the basis of these results, authors concluded that single doses of sage leaf dose dependently can improve cognitive performance and mood in healthy young volunteers. In the same study, a cholinesterase assay was performed with an ethanolic extract from S. officinalis dried leaves showing a dose-dependent inhibitory effect on acetylcholinesterase activity. However, herbal preparations used for human treatment or in vitro experiments seem to be different (the first could be raw material and the second is certainly an ethanolic extract) because it is not cleared by authors (13).
In another randomized, placebo-controlled, double-blind, crossover study, the acute effects on cognitive performance of a standardized extract of S. officinalis L. in elder adults were investigated. Each one of twenty healthy volunteers (>65 years of age, mean 72.95) received four doses of an ethanolic extract of dried leaves and a placebo with a 7 days wash-out period between treatments. The investigators evaluated cognitive performance with CDR computerized assessment battery. On study days, treatments were administered immediately following a baseline assessment with further assessments at 1, 2.5, 4, and 6 h post-treatment. Authors reported that sage was associated with significant enhancement of secondary memory performance at all testing times, placebo exhibited the characteristic performance decline over the day. Although to a lesser extent, similar effects were observed with the other doses. There also was a subsequent significant improvement to accuracy of attention. Performance of in vitro analysis showed cholinesterase inhibiting properties of the extract. Results revealed a dose-related benefit to processes involved in efficient stimulus processing and/or memory consolidation rather than retrieval or working memory efficiency (6).
A single-blind randomized, controlled trial evaluated the putative action of the aromas of S. officinalis and S. lavandulae folia essential oils on cognition and mood. One hundred and thirty five healthy volunteers were recruited, 45 of them were assigned to each group. Authors reported an improvement in cognitive performance and mood measured through Cognitive Drug Research (CDR) System and Bond–Lader mood scales, respectively. Five drops of the essential oil and 5 mL of water were placed on a stone and left to diffuse in a testing cubicle, as a result of a constant temperature warming provided by the stone, for 5 min prior to testing. Data collected revealed that the S. officinalis aroma group performed significantly better than the control group on the quality of memory outcome factors from the test battery. The Alert mood measure displayed significant differences between both aromas and the control condition.
Results revealed that aromas of essential oils of S. officinalis reproduced a significant enhancement of quality of memory factor. This enhancement was restricted to long-term or secondary memory with no impact of working memory. No significant effects were found for S. lavandulae folia (14).
The effect of a S. officinalis leaf liquid extract has been evaluated in a randomized, double-blind, placebo-controlled study on 39 patients (aged 65–80 years). The eligible patients had a diagnosis of mild-to-moderate dementia according to the criteria of the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-cog) and Clinical Dementia Rating Scale (CDR); or a probably Alzheimer‘s disease according to the criteria of National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS⁄ ADRDA). The participants allocated to two groups received 60 drops daily of sage liquid extract or placebo for 16 weeks. Thirty patients completed the trial, in the Salvia extract and placebo group, the number of dropouts were four and five, respectively, accordingly to authors no significant difference are observed in the two groups in terms of dropout. Authors reported that, compared with the placebo group, patients who received S. officinalis experienced significant benefits in cognitive function by the end of the treatment, as indicated by improved scores in the Clinical Dementia Rating and the Alzheimer’s Disease Assessment Scale (15).
1. Blumenthal M, Goldberg A, Brinckmann J. Herbal medicine: Expanded commission E monographs. Boston, MA: American Botanical Council, 2000.
2. Barnes J, Phillipson DJ. Sage. Herbal medicines, 3rd edn. London: The Pharmaceutical Press, 2007.
3. Tildesley N, Kennedy D, Perry E, et al. Pharmacol Biochem Behav 2003;75:669–674.
4. Howes MJR, Perry NS, Houghton PJ. Phytother Res 2003;17:1–18.
5. Perry NS, Bollen C, Perry EK, Ballard C. Pharmacol Biochem Behav 2003;75:651–659.
6. Scholey AB, Tildesley NT, Ballard CG, et al. Psychopharmacology 2008;198:127–139.
7. Imanshahidi M, Hosseinzadeh H. Phytother Res 2006;20:427–437.
8. Perry NB, Anderson RE, Brennan NJ, et al. J Agric Food Chem 1999;47:2048–2054.
9. Abu-Darwish M, Cabral C, Ferreira I, et al. Biomed Res Int 2013;2013:538940.
10. Zupk_o I, Hohmann J, R_edei D, et al. Planta Med 2001;67:366–368.
11. Savelev S, Okello E, Perry N, Wilkins R, Perry E. Pharmacol Biochem Behav 2003;75: 661–668.
12. Eidi M, Eidi A, Bahar M. Nutrition 2006;22:321–326.
13. Kennedy DO, Dodd FL, Robertson BC, et al. Psychopharmacol 2010;25:1088–1100.
14. Moss L, Rouse M, Wesnes KA, Moss M. Hum Psychopharmacol 2010;25:388–396
15. Akhondzadeh S, Noroozian M, Mohammadi M, et al. J Clin Pharm Ther 2003;28:53–59.