Effects of Cholinesterase Inhibiting Sage on Mood, Anxiety, and Performance on a Psychological Stressor Battery

Salvia officinalis (sage) has been shown to have in vitro cholinesterase inhibiting properties and enhance mnemonic efficiency and mood in healthy young participants. 

In this double-blind, placebo-controlled crossover study, 30 healthy participants attended the laboratory on three separate days, seven days apart, receiving specific counterbalanced treatment each time (placebo, 300, 600 mg dried sage leaf). 

— mood assessment included completion of the Bond – Lader mood scales and the State 

Trait Anxiety Inventory (STAI) before and after the Defined Intensity Stress Simulator (DISS) computerized multitasking battery. 

A sage leaf extract exhibited dose-dependent, acetylcholinesterase in vitro inhibition and, to a greater degree, butyrylcholinesterase in a concomitant study. 

Both doses of sage resulted in better mood ratings in the absence of postdose stressor (i.e., pre-DISS mood 

scores), with a lower amount decreasing anxiety and higher amount raising ‘alertness,’ ‘calmness’ and ‘quality’ on Bond–Lader mood scales. 

Nevertheless, the decreased anxiety effect following the lower dose was eliminated by conducting 

the DISS, with the same amount, also correlated with reduced alertness during training. 

The DISS battery task efficiency was increased for the higher dose at both 

postdose tests, but decreased for the lower amount at the later test session. 

The findings support previous S-inhibiting cholinesterase observations. 

The Research

The tradition of using sage (many Salvia genus plants) as a medicinal remedy covers many centuries, both ancient and modern cultures. Indications from the earliest texts onwards include its use as a therapy to improve memory loss due to age (Perry et al., 1999). Several studies have shown that both Salvia lavandulaefolia (Spanish Sage) and Salvia officinalis (Garden Sage) possess potentially important properties to attenuate the cognitive loss associated with normal aging and dementia. Most relevantly, both were shown to inhibit the enzyme cholinesterase group. In human postmortem brain tissue or bovine erythrocytes, dose-dependent inhibition of butyrylcholinesterase (BuChE) by Salvia officinalis purpurea essential oil (Savelev et al., 2004) and inhibition of acetylcholinesterase ( AChE) by both essential oils and extracts (Perry et al., 1996, 2000; Savelev et al., 2003). Notably, the CNS availability was confirmed by observing that five days in vivo oral administration to essential oil rats led to dose-dependent declines in AChE activity in selected brain regions (Perry et al., 2002).

Cognitive and mood effects of single-dose extracts with established AChE-inhibiting properties were assessed in placebo-controlled, randomized, healthy crossover trials in both young (Tildesley et al., 2003, 2005) and older (> 65 years) cohorts (Tildesley et al., submitted). Treatment with both encapsulated S for the three such studies mainly evaluating the cognitive function. lavandulaefolia essential oil (Tildesley et al., 2003, 2005) and S pure ethanol extract officinalis (Tildesley et al., submitted) led to improved memory performance on a computerized cognitive assessment battery, all of which had AChE-inhibiting properties. The older cohort also improved attention task performance (Tildesley et al., submitted), while the young improved self-ratings of ‘alertness,’ ‘calmness’ and ‘content’ (Tildesley et al., 2005).

Previous work has shown that in healthy young participants, certain plant species with cholinergic properties (Melissa officinalis; which has been shown to have the ability to bind to nicotinic and muscarinic receptors in human brain tissue) increased self-rated calmness (Kennedy et al., 2002, 2003). Sometimes, a Methanolic extract. Officinalis significantly improved the harmful effects of 20 min completion of a mild psychological stressor battery (DISS) in healthy young people (Kennedy et al., 2004).

The current double-blind, placebo-controlled study borrowed elements of this previous study’s methodology, assessing the anxiety and mood modulating properties of two separate single doses (300 and 600 mg, plus placebo, counterbalanced) of dried S. Officinalis leaf in balanced children. Mood and anxiety were measured before the DISS battery was done, and after 20 min. Assessments were done predose and after 1 and 4 h.

The AChE and BuChE inhibiting properties of ethanolic extracts of the dried leaf were tested in vitro.

The full article can be found at Nature research (, Neuropsychopharmacology or here


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