Evidence for anti-inflammatory effects and modulation of neurotransmitter metabolism by Salvia officinalis L

Background: Cognitive health is of great interest to society, with neuroinflammation and systemic inflammation age-related risk factors that are linked to declines in cognitive performance. Several botanical ingredients have been suggested to have benefits in this area including Salvia officinalis (sage), which has shown anti-inflammatory effects and exhibited promising cognitive improvements in multiple human studies. The current study demonstrates anti-inflammatory effects for S. officinalis across a broad set of in vitro models in human cells, and adds further evidence to support modulation of acetylcholine and monoamine neurostransmitter levels as mechanisms that contribute towards the benefits of the herb on cognitive health.

Methods: The effect of S. officinalis extract on release of multiple cytokines and chemokines was measured in human primary intestinal epithelial cells treated with or without LPS stimulation, and Blood Brain Barrier (BBB) cells in presence or absence of recombinant IL-17A and/or Human IL-17RA/IL-17R Antibody. Antioxidant effects were also assessed in BBB cells incubated with the extract and H₂O₂. The anti-inflammatory effects of S. officinalis extract were further assessed based on clinically-relevant biomarker readouts across 12 human primary cell-based disease models of the BioMAP Diversity PLUS panel.

Results: S. officinalis showed significant attenuation of the release of most cytokines/chemokines into apical media in LPS-stimulated intestinal cells, but small increases in the release of markers including IL-6, IL-8 in basolateral media; where TNF-α was the only marker to be significantly reduced. S. officinalis attenuated the release of CRP and VCAM-1 from BBB cells under IL-17A induced conditions, and also decreased H₂O₂ induced ROS overproduction in these cells. Phenotypic profiling with the BioMAP Diversity PLUS Panel identified additional anti-inflammatory mediators, and based on a similarity search analysis suggested potential mechanistic similarity to caffeic acid and drugs known to inhibit COMT and MAO activity to modulate monoamine metabolism. Subsequent in vitro assessment showed that S. officinalis was able to inhibit the activity of these same enzymes.

Conclusions: S. officinalis extract showed anti-inflammatory effects across multiple human cell lines, which could potentially reduce peripheral inflammation and support cognitive health. S. officinalis extract also showed the ability to inhibit enzymes related to the metabolism of monoamine neurotransmitters, suggesting possible dopaminergic and serotonergic effects acting alongside proposed cholinergic effects to mediate acute cognitive performance benefits previously demonstrated for the extract.