|Date: October 15, 2004||HC# 060242-266|
Re: Sage Used to Treat Alzheimer's Disease
Houghton P. Activity and constituents of sage. HerbalGram. 2004;61:48-53.
Sage (Salvia officinalis) is used to treat indigestion and inflammation of the throat, to reduce sweating (including that associated with hot flashes during perimenopause), and to suppress lactation in nursing mothers. Some older literature reveals that it may improve memory. The author reviews studies conducted to investigate the bioactivity and constituents of sage (Salvia officinalis and S. lavandulifolia) that might be useful in treating Alzheimer's disease (AD).
Studies reviewed by the author include preliminary investigations of the herb's bioactivity conducted at the Medical Research Council Neurochemistry Laboratories at Newcastle General Hospital in Northeast England. More detailed investigations at King's College London into relevant activities of the herb and its chemical constituents responsible for such activity were also included. The author reviews both in vitro and in vivo tests on the following effects of sage extracts on the factors associated with AD or with a reduction in its incidence.
Most drugs used in the early stages of AD inhibit the enzyme acetylcholinesterase (AChE). Preliminary tests using the assay for cholinesterase inhibition were conducted on both the 96% ethanolic extract and the steam-distilled oil of three samples of S. officinalis and three samples of oil of S. lavandulifolia. All six samples produced inhibition of the enzyme at low concentrations.
To determine active constituents, the oil of S. lavandulifolia was fractionated by droplet counter-current chromatography, and the chemical composition of the fractions were analyzed by thin-layer and gas chromatography. The investigators measured the cholinesterase inhibitory activity of each fraction. From the active fractions, several cyclic monoterpenes were identified as the most active compounds; 1,8-cineole is likely to contribute most to the activity of the oil as it is present in the greatest concentration.
In vivo studies of sage oil and its AChE activity include one in which normal rats were given orally on separate occasions (four months apart) either 20 mcL or 50 mcL of S. lavandulifolia essential oil in a standard dose of sunflower oil once per day for five days, with a control group given sunflower oil alone. Results suggest that one or more constituents of the S. lavandulifolia oil, or their metabolites, reach the brain (crossing the gastrointestinal and blood-brain barriers) and inhibit cholinesterase in select brain areas, consistent with evidence of inhibition of the brain enzyme in vitro.
The in vitro study revealed antioxidant effects present in the ethanolic extract of S. lavandulifolia. Both water-soluble and chloroform-soluble fractions of the extract gave similar antioxidant activity to the propyl gallate, thus indicating that a mixture of substances is present that might prevent brain cells from damage by reactive oxygen species.
Individual components of the volatile oil were tested for antioxidant effects. Such effects were noted with 1,8-cineole, alpha-pinene, and beta-pinene, but a pro-oxidant effect was produced by camphor, a major component oil. This pro-oxidant activity is likely eclipsed by the antioxidant compounds so that the total oil would have an overall antioxidant effect, says the author.
Eicosanoid synthesis is part of the inflammatory response, and a reduced level of these compounds is indicative of reduced inflammation. The S. lavandulifolia ethanol extract at 50 mcg/mL showed only weak inhibition of eicosanoid synthesis. When the ethanol extract was fractionated, the chloroform-soluble portion produced a greater inhibition than the water-soluble fraction. The S. lavandulifolia extracts also showed only weak inhibition of eicosanoid synthesis. Alpha-pinene, comprising 5% of the essential oil, was the only constituent that produced significant activity.
According to the author, estrogen-receptor binding studies were carried out at a time when AD was thought to be prevented by estrogen replacement therapy. Estrogenic activity was observed in the ethanolic extract and the essential oil of S. lavandulifolia. A dose-dependent activity was observed with the ethanol extract over the range of 1 to 5 mg/mL and appeared to be concentrated in the water-soluble fraction. Of the five monoterpenoid constitutions of S. lavandulifolia essential oil screened, only geraniol exhibited estrogenic activity (P < 0.001). Because recent research has shown that estrogenic compounds actually increase the incidence of AD rather than reduce it, these findings are of little consequence, says the author.
Effects on cognition
In a placebo-controlled, double-blind, balanced, crossover study, healthy volunteers received a standardized extract of S. lavandulifolia in sunflower oil as well as the sunflower oil alone. Significant effects of cognition were associated with the lowest dose of the sage, including improvements in both immediate and delayed-word recall scores and decreases in both accuracy and speed of attention. Following the highest dose, both "calmness" and "contentedness" were reduced. These results, say the author, represent the first systematic evidence that sage oil is capable of acute modulation of mood and cognition in health young adults.
The author concludes that the results of these studies demonstrate that S. lavandulifolia, its essential oil, and some chemical constituents have properties relevant to the treatment of AD and provide further data supporting the value of carrying out clinical studies in patients with AD using this plant species.