Hot flushes and excessive sweating are cardinal post-menopausal symptoms which occur with hormonal fluctuations during climacterium. Frequency and severity of complaints however correlate with presence of neurotransmitters rather than estrogen levels in blood and serum. Neurogenic processes are not only involved in thermoregulation by the hypothalamus and sweating, but also in mood and cognitive impairment.
Salvia officinalis has traditionally been used for the treatment of extensive sweating and hot flushes, it reduced intensity and frequency of hot flushes significantly in clinical trials. The mode of action of Salvia is still unclear and we investigated Menosan®, a hydroalcoholic extract from freshly harvested Salvia off. leaves. and manufacturing variants thereof on receptors and transporters involved in thermoregulation.
Competition binding of Menosan® with specific radioligands was measured at recombinant human receptors and findings confirmed on native receptors in hypothalamic tissue originating from 37- and 51-year old women. High binding affinities (low IC50-values = dry mass concentration to reduce the specific binding of the radioligand by 50%) were observed for adrenergic α2A receptors (IC50= 13 µg/ml); μ-opioid receptors (IC50 = 18 µg/ml); muscarinic M3 receptors (IC50= 28 µg/ml) and serotonin 5-HT1A receptors (IC50 = 22 µg/ml). In addition, Serotonin re-uptake was inhibited with an IC50-value of 32 μg/ml.
Usage of freshly harvested Salvia leaves resulted in a much higher binding affinity compared to material from dried plants or stipes, e.g. at the adrenergic α2A receptor an about 4-fold higher binding affinity was measured.
In conclusion, we suggest modulation of receptors (adrenergic, serotonergic, muscarinic and μ-opioid) and transporters (Serotonin reuptake) involved in thermo- and mood-regulation as mode of action for the effectiveness of Salvia off. In addition, we provide evidence that the production process (i.e. usage of fresh Salvia off. leaves) is crucial for maximal activity.