Background: Salvia officinalis has been used successfully for the treatment of hot flushes and excessive sweating during menopause. However, modes of actions have not been elucidated conclusively. We explored its pharmacology beyond any hormonal activity with a focus on neurologic impulse transmission.
Methods: A hydroalcoholic, thujone-free extract from freshly harvested Salvia officinalis leaves (A.Vogel Menosan®) was investigated in an acetylcholinesterase enzyme assay and several receptor binding assays (adrenergic alpha 2A, GABA (benzodiazepine site), GABAB; muscarinic M3, μ-opioid, serotonin 5-HT1A, serotonin 5-HT2B, serotonin 5-HT2C and serotonin transporter). The influence of the manufacturing process on additional extracts from different fresh or dry plant parts was studied.
Results: The Salvia officinalis extract replaced 50% of specific ligand binding to GABAA and GABAB receptors at an inhibitory concentration (IC50) of 89 and 229 μg/ml, respectively. Strong binding affinity was observed for the adrenergic α2A receptor, μ-opioid receptors, muscarinic M3 receptors, and serotonin 5-HT1A receptors, with IC50 values of 15 μg/ml, 20 μg/ml, 25 μg/ml and 19 μg/ml, respectively. Moderate interference with 5-HT2B, 5-HT2C receptors, and the human serotonin transporter was found, all with IC50 values above 32 μg/ml. Receptor binding data of Salvia extract were confirmed in native female hypothalamic tissue from two women (51 and 37 years old). Use of freshly harvested Salvia leaves resulted in 2- to 4-fold higher activity/lower IC50 values compared to extracts from dried plants or stipes.
Conclusion: Our results suggest potent modulation of neuro-receptors and of serotonin transporters as mode of action for Salvia officinalis alcoholic extract, which may normalize thermoregulation and possibly also mental impairment during menopause.
Keywords: Adrenergic; Hot flushes; Menopause; Muscarinic; Salvia officinalis; Serotonergic; μ-Opioid neurotransmitter.