Usually, people chew fresh S. The dried leaves of S. Researchers are studying salvia to learn exactly how it acts in the brain to produce its effects. What is currently known is that salvinorin A, the main active ingredient in salvia, changes the way the brain works by changing the way nerve cells communicate. Nerve cells, called neurons, send messages to each other by releasing chemicals called neurotransmitters.
Salvia affects this signaling process. Salvinorin A attaches to parts of nerve cells called kappa opioid receptors. Note: These receptors are different from the ones involved with opioid drugs like heroin and morphine. Learn more about how the brain works and what happens when a person uses drugs.
These results are now published online in the journal NeuroImage. DOE has a long-standing interest in research on brain chemistry gained through brain-imaging studies. Note: Content may be edited for style and length. Science News. ScienceDaily, 28 April Retrieved November 11, from www. Their study shows that even small amounts of the plasticizers bisphenol A and bisphenol However, fine motor skills such as using tools can take time to learn, and humans take the longest of Page last reviewed and clinically fact-checked June 14, We're Open 24 hours a day, 7 days a week Contact us for caring and confidential advice from one of our specialists.
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We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. Sometimes hot flushes are accompanied by red, blotchy skin or palpitation [ 1 ]. In fact, an increase of core body temperature has been observed, preceded by chilliness as hot flushes subside [ 2 , 3 ]. They appear to evolve from disturbed thermoregulation in the hypothalamic region, which is equipped with thermosensitive neurons [ 4 ].
Symptoms like sleep disturbance, emotional lability and even depression further add to the syndrome and a high proportion of women are urged to seek medical help [ 5 ].
The etiology of hot flushes is unknown, although several mechanisms have been discussed. The reduction of hot flushes with estrogen replacement therapy suggests a hormonal etiology. However, blood levels of estrogens do not appear to correlate with hot flushes [ 6 ].
The serotonergic and noradrenergic systems are believed to play an immediate role in the maintenance of temperature regulation in the brain, as well as in the periphery. There is supporting evidence that estrogens regulate these two systems by modulating the production, release, and reuptake of serotonin and noradrenaline and the activity of their receptors.
Therapy of menopausal symptoms increasingly abstains from classical hormone replacement therapy HRT , taking into account the reported side effects, like breast cancer or heart disease [ 7 ]. Although the risk seems to depend on hormonal preparation, composition, and application, as well as on patient characteristics, a basic suspicion remains and novel, tolerable alternatives are sought.
Firstly, from a pharmacological point of view the investigation of neurotropic substances makes a lot of sense because cholinergic and adrenergic nerve terminals are adjacent to sweat glands [ 13 , 14 ]. Secondly, norepinephrine, dopamine, 5-hydroxytryptamine serotonin , and acetylcholine are involved in thermoregulation in the hypothalamus [ 15 , 16 ]. Whether and where centrally or at the periphery a substance will be active finally depends on the ability to cross the blood-brain barrier.
Considering the multifactorial pathological process behind menopausal complaints, multicomponent herbal preparations could present an interesting therapy option. Salvia officinalis and Cimicifuga racemosa as well as phytoestrogens e.
Salvia officinalis has traditionally been used against excessive sweating and hot flushes in menopause, to improve lipid status and liver function and for increase of mental capacity as referenced in [ 17 ].
In clinical trials a hydroethanolic, thujone-free extract A. No conclusive pharmacodynamic mode of action has been identified so far. Rahte observed no effects on serotonin re-uptake, very limited acetylcholinesterase AChE inhibition, and estrogenic activity in only one subfraction, which was lost in the total extract [ 21 ]. Biologically active substances in Salvia comprise mono-, di- and triterpenes like 1,8—cineol, carnosic acid, carnosol or ursolic acid as well as phenolic compounds including caffeic- or rosmarinic acid or flavonoids e.
Finally, essential oils are considered to contribute to the pharmacological spectrum of the plant [ 26 ]. In our experiments, we aimed to screen the actions of a proprietary Salvia officinalis extract A. A thujone-free sage spissum extract A.
Dry mass content of the spissum extract was The plant material was sourced from organic cultivations in Switzerland, verified and manufactured by A. Vogel AG Roggwil, Switzerland. Vogel AG also provided tinctures from fresh plants [FE only leaves , FE only stipes , and FE leaves and stipes ] and from dried plants [FE only leaves , FE only stipes , and FE leaves and stipes ], which have been produced according to the same extraction procedures as stated above.
Dilutions of herbal preparations were made in H 2 O Milli-Q. Folium rec. Louis, USA. Human frozen hypothalami were from a healthy year old and a healthy year-old woman Tissue Solutions Ltd. Inhibition of AChE was assessed by a modified version of the colorimetric method of Ellman et al. The thiocholine formed during hydrolysis of acetylthiocholine rapidly reacts with DTNB and releases a yellow 5-thionitrobenzoic acid anion. The alpha 2A receptor binding assay was performed according to the data sheet provided by the supplier of the receptor preparation, with modifications.
Non specific binding was determined with 3. The serotonin 5-HT 1A receptor binding assay was performed according to the data sheet provided by the supplier of the receptor preparation, with modifications. The serotonin 5-HT 2B receptor binding assay was performed as described by Wainscott et al. The serotonin 5-HT 2C e receptor binding assay was performed according to the data sheet provided by the supplier of the receptor preparation, with modifications.
The muscarinic M3 receptor binding assay was performed according to the data sheet provided by the supplier of the receptor preparation, with modifications. The 5-HTT serotonin transporter binding assay was performed according to the data sheet provided by the supplier of the receptor preparation, with modifications. Every receptor binding assay was validated by suitable well-characterised reference compounds for the respective receptor. Inhibition of AChE was assessed by a modified version of the colorimetric method of Ellmann et al.
The enzyme assay was validated by the determination of the IC 50 value of the prototypic AChE inhibitor neostigmine. Competition binding at several receptors. The calculated IC 50 values are indicated above the figure. In membranes from native female hypothalami the reference antagonist rauwolscine and the test item, Salvia officinalis extract, competed for the binding of [ 3 H]-MK with IC 50 values of 3. In membranes from human native female hypothalami, the reference antagonist 4-DAMP and the test item, Salvia off.
The obtained IC 50 value of 0. In the former case, the action of the extract would be located in signal transduction rather than in central thermoregulation. Serotonin reuptake was investigated via a serotonin transporter binding assay. The binding assay delivers comparable data to direct uptake measurements, but is much easier to handle. The tricyclic antidepressant imipramine — a reference inhibitor of serotonin transporters — competed for the binding of [ 3 H]-imipramine to human serotonin transporters expressed in HEK cells in a concentration-dependent manner Fig.
The calculated IC 50 value of 2. To complete the investigation of the serotonergic system, the binding of the Salvia officinalis to one member of the 5-HT 1 -family, namely the 5-HT 1A -receptor, and to two members of the 5-HT 2 -family, namely the 5-HT 2B and the 5-HT 2C e receptors, was investigated.
In membranes from human native female hypothalami, no specific binding of the radioligand for the 5-HT 1A , [ 3 H]OH-DPAT, could be observed, indicating the absence of the serotonin 5-HT 1A receptor at least in the investigated preparation.
The initial experiments were mostly performed on human receptors originating from expression systems, e.
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