Background: Bergamot essential oil (BEO) is commonly used against psychological stress and anxiety in aromatherapy. The primary aim of the present study was to obtain first clinical evidence for these psychological and physiological effects. A secondary aim was to achieve some fundamental understanding of the relevant pharmacological processes. Methods: Endocrinological, physiological, and psychological effects of BEO vapor inhalation on 41 healthy females were tested using a random crossover study design. Volunteers were exposed to 3 experimental setups (rest (R), rest + water vapor (RW), rest + water vapor + bergamot essential oil (RWB)) for 15 min each. Immediately after each setup, saliva samples were collected and the volunteers rested for 10 min. Subsequently, they completed the Profile of Mood States, State-Trait Anxiety Inventory, and Fatigue Self-Check List. High-frequency (HF) heart rate values, an indicator for parasympathetic nervous system activity, were calculated from heart rate variability values measured both during the 15 min of the experiment and during the subsequent 10 min of rest. Salivary cortisol (CS) levels in the saliva samples were analyzed using ELISA. Results: CS of all 3 conditions R, RW, and RWB were found to be significantly distinct (p = 0.003). In the subsequent multiple comparison test, the CS value of RWB was significantly lower when compared to the R setup. When comparing the HF values of the RWB setup during the 10 min of rest after the experiment to those of RW, this parameter was significantly increased (p = 0.026) in the RWB setup for which scores for negative emotions and fatigue were also improved. Conclusion: These results demonstrate that BEO inhaled together with water vapor exerts psychological and physiological effects in a relatively short time.
Although several antiarrhythmic drugs of chemical origin are in clinical use since decades, their application is often limited by their adverse effects and especially by their inherited proarrhythmic risk, which can lead to a significantly increased mortality in patients receiving these compounds. On the other hand, aqueous extracts from the aerial parts of the European Lamiaceae Leonurus cardiaca (Ph.Eur.) have been used for centuries as a remedy against tachyarrhythmia and other cardiac disorders. Nevertheless, a scientific basis for the claim of direct cardiac electrophysiological, antiarrhythmic, or functional effects of Leonurus cardiacae herba (LCH) preparations has not been established until now. In order to enrich the active constituents from the primary extract which was tested as the most cardioactive, namely the aqueous Soxhlet extract, and to eliminate undesired substances such as the dichloromethanic fraction or potassium, a bioassay guided fractionation procedure was applied, resulting in the development of a Leonurus cardiaca refined extract (LCRE) which was characterised together with Leonurus crude extracts by a newly developed gradient elution HPLC fingerprint analysis for separation and quantification of six major phenolics as well as by qNMR for determining the stachydrine content. This refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased. In addition, voltage-clamp measurements were performed on the following cell models in order to characterise the electrophysiological profile of LCRE: neonatal rat ventricular cardiomyocytes to investigate the effect on I(Na) and I(Ca.L), sinoatrial node cells and ventricular myocytes isolated from adult guinea pigs to test effects on I(f) and action potential (AP) duration, as well as HERG-transfected HEK 293 cells to analyse the influence on the I (K.r). In these voltage clamp experiments LCRE exerted a calcium-antagonistic activity by I(Ca.L) blockade, reduced the repolarising current I(K.r), and prolonged the AP-duration, while I(Na) was not affected. Although LCRE displayed only weak effects on the I(f) amplitude and voltage dependence, it significantly prolonged the activation time constant of I(f). Thus, LCRE acts on multiple electrophysiological targets, specifically I(Ca.L), I(K.r), and I(f), observed both at whole organ and single cell level.
Based on a screening program of medicinal plants for their possible calcium antagonistic mode of action, the most active lipophilic extract of Ammi visnaga fruits (DAB 10) was fractionated by CC and investigated pharmacologically at K+ (60 mM)-depolarized guinea-pig aortic strips. Visnadin, khellin, and visnagin were identified and determined as the effective principles in this testing model with the dihydropyranocoumarin visnadin being the most active. Further selectivity tests against norepinephrine (100 microM)-induced contractions evaluated a possible pharmacological differentiation between these compounds as the furanochromones khellin and visnagin inhibited both spasms to a similar extent while visnadin's activity was significantly higher against K(+)-spasms, suggesting an involvement of a calcium channel blocking mode of action for visnadin.
From an ethanol extract of the roots of Cryptolepis sanguinolenia the alkaloid fraction and its main constituent cryptolepine were isolated by partitioning at pH 11 and column chromatography using silica gel and chloroform/methanol as eluent. Cryptolepine was identified mainly by EI-MS and 1H/13C-NMR spectroscopy. Cryptolepine (3-30 microM) and the alkaloid fraction of Cryptolepis sanguinolenta (3-10 micrograms/ml) antagonized muscarinic effects at M1 receptors in rabbit vas deferens, M2 receptors in guinea-pig atria, and M3 receptors in guinea-pig ileum. The experiments, using N-methylatropine as reference drug, showed a significant antimuscarinic activity for both cryptolepine and the alkaloid fraction, but no appreciable receptor subtype selectivity (pA2 = 5.00-5.73). Cryptolepine was determined as the antimuscarinic principle of Cryptolepis sanguinolenta. At higher concentrations both materials displayed negative inotropic effects.
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