ECHINACEA AND ANXIETY

05/04/2016


Human Clinical Studies
1. The Anxiolytic Potential and Psychotropic Side Effects of an Echinacea Preparation in Laboratory Animals and Healthy Volunteers. We investigate that toxicity, psychotropic side effects and anxiolytic potential of and Echinacea angustifolia extract that produced promising effects in laboratory tests performed earlier. Rats were studied in the elevated plus-maze, conditioned fear, open-field, object recognition and conditioned place preference test. Toxicity was studied in rats after intragastric administration. The preparation decreased anxiety in the elevated plus-maze and ameliorated contextual conditioned fear. No lethality or behavioral signs of discomfort were noticed in rats treated with 1000 and 3000mg/kg Echinacea angustifolia. The extract was without effect in tests of locomotion (open-field), memory (object recognition) and rewarding potential (conditioned place preference) within a wide dose range. A pharmacological formulation based on the same Echinacea angustifolia extract was tested in human subjects. One or two tablets per day were administered for 1 week to healthy volunteers scoring high on the State-Trait Anxiety Inventory (STAI). The tablets contain 20mg of the plant extract. Data were collected using a structured self-assessment diary technique. The high dose (2 tablets per day) decreased STAI scores within 3 days in human subjects, an effect that remained stable for the duration of the treatment (7 days) and for the 2 weeks that followed treatment. The lower dose (1 tablet per day) did not affect anxiety significantly. [Haller J, et al. The Anxiolytic Potential and Psychotropic Side Effects of an Echinacea Preparation in Laboratory Animals and Healthy Volunteers. Phytother Res. 2013 Jan;27(1):54-61.]

Animal Studies
2. The Effect of Echinacea Preparations in Three Laboratory Tests of Anxiety: Comparison with Chlordiazepoxide. Echinacea preparations are traditionally used to treat upper respiratory infections and inflammation. No psychotropic effects of Echinacea have been reported so far, although some recently reported active constituents are behaviorally active. Prompted by these finding, the anxiolytic potential of five different Echinacea preparations was evaluated. Three of these decreased anxiety but two of them had a very narrow effect dose range. Only one extract decreased anxiety within a wide dose-range (3-8mg/kg). Anxiolytic effects were consistently seen in three different tests of anxiety, the elevated plus-maze, social interaction and shock-induced social avoidance test. No locomotor suppressant effects were seen at nay dose. Noteworthy, the doses that showed anxiolytic effects in the present study were much lower than those used in the laboratory models of the traditional indications; Chlordiazepoxide robustly decreased anxiety-like behavior in all texts but suppressed locomotion at higher doses. Perceived and real risks of conventional medications increase the demand for alternative therapies, provided that these are safe and efficient. Earlier evidence shows that Echinacea preparations have an excellent safety profile, where our finding suggest for the first time that certain preparations have a considerable anxiolytic potential. Further research is required to identify facts that differentiate efficient and inefficient preparations. [Haller J, et al. The Effect of Echinacea Preparations in Three Laboratory Tests of Anxiety: Comparison with Chlordiazepoxide. Phytother Res. 2010 Nov;24(11):1605-13.]

Cell Studies
3. The Effects of an Echinacea Preparation on Synaptic Transmission and the Firing Properties of CA1 Pyramidal Cells in the Hippocampus. Traditionally, Echinacea preparations are used as anti-inflammatory agents and immune-enhancers. In addition to these effects, their anxiolytic potency has been recognized recently in laboratory tests. Our aim in this study was to uncover the potential effects of an Echinacea preparation on neuronal operations in the hippocampus, a brain region this is involved in anxiety and anxiety-related behaviors. Using in vitro electrophysiological techniques, we observed that excitatory synaptic transmission is hippocampal slices was significantly suppressed by an Echinacea extract found to be effective in anxiety tests. In contrast, no change in inhibitory synaptic transmission could be detected upon application on this extract. In addition, our experiments revealed that at low concentration the Echinacea extract reduced the spiking activity of CA1 pyramidal cells, while at high concentration increased it. This later observation was parallel to the reduction in the magnitude of the h-current-mediated voltage responses in pyramidal cells. At any concentrations, the passive membrane properties of CA1 pyramidal cells were found to be unaltered by the Echinacea extract. In summary, the Echinacea extract can significantly regulate excitatory, but not inhibitory, synaptic transmission in the hippocampus, and this action might be involved in its anxiolytic effects observed in behavior tests. [Hájos N, et al. The Effects of an Echinacea Preparation on Synaptic Transmission and the Firing Properties of CA1 Pyramidal Cells in the Hippocampus. Phytother Res. 2012 Mar;26(3):354-62.]

4. Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors. Multiple chromatographic separations of the CHCL3-soluble extract of the roots of Echinacea purpurea led to the isolation of 19 compounds. Four natural products, three alkamides and nitidanin diisovalerianate, were identified, and five further compounds were detected for the first time in the spices. Additionally, 10 known Echinacea purpurea metabolites were isolated. The structures were determined by mass spectrometry and advanced 1D and 2D NMR techniques. The bioactivity of the isolated compounds was studied in the [35S] GTPγS-binding experiments performed on rat brain membrane preparations. Both partial and inverse agonist compounds for cannabinoid (CB1) receptors were identified among the metabolites, characterized by weak to moderate interactions with the G-protein signaling mechanisms. The G-protein-modulating activities of the Echinacea compounds are rather far from the full agonist effects seen with the CB1 receptor agonist reference compound arachidonyl-2’-chloroethylamide (ACEA). However, upon coadministration with ACEA, a number of them proved capable of inhibiting the stimulation of the pure agonist, thereby demonstrating cannabinoid receptor antagonist properties. [Hohmann J, et al. Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors. Phytochemistry 2011 Oct;72(14-15):1848-53.]