Research - Gelsemium sempervirens
Short Review
Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues
Paolo Bellavite* , Clara Bonafini, Marta Marzotto
Department of Medicine, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
Abstract
Gelsemium sempervirens L. (Gelsemium) is traditionally used for its anxiolytic-like properties and its action mechanism in laboratory models are under scrutiny. Evidence from rodent models was reported suggesting the existence of a high sensitivity of central nervous system to anxiolytic power of Gelsemium extracts and Homeopathic dilutions. In vitro investigation of extremely low doses of this plant extract showed a modulation of gene expression of human neurocytes. These studies were criticized in a few commentaries, generated a debate in literature and were followed by further experimental studies from various laboratories. Toxic doses of Gelsemium cause neurological signs characterized by marked weakness and convulsions, while ultra-low doses or high Homeopathic dilutions counteract seizures induced by lithium and pilocarpine, decrease anxiety after stress and increases the anti-stress allopregnanolone hormone, through glycine receptors. Low (non-Homeopathic) doses of this plant or its alkaloids decrease neuropathic pain and c-Fos expression in mice brain and oxidative stress. Due to the complexity of the matter, several aspects deserve interpretation and the main controversial topics, with a focus on the issues of high dilution pharmacology, are discussed and clarified.
Source : Journal of Ayurveda and Integrative Medicine
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Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in Response to Novel Environments
Paolo Bellavite, 1 ,* Paolo Magnani, 1 Elisabetta Zanolin, 2 and Anita Conforti 3
Abstract
Gelsemium sempervirens is used in homeopathy for treating patients with anxiety related symptoms, however there have been few experimental studies evaluating its pharmacological activity. We have investigated the effects of homeopathic doses of G. sempervirens on mice, using validated behavioral models. Centesimal (CH) dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg body weight) or a placebo (solvent vehicle) were intraperitoneally delivered to groups of mice of CD1 strain during 8 days, then the effects were assessed by the Light-Dark (LD) choice test and by the Open-Field (OF) exploration test, in a fully blind manner. In the LD test, the mean time spent in the illuminated area by control and placebo-treated animals was 15.98%, for mice treated with diazepam it increased to 19.91% (P = .047), while with G. sempervirens 5 CH it was 18.11% (P = .341, non-significant). The number of transitions between the two compartments increased with diazepam from 6.19 to 9.64 (P < .001) but not with G.Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the time spent and the distance traveled in the central zone (P = .009 and P = .003, resp.), while diazepam had no effect on these OF test parameters. In a subsequent series of experiments, G. sempervirens 7 and 30 CH also significantly improved the behavioral responses of mice in the OF test (P < .01 for all tested variables). Neither dilutions of G.sempervirens affected the total distance traveled, indicating that the behavioral effect was not due to unspecific changes in locomotor activity. In conclusion, homeopathic doses of G. sempervirens influence the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a diminution of thigmotaxis or neophobia.
Source : Evid Based Complement Alternat Med. 2011; 2011: 362517.
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Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice
Paolo Magnani,1 Anita Conforti,2 Elisabetta Zanolin,2 Marta Marzotto,1 and Paolo Bellavite1
Abstract
Introduction
This study was designed to investigate the putative anxiolytic-like activity of ultra-low doses of Gelsemium sempervirens (G. sempervirens), produced according to the homeopathic pharmacopeia.
Methods
Five different centesimal (C) dilutions of G. sempervirens (4C, 5C, 7C, 9C and 30C), the drug buspirone (5 mg/kg) and solvent vehicle were delivered intraperitoneally to groups of ICR-CD1 mice over a period of 9 days. The behavioral effects were assessed in the open-field (OF) and light–dark (LD) tests in blind and randomized fashion.
Results
Most G. sempervirens dilutions did not affect the total distance traveled in the OF (only the 5C had an almost significant stimulatory effect on this parameter), indicating that the medicine caused no sedation effects or unspecific changes in locomotor activity. In the same test, buspirone induced a slight but statistically significant decrease in locomotion. G. sempervirens showed little stimulatory activity on the time spent and distance traveled in the central zone of the OF, but this effect was not statistically significant. In the LD test,G. sempervirens increased the % time spent in the light compartment, an indicator of anxiolytic-like activity, with a statistically significant effect using the 5C, 9C and 30C dilutions. These effects were comparable to those of buspirone. The number of transitions between the compartments of the LD test markedly increased with G. sempervirens 5C, 9C and 30C dilutions.
Conclusion
The overall pattern of results provides evidence that G. sempervirens acts on the emotional reactivity of mice, and that its anxiolytic-like effects are apparent, with a non-linear relationship, even at high dilutions.
Source : Psychopharmacology (Berl). 2010 Jul; 210(4): 533–545.
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Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens
Marta Marzotto1, Debora Olioso1, Maurizio Brizzi2, Paola Tononi3, Mirco Cristofoletti1 and Paolo Bellavite1*
1 Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, Verona 37134, Italy
2 Department of Statistical Sciences, University of Bologna, Via delle Belle Arti 41, Bologna 40126, Italy
3 Department of Biotechnology, University of Verona, Strada Le Grazie 15, Verona 37134, Italy
Abstract
Background
Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract.
Methods
Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions.
Results
Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10-9 M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range.
Conclusions
The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation.
Source : BMC Complementary and Alternative Medicine
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Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies
Paolo Bellavite,1 Anita Conforti,2 Marta Marzotto,1 Paolo Magnani,1 Mirko Cristofoletti,1 Debora Olioso,1 and Maria Elisabetta Zanolin2
1Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy
2Department of Public Health and Community Medicine, University of Verona, 37134 Verona,
Abstract
Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1 mg/kg body weight) or buspirone (5 mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD) choice test and the open-field (OF) exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter “time spent in central area” and of Gelsemium s. 5C, 9C, and 30C on the LD parameters “time spent in lit area” and “number of light-dark transitions,” without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization.
Source : Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 954374, 9 pages doi:10.1155/2012/954374
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