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Paolo Bellavite - One of the best experts on this subject based on the ideXlab platform.

  • Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues.
    Journal of Ayurveda and integrative medicine, 2018
    Co-Authors: Paolo Bellavite, Clara Bonafini, Marta Marzotto
    Abstract:

    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.

  • Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues
    Elsevier, 2018
    Co-Authors: Paolo Bellavite, Clara Bonafini, Marta Marzotto
    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. Keywords: Gelsemium sempervirens, Anxiety, Neurocytes, Animal models, Homeopathic medicine, Behavior, Gene expressio

  • Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens
    BMC Complementary and Alternative Medicine, 2014
    Co-Authors: Marta Marzotto, Debora Olioso, Maurizio Brizzi, Paola Tononi, Mirco Cristofoletti, Paolo Bellavite
    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.

  • Effects of Gelsemium sempervirens L. on pathway-focused gene expression profiling in neuronal cells
    Journal of ethnopharmacology, 2014
    Co-Authors: Debora Olioso, Marta Marzotto, Maurizio Brizzi, Elisabetta Moratti, Paolo Bellavite
    Abstract:

    Abstract Ethnopharmacological relevance Gelsemium sempervirens L. is a traditional medicinal plant mainly distributed in the southeastern of the United States, employed in phytotheraphy and homeopathy as nervous system relaxant to treat various types of anxiety, pain, headache and other ailments. Although animal models showed its effectiveness, the mechanisms by which it might operate on the nervous system are largely unknown. This study investigated for the first time by a real-time PCR technique (RT-PCR Array) the gene expression of a panel of human neurotransmitter receptors and regulators, involved in neuronal excitatory signaling, on a neurocyte cell line. Materials and methods Human SH-SY5Y neuroblastoma cells were exposed for 24 h to Gelsemium sempervirens at 2c and 9c dilutions (i.e. 2 and 9-fold centesimal dilutions from mother tincture) and the gene expression profile compared to that of cells treated with control vehicle solutions. Results Exposure to the Gelsemium sempervirens 2c dilution, containing a nanomolar concentration of active principle gelsemine, induced a down-regulation of most genes of this array. In particular, the treated cells showed a statistically significant decrease of the prokineticin receptor 2, whose ligand is a neuropeptide involved in nociception, anxiety and depression-like behavior. Conclusions Overall, the results indicate a negative modulation trend in neuronal excitatory signaling, which can suggest new working hypotheses on the anxiolytic and analgesic action of this plant.

  • Cellular and transcriptional responses of SH-SY5Y human neurocytes following in vitro exposure to Gelsemium sempervirens
    International Journal of High Dilution Research, 2012
    Co-Authors: Paolo Bellavite, Marta Marzotto, Debora Olioso, Maurizio Brizzi, Paola Tononi, Mirco Cristofoletti, Ilaria Pierpaola Dal PrÃÂÂ, Ubaldo Armato
    Abstract:

    Background: Gelsemium sempervirens (Gelsemium s.) is a highly toxic plant but is employed at low doses and/or high dilutions as an anxiolytic and antidepressant. Previous investigations in our laboratory [1,2] have shown a significant anxiolytic-like activity of Gelsemium s., using emotional response models in laboratory mice. Although there is some biochemical evidence of a possible role of neurosteroid metabolism [3], the cellular and molecular mechanisms involved in the effects of Gelsemium s. at the level of nervous system are largely unknown. To help determine these pathways, we used human neurocytes (SH-SY5Y cell line) treated in vitro with different dilutions of Gelsemium s. and evaluated their vitality and gene expression changes. Methods: The drugs were produced by Boiron Laboratoires, Lyon (F), starting from a whole-planthydroalcoholic extract of Gelsemium s. Solutions 1C, 2C, 3C, 4C, 8C and 29C (C= centesimal dilution/dynamization prepared in 30% ethanol/distilled water) were provided in 30-ml glass bottles, wrapped in aluminium foil and were stored in the dark at room temperature in a metal cupboard. Control solutions (“placebo”) were serially diluted/dynamized 30% ethanol/distilled water. Before each experiment, 0.05 ml samples of Gelsemium s. and placebo were added to 5 ml of distilled sterile and apyrogenic water in a 15 ml Falcon polystyrene plastic tube, closed and shaken in mechanical shaker DinaA for 7.5 sec (150 strokes) to obtain the final 2C, 3C, 4C, 5C, 9C and 30C succussed dilutions, with ethanol concentration of 0.3% (v/v) (final 0.03% in the assay system).

John B. Pascarella - One of the best experts on this subject based on the ideXlab platform.

  • The Relationship Between Soil Environmental Factors and Flowering Phenology in Two Sympatric Southeastern Gelsemium Species—Does Habitat Specialization Determine Differences in Flowering Time?
    Castanea, 2011
    Co-Authors: John B. Pascarella
    Abstract:

    Abstract Previous research has found significant differences in flowering time between sympatric, non-hybridizing populations of congeners in the genus Gelsemium (Gelsemium sempervirens and G. rankinii). An experimental approach using a common garden, reciprocal transplant experiments, and observations of natural populations were used to test the hypothesis that soil environmental variables (soil moisture and soil temperature) related to habitat specificity of the two species influence differences in flowering phenology. Replicated pairs of both species were planted into a common garden and into wet and dry habitats that typify the two species (dry for earlier flowering G. sempervirens and wet for later flowering G. rankinii). Two sites with sympatric natural populations of both species were also studied for comparison. The number of open flowers was counted every two weeks in 2007 and 2008 in all sites and in 2009 for the reciprocal transplant experiment. Soil moisture and soil temperature varied by site...

  • Pollination biology of Gelsemium sempervirensL. (Ait.) (Gelsemiaceae): do male and female Habropoda laboriosa F. (Hymenoptera, Apidae) differ in pollination efficiency?
    Journal of Apicultural Research, 2010
    Co-Authors: John B. Pascarella
    Abstract:

    SummaryIn the outer coastal plain of Georgia, USA, Gelsemium sempervirens (Gelsemiaceae) is heavily visited (69–100% of all flower visits) by male and female blueberry bees, Habropoda laboriosa (Hymenoptera-Apidae). Fruit set is, however, consistently low (8–36% range). The pollination efficiency of male and female blueberry bees was studied using: 1. comparison of pollen loads on foraging male and female bees; 2. calculation of pollen loads on fresh stigmas of flowers exposed to a single visit by a female bee; and 3. an experimental test of fruit and seed set following exposure to one to eight visits by both male and female bees. Females had larger pollen loads in four of five body regions, but male bees consistently carried pollen in quantities sufficient for fertilization. A single visit from a female bee resulted in mixed pollen deposition of 76 pollen grains, 20 of which were from Gelsemium and 56 from Vaccinium. There was no significant relationship of either fruit or seed set with number of visits ...

  • Mechanisms of prezygotic reproductive isolation between two sympatric species, Gelsemium rankinii and G. sempervirens (Gelsemiaceae), in the southeastern United States
    American journal of botany, 2007
    Co-Authors: John B. Pascarella
    Abstract:

    Natural hybridization plays a critical role in speciation, the maintenance of reproductive isolation, and genetic introgression. While many plant species have hybrid swarms in areas of sympatry, the lack of hybrids among closely related sympatrically distributed species suggests that strong pre- and/or postzygotic barriers exist to hybridization. Gelsemium sempervirens and G. rankinii (Gelsemiaceae) are sympatrically distributed southeastern sister taxa that have strong postzygotic barriers to hybrid formation and high levels of genetic differentiation. In this study, two sympatric populations in Lowndes County, Georgia were surveyed from 1999-2005 to assess the role of temporal and pollinator isolation as potential prezygotic barriers. The populations had mostly non-overlapping flowering periods in 2003-2005, with significant differences in time of peak flowering and length of flowering. Both species shared a similar community of flower visitors, with the apid bee Habropoda laboriosa the dominant visitor to both species. A choice experiment found that H. laboriosa visited both species but preferred G. sempervirens. The primary prezygotic barrier is temporal isolation preventing hybridization in spite of the shared pollinators. This study suggests that reliance on a shared pollinator during speciation may limit opportunity for divergent selection on flowering time.

Hiromitsu Takayama - One of the best experts on this subject based on the ideXlab platform.

Marta Marzotto - One of the best experts on this subject based on the ideXlab platform.

  • Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues.
    Journal of Ayurveda and integrative medicine, 2018
    Co-Authors: Paolo Bellavite, Clara Bonafini, Marta Marzotto
    Abstract:

    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.

  • Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues
    Elsevier, 2018
    Co-Authors: Paolo Bellavite, Clara Bonafini, Marta Marzotto
    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. Keywords: Gelsemium sempervirens, Anxiety, Neurocytes, Animal models, Homeopathic medicine, Behavior, Gene expressio

  • Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens
    BMC Complementary and Alternative Medicine, 2014
    Co-Authors: Marta Marzotto, Debora Olioso, Maurizio Brizzi, Paola Tononi, Mirco Cristofoletti, Paolo Bellavite
    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.

  • Effects of Gelsemium sempervirens L. on pathway-focused gene expression profiling in neuronal cells
    Journal of ethnopharmacology, 2014
    Co-Authors: Debora Olioso, Marta Marzotto, Maurizio Brizzi, Elisabetta Moratti, Paolo Bellavite
    Abstract:

    Abstract Ethnopharmacological relevance Gelsemium sempervirens L. is a traditional medicinal plant mainly distributed in the southeastern of the United States, employed in phytotheraphy and homeopathy as nervous system relaxant to treat various types of anxiety, pain, headache and other ailments. Although animal models showed its effectiveness, the mechanisms by which it might operate on the nervous system are largely unknown. This study investigated for the first time by a real-time PCR technique (RT-PCR Array) the gene expression of a panel of human neurotransmitter receptors and regulators, involved in neuronal excitatory signaling, on a neurocyte cell line. Materials and methods Human SH-SY5Y neuroblastoma cells were exposed for 24 h to Gelsemium sempervirens at 2c and 9c dilutions (i.e. 2 and 9-fold centesimal dilutions from mother tincture) and the gene expression profile compared to that of cells treated with control vehicle solutions. Results Exposure to the Gelsemium sempervirens 2c dilution, containing a nanomolar concentration of active principle gelsemine, induced a down-regulation of most genes of this array. In particular, the treated cells showed a statistically significant decrease of the prokineticin receptor 2, whose ligand is a neuropeptide involved in nociception, anxiety and depression-like behavior. Conclusions Overall, the results indicate a negative modulation trend in neuronal excitatory signaling, which can suggest new working hypotheses on the anxiolytic and analgesic action of this plant.

  • Cellular and transcriptional responses of SH-SY5Y human neurocytes following in vitro exposure to Gelsemium sempervirens
    International Journal of High Dilution Research, 2012
    Co-Authors: Paolo Bellavite, Marta Marzotto, Debora Olioso, Maurizio Brizzi, Paola Tononi, Mirco Cristofoletti, Ilaria Pierpaola Dal PrÃÂÂ, Ubaldo Armato
    Abstract:

    Background: Gelsemium sempervirens (Gelsemium s.) is a highly toxic plant but is employed at low doses and/or high dilutions as an anxiolytic and antidepressant. Previous investigations in our laboratory [1,2] have shown a significant anxiolytic-like activity of Gelsemium s., using emotional response models in laboratory mice. Although there is some biochemical evidence of a possible role of neurosteroid metabolism [3], the cellular and molecular mechanisms involved in the effects of Gelsemium s. at the level of nervous system are largely unknown. To help determine these pathways, we used human neurocytes (SH-SY5Y cell line) treated in vitro with different dilutions of Gelsemium s. and evaluated their vitality and gene expression changes. Methods: The drugs were produced by Boiron Laboratoires, Lyon (F), starting from a whole-planthydroalcoholic extract of Gelsemium s. Solutions 1C, 2C, 3C, 4C, 8C and 29C (C= centesimal dilution/dynamization prepared in 30% ethanol/distilled water) were provided in 30-ml glass bottles, wrapped in aluminium foil and were stored in the dark at room temperature in a metal cupboard. Control solutions (“placebo”) were serially diluted/dynamized 30% ethanol/distilled water. Before each experiment, 0.05 ml samples of Gelsemium s. and placebo were added to 5 ml of distilled sterile and apyrogenic water in a 15 ml Falcon polystyrene plastic tube, closed and shaken in mechanical shaker DinaA for 7.5 sec (150 strokes) to obtain the final 2C, 3C, 4C, 5C, 9C and 30C succussed dilutions, with ethanol concentration of 0.3% (v/v) (final 0.03% in the assay system).

Noriyuki Kogure - One of the best experts on this subject based on the ideXlab platform.