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Neurotropic, immunological and gastric effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine in stressed mice

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Abstract

Previous studies realized in the laboratory have indicated that application of experimental stress (such as unavoidable footshock) induced significant behavioral, gastric and immunological alterations in mice. The aim of this study was to evaluate effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine on stress-induced behavioral, immunological and gastric alterations. Locomotor, postural and exploratory activities have been evaluated by two behavioral tests: light/dark box and staircase tests. Immunological studies were investigated to count white blood cells subpopulations (lymphocytes, neutrophils, monocytes and basophils) by coulter counter. The severity of gastric erosions was evaluated by microscopic technique in mice after experimental stress. The results have demonstrated that low doses of G. sempervirens L. and A. belladonna L. had a significant neurotropic and protective effects on behavioral and gastric alterations induced by experimental stress. The immunological protective effects observed were probably induced via their neurotropic effects. The P. histamine showed a significant immunoprotective and gastroprotective effect in mice exposed to experimental stress.

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... GELS is used clinically in both traditional Ayurvedic herbal medicine and homeopathy [24,25]. Gelsemium (GELS) botanical extracts prepared as a homeopathic medicines (HMs) reportedly exhibit anticancer [26,27], analgesic [28], and anxiolytic effects [29,30]. Gelsemium encapsulated in poly (lactide-co-glycolide) (PLGA) nanoparticles (NPs) exhibits enhanced cellular uptake and proapopotic effects in a skin cancer cell line [27]. ...
... However, as the verum source material Gelsemium sempervirens in the present study was, like the natural corks, also a plant-derived extract rather than a metal, we anticipated greater difficulty in distinguishing plant medicine verums from succussed controls with cork stoppers. Identifying a specific biological assay for activity of the different samples might help distinguish between Gelsemium versus Quercus suberrelated effects on recipient living systems [16,17,28,29,32,35,74,75]. Including silicone stoppered controls in future NP characterization studies of other HMs, including metal, animal, and other plant sources, would be helpful. ...
... At the same time, do the findings have implications for biological effects and therapeutics of HMs? The present data create a nanotechnology context for the extensive prior research literature on biological and behavioral effects of homeopathic Gelsemium sempervirens [26][27][28][29][30][31][32]. In homeopathic clinical practice, choice of a specific HM such as GELS is based upon clinical pattern matching the integrative biopsychosocial symptom picture of the affected patient to the previously-documented effects of specific source materials on living systems [42]. ...
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Multiple studies have observed nanostructures in traditionally-manufactured homeopathic medicines. Homeopathy is a 200-year-old system of complementary and alternative medicine used worldwide. The nature of homeopathic medicines has historically stimulated much debate. The present placebo-controlled study extended previous work to characterize nanoparticles (NPs) in homeopathically-prepared Gelsemium sempervirens (GELS), a natural botanical source with previously-documented anxiolytic, analgesic, and anticancer properties. An ethanolic GELS herbal extract was serially diluted and succussed (agitated) in a 95% ethanol-water diluent solvent in glass vials, following Homeopathic Pharmacopoeia of the U.S. guidelines. GELS (VERUM, at homeopathic potencies of 6C, 30C, 200C, each n=3 vials), succussed controls (SUCC-CONT, at homeopathic potencies of 6C, 30C, 200C, each n=3), and one set of unsuccussed solvent control vials also used natural cork (Quercus suber) stoppers (UNSUCC-cork, n=3). A final set of unsuccussed solvent controls used silicone stoppers (UNSUCCsilicone, n=3). Analytical methods included nanoparticle tracking analysis (NTA), zeta potentials, and UV-Visible spectroscopy. NTA revealed >4 x 108 nanoparticles per millliliter in all VERUM, SUCC-CONT, and UNSUCC-cork vials, significantly more than the UNSUCC-silicone controls. Particle sizes were polydisperse, significantly larger in the VERUM 30C at 129.8 nanometers versus SUCC-CONT at 6C, 30C, 200C and the UNSUCC-cork controls. Zeta potentials consistent with greater particle stability were signficantly most negative in the VERUM GELS 200C (-47.75 mV). Within the UV-vis wavelength range 300-400 nm, the SUCC-CONT 30C exhibited significantly higher, whereas UNSUCC-silicone stopper controls had significantly lower, mean absorbance than all other samples. Taken together, the data suggest that traditional homeopathic methods involving succussions release not only the previously-shown silica from glassware walls, but also Quercus suber materials from natural cork stoppers to stabilize NPs in solution. With verum source material Gelsemium, additional NP size growth and surface stabilization can occur. Further study of homeopathic manufacturing materials and methods and their biological correlates is indicated.
... Belladonna (Bell) is used to treat inflammatory diseases in homeopathy. Bell is a valuable homeopathic medicine with proven pharmacological effects such as antibacterial, neurotropic, antiseptic, antiprotozoal and anti-inflammatory effects [3][4][5][6][7]. Bell showed a marked decrease of Staphylococcus aureus MRSA growth [3], neurotropic and protective effects in rats [4], decrease in the proportion of degenerated leukocytes in an inflammatory model of experimental peritonitis [5] and controlled parasitic infection Trypanosoma cruzi in Swiss male mice [6]. ...
... Bell is a valuable homeopathic medicine with proven pharmacological effects such as antibacterial, neurotropic, antiseptic, antiprotozoal and anti-inflammatory effects [3][4][5][6][7]. Bell showed a marked decrease of Staphylococcus aureus MRSA growth [3], neurotropic and protective effects in rats [4], decrease in the proportion of degenerated leukocytes in an inflammatory model of experimental peritonitis [5] and controlled parasitic infection Trypanosoma cruzi in Swiss male mice [6]. ...
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Background Belladonna and Pyrogenium are commonly used to treat fever in homeopathy. But in vivo antipyretic activity of these medicines is not reported yet. The study was conducted to evaluate the effectiveness of ultrahigh dilutions of Belladonna ( Bell ) and Pyrogenium ( Pyro ) in fever model of rabbits induced by Baker's yeast. Methods Healthy, local strain rabbits (♂ and ♀) were divided into seven groups (n=42): Normal control, negative control, standard control, pyro 1000c, pyro 200c, Bell 1000c and Bell 200c. Fever was induced by intra peritoneal injection of 135 mg/kg Baker’s yeast suspension. Rectal temperature was measured hourly. All the medicines were administered once a day. The results were expressed as mean ± SEM. ANOVA and least significant difference post hoc test were applied for checking the level of significance, p-value of ≤0.05 was considered significant statistically. Results Pyro in both potencies significantly reduced fever in rabbits compared to negative control group, while both potencies of Bell were ineffective. Paracetamol and Pyro 1000c reduced by 1.2 °C (39.7 ± 0.1 to 38.5 ± 0.1), while Pyro 200c reduced by 1 °C temperature (39.7 ± 0.5 to 38.7 ± 0.2). Conclusions Pyro possesses marked antipyretic activity in rabbit’s Baker's yeast fever model. It would embolden its clinical use in fever with more guarantee of its efficacy. However, caveat of small sample size necessitates replication of experiment in large sample size.
... Bellavite and co-workers have demonstrated that low doses and high dilutions of extract of Gelsemium e traditionally used for patients with anxiety-like symptoms e reduce anxiety and fear in validated mice behavioral models [11,29]. These effects confirm previous reports [30,31] and were followed by other similar evidence by other's laboratories [24,32]. ...
... A 9c dilution should contain a theoretical concentration of 10 À22 mol/L, that is near the limit of AvogadroeLoschmidt constant, and the 30c should be far below that limit [57]. Bousta et al. [30] reported that Gelsemium at 5c and 15c dilutions caused a significant increase in steps climbed in the staircase test in stressed mice and in the light/dark box test caused a significant increase of transitions at 5c, 9c and 15c. Interestingly, the authors observed concomitant variation of some immunological parameters like an increase of lymphocytes and neutrophils. ...
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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.
... Even then, the state of the recipient organism at the time of administration determines the direction of change to salient HMs [183]. HMs act most clearly in already previously-stressed cells or organisms rather than those at rest and may have no effect at all in unstressed recipients [184][185][186]. Finally, some HMs such as Calcarea Carbonica (calcium carbonate) in potency initiate immune-modulation, but at the level of the intact host organism as a larger network or system rather than isolated cells in vitro [187]. ...
... Clinically and experimentally, homeopaths report that HMs act best in an organism that is already sick or stressed [183,184,276]. In fact, to trigger a reversal in direction, the biological activity of salient HMs probably leverages the pattern of pre-existing large magnitude adaptations that the organism has already generated to the original severe stressor(s) (i.e., oscillation after pre-sensitization or post conditioning hormesis) [2,182]. ...
... Previous investigations in our laboratory [26,27] have shown a significant anxiolytic-like activity of Gelsemium s. high dilutions (namely 5c, 7c, 9c and 30c according to different test paradigms) in mice, using emotional response models. Other laboratories have also reported in vivo [16,19,28,29] or in vitro [30] effects of Gelsemium s. in extremely low doses or high dilution/dynamization, but its action at the cellular level has not been fully clarified. To follow up the above evidence of an anxiolytic effect in animal models, we decided to investigate the Gelsemium s. mechanism of action in neuronal models by assessing the drug effects on whole genome expression changes. ...
... In previous recent trials, Gelsemium s. showed anxiolytic-like effects in mouse emotional response models and appeared to work even at the high dilutions 9c and 30c [26,27]. Two other studies have also found that high dilutions of Gelsemium s. exert a preventive action against experimental stress (electric shock) in mice [29] and against convulsions provoked by lithium and pilocarpine in rats [5]. Other researchers have reported an anti-anxiety activity of Gelsemium s. [12] and of the alkaloids gelsemine, koumine, and gelsevirine [14,16], but have not explored the effect of ultra-low doses and high dilutions/dynamizations. ...
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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. Starting from the crude extract, six 100 x (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. Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 x 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. 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.
... -les profils antidépresseurs, immunomodulateurs et gastroprotecteur [6,7,[9][10][11] ; ...
... -d'autres activités apoptotique, antitumorale, antibactérienne, antivirale, cardiovasculaire [3,11,21] ; -et de manière précise, la recherche du profil pharmacologique sédatif/anxiolytique dans une plante réputée par sa sédation dans la pratique médicale traditionnelle [7,23]. ...
Article
Au Maroc, la phytothérapie est une pratique très ancienne; elle y doit énormément à la médecine « arabo-islamique », même si des non-musulmans, juifs et chrétiens notamment, ont joué un rôle important. Les connaissances empiriques se sont transmises verbalement à travers les générations et se sont enrichies grâce à la situation géographique stratégique bien connue du Maroc (diversité bioclimatique et brassage des civilisations à travers l’histoire). À l’heure actuelle, les plantes médicinales peuvent nous apporter des solutions intéressantes aux contraintes liées à la santé surtout dans des pays en voie de développement. La promotion de la phytothérapie nous permettra de sauvegarder le savoir de nos ancêtres qui tend à disparaître. De par ses missions, l’Institut national des plantes médicinales et aromatiques-Maroc, tend à contribuer à l’élaboration de nouveaux médicaments naturels en étroite collaboration avec des décideurs de ce secteur pour sauvegarder la biodiversité végétale d’une part, et contrôler l’innocuité et la qualité des sous-produits de la médecine traditionnelle d’autre part.
... In homeopathic Materia Medica, Gelsemium s. is described as a remedy for a variety of anxiety-like neurological and behavioural symptoms [6– 8], and there is a preliminary report [9] that homeopathic dilutions/dynamizations of Gelsemium s. in mice counter the effects of the anxiogenic compound RO 15-3505 (inverse agonist of benzodiazepines) in the labyrinth test. More recently, Bousta et al. have reported that, in some but not all experimental conditions, Gelsemium s. at the 5th, 9th, and 15th centesimal homeopathic dilutions/dynamizations (C) reduces stress-induced behavioural alterations of mice in the staircase test and light-dark test [10]. However, all these results represent reversals of the effects of severe stress (conditioned paradigm), and the findings vary widely depending on the dose administered and the test performed. ...
... It has been noted that the extent to which an anxiolytic compound facilitates exploratory activity depends on its baseline level in the control group [25]. Bousta et al. [10] report some anxiolytic-like effects of G. sempervirens in mice stressed by repeated electric shocks, but no such effects in normal unstressed mice. Differences between the nature and severity of external stressors, or between experimental setups, environment, handling and testing, and individual biological responses to drugs, might account for the high variability of results reported under different experimental conditions [24, 32, 33]. ...
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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.
... [81] Low doses of G. sempervirens and Atropa belladonna showed significant neurotropic and protective effects on behavioral and gastric alterations induced by foot shock stress in mice. [82] Ethanolic extract of G. sempervirens has been reported to increase the resistance of rabbits to pneumococcus toxin. [83] G. sempervirens alkaloidal fraction possessed anticancer activity as evidenced by significant inhibition of hepatic carcinoma HepG 2 cells in vitro using crystal violet dyeing method. ...
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The review includes 103 references on the genus Gelsemium, and comprises ethnopharmacology, morphology, phytoconstituents, pharmacological reports, clinical studies and toxicology of the prominent species of Gelsemium. Alkaloids and iridoids constitute major classes of phytoconstituents of the genus. Most popular species of the genus are the Asian G. elegans and the two North American related species, G. sempervirens and G. rankinii. Gelsemium species are categorized under medicinal as well as poisonous plants. Amongst various species, G. elegans and G. sempervirens possess medicinal value, and have been traditionally used as nervous system relaxant. These plants have been explored exhaustively for their anticancer activity. In the concluding part, the future scope of Gelsemium species has been emphasized with a view to establish their multifarious biological activities and mode of actions.
... The extent to which an anxiolytic compound facilitates exploratory activity has been shown to depend on its baseline level in the control group [14]. Bousta et al. [15] report some anxiolytic-like effects of Gelsemium in mice stressed by repeated electric shocks, but no such effects in normal unstressed mice. For these reasons and in connection with the well-known complexity of animal behaviour studies, we had to use a large number of animals in each group and experimental phase. ...
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As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-field), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this field, disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.
... Arnica montanaAnti-inflammatory, Antioxidant, and Helenalin (sesquiterpene lactone),(Olioso et al., 2016; Craciunescu et cytoprotective flavonoids, and phenolic acids al., 2012;Lyß et al., 1998) Atropa belladonna Sedative, local analgesic, hypertensive Atropine (alkaloid), scopolamine(Bousta et al., 2001; Kwakye et al.Rakelly de Oliveira et al., 2015; marianum L. Gaertn inflammatory, antitumor, antibacterial, flavonolignans): major components Ebrahimpour koujan et al., 2015;are silybin, taxifolin, and quercetinWellington and Jarvis, 2001) (flavonoids)ChenopodiumCytotoxic against tumor cell linesAscaridol isolated from essential(Yadav et al., 2007; anthelminticum Linnoils Efferth et al., 2002) Cinnamomum Antidiabetic, antioxidant, antimutagenic, Essential oils, such as eugenol and (Cardoso-Ugarte et al., 2016; zeylanicum antitumor, and antimicrobial cinnamaldehyde, and cynammic Husain et al., 2018; acetate Verspohl et al., 2005) Colchicum autumnale Antirheumatic and anti-inflammatory Colchicine (alkaloid) (Akram, 2012; Kurek, 2018) Echinacea Anti-inflammatory, immunostimulator, Flavonoids, lipophilic compounds, (Shaffique et al., 2018; Bonomo et angustifolia antioxidant and antimicrobial such as alkamides and ketoalkenes, al., 2017; Kindscher, 2016) and hydrophilic phenolic compounds, such as caffeic acid derivatives TABLE 8.ContinuedSánchez-Tena et al., 2012; Touriño virginiana antiviral, and inhibits cancer cell proliferation dins, hamamelitannin pentagalloyl-et al., 2008; Theisen et al., 2014) glucose, gallotannins, and gallates Juglans regia Cytotoxic against various human cancer cell Juglone (Panth et al., 2016) lines: lung (NCI-H322 and A549), breast (T47D), skin (A-431), prostate colon (Colo-205 and HCT-116), and prostate (PC- ...
... Furthermore, practical evidence and explanation regarding physico-chemical (Elia et al., 2007;Elia and Niccoli, 1999;Rey, 2003;Rao et al., 2007Rao et al., , 2008Roy et al., 2005;Ives et al., 2010) and nanoparticulate (Chikramane et al., 2010;Montagnier et al., 2009;Bhattacharyya et al., 2008;Upadhyay and Nayak, 2011) charactristics of homeopathic remedies discourages simplistic dismissal of this traditional system of medicine. These remedies are cost effective and have shown adaptive non-linear response on the living systems thereby stamping their effectiveness in disease treatment and management (Calabrese and Jonas, 2010;Van Wijk and Wiegant, 2010;Iavicoli et al., 2010;Bertani et al., 1999;Malarczyk et al., 2011;Van Wijk and Wiegant, 2011;Bousta et al., 2001). Thus there is need for more laboratory and clinical research to substantiate the efficacy of homeopathic preparations against complex disorders. ...
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Ethnopharmacological relevance Processed Nux vomica seed extracts and homeopathic medicinal preparations (HMPs) are widely used in traditional Indian and Chinese medicine for respiratory, digestive, neurological and behavioral disorders. Antioxidant property of Nux vomica is well known and recent investigation has highlighted the anticonvulsant potential of its homeopathic formulation. Aim of the study To explore the anticonvulsant and antiepileptogenic potential of Nux vomica HMPs (6CH, 12CH and 30CH potency) in pentylenetetrazole (PTZ) induced acute and chronic experimental seizure models in mice and investigate their effects on cognition, memory, motor activity and oxidative stress markers in kindled animals. Materials and methods Acute seizures were induced in the animals through 70 mg/kg (i.p.) administration of PTZ followed by the evaluation of latency and duration of Generalized tonic-clonic seizures (GTCS). Subconvulsive PTZ doses (35 mg/kg, i.p.) induced kindling in 29 days, which was followed by assessment of cognition, memory and motor impairment through validated behavioral techniques. The status of oxidative stress was estimated through measurement of MDA, GSH and SOD. Results HMPs delayed the latency and reduced the duration of GTCS in acute model signifying possible regulation of GABAergic neurotransmission. Kindling was significantly hindered by the HMPs that justified the ameliorated cognition, memory and motor activity impairment. The HMPs attenuated lipid peroxidation by reducing MDA level and strengthened the antioxidant mechanism by enhancing the GSH and SOD levels in the kindled animals. Conclusions Nux vomica HMPs showed anticonvulsant and antiepileptogenic potency in acute and chronic models of epilepsy. The test drugs attenuated behavioral impairment and reduced the oxidative stress against PTZ induced kindling owing to which they can be further explored for their cellular and molecular mechanism(s).
... Əsas fəal komponenti atropindir. Hipertenziv və antiaritmik təsirləri də məlumdur [26]. ...
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Tropane and nortropane alkaloids containing plants (Atropa, Datura, Hyoscyamus etc.) have been found in several families - mainly nightshades (Solanaceae). These species are naturally found in various countries over the world (America, European countries, Russia, Iran, Arabia, India etc.), as well as in Azerbaijan. More than 250 tropane alkaloids have been extracted by various methods, their chemical structure have been identified with modern analytical methods (HPLC-MS, GC-MS, UV-, IR-, NMR-spectroscopy, etc.) after separation into individual substances by various researchers. Although several tropane alkaloids are metabolised in various ways in the body and have toxic effects, these alkaloids and plants are used in medicine and traditional medicine. Key words: plants containing tropane alkaloids, datura, hyoscyamus, atropa, scopolamine, atropine
... Eupatorium perfoliatum, Rhustox and Atropa belladonna are the homeopathic prescriptions that may be utilized for ZIKV infection treatment. These medicinal agents are effective against the symptoms of ZIKV infection [64]. During epidemics homeopathic pharmaceuticals are more effective in reduction of mortality and morbidity as compare to conventional system of medicines [65]. ...
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Zika virus (ZIKV) is a newly emergent relative of the Flaviviridae family and linked to dengue (DENV) and Chikungunya (CHIVKV). ZIKV is one of the rising pathogens promptly surpassing geographical borders. ZIKV infection was characterized by mild disease with fever, headache, rash, arthralgia and conjunctivitis, with exceptional reports of an association with Guillain–Barre syndrome (GBS) and microcephaly. However, since the end of 2015, an increase in the number of GBS associated cases and an astonishing number of microcephaly in fetus and new-borns in Brazil have been related to ZIKV infection, raising serious worldwide public health concerns. ZIKV is transmitted by the bite of infected female mosquitoes of Aedes species. Clarifying such worrisome relationships is, thus, a current unavoidable goal. Here, we extensively described the current understanding of the effects of ZIKV on heath, clinical manifestation, diagnosis and treatment options based on modern, alternative and complementary medicines regarding the disease.
... been used in human medicine for the treatment of inflammation, headache, peptic ulcer, menstrual symptoms and histaminic reaction88,89 . In our studies Belladonna treatment productively abridged the Japanese encephalitis virus infection90 . ...
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The mosquito-borne arbovirus Zika virus (positive-stranded RNA virus, ZIKV, Flavivirus, Flaviviridae), has caused an outbreak imposing by its extent and quick spread. This became the focus of a current pandemic and public health crisis all around the world because of the incessant geographic growth of both the virus and its mosquito vectors; it is often misdiagnosed with other disease like yellow fever, west nile, dengue and chikungunya because of same clinical manifestation. After unprecedented huge scale outbreak of ZIKV in Pacific, Micronesian island of Yap in 2007, though ZIKV infections are in general sporadic cases or causing mild self-limiting illness, harsh symptoms have been explained including neurological disorders, autoimmune disorder, fetal anomalies, impaired central nervous system of the fetus, microcephaly in newborns, meningoencephalitis, myelitis and Guillain Barre´Syndrome supposed to be linked with ZIKV. The virus is transmitted mainly by a mosquito Aedes aegypti, whereas, other routes of viral broadcast includes monkey bite, coitus and body fluids such as semen, blood and saliva which needs further corroboration. The relationship between these conditions with ZIKV infection is still not established and is under assessment. Till now there is no vaccine or specific antiviral against ZIKV, therefore the public health authority focuses on preventing infection, mainly in pregnant women and virus transmitted area. WHO and other health officials are working on the expansion of new projects and mosquito control techniques to manage up with infection as there is very fewer literature present on the pathogenesis of the ZIKV to help understand the clinical disease spectrum and target treatments to decrease or stop infection. The future status of ZIKV dispersal to other parts of the world is still unknown. The present review emphasizes various features of ZIKV and its history, epidemiology, transmission, clinical manifestations, progress and advances in developing effective diagnostics, vaccines and drugs/therapeutics along with accepting suitable avoidance and control strategies to undertake this deadly emerging disease. Keywords: Zika virus, Flavivirus, Aedes aegypti, Pregnancy, Transmission, Microcephaly, Africa
... [25] More recently, it has been reported that in some but not all the experimental conditions Belladonna, Gelsemium and Poumon histamine (5C, 9C, 15C) reduced the stress-induced behavioural alterations of mice in staircase test and light-dark test. [26] However, those results were obtained as reversal of the effects of severe stress (conditioned paradigm) and the findings were highly variable according to the potency used and test performed. Two validated tests on animal models, namely the Light Dark (LD) choice test and the OF test, were used in order to acquire various behavioural parameters widely used in neuropsychopharmacology for drug screening. ...
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Background: Before the 20th century, research in Homeopathy was limited either for its proving in healthy human volunteers or to its clinical verification/clinical efficacy in diseased individuals. However, in recent years, there has been an increased trend in the number of pre-clinical studies aimed to evaluate the pharmacological activity produced by homeopathic medicines. The objective of this review is to make a systemic compilation of results of experimental pharmacological findings of homeopathic medicines, both in vitro and in animal models, and to present the same in a summarised form. Methods: Articles published up to March 2017 having information of in vitro and in vivo studies using homeopathic medicines were collected from the PubMed database, review articles, scientific reports, research articles, thesis, online information extracted from Medline, etc. to compile this review. The articles from the most common therapeutic areas such as antimicrobial effect, central nervous system disorders, anti-inflammatory and analgesic, anticancer, wound healing, antiasthmatic and liver toxicity and other therapeutic areas such as diabetes and malaria were included in this review. Results: This review article not only provides the scientific approaches applied in Homeopathy research but also provides evidence-based information on pharmacological effects of dilutions/potencies as well as mother tincture of different homeopathic drugs. This review article also reveals the use of improved methodology, molecular techniques and analytical part adopted in recently published research articles to understand the mechanism of action of homeopathic medicines. Conclusion: Homeopathy has substantial scope in pre-clinical research where therapeutic and biological effects of homeopathic medicines with proper mechanism of action can be traced out with the use of modern molecular techniques in in vivo and in vitro experiments.
... Además se han observado efectos gástricos e inmunológicos 16 . Igualmente, el efecto ansiolítico se ha observado en extractos de fitoterapia de Gelsemium en metanol 17,18 . Argentum nitricum ha mostrado resultados dispares en un estudio piloto de 2017 en peces cebra, administrado en potencia 30 CH junto con cafeína; Argentum nitricum y Gelsemium mostraron reducción en la expresión génica de CRF y CDK5 indicando potencial ansiolítico, así como mejorías en los parámetros estudiados relacionados con la ansiedad 19 ; un estudio sobre ansiedad en estudiantes en potencia 12 CH no mostró reducción en el test de ansiedad y no se logró replicar el resultado de un estudio previo 20 . ...
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Resumen Las fobias específicas son un problema de salud mental muy frecuente que interfiere con la vida normal de los individuos, con la aparición de síntomas ansiosos ante la presencia del objeto de la fobia. Esto puede dar lugar a situaciones difíciles o a disminución de la calidad de vida y, al ser un problema reducido al objeto de la fobia, puede permanecer sin tratamiento, y el enfoque psicoterapéutico es lento cuando surge una situación aguda. Esto puede ser un serio problema si, por ejemplo, genera la evitación de un procedimiento necesario para el diagnóstico. Se presenta el caso de un varón de 29 años con síntomas y signos de hepatitis aguda que no aceptaba las extracciones de sangre por fobia a las agujas a quien finalmente se le pudieron realizar las extracciones con la ayuda de un tratamiento homeopático.
... Thus, Gelsemium is prescribed at ultra low doses, according to the principles of homeopathy, for its action against anxiety, its effects on curarization and sedation. Some studies have shown that, in mice, Gelsemium could prevent induced stress [3] or will have anxiolytic-like effects [4]. Furthermore, recent studies [5,6] explored the pharmacological effects of Gelsemium on allopregnanolone that plays a key role in the modulation of neurological and psychopathologic symptoms such as anxiety. ...
... Nel caso in cui l'individuo sia sottoposto a fonti di stress eccessive ripetute o protratte nel tempo ha luogo un processo di cronicizzazione che è all'origine di alterazioni funzionali sia a livello psicologico che fisiologico. Secondo gli studi di Bousta et al. (2001) l'organismo può raggiungere livelli di stress patologico se la fonte di minaccia (stressors) è al tempo stesso inevitabile, indesiderabile e reiterata nel tempo. ...
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L’accento sul risultato della prestazione, sulla performance del singolo e dell’organizzazione ha nel caso delle organizzazioni che producono servizi alla persona un valore aggiuntivo legato all’oggetto di lavoro, al mandato sociale di queste organizzazioni. È infatti comprovata la relazione esistente tra le condizioni di agio/disagio dei produttori di questi servizi e la qualità delle loro prestazioni, una relazione che si evidenzia tanto quando si rileva la percezione che i lavoratori hanno della qualità della loro vita organizzativa e la corrispondente percezione che i fruitori hanno delle prestazioni ricevute, tanto quando si analizzano le condizioni contestuali nel caso, per esempio, di errori medici o di infortuni. Le condizioni di malessere e/o benessere agiscono cioè in una prospettiva circolare di causa/effetto (diretta e indiretta) sui singoli nel loro legame con il lavoro e l’organizzazione, nonché tra operatori e utenti.
... Although, all alkaloids in Atropa belladonna are distributed in the entire plant, but the majority of the alkaloid content is found in green leaves and ripe fruit. It has long been used in human medicine for the treatment of inflammation, headache, peptic ulcer, menstrual symptoms and histaminic reaction [3,17]. In our studies Belladonna treatment successfully reduced the Japanese encephalitis virus infection [Saxena and Gadugu. ...
Article
Zika virus (ZIKV) infection is a new emerging threat around the globe which might be responsible for microcephaly and Guillain–Barre syndrome in the infants. Recently, ZIKV outbreak has caused a public health crisis in Brazil after being linked to a sharp increase in birth defects. ZIKV is ssRNA virus belongs to the family Flaviviridae. It is mainly transmitted by mosquito bite specifically Aedes species and disease symptoms include fever, joint pain, muscle pain, rash, conjunctivitis, and headache. The reservoir of ZIKV is still not known. Protection at personal level by avoiding mosquito bite would help to reduce the incidence of the disease. Control of ZIKV infection by vaccination or antiviral drug either from modern, complementary and alternative medicines may be considered to be one of the most effective strategies in the long run. Large scale immunization of susceptible human population is highly required to prevent this deadly disease. Attempts should be made as soon as possible to develop effective vaccines or antiviral to prevent ZIKV infection. This article provides a current overview of the experimental therapeutics and treatment options based on modern, complementary and alternative medicines.
... Several plants are used in medicine or food. [3][4][5][6][7][8][9][10][11] Ain Leuh a landlocked town in the Middle Atlas; it has characterized by a high socio-cultural mixture and traditional therapeutics are mostly based on the contributions of several ethnics from different regions of Morocco (Ait Mouly, Ait Ghriss, Ait Atta, Soussi, Ait Ouirra Arabic kalaat sraghna.), and several foreign nations (Lebanese, French, Spanish and Jews). Therefore, this mixture of cultures offers a wealth of knowledge in uses of plants by the local population of Ain leuh region in health care. ...
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Objective: The present study aimed to analyse and evaluate the ethnobotanical and ethnopharmacological informations related to the use of plants for medicinal purposes by the native people of Ain Leuh region. Methods: The ethnobotanical study of medicinal plants in the area of Ain Leuh is done firstly by a sampling plan and by using a questionnaire to get an overview on various local traditional uses and floristic diversity of traditional medicine in the region, with reference to other ethnobotanical studies in Morocco. Results: A total of 123 medical plants belonging to 53 families were identified in the region. The most encountered medicinal plant families were Lamiaceae (11.4%), Rosaceae (8.94 %), Asteraceae (8.13 %), Apiaceae (6.5 %), liliaceae (4.9 %), Poaceae (3.25%). Conclusion: The knowledge of medicinal plants used by the people of Ain Leuh seems to be well known. It is, therefore, urgent to save the cultural heritage of the natives, by confirming the therapeutical uses of the plants with scientific criteria.
... In vivo experiments using highly/ultra diluted substances demonstrate that they are able to influence the clinical with direct reflects in the animal´s behavioral equilibrium [3]. The A. belladonna is a plant rich in primary alkaloids [4] and it is used as a modulator of inflammatory processes [5,6]. ...
Article
Background: The Multicentre International Project on High Dilutions suggests evaluating the effect of the compound A. belladonna in different experimental models. Aim: The aim is to evaluate the effect of A. belladonna ultra-diluted in the course of murine infection caused by T. cruzi. Methodology: The experiments, approved by the UEM's Animal Ethics Committee, will be performed as a blind controlled, randomized assay by chance. Animals will be maintained in an environment with temperature (18-20 °C), humidity (70%) and lighting controlled, in a 12 hours light and dark cycle, and will receive water and food ad libitum in micro-acclimated cages. Provided by the UEM's Central Animal Vivarium, swiss male mice, 56 days old were divided in groups of 12 animals each according to the treatment: CI- infected untreated; CNI- not infected and not treated; and animals infected and treated with the TM - mother tincture of A. belladonna and their dynamized solutions: 2cH; 3cH; 5cH; 6cH; 12cH and 30cH. Infection: 1400 blood trypomastigotes of the Y strain of T. cruzi, via i.p. Treatment: Will be provided ad libitum diluted in water (1mL/100mL water) 48 hours before and after the infection, subsequently in 56/56 hours until complete nine days of infection. It will be available to the animals during 16 hours. Dynamizations will be prepared from the A. belladonna TM (commercially purchased) according to the Brazilian Homeopathic Pharmacopoeia, with microbiological testing (RDC67-MS Brazil) and in vivobiological test. Analyses: Clinical parameters (temperature, weight, water/food intake and excreta) [1,2] and parasitological parameters (pre-patent, patent period, parasitemia peak, total parasitemia, mortality and survival time) will be assessed daily. The dynamization that presents the best performance will be elected for behavioral study through the automated system NoldusEthoVision XT6 (Noldus, Leesburg, Netherlands). The analysis will include assessment of motor activity (distance covered in the arena and average speed of each animal), andthe exploratory activity (frequency of events and time spent by the animal in fields determined by the software). Considerations: In vivo experiments using highly/ultra diluted substances demonstrate that they are able to influence the clinical with direct reflects in the animal's behavioral equilibrium [3]. The A. belladonna is a plant rich in primary alkaloids [4] and it is used as a modulator of inflammatory processes [5,6].
... Ramoutsaki et al. 34 reported belladonna as an analgesic and emetic against miscellaneous diseases or ailments and as an antidote for snakebite. Bousta et al. 35 reported that A. belladonna possesses significant neurotropic and protective effects on behavioral and gastric alterations induced by experimental stress. 36 used rat model to suggest the ability of A. belladonna and atropine for urinary retention, and A. belladonna was found to be more effective. ...
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Atropa belladonna L. (Family: Solanaceae; commonly known as belladonna, deadly nightshade, devil’s berries amongst others), a perennial herb (2n=72) is native of Europe, North Africa and Western Asia, possesses a long tradition as one of the classic poisons of antiquity. The species is also the source of atropine alkaloid (dl-hyoscyamine) and is important in the study of autonomic pharmacology. Considering the therapeutic uses of A. belladonna as well as its significant toxic effects (due to tropane alkaloids including scopolamine and hyoscyamine), an overview on all necessary aspects is documented to provide information for further exploration of the species for human benefits.
... Many studies have shown that the extracts and active alkaloids of Gelsemium have a variety of biological effects, including immunosuppressive and antitumor effects [2,3,[14][15][16][17]. Gelsemium has also been used to treat asthma, skin ulcers, whooping cough, hysteria, dysmenorrhea, chorea, pneumonia and bronchitis [18]. ...
... But this heritage is still unknown and under-exploited (Kassel, 2001), and treatment with medicinal plants, among the therapeutic methods, presents an interest in parallel to the modern medicine. Several plants are used in medicine or food (Soulimani et al., 1997Ennabili et al., 2000Ennabili et al., , 2006Bousta et al., 2001Bousta et al., , 2008Daoudi et al., 2008;El Meskaoui et al., 2008;Greche et al., 2009). ...
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The survival and sustenance of man depends largely on plants which generate directly 87% of its food needs and constitute a source of basic health care in developing countries. Based on socio-economic surveys and field observations led in the Rissani oasis (SE of Morocco), we have identified 109 species belonging to 45 botanical families and 102 genera. The distribution in families is: Lamiaceae (15.2%), Asteraceae (11.5%), Fabaceae (8.46 %), Poaceae (8.12%) and Apiaceae (6.75%). The species used in traditional medicine correspond to 57.8%, for food 10.1% and for other uses 28.4%. Of these species, 10.1% are cultivated, naturalized, introduced and/or weeds. Byproducts of 46.8% of these species are imported from other regions of Morocco and locally marketed. Many medicinal species from this area are not recognized by the inhabitants, and their sensitization towards the use and conservation of local plant diversity is needed.
... Atropa belladonna is a rich source of flavonoids, coumarin, atropa-amine, scopolamine, and hyoscyamine [11,12]. It has long been used in human medicine for an assortment of conditions including headache, menstrual symptoms, peptic ulcer disease, histaminic reaction, inflammation, and motion sickness and as a sedative as well as in homeopathic drugs [12][13][14][15]. However, to the best of our knowledge, no study was conducted to investigate the acaricidal activity of A. belladonna extract and its active components, scopolamine and atropine. ...
... Atropa belladonna is a rich source of flavonoids, coumarin, atropa-amine, scopolamine, and hyoscyamine [11,12]. It has long been used in human medicine for an assortment of conditions including headache, menstrual symptoms, peptic ulcer disease, histaminic reaction, inflammation, and motion sickness and as a sedative as well as in homeopathic drugs [12][13][14][15]. However, to the best of our knowledge, no study was conducted to investigate the acaricidal activity of A. belladonna extract and its active components, scopolamine and atropine. ...
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In vitro efficacy of methanolic extract of Atropa belladonna and its components scopolamine and atropine was assessed against Rhipicephalus (Boophilus) microplus. Five concentrations of the extract (1.25%, 2.5%, 5%, 10%, and 20%) were used whereas scopolamineandatropinewereeachtestedat0.1%.Inadultimmersiontest,theextractwaslethaltoticksat20%concentration.The LC50andLC95valuesweredeterminedas6.875%and17.306%,respectively.Theextractcausedasignificantreduction(𝑃 < 0.05) in egg mass production at 10% concentration. In larval packet test, the extract was lethal to larvae in the concentrations of 10% and20%after24h,withLC50andLC95valuesof1.321%and4.935%,respectively.Scopolamineandatropineshowed93.3%and 60.0%mortalityofadultticks,respectively,buttheycausedcomplete(100%)blockingofhatchingaswellas100%larvalmortality. Scopolamine and atropine were observed to be more potent than the crude extract at an equivalent concentration in both the bioassays.
... Sempervirine, isolated from G.sempervirens has been reported to possess vasoconstrictor action in the perfused isolated rabbit ear (7). Low doses of G.sempervirens and Atropa belladonna showed significant neurotropic and protective effects on behavioral and gastric alterations induced by experimental stress on mice (8). Based on the above information, we carryout pharmacological evaluation of G.sempervirens roots for CNS depressant activity. ...
Article
The aim of the present study was to investigate CNS depressant activity of methanolic extract of Gelsemium sempervirens roots. G. sempervirens Ait (Loganiaceae) is used traditionally in the treatment of migraine, neuralgia, rheumatism, restlessness, mental irritability, insomnia and ovarian and uterine pain. The plant was found to contain alkaloids gelsemine, gelseminine, gelsemoidine and gelsevirine. Since roots of Gelsemium sempervirens are used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbiton-induced sleep, test for locomotor activity, effect on muscle co-ordination, and antianxiety activities. The results of the study reflected that methanolic extract of the roots (100 mg/kg p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety activity. This substantiates the traditional use of roots of Gelsemium sempervirens for CNS depressant activity.
... Our (Bellavite et al., 2012;Magnani et al., 2010) and other's (Bousta et al., 2001) (Meyer et al., 2013) results have shown that very low doses of G. sempervirens have anxiolytic-like properties in rodent behavioural models, but its action at the cellular level still needs to be clarified. In order to further investigate the action mechanism(s) of this plant at the level of neuronal cells, we decided to assess a possible modulation of gene expression. ...
Article
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 24h 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.
... The extent to which an anxiolytic compound facilitates exploratory activity has been shown to depend on its baseline level in the control group [14]. Bousta et al. [15] report some anxiolytic-like effects of Gelsemium in mice stressed by repeated electric shocks, but no such effects in normal unstressed mice. For these reasons and in connection with the well-known complexity of animal behaviour studies, we had to use a large number of animals in each group and experimental phase. ...
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As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-field), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this field, disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.
... (commonly known as Yellow Jasmine), native to the southwest United States and the state flower of South Carolina (Fig. 1), as well as native to parts of Mexico and Central America, where it is widely cultivated as an ornamental; (2) Gelsemium elegans Benth., native to Southeast Asia, particularly in China; and (3) Gelsemium rankinii Small, native to North America [4,10,26,39,54,55]. Although clinical use of Gelsemium extracts has been greatly limited by its toxicity and narrow therapeutic window, a rich body of evidence has shown that Gelsemium extracts or its active ingredients have a variety of biological actions, such as antinociceptive, antidepres-sant, anxiolytic, antispastic, and antitumor effects in preclinical models and clinical practice [3,10,12,26,34]. Antinociception and pain management are common primary indications for Gelsemium, a methanol-extracted crude alkaloidal fraction from Gelsemium elegans Benth. ...
Article
The present study examined the antinociceptive effects of gelsemine, the principle alkaloid in Gelsemium sempervirens Ait. Single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia and spinal nerve ligation-induced painful neuropathy. The antinociception was dose-dependent, with maximal inhibition of 50-60% and ED50 values of 0.5-0.6 μg. Multiple daily intrathecal injections of gelsemine for 7 days induced no tolerance to antinociception in the rat model of bone cancer pain. Spinal gelsemine was not effective in altering contralateral paw withdrawal thresholds, and had only a slight inhibitory effect on formalin-induced acute nociception. The specific antinociception of gelsemine in chronic pain was blocked dose-dependently by the glycine receptor (GlyR) antagonist strychnine with an apparent ID50 value of 3.8 μg. Gelsemine concentration-dependently displaced H(3)-strychnine binding to the membrane fraction of rat spinal cord homogenates, with a 100% displacement and a Ki of 21.9 μM. Gene ablation of the GlyR α3 subunit (α3 GlyR) but not α1 GlyR, by a 7-day intrathecal injection of siRNA targeting α3 GlyR or α1 GlyR, nearly completely prevented gelsemine-induced antinociception in neuropathic pain. Our results demonstrate that gelsemine produces potent and specific antinociception in chronic pain states without induction of apparent tolerance. The results also suggest that gelsemine produces antinociception by activation of spinal α3 GlyRs, and support the notion that spinal α3 GlyRs are a potential therapeutic target molecule for the management of chronic pain.
... Low doses of gelsemium root extracts have protected mice against neurologic damage and gastric erosions induced by stress. 12 A fluid extract of gelsemium root has also demonstrated antiseizure ability in rats with epilepsy that was induced by lithium and pilocarpine injections. 13 A warning to patients is vital: Gelsemium should only be administered by an experienced practitioner. ...
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A group of physicians treated victims of the 1918 influenza pandemic with botanical medicines and the treatments were very successful. This article reviews some of the botanicals that were used to treat patients who had influenza. It also reviews research indicating that herbs can counteract the cytokine dysregulation induced by severe types of influenza. Coverage includes Gelsemium sempervirens (gelsemium root; also known as yellow jasmine and yellow jessamine), Eupatorium perfoliatum (boneset; also known as thoroughwort and Indian sage), Actea racemosa (black cohosh; also known as macrotys; formerly Cimicifuga racemosa), Asclepias tuberosa (pleurisy root; also known as butterfly weed), and Atropa belladonna (belladonna) as well as the roles that interleukin (IL)-6, interferon-γ-inducible protein (IP)-10, cytokines, and chemokines play in influenza.
... In a recent research, we have also found that anxiety exerts a significant suppressive effect on the cellular and humoral immunity (Rammal et al., 2010a), which leads us to study the action of natural products on the peripheral immune status in anxious mice. Currently, there is an increasing evidence that natural products have beneficial effect on anxiety (Vignes et al., 2006; Bouayed et al., 2007b), oxidative stress (Bouayed et al., 2007b and c) and immunity (Bousta et al., 2001; Elhabazi et al., 2006). G. sempervirens L. is a medicinal plant which possesses sedative and analgesic properties (Valnet, 1992), it decreases seizures (Peredery and Persinger, 2004 ), and has potent effects on the central and peripheral nervous system (Newall et al., 1996; Ellingwood, 1919). ...
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Anxiety is associated with subjective distress and many harmful physiological effects including oxidative stress, immunodepressive effect, and an increase in blood pressure. Anxiety is also implicated in a number of psychiatric disorders. The objective of this work was to study the protective property of homeopathic drugs on immunodepression caused by high anxiety level by evaluating the immunological effect of both acute and subacute intraperitoneally administration of high dilutions (9 CH, 15 CH and 30 CH) of Gelsemium sempervirens L., Histaminum and Poumon histamine in mice with contrasting level of anxiety evaluated in the light/dark choice test. Our results showed that these homeopathic drugs at different dilutions exert an important immunotrope effect on the cellular (granulocytes, monocytes, total lymphocytes, TCD4 + , TCD8 + and NK cells) and humoral (immunoglobulins A, E and G) immunity in anxious mice.
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Background: Clinical studies have shown that adverse events in early life are quite stressful and can lead to the development of psychiatric disorders, such as anxiety, in adolescence and adulthood in humans. Experimental models of maternal deprivation (MD) in rats can be a useful tool for the understanding how these events in the early period of development can lead to behavioral changes in adulthood. Aims: The objective of this study was to evaluate the long-term effects of Zincum metallicum (Zinc met) homeopathic treatment in rats subjected to maternal deprivation (MD) in their early days of life. Methods: Newborn female rats were subjected to MD during 10 days, one hour per day, from PND10 to PND21, and treated from the 10th day of lactation (PND10) up to weaning (PND21). On the PND21 the rats were divided in 4 groups (N=8): a) treated with Zinc met 30c; b) treated with Zinc met 6c; c) treated with 10% hydroalcoholic solution (HS); and “blank control”, rats without any treatment nor experienced deprivation (ND). The medicines were administered in blind trials, identified by codes. The animals were weighed weekly, from weaning until the end of the experiment, and evaluated in the Open Field (OF) and in the Elevated Plus Maze (EPM) devices, to evaluate mobility, emotionality and anxiety, in 3 moments of life: in PND21 (childhood), during puberty (PND 40) and adulthood (PND75). Data were analyzed statistically by ANOVA, followed by the Bonferroni's Multiple Comparison Test, being p?0.05. Results: 1) relative to ND group the Zinc met 6c showed reduced body weight while no differences were observed between the other groups; 2) In the OF, the MD group showed increased rearing behavior at PND 40. The Zinc met 6c group reversed this effect showing similar profile as the ND group. Moreover, Zinc met 6c group showed increase in the immobility time at this age; 3) In the EPM, the MD group showed increased time in closed arms and decreased head dips relative to ND group in PND21 period of observation. Treatment with Zinc met 6c but not with Zinc met 30c was effective to reduce this anxiety-like behavior in PND21. Conclusion: According to the proposed model, Zincum metallicum 6c seems to be able to prevent in anxiety-like behavior induced by maternal deprivation in the childhood, mainly in behavioral models related to anxiety. However, other studies still need to be developed to understand the physio-pathological basis of these effects.
Article
Atropa belladonna L. is a perennial plant endemic to Central and Southern Europe and India and is being cultivated worldwide. It is used in the treatment of headache, menstrual symptoms, peptic ulcer, inflammation and motion sickness, bronchial spasms and whooping cough, Parkinson’s disease, antidote for snake bite, and gastric agent. The plant species is considered as extremely toxic due to the presence of alkaloids. The toxic Atropa alkaloids cause delirium, hallucination, tachycardia, mydriasis, dry mouth, flushed skin, urinary retention, vomiting, and anhidrosis in humans. Besides A. belladonna, four other species of Atropa are found: Atropa acuminata in Asia, Atropa baetica in Spain and Morocco, and Atropa caucasica and Atropa komarovii in Russia. Cell culture studies were established in Atropa plant by using various explants of A. belladonna for the enhancement of yield of the tropane alkaloids.
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Las bacterias son los patógenos principales relacionados con infecciones que afectan las estruc¬turas del ojo de forma intra- o extraocular; el género Staphylococcus es el grupo más prevalente asociado con este tipo de infección. Para el control de las infecciones oculares se utilizan an¬tibióticos como oxacilina y meticilina, que en muchos casos llevan a la resistencia bacteriana. Además, el alto costo de los medicamentos, que en Colombia alcanzan cifras tres o cuatro veces mayores que en otros países, se constituyen en desventajas para su uso. Lo anterior ha llevado a estudiar la actividad antimicrobiana de las plantas frente a los microorganismos asociados a las infecciones oculares bacterianas. El propósito de este artículo de revisión es conocer los bene¬ficios potenciales de las plantas o sus productos para el control de estas infecciones como una alternativa para su tratamiento.
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Background: Homeopathy is a controversial alternative system of medicine. The action of homeopathic medicines is considered slow and it is assumed that homeopathic medicines are ineffective in acute conditions such as fever. Objective: In the present study, effects of 3 homeopathic medicines on baker's yeast induced fever were investigated. Materials and methods: 42 local strain rabbits were equally divided into 7 groups. Normal saline was orally administered to group 1 (normal control) rabbits without fever induction. Group 2 underwent baker's yeast-induced fever (negative control). Groups 3, 4, 5, 6 and 7 underwent baker's yeast-induced fever and were thereafter treated orally with paracetamol, Nux vomica 200C and 1M, Calcarea phos 200C and Belladonna 200C respectively. Rectal temperature was checked hourly. The abdominal writhing and frequency of loose stools were also monitored. ANOVA was applied for checking statistical significance. p ≤ 0.05 was considered significant. Results: The rectal temperature increased significantly (p < 0.05) in the negative control group when compared to the normal control. Abdominal writhing and loose stools monitoring showed increased writhing and loose stools frequency of group 2, 3, 6 and 7 rabbits. However, treatment of paracetamol significantly reduced rectal temperature. Group 4 & 5 showed significant reduction of rectal temperature together with abatement of abdominal writhing and loose stools. Conclusion: N. vomica ultra-high dilutions have normalized rectal temperature and prevented the abdominal writhing and loose stools in baker's yeast-induced fever model of rabbits. It could be due to antidotal activity of N. vomica ultra-high dilutions. Therefore, N. vomica ultra-high dilutions can be useful antipyretic agents and can treat conditions associated with gastrointestinal symptoms. However, fixed conclusion can't be asserted due to caveat of small sample size.
Article
Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.
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Homeopathy is one of the most widely practiced alternative systems of medicine in the world. Current scientific understanding is unable to explain its mode of action, and the therapy is often dismissed by detractors who claim—despite growing evidence to the contrary— that it is ineffective. While homeopathy's philosophical foundations and the nature of its medicines differ markedly from those of its mainstream counterpart, biomedical researchers are nevertheless employing conventional methods to study it—including lab-based animal experimentation. This article considers the implications of using violent methodology to investigate a gentle system of medicine founded on treating the individual and on doing no harm.
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Allergic rhinitis is a common immunemediated disease that affects a large part of the global population. Its symptoms may not be life-threatening but nonetheless have a strong impact on quality of life and productivity. Current therapeutic options are manifold and include intranasal glucocorticoids, antihistamines and leukotriene receptor antagonists. The current guidelines recommend intranasal glucocorticoids and antihistamines as effective and safe first-line therapies. However, some patients remain uncontrolled with the current treatment options. Therefore, it is necessary to develop new treatment strategies and/or improve current therapy options. Over the last years a few new agents have been developed which may have an impact on the way allergic rhinitis is treated in the nearest future. These include new compounds such as SYK-inhibitors, which inhibit the signalling pathway of the allergic reaction, new antihistamines targeting not only the H1-receptor but also the H3-receptor, new improved glucocorticoids in the form of prodrugs as well as a novel formulation (MP29-02) combining the administration of a nasal antihistamine and glucocorticoid. In allergen-specific immunotherapy, new promising approaches such as intralymphatic and epicutaneous immunotherapy are currently being investigated.
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Allergic rhinitis is a common immunemediated disease that affects a large part of the global population. Its symptoms may not be life-threatening but nonetheless have a strong impact on quality of life and productivity. Current therapeutic options are manifold and include intranasal glucocorticoids, antihistamines and leukotriene receptor antagonists. The current guidelines recommend intranasal glucocorticoids and antihistamines as effective and safe first-line therapies. However, some patients remain uncontrolled with the current treatment options. Therefore, it is necessary to develop new treatment strategies and/or improve current therapy options. Over the last years a few new agents have been developed which may have an impact on the way allergic rhinitis is treated in the nearest future. These include new compounds such as SYK-inhibitors, which inhibit the signalling pathway of the allergic reaction, new antihistamines targeting not only the H1-receptor but also the H3-receptor, new improved glucocorticoids in the form of prodrugs as well as a novel formulation (MP29-02) combining the administration of a nasal antihistamine and glucocorticoid. In allergen-specific immunotherapy, new promising approaches such as intralymphatic and epicutaneous immunotherapy are currently being investigated.
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Background: There are serious challenges for treatment of depression in the war veterans. Complementary therapies; such as homeopathy, are proposed to incease successful of their treatment. In one study, ultrahigh-dilution of NaCl (Natrium muriaticum) was used in depressed war veterans for this aim and in this study, their homeopathic dynamisms were evaluated for preparing the special treatment protocols. Methods: The patients got the remedies every 2-3 weeks and changing of their symptoms after using natruium muriaticum were evaluated. One homeopath diagnosed their homeopathic dynamisms via discussing about their mental and somatic symptoms with the help of software. Aggravations were defined as both, increasing of previous or appearing new trouble symptoms. Accessory symptoms related to remedy proving were omitted by waiting. At the end of study, data were extracted from the patients’ files and classified. Findings: Files of 28 patients had adequate information and in 7 of them, had not. The most common homeopathic dynamisms were similar to Sulphurous, with rage and eczema as main symptoms, and Belladaonna, with headache and anger. The other dynamisms were Phosphorous, Aconitum, and Calcarea, respectively. 25 percent of patients reported mild to moderate aggravation. They were headache, desquamation of skin eruptions, anxiety and obstinacy with their families. Conclusion: Trend of clinical course of war survivor depressed, after getting a homeopathic remedy, indicated various polycrest myazmatic dynamisms. This is an opportunity to prepare a special protocol with speed use of remedies for treatment of them in another research.
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The purpose of the present paper is to (a) summarize evidence for the nanoparticle nature and biological effects of traditional homeopathically-prepared medicines at low and ultralow doses; (b) provide details of historically-based homeopathic green manufacturing materials and methods, relating them to top-down mechanical attrition and plant-based biosynthetic processes in modern nanotechnology; (c) outline the potential roles of nonlinear dose-responses and dynamical interactions with complex adaptive systems in generating endogenous amplification processes during low dose treatment. Possible mechanisms of low dose effects, for which there is evidence involving nanoparticles and/or homeopathically-manufactured medicines, include hormesis, time-dependent sensitization, and stochastic resonance. All of the proposed mechanisms depend upon endogenous nonlinear amplification processes in the recipient organism in interaction with the salient, albeit weak signal properties of the medicine. Conventional ligand-receptor mechanisms relevant to higher doses are less likely involved. Effects, especially for homeopathically-prepared nanophytomedicines, include bidirectional host state-dependent changes in function. Homeopathic clinicians report successful treatment of serious infections and cancers. Preclinical biological evidence is consistent with such claims. Controlled biological data on homeopathically-prepared medicines indicate modulation of gene expression and biological signaling pathways regulating cell cycles, immune reactions, and central nervous system function from studies on cells, animals, and human subjects. As a 200-year old system of traditional medicine used by millions of people worldwide, homeopathy offers a pulsed low dose treatment strategy and strong safety record to facilitate progress in translational nanomedicine with plants and other natural products. In turn, modern nanotechnology methods can improve homeopathic manufacturing procedures, characterize nanoparticle end-products, and describe interactions of homeopathic nanophytomedicines with living systems at the nanoparticle and even individual organism level of detection. Faster progress toward safe and effective personalized nanophytomedicine treatments can result.
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The carvacrol is thought to promote optimal health via its antioxidant and free radical scavenging effects. The aim of our present study was to investigate the efficacy of carvacrol on the development of kidney injury in acute pancreatitis model (AP) induced by cerulein and to explore the underlying mechanism. The rats were randomised into groups to receive (I) no therapy; (II.) 50 mu g/kg cerulein at 1-h intervals by four intraperitonally injection (i.p.); (III) 50, 100 and 200 mg/kg carvacrol by one i.p.; and (IV) cerulein+carvacrol after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood urea nitrogen (BUN), creatinine (CRE) and uric acid (UA) values. Also, renal tissues were obtained for histological and biochemical measurements. Kidney oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in tissue antioxidant enzyme levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX). Histopathological examination was performed using scoring systems. We found that the increasing doses of carvacrol decreased pancreatitis-induced MDA levels. Moreover, the renal SOD, CAT and GSH-Px activities in the AP+carvacrol group were higher than that of the rats in the AP group. In the treatment groups, the BUN, CRE and UA were reduced. Besides, necrosis, coagulation and inflammation in the kidney were alleviated (p < 0.05). Finally, the magnitude of the protective effect on kidney is certain, and 200 mg/kg carvacrol is an effective theraphy for oxidative stress caused by AP.
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Two total syntheses of the indolo[2,3-a]quinolizinium cation have been accomplished through the application of two ring-closing metathesis reactions to form the pyridinium ring. One of these approaches provides the tetracyclic cation in only five steps from commercially available harmane. Fluorescence-based thermal denaturation experiments, as well as spectrofluorimetric titration, circular dichroism measurements, and theoretical simulations, showed a consistent DNA-binding capacity by intercalation with a marked preference for AT-rich sequences.
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Ethnopharmacological relevance: In the genus Gelsemium, Gelsemium elegans (Gardn. & Champ.) Benth. has been recognized as a toxic plant that is widely distributed in Southeast Asia and has been used as traditional Chinese medicine for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers and cancers for many years. Gelsemium sempervirens (L.) J.St.-Hil. has been used since the nineteenth century in homeopathy for treating anxiety, neuralgia, migraine and spasmodic disorders, such as asthma and whooping cough in North America. This review aims to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research and toxicology of medicinal plants in the genus Gelsemium. The overall objective is to explore the evidence supporting its ethnopharmacological effectiveness. Materials and methods: A literature survey was performed by searching the scientific databases Pubmed, Google Scholar, SciFinder, Scopus, Web of Science and the Chinese CNKI, in addition to traditional Chinese medicine and homeopathic texts for information on Gelsemium. Results: Plants of the genus Gelsemium have been used in traditional medicine for the treatment of migraines, neuralgia, sciatica, cancer and various types of sores. Studies into the phytochemical composition of this genus have shown that all of the species are rich sources of monoterpene indole alkaloids and that they have attracted the attention of many researchers due to their markedly diverse and complex architecture. To date, a total of 121 alkaloids have been isolated and identified from the genus. The crude extracts, as well as the monomeric compounds, from the genus possess anti-tumor, analgesic, anxiolytic, anti-inflammatory and immunomodulating pharmacological activities. Conclusion: It is evident from the available literature that Gelsemium species possess potential for use as a beneficial therapeutic remedy. However, the analysis of previous pharmacological research suggests that a clear assignment of active molecules and mechanisms of action is remain lacking. Due to their high toxicity, the studies available on toxicity and safety are inadequate for providing information on clinical utilization.
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The public health and individual risks of inappropriate antibiotic prescribing and conventional over-the-counter symptomatic drugs in pediatric treatment of acute otitis media (AOM) and upper respiratory infections (URIs) are significant. Clinical research suggests that over-the-counter homeopathic medicines offer pragmatic treatment alternatives to conventional drugs for symptom relief in children with uncomplicated AOM or URIs. Homeopathy is a controversial but demonstrably safe and effective 200-year-old whole system of complementary and alternative medicine used worldwide. Numerous clinical studies demonstrate that homeopathy accelerates early symptom relief in acute illnesses at much lower risk than conventional drug approaches. Evidence-based advantages for homeopathy include lower antibiotic fill rates during watchful waiting in otitis media, fewer and less serious side effects, absence of drug-drug interactions, and reduced parental sick leave from work. Emerging evidence from basic and preclinical science research counter the skeptics' claims that homeopathic remedies are biologically inert placebos. Consumers already accept and use homeopathic medicines for self care, as evidenced by annual US consumer expenditures of $2.9 billion on homeopathic remedies. Homeopathy appears equivalent to and safer than conventional standard care in comparative effectiveness trials, but additional well-designed efficacy trials are indicated. Nonetheless, the existing research evidence on safety supports pragmatic use of homeopathy in order to "first do no harm" in the early symptom management of otherwise uncomplicated AOM and URIs in children.
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The chemical compound gelsemine is the major active principle of the yellow jasmine (Gelsemium) that is generally claimed as possessing anxiolytic properties based on empirical and indirect knowledge. Surprisingly, gelsemine effect on anxiety has until now received only little attention. Here, we used the well-validated method for anxiety assessment, the elevated plus-maze combined with video-tracking, to measure gelsemine action on rat anxiety-like behavior. Rats were intraperitoneally injected (500μl/daily/7days) with gelsemine (10(-6), 10(-10) or 10(-14)M) or control solution. Diazepam (DZP) was used as positive standard anxiolytic and additional controls were naive rats similarly manipulated except being injected. Gelsemine or diazepam treatment did not affect the number of closed arm entries and rears illustrating the rat general activity. In contrast, gelsemine (10(-6) to 10(-10)M) or DZP increased dose-dependently the number of entries and the percent of time spent in the open arms indicating that gelsemine is an anxiolytic. Consistently, we observed that gelsemine (10(-6) to 10(-10)M) or DZP also decreased dose-dependently the percent of protected stretched attend postures, an ethological index of anxiety-like state. Altogether, our results constitute a solid set of fundamental data directly demonstrating anxiolytic properties of gelsemine. The report also opens new perspectives for the development of safe and effective gelsemine- or Gelsemium-based strategies against pathological anxiety.
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Total synthesis of the two series of new pentacycilc cycloalk[g]indolo[2,3-a]quinolizine alkaloids (modified sempervirine possessing the wide range of activity), has been elaborated in five steps from 5-acetyl-3-methylthio-1,2,4-triazine (obtained from the simple acyclic materials). In the two key steps: inverse electron demand Diels–Alder reaction of precursor with cyclic enamines and the following Fischer indolization of 3-acetyl-1-methylthiocycloalka[c]pyridines, the AB–DE synthons, has been obtained. The final stages: desulfuration, and formation of the C-ring via the Gribble method have led to the expected zwitterionic alkaloids. Model syntheses of the indolopyridocoline and its methoxy analogue from 2-acetylpyridine have been performed for investigation of the microwave-induced Fischer synthesis of sensitive indoles and for obtaining compounds for comparative study of spectroscopic data.
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Six new isoflavones each having a prenyl (3,3-dimethylallyl) or a modified prenyl group at C-6 or C-8 of the isoflavone skeleton, lupiwighteone [5,7,4'-trihydroxy-8-(3,3-dimethylallyl)isoflavone, 1], luteone hydrate [5,7,2',4'-tetrahydroxy-6-(3-hydroxy-3-methylbutyi)isoflavone, 3 (already known as a fungal metabolite of luteone)], lupiwighteone hydrate [5,7,4'-trihydroxy-8-(3-hydroxy-3-methylbutyl)isoflavone, 4], 2,3-dehydrokievitone hydrate [5,7,2',4'-tetrahydroxy-8-(3-hydroxy-3-methylbutyl)isoflavone, 5], hydroxywighteone [5,7',4'-trihydroxy-6-(3-hydroxymethyl-3-methyl-allyl)isoflavone, 6], hydroxyparvisoflavone A [a 2-hydroxymethyl-2-methylpyrano-isoflavone, 7], and a new coumaronochromone, lupilutin [5,7,4'-trihydroxy-8-(3-hydroxy-3-methylbutyl)-coumaronochromone, 8], were isolated from the roots of yellow lupin (Lupinus luteus L., cv. Barpine). Together with these new isoflavonoids, the presence of simple isoflavones (genistein and 2'-hydroxygenistein) and complex isoflavones (wighteone, luteone, 2,3-dehydrokievitone (2), parvisoflavones A and B, and lupinisoflavones A and B) in the yellow lupin roots has also been confirmed.
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Freeze dried and finely ground leaves of two plants with known antimicrobial activity, Anthocleista grandiflora and Combretum erythrophyllum were extracted with acetone, ethanol, methanol, methylenedichloride, methanol/chloroform/water and water at a 1 to 10 ratio in each case. The quantity and diversity of compounds extracted, number of inhibitors extracted, rate of extraction, toxicity in a bioassay, ease of removal of solvent and biological hazard were evaluated for each extractant. An arbitrary scoring system was developed to evaluate the above parameters for the different extractants. Acetone gave the best results with these plants with an arbitrary value of 102 followed by methanol/chloroform/water (81), methylene dichloride (79), methanol (71), ethanol (58) and water (47). Four five minute sequential extractions of very finely ground A. grandiflora shaking at a high rate extracted 97% of the total antimicrobial activity.
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A novel trypsin-like protease associated with rat bronchiolar epithelial Clara cells, named Tryptase Clara, was purified to homogeneity from rat lung by a series of standard chromatographic procedures. The enzyme has apparent molecular masses of 180 +/- 16 kDa on gel filtration and 30 +/- 1.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Its isoelectric point is pH 4.75. Studies with model peptide substrates showed that the enzyme preferentially recognizes a single arginine cleavage site, cleaving Boc-Gln-Ala-Arg-4-methylcoumaryl-7-amide most efficiently and having a pH optimum of 7.5 with this substrate. The enzyme is strongly inhibited by aprotinin, diisopropylfluorophosphate, antipain, leupeptin, and Kunitz-type soybean trypsin inhibitor, but inhibited only slightly by Bowman-Birk soybean trypsin inhibitor, benzamidine, and alpha 1-antitrypsin. Immunohistochemical studies indicated that the enzyme is located exclusively in the bronchiolar epithelial Clara cells and colocalized with surfactant. An immunoreactive protein with a molecular mass of 28.5 kDa was also detected in airway secretions by Western blotting analyses, suggesting that the 30-kDa protease in Clara cells is processed before or after its secretion. Proteolytic cleavage of the hemagglutinin of influenza virus is a prerequisite for the virus to become infectious. Tryptase Clara was shown to cleave the hemagglutinin and activate infectivity of influenza A virus in a dose-dependent way. These results suggest that the enzyme is a possible activator of inactive viral fusion glycoprotein in the respiratory tract and thus responsible for pneumopathogenicity of the virus.
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Different doses of 95% alcoholic extract of whole plant of Rivea hypocrateriformis (Convolvulaceae) was tested for antiimplantation activity in female albino rats. The alcoholic extract at a dose of 200 mg/ kg body weight has showed 66.66% antiimplantation activity.Whereas, at 400 mg/kg body weight, significantly prevented pregnancy by 100%.The antiimplantation activity was reversible on withdrawal of the treatment of the extract.
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Aus der Rinde von Erythrina variegata werden die drei neuen Isoflavone (I)-(III) neben den bekannten Alpinumisoflavon (IV) und Osajin (V) sowie Oxyresveratrol und Dihydrooxyresveratrol isoliert.
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The cultivation ofPhytolacca dodecandra has been studied in Zimbabwe in order to initiate local production of the berries from which molluscicidal saponins can be extracted and used in schistosomiasis control programs. The effect of shading, water and nutrient type on growth and berry yield of an imported Ethiopian and a Zimbabwean cultivar were monitored. The molluscicidal potency and saponin concentration of the aqueous extracts of berries, harvested at the full grown, unripe development stage, were determined. There was a marked seasonal variation in berry production with both cultivars being highly productive in the dry season. The best growth and the highest berry yield was obtained with plants grown in full sunlight, under irrigation and with application of cattle manure. The Ethiopian cultivar showed in general better growth and higher berry yield than the Zimbabwean cultivar. Cultivation in shade gave a substantially lower berry yield and saponin concentration in both cultivars, compared to full sunlight. Irrigation was beneficial to the berry yield in both cultivars but lowered the saponin concentration in berries of the Ethiopian cultivar. However, it did not counteract the advantage of irrigation on the total yield. Addition of manure did significantly increase the growth and the berry yield of both cultivars compared to fertilizer application and to the control. The saponin concentration was in general lower with addition of manure, with exception of irrigated Ethiopian plants. The combination of cattle manure and irrigation resulted in the highest saponin yield. Although the two cultivars had different saponin patterns, these patterns and the relative proportions of the saponins were constant, irrespective of the treatments.
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Organic solvent extracts of 300 southwestern U.S.A. plant species in 69 families were evaluated against four microorganisms in an agar-streak bioassay. The dichloromethane extract of Guardiola platyphylla and ethanol extracts of Plumbago scandens, Acacia angustissima and Salvia sonomensis demonstrated the best spectrum of activity by completely inhibiting the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae and Candida albicans. Of the 300 species, 12 completely inhibited the growth of the gram-negative K. pneumoniae and 36 inhibited the yeast C. albicans. B. subtilis proved to be very susceptible with 188 species either completely inhibiting or slowing the growth of this gram-positive organism. S. aureus proved to be more selective with only 107 species affecting its growth. Ninety-one species demonstrated no inhibitory effects on any test organisms.
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A fraction consisting of an equimolar mixture of quercetin 3-sulphate and patuletin 3-sulphate was isolated from a methanolic leaf extract of Flaveria chloroefolia. Structures were established by UV and NMR spectroscopy as well as FAB-MS. The effect of 3-sulphation on the 13C NMR spectrum is discussed and the nature of a possible linkage of the two flavonol sulphate moieties is postulated.
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A variety of stressors active the hypothalamic-pituitary-adrenal (HPA) axis, thereby resulting in elevated levels of circulating ACTH, β-endorphin and corticosterone. Since these hormones have been shown previously to alter measures of immune function, we determined whether presentation of a stressor which activates the HPA axis produces alteration in immune function. Restraint stress resulted in significantly elevated levels of corticosterone and β-endorphin without affecting either proliferative or cytolytic activities of lymphocytes. At concentrations similar to those achieved during stress, in vivo, corticosterone exhibited a dose- and time-dependent reduction in both lymphocyte proliferation as well as natural killer cytotoxicity, in vitro. β-Endorphin, on the other hand, was without direct or modulatory effects. These results indicate that restraint stress-induced activation of the HPA axis occurs witho-ut accompanying in immune function.
Article
The crude aqueous extract of a field collected strain of Microcystis aeruginosa (Kütz) showed antiviral activity against influenza A virus. The concentration for 50% inhibition of virus replication in MDCK cells was 11 μg dry extract/mL. The virus specific protein synthesis decreased if the extract was present over the whole time of replication. Furthermore protease inhibitory activity was estimated for the crude aqueous extract and subextracts. © 1997 by John Wiley & Sons, Ltd.
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The bioassay-directed fractionation of an acetone extract of the root bark of Erythrina X bidwillii which shows a significant antibacterial activity against oral bacteria led to isolate three new phenolic compounds (bidwillols A and B, and bidwillon C) and a known pterocarpene (erycristagallin), the structures of which were characterized by spectral and physical properties. Among them, erycristagallin showed potent microbial activity against Streptococcus mutans, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.
Article
A low-pressure liquid chromatographic method on silica gel 60, with chloroform containing 0–1% (v/v) of methanol as eluent, is described that allows the isolation of isorhoeadine from the total alkaloids of petals of Papaver rhoeas L.A. preparative high-performance liquid chromatographic (HPLC) method with a LiChrosorb Si 60 column, using chloroform containing 0–5% (v/v) of methanol (isocratic and then linear gradient) as mobile phase, is described that allows the isolation of rhoeagenine from a few fractions issuing from the previous low-pressure liquid chromatographic run. Finally, a selective analytical HPLC method with a Superspher Si 60 column using chloroform-methanol (90:10, v/v) containing 0.1% of trifluoroacetic acid as mobile phase and UV detection at 292.5 nm is described that allows the determination of isorhoeadine and rhoeagenine in red poppy extracts. In comparison with a classical chloroformic alkaloid extraction of petals from Maine et Loire (France) (total alkaloid efficiency = 0.203% dry material), a weak aqueous alcoholic acidic extract (30% ethanol) (0.216%) and an aqeous acidic extract (0.123%) of the same material, the amount of isorhoeadine is 71.1, 42.4 nad 10.5 mg/g total alkaloids, respectively, and the amount of rhoeagenine is 629.7, 424.2 and 117.3 mg/g total alkaloids, respectively. Hence, the aqueous alcoholic acidic extract seems to be the most appropriate for conceiving a red poppy remedy.
Article
Alchornea cordifolia (Euphorbiaceae), a traditional African medicinal plant, is widely distributed in West Africa. A number of phenolic acids, notably gallic acid, protocatechuic acid, quercetin, quercetin arabinose and galactose glycosides, together with triisopentenyl guanidine were isolated from a methanolic extract of the leaves. The first two, and last one of these compounds showed considerable antibacterial activity.
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Citral showed appreciable antimicrobial activity against Gram-positive and Gram-negative bacteria as well as fungi. Media composition and inoculum size had no observable effect on activity but alkaline pH increased citral activity. The growth rates of Escherichia coli cultures were reduced at concentrations of citral ≥0·01% v/v while concentrations ≥0·03% v/v produced rapid reduction in viable cells followed by limited regrowth. In a non-growth medium, 0·08% and 0·1% v/v showed rapid bactericidal effects. Citral may therefore be of preservative use in addition to its other uses in the food, soap and cosmetic industries.
Article
The variation in anthocyanins content of the petals of red poppy (Papaver, Rhoeas) during development of the flower from the closed bud stage have been investigated. Six-stage gradient thin-layer chromatography of the polyzonalstepwise type was used, starting from ethyl acetate, the last eluent fraction being isopropanol-water-acetic acid (65323). Silica Si 60 was used as adsorbent. The densitograms were recorded at 465 nm; they show gradually increasing peaks of red anthocyanins in the petals of closed buds, partly opened buds and fully developed flower and changes in the proportions of several anthocyanins, with various RF values, during the growth of the flower.
Article
The effects of several doses from 0.125–3 mg/kg of methamphetamine on the novelty-seeking behaviour of male Swiss albino mice were studied. Methamphetamine induced a dose-dependent inhibition of novelty preference. Furthermore, a dose of methamphetamine (1 mg/kg) which strongly decreased novelty preference in naive mice induced a significantly lower decrease in exploration of subjects previously exposed to novelty. These data provide some support for Berlyne's (1967) suggestion that amphetamine has a disruptive effect on exploration by producing over-arousal.
Article
The effects of short-term handling and different durations of immobilization on serum levels of catecholamines, ACTH, prolactin, and corticosterone and in vitro functions of lymphocytes were examined in rats. The results show that changes in the immune response of peripheral blood lymphocytes (PBL) depend on the intensity of the stressor: Short (1 min) handling of cannulated rats induced an enhanced stimulation of PBL to respond to T and B cell mitogens, whereas immobilization of the same animals led to suppression, dependent on the time this stressor was applied. The decrease in the mitogen reactivity of PBL after 120 min of immobilization was reversible within 24 h, and could be largely prevented by adrenalectomy, confirming that factors released by this gland are mainly responsible for immunosuppression. In contrast to PBL, spleen cells showed an enhanced mitogen response to immobilization and adrenalectomy, indicating that the immune response is differently regulated in the various compartments of the immune system. Possible correlations of the various effects with changes in stress hormone levels are discussed.
Article
Hockley D. J. and McLaren D. J. 1973. Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. International Journal for Parasitology3: 13–25. The tegumental outer membrane of the cercaria is trilaminate: the adult worm, however, has a seven-layered membrane. Formation of the heptalaminate membrane commences immediately after the cercaria has penetrated the vertebrate host: multilaminate membrane-bounded vacuoles are passed from subtegumental cells into the tegument where they enlarge, join to the outer membrane and open to the exterior. The heptalaminate limiting membrane of the vacuole thus becomes the outer membrane of the tegument. At the same time the original trilaminate tegumental membrane is formed into microvilli which are cast off and thus the cercarial outer membrane is lost. Schistosomula usually have a heptalaminate outer membrane within three hours of penetration. After this time the large vacuoles are replaced by smaller membraneous bodies which presumably contribute to the outer membrane during growth of the schistosomulum. The membraneous bodies are also present in the tegument of the adult worms and there is some evidence that the outer membrane is continually renewed.
Article
Flavonoids are widely present in plants as water-soluble glycosides but the lipophilic free aglycones are far less abundant. The 462 flavonoids reported so far to be present in the free state and their plant sources are listed. Evaluation of these data reveals a correlation in most cases between the occurrence of flavonoid aglycones, the presence of secretory structures and the production of other lipophilic plant products. Their accumulation in some plant organs and in certain taxa is discussed. Special attention is given to their occurrence in materials deposited externally on leaves and buds.
Article
A simple system is described to analyze the possibility that increased exploratory behavior is an index for the anxiolytic effects of benzodiazepines in laboratory rodents. Mice were allowed free run in a two-chambered arena, where two-thirds of the area was illuminated and one-third was darkened. The two chambers were separated by a black partition equipped with photocells across the opening, and the entire cage rested on an Animex activity monitor. Transitions across the partition between the light and dark chambers, and total Animex locomotor activity, were increased by clonazepam and chlordiazepoxide, in dose-dependent ranges consistent with previously reported behavior models. The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.
Article
10 food-deprived rats and 10 non-deprived rats were observed for 15 minutes each in an exploration box allowing free choice between novel and familiar units. Although all subjects showed a preference for novelty, there were no significant differences in these preferences between the two groups as measured by the number of 10-second periods spent in the novel half of the box and by the percentage of novel units entered. However, the food-deprived rats entered a significantly greater total number of units. It was concluded that, contrary to earlier studies, food deprivation had not effected exploration of novelty but had possibly influenced activity of some origin other than strict exploratory tendencies.
Article
In addition to the known alkaloid mucronine-D, two new cyclopeptide alkaloids were isolated from the roots of Ziziphus mucronata. The structures were elucidated by 1- and 2-DNMR techniques.
Article
The spectra of 151 flavonoids were measured in methanol alone and with added aluminium chloride and hydrochloric acid. A bathochromic shift in the presence of aluminium chloride separated flavonoids with a 3′,4′-o-dihydroxy system. The different flavonoids may be divided into two classes according to the shape of band I (single or double peak) in the presence of aluminium chloride + hydrochloric acid. Flavones and 3-methoxyflavones may be differentiated through their different UV spectral properties. In addition, it is possible to define the positions of substituents on the A (6; 8 and 6,8)- and B (4′; 3′, 4′; 3′, 4′, 5′)-rings in most cases.
Article
We examined the effects of the restriction of environmental space on hippocampal acetylcholine release and spontaneous locomotor activity. Four days after the housing in a large or small cage, sampling for microdialysis study was begun. The locomotor activity counts exhibited significant daily changes in all rats in either the large or small cage. But, the mean locomotor activity counts in rats in the small cage was significantly less than that in the large cage. In contrast, the amount of acetylcholine collected per 20-min sample exhibited significant diurnal changes in all six rats in the large cage and in 5 of 6 rats in the small cage. The mean acetylcholine release in the rat in the small cage was significantly lower than that in the rat in the large cage during the dark phase, but not during the light phase. In addition, during the dark phase, hippocampal acetylcholine release was closely associated with spontaneous activity in all six rats in the large cage but not in 3 of 6 rats in the small cage. The present study suggests that the restriction of environmental space somehow interfere with the spontaneous locomotor activity and hippocampal acetylcholine release during the dark phase.
Article
The evidence that in the human P is indispensable in early normal pregnancy maintenance complements current concepts regarding the regulatory background, diagnosis and treatment of corpus luteum insufficiency. In a recent report Jones defined Luteal Phase Defect as a deficiency of corpus luteum progesterone steroidogenesis, either in amount or duration, or both. The clinical manifestations include either primary infertility or repeated first trimester abortions. The diagnosis can only be made clinically on the basis of a well-timed endometrial biopsy that is read histologically as two or more days out of phase with the next period in at least two cycles. The deficiency is not due to a single etiology and an etiologic diagnosis is often difficult or impossible to make in routine clinical practice. The treatment, therefore, usually requires substitution with progesterone. In some patients with severe defects of prolonged irregular cycles, clomiphene citrate can be used successfully, and, if the patients respond to HCG, this can also be used as a luteotropic agent. Some corpora lutea, however, cannot be 'rescued' by this stimulus. The present report also exposes the corpus luteum as a target of postconceptional therapy. While luteolysis has not been achieved as yet in the human by a direct, but only by an indirect PG-action, the possibility remains that new PG-analogues or P-synthesis inhibitors will affect luteal P-genesis directly. These therapeutic agents could qualify as ideal postconceptional drugs.
Article
To analyze the control mechanism of luteal function during pregnancy, a new crop of corpora lutea was introduced in pregnant rats from Day 4 to Day 19 of pregnancy (Day 1, first day of leukocytic smear) with a single i.v. injection of 20 μg LH. Between Days 12-16, pretreatment with 30 IU PMSG before the LH treatment was needed for ovulation to occur. Pregnancy was not interrupted by these treatments. Induction of ovulation before Day 10 had an effect on peripheral progesterone and 20α-dihydroprogesterone levels but had no effect on the duration of gestation. Hypophysectomy of these rats on Day 11 but not on Day 19 prevented the onset of parturition and prolonged gestation. Formation of new corpora lutea later than Day 12 also delayed parturition which then occurred between Days 25-27 and usually resulted in the death of either the mothers or fetuses. Elevated progesterone levels were observed during this extended pregnancy. These levels appeared to be maintained by placental luteotropin, since removal of the conceptus was followed by an immediate decrease in progesterone concentrations. Thus, a particular period was defined: before Day 10 of pregnancy when induction of ovulation was possible with LH alone luteolysis and parturition occurred at term; after Day 12, however, pretreatment with PMSG was needed for ovulation to occur and the function of the corpora lutea was extended beyond term.
Article
The effects of 0.4 to 1.5 mg intravenously administered atropine were evaluated in 100 patients with a heart rate <60/min following acute myocardial infarction. Prior to the administration of atropine the mean heart rate was 45 ± 7/min, the incidence of ventricular premature beats was 12 ± 4/min, and two patients had angina. Based on the maximum heart rate response to atropine, the patients were divided into two groups. Heart rate increased to <100/min in 79 patients (group I) and ⪰ 100/min in 21 patients (group II). Ventricular premature beats decreased significantly (p < 0.01) in both groups; (2 ± 4/min in group I and 2.4 ± 0.8 in group II). In only one patient in group II did ventricular premature beats first appear following the administration of atropine. Blood pressure did not change significantly after the administration of atropine in either group. In two patients (group I), angina disappeared and in two others (group II) angina appeared following the administration of atropine. Doseheart rate analysis revealed that 70 per cent of the patients in group II and only 17 per cent of those in group I received ⪰0.8 mg atropine (p < 0.01). There was a statistically significant correlation between the dose of atropine and the increment in heart rate (r = 0.41, p < 0.01).Thus, a relatively lower dose of atropine (<0.8 mg) had a beneficial antiarrhythmic effect. Higher dosage caused an inappropriate tachycardia, angina and ventricular premature beats, and should be avoided.
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Circulating plasma progesterone (P) has been quantitatively controlled in the rat "model" through highly specific binding by treatment with anti-P (A-P). Knowing the constant, which characterizes the binding of P to A-P in plasma, sequential assays of circulating A-P and A-P bound total P (Pt) revealed the levels of the biologically active unbound P (Pu). The studies showed that at different stages of gestation the mechanisms through which A-P reduces Pu and terminates pregnancy are the same. However, the doses of AP which effectively reduce Pu and also the critical levels of Pu at which pregnancy terminates are different. The moderate and transient physiologic P-withdrawal (Pw) at midterm permits the continuation of normal gestation, but pregnancy is terminated by a drastic and sustained reduction in Pu. In contrast, when Pu is only slightly and briefly reduced below physiologic levels, pregnancy continues and only retarded conceptus growth signals that Pw occurred. Apparently Pw has to be controlled and measured with "razor's-edge" precision to fully expose and define the regulatory significance of this steroid in the maintenance and termination of pregnancy. Short of this precision, the key regulator of the pregnant uterus will remain buried, as it has been during 40 years, in controversial findings.
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The electrophretic pattern of the red cell membrane protein, after the in vitro action on them of antimalarial agents, primaquine, quinine and chloroquine, is described. This electrophoretic study has proved that all studied antimalarial agents after the membrane proteins, causing a total loss of certain bands. This method has proved to be a new way of appreciation of the action of different agents on the red cell membrane.
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Mild electric footshock stress was delivered during the dark portion of a 12:12 h light:dark cycle to C57BL/6 female mice that were infected with herpes simplex virus-type 1 (HSV). The studies were designed to correlate viral titer with both humoral and cell-mediated immune responses to HSV infection. Footshock was observed to result in decreased HSV-specific immunity. The numbers of leukocytes in spleens and draining popliteal lymph nodes of footshocked mice were depressed compared to both apparatus control and home cage control mice. A significant suppression of the HSV-specific cytotoxic T lymphocyte (CTL) response was observed in both the spleen and popliteal lymph nodes of footshocked mice. Serum IgM anti-HSV antibody titers were also depressed in footshocked mice. These changes were shown to be correlated with significantly increased viral titers in footshocked mice compared to control mice. These data demonstrate that administration of a relatively mild stressor is associated with depressed HSV-specific cellular and humoral immunity and is associated with increased pathogenicity.
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A polyphenolic complex (PC), isolated from the Bulgarian medicinal plant Germanium sanguineum L., inhibited the reproduction of influenza virus types A and B in vitro and in ovo. It protected white mice in an experimental lethal influenza infection. When influenza viruses were treated with a high dose (1 mg/mL), their hemagglutination, neuraminidase and infections activities were reduced completely. It was assumed that the PC-specific inhibitory effect on influenza virus reproduction in tissue cultures (50 micrograms/mL) was mediated by partial inactivation of viral glycoproteins which prevented the initial stages of reproduction. The PC also affected the intracellular stages of viral replication. The effect was dependent on the mode of application, the viral strain, and the biological test system. The PC also inhibited the reproduction of herpes simplex virus in vitro. Infectious titers were reduced and newly synthesized virion with damaged protein envelopes were observed by electron microscopy.