Gelsemium sempervirens and Animal Behavioral Models

A commentary on : Gelsemine and Gelsemium sempervirens L. extracts in animal behavioral test: comments and related biases by Chirumbolo, S. (2011). Front. Neur. 2:31. doi: 10.3389/fneur.2011.0003

Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in Response to Novel Environments

Gelsemium sempervirens is used in homeopathy for treating patients with anxiety related symptoms, however there have been few experimental studies evaluating its pharmacological activity. We have investigated the effects of homeopathic doses of G. sempervirens on mice, using validated behavioral models. Centesimal (CH) dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg body weight) or a placebo (solvent vehicle) were intraperitoneally delivered to groups of mice of CD1 strain during 8 days, then the effects were assessed by the Light-Dark (LD) choice test and by the Open-Field (OF) exploration test, in a fully blind manner. In the LD test, the mean time spent in the illuminated area by control and placebo-treated animals was 15.98%, for mice treated with diazepam it increased to 19.91% (P = .047), while with G. sempervirens 5 CH it was 18.11% (P = .341, non-significant). The number of transitions between the two compartments increased with diazepam from 6.19 to 9.64 (P < .001) but not with G. Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the time spent and the distance traveled in the central zone (P = .009 and P = .003, resp.), while diazepam had no effect on these OF test parameters. In a subsequent series of experiments, G. sempervirens 7 and 30 CH also significantly improved the behavioral responses of mice in the OF test (P < .01 for all tested variables). Neither dilutions of G. sempervirens affected the total distance traveled, indicating that the behavioral effect was not due to unspecific changes in locomotor activity. In conclusion, homeopathic doses of G. sempervirens influence the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a diminution of thigmotaxis or neophobia

Reappraisal of Dietary Phytochemicals for Coronavirus Infection: Focus on Hesperidin and Quercetin

Food polyphenols constitute a large family of substances with beneficial properties in a large group of communicable and non-communicable diseases. These compounds support and improve the body’s defences against oxidative stress and are helpful in the prevention of pathologies related to metabolic syndrome. Furthermore, they exhibit anti-inflammatory, antiviral, and antimicrobial properties. This chapter draws attention to certain nutritional components such as hesperidin and quercetin, which are emerging as good candidates for a complementary beneficial effect in the case of diseases caused by viruses, including COVID-19. These nutraceuticals have a complex mechanism of action, which involves both cellular defence against oxidative stress and the modulation of inflammation, which although normally is a defence, repair and activation mechanism of the immune system, it can elude its controls and become a systemic and destructive pathology (cytokine storm, respiratory distress syndrome). Furthermore, recent in silico simulation tests suggest that both hesperidin and quercetin may interfere with SARS-CoV-2 by binding to cell receptors and the proteolytic enzymes involved in its replication. In addition to the inhibitory effects on the virus at cellular level, the two flavonoids can have indirect effects in respiratory infectious diseases as they prevent or improve metabolic and vascular comorbidities that can complicate the clinical course. This brief review focuses on biochemical and pharmacological mechanisms of action of polyphenols in the context of the revaluation of dietary approaches to the prevention and treatment of infectious diseases caused by viruses, with a special application to COVID-19

Immunology and Homeopathy. 3. Experimental Studies on Animal Models

A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the ‘simile’, the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional ‘simile’ rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials

Response to a comment by Luigi Cervo and Valter Torri on: “Dose–effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice” (Magnani P. et al., Psychopharmacology, 2010)

Commentar

Immunology and Homeopathy. 1. Historical Background

Homeopathy was born as an experimental discipline, as can be seen from the enormous amount of homeopathic data collected over more than two centuries. However, the medical tradition of homeopathy has been separated from that of conventional science for a long time. Conventional scientific wisdom dictates that homeopathy should have no effect above placebo but experiments on ultra-high dilutions of solutes together with some clinical data suggest the intriguing possibility that it might do in some circumstances. Today, an osmotic process between disciplines, previously seen as in conflict, is facilitated because over the last few decades homeopathy has initiated the methods of current medical science and a substantial number of experimental studies—at molecular, cellular and clinical levels—are available. One area of dialogue and of common progress is that of inflammation and immunity, probably because these are closely related to the traditional ‘vital force’ of the body's self-healing power. In a series of papers we review the historical origins of homeopathy, the laboratory and animal models related to the field of immunopharmacology, the clinical evidence in favor and against the use of homeopathy in the inflammatory diseases and the hypotheses regarding its action mechanism(s). Finally, we will enlighten the specific characteristics of the homeopathic approach, which places great emphasis on identifying a cure for the whole organism

Immunology and Homeopathy. 5. The Rationale of the ‘Simile’

The foundation of homeopathic medicine is the ‘Similia Principle’, also known as the ‘Principle of Similarity’ or also as the ‘Simile’, which reflects the inversion of pharmacological effects in healthy subjects as compared with sick ones. This article describes the inversion of effects, a widespread medical phenomenon, through three possible mechanisms: non-linearity of dose–response relationship, different initial pathophysiological states of the organism, and pharmacodynamics of body response to the medicine. Based on the systemic networks which play an important role in response to stress, a unitary and general model is designed: homeopathic medicines could interact with sensitive (primed) regulation systems through complex information, which simulate the disorders of natural disease. Reorganization of regulation systems, through a coherent response to the medicine, could pave the way to the healing of the cellular, tissue and neuro-immuno-endocrine homeodynamics. Preliminary evidence is suggesting that even ultra-low doses and high-dilutions of drugs may incorporate structural or frequency information and interact with chaotic dynamics and physical-electromagnetic levels of regulation. From the clinical standpoint, the ‘simile’ can be regarded as a heuristic principle, according to which the detailed knowledge of pathogenic effects of drugs, associated with careful analysis of signs and symptoms of the ill subject, could assist in identifying homeopathic remedies with high grade of specificity for the individual case

Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies

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

Cell sensitivity, non-linearity and inverse effects

It has been claimed that the homeopathic principle of 'similarity' (or 'similia') and the use of individualized remedies in extremely low doses conflicts with scientific laws, but this opinion can be disputed on the basis of recent scientific advances. Several mechanisms to explain the responsiveness of cells to ultra-low doses and the similarity as inversion of drug effects, have again been suggested in the framework of hormesis and modern paradoxical pharmacology. Low doses or high dilutions of a drug interact only with the enhanced sensitivities of regulatory systems, functioning as minute harmful stimuli to trigger specific compensatory healing reactions. Here we review hypotheses about homeopathic drug action at cellular and molecular levels, and present a new conceptual model of the principle of similarity based on allosteric drug action. While many common drugs act through orthostatic chemical interactions aimed at blocking undesired activities of enzymes or receptors, allosteric interactions are associated with dynamic conformational changes and functional transitions in target proteins, which enhance or inhibit specific cellular actions in normal or disease states. The concept of allostery and the way it controls physiological activities can be broadened to include diluted/dynamized compounds, and may constitute a working hypothesis for the study of molecular mechanisms underlying the inversion of drug effects

Immunology and Homeopathy. 4. Clinical Studies—Part 1

The evidence-based research of the effectiveness of homeopathic medicines in common immunologic disorders is reviewed. In part 1, we introduce methodological issues of clinical research in homeopathy, and criteria utilized to evaluate the literature. Then 24 studies (12 randomized and 12 non-randomized) on common upper respiratory tract infections and otorhinolaryngologic complaints are described. In part 2, the focus will be on allergic diseases and the effectiveness of homeopathy will be globally evaluated and discussed using the criteria of evidence-based medicine