Fibronectin Gene Up-regulation by Arnica montana in Human Macrophages: Validation by Real-Time Polymerase Chain Reaction Assay.

BACKGROUND AND AIM: Arnica montana L. (Arnica m.) is a popular traditional medicine, used for its therapeutic properties in healing traumas, but little is known about its biological action on tissue formation and repair. This new work tested the effects of Arnica m. homeopathic dilutions on human macrophages, key cells in tissue defence and repair. MATERIALS AND METHODS: Macrophages derived from the THP-1 cell line were differentiated with interleukin-4 to induce a 'wound-healing'-like phenotype, and treated with various dilutions of Arnica m. centesimal (100 times) dilutions (2c, 3c, 5c, 9c, and 15c) or control solvent for 24 hours. RNA samples from cultured cells were analysed by real-time quantitative polymerase chain reaction in five separate experiments. RESULTS: Arnica montana at the 2c dilution (final concentration of sesquiterpene lactones in cell culture = 10-8 mol/L) significantly stimulated the expression of three genes which code for regulatory proteins of the extracellular matrix, namely FN1 (fibronectin 1, % increase of 21.8 ± standard error of the mean 4.6), low-density lipoprotein-receptor-related protein 1 (% increase of 33.4 ± 6.1) and heparan sulphate proteoglycan 2 (% increase of 21.6 ± 9.1). Among these genes, the most quantitatively expressed was FN1. In addition, FN1, unlike other candidate genes, was upregulated in cells treated with higher dilutions/dynamisations (3c, 5c, and 15c) of Arnica m. CONCLUSION: The results support evidence that the extracellular matrix is a potential therapeutic target of Arnica m., with positive effects on cell adhesion and migration during tissue development and healing.

Comments on the Retraction by PLoS ONE of a Laboratory Study on Arnica montana.

In June 2019, the journal PLoS ONE retracted an original research article, published in 2016, which described the effects of homeopathic Arnica montana on interleukin-4 treated human macrophages. The results showed an increase in extracellular matrix gene expression, including the gene encoding fibronectin, which is one of the main proteins involved in connective tissue healing. Here, the authors of the article discuss the critical points raised by the journal in the retraction note, with a focus on the specific methodological aspects of research on high dilutions of natural compounds. The editorial arguments made to justify the retraction did not prove any methodological errors, nor scientific misconduct. As a general rule, when a study published by a group of researchers raises scientific doubts because the results appear at variation with the commonly accepted knowledge in a field, the study is repeated by other scholars and any contrasting results are published and/or discussed. Therefore, retraction of the Arnica m. study by PLoS ONE is a violation of the conventions of scientific publication and knowledge-sharing methods derived from honest experimental method.

In vitro effects of Zinc in soluble and homeopathic formulations on macrophages and astrocytes.

Zinc is an important metal in body homeostasis. Zinc in soluble form (Zn2+) and homeopathic Zincum metallicum were tested in macrophages and astrocytes in order to investigate its potential toxic or therapeutic effects. We evaluated cell viability (WST assay), cytokine production such as tumour necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) by enzyme-linked immunosorbent assay (ELISA) and nitric oxide release by Griess reaction. The effect of zinc-depletion and high zinc pre-treatments on the cell adaptation capability was also investigated. In THP-1 macrophage cell line and in human primary macrophages, Zn2+ at sub-toxic doses (30 µM) caused stimulation of TNF-α and IL-10 with different dynamics reaching the maximum peak at the zinc concentration 100 µM, before the cell death. Highest doses (300 µM) impaired dramatically cell vitality. Similar effects on cell viability were obtained also in C6 astrocytes, where Zn2+ slightly increased the nitric oxide release only in cells activated by one of the pro-inflammatory stimuli used in our cellular model (interferon gamma plus TNF-α). Zinc depletion markedly reduced IL-10 production and cell viability. Zincum metallicum did not cause toxicity in any cell type and showed some small stimulation in WST assay that was statistically significant in a few experimental conditions.

Structural and thermal analyses of zinc and lactose in homeopathic triturated systems.

BACKGROUND: A series of different experimental approaches was applied in Zincum metallicum (Zinc met.) samples and lactose controls. Experiments were designed to elucidate the effect of zinc trituration and dynamization on physicochemical properties of homeopathic formulations, using lactose as excipient. METHODS: Zinc met. potencies (Zinc met 1-3c) were triturated and dynamized using lactose as excipient, according to Brazilian Homeopathic Pharmacopoeia. Lactose samples (LAC 1-3c) were also prepared following the same protocol and used as controls. The samples were analyzed structurally by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDX) and Scanning Electron Microscopy (SEM), and thermodynamically by Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC). RESULTS: AAS analysis detected 97.0 % of zinc in the raw material, 0.75 % (Zinc met 1c) and 0.02% (Zinc met 2c). XRD analysis showed that inter-atomic crystalline spacing of lactose was not modified by dynamization. Amorphous and crystalline lactose spheres and particles, respectively, were observed by TEM in all samples, with mean size from 200 to 800 nm. EDX obtained with TEM identified zinc presence throughout the amorphous matter but individualized zinc particles were not observed. SEM images obtained from dynamized samples (LAC 1c and Zinc met 1c) with electron backscattering could not identify zinc metal grains. The dynamization process induced Derivatives of Thermal Gravimetric (DTg) peak modification, which was previously centered near 158°C to lactose, to a range from 140 to 170°C, suggesting the dynamization process modifies the temperature range of water aggregation. Thermal phenomena were analyzed and visualized by Analysis of Variance (ANOVA) and Principal Component Analysis (PCA) statistics. Both indicated that fusion enthalpy of dynamized samples (DynLAC 1-3c; DynZn 1-3c) increased 30.68 J/g in comparison to non-dynamized lactose (LAC; p < 0.05). CONCLUSIONS: Our results suggested no structural changes due to the trituration and dynamization process. However, TG and DSC analyses permit the differentiation of dynamized and non-dynamized groups, suggesting the dynamization process induced a significant increase in the degradation heat. These results call for further calorimetric studies with other homeopathic dilutions and other methodologies, to better understand the dynamics of these systems.

Arnica montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR.

BACKGROUND: Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing. METHODS: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors. RESULTS: On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited the most consistent increase of expression, while also CXC chemokine ligand 2 (CXCL2), Interleukin8 (IL8) and bone morphogenetic protein (BMP2) were slightly up-regulated, suggesting a positive influence of A. montana on neutrophil recruitment and on angiogenesis. MMP1, coding for a metalloproteinase capable of cleaving extracellular matrix substrates, was down-regulated. Most results showed non-linearity of the dose-effect relationship. CONCLUSIONS: This exploratory study provides new insights into the cellular and molecular mechanisms of action of A. montana as a promoter of healing, since some of the genes it modifies are key regulators of tissue remodelling, inflammation and chemotaxis.

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.

Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens.

BACKGROUND: Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract. METHODS: Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions. RESULTS: Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10(-9) M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range. CONCLUSIONS: The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation.

High-dilution effects revisited. 1. Physicochemical aspects.

Several lines of evidence suggest that homeopathic high dilutions (HDs) can effectively have a pharmacological action, and so cannot be considered merely placebos. However, until now there has been no unified explanation for these observations within the dominant paradigm of the dose-response effect. Here the possible scenarios for the physicochemical nature of HDs are reviewed. A number of theoretical and experimental approaches, including quantum physics, conductometric and spectroscopic measurements, thermoluminescence, and model simulations investigated the peculiar features of diluted/succussed solutions. The heterogeneous composition of water could be affected by interactive phenomena such as coherence, epitaxy and formation of colloidal nanobubbles containing gaseous inclusions of oxygen, nitrogen, carbon dioxide, silica and, possibly, the original material of the remedy. It is likely that the molecules of active substance act as nucleation centres, amplifying the formation of supramolecular structures and imparting order to the solvent. Three major models for how this happens are currently being investigated: the water clusters or clathrates, the coherent domains postulated by quantum electrodynamics, and the formation of nanoparticles from the original solute plus solvent components. Other theoretical approaches based on quantum entanglement and on fractal-type self-organization of water clusters are more speculative and hypothetical. The problem of the physicochemical nature of HDs is still far from to be clarified but current evidence strongly supports the notion that the structuring of water and its solutes at the nanoscale can play a key role.

High-dilution effects revisited. 2. Pharmacodynamic mechanisms.

The pharmacodynamics aspects of homeopathic remedies are appraised by laboratory studies on the biological effects at various levels (cellular, molecular and systemic). The major question is how these medicines may work in the body. The possible answers concern the identification of biological targets, the means of drug-receptor interactions, the mechanisms of signal transmission and amplification, and the models of inversion of effects according to the traditional 'simile' rule. These problems are handled by two experimental and theoretical lines, according to the doses or dilutions considered (low-medium versus high dilutions). Homeopathic formulations in low-medium dilutions, containing molecules in the range of ultra-low doses, exploit the extreme sensitivity of biological systems to exogenous and endogenous signals. Their effects are interpreted in the framework of hormesis theories and paradoxical pharmacology. The hypotheses regarding the action mechanisms of highly diluted/dynamized solutions (beyond Avogadro-Loschmidt limit) variously invoke sensitivity to bioelectromagnetic information, participation of water chains in signalling, and regulation of bifurcation points of systemic networks. High-dilution pharmacology is emerging as a pioneering subject in the domain of nanomedicine and is providing greater plausibility to the puzzling claims of homeopathy.

Basic research in homeopathy and ultra-high dilutions: what progress is being made?

This report summarises the latest research developments in the field of high dilutions and homeopathy, as presented at the GIRI symposium of the leading international organisation of scientists in this field, in Florence, Italy in September 2012. The scientific community's early scepticism concerning the possible biological and pharmacological activity of highly diluted solutions, is giving way to a more open-minded attitude that no longer obstructs critical and experimental investigations in this emerging field of biomedicine.

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.

Effects of Ignatia amara in mouse behavioural models.

BACKGROUND: Ignatia amara (Ignatia), a remedy made from the Strychnos ignatii seeds, is used for anxiety-related symptoms, but consistent evidence of its activity in reproducible experimental models is lacking. An investigation was performed in order to assess on mice, by means of emotional response models, the activity of homeopathic Ignatia dilutions/dynamizations. METHODS: Groups of 8 mice of the CD1 albino strain were treated intraperitoneally for 9 days with 0.3ml of five centesimal (C) dilutions/dynamizations of Ignatia (4C, 5C, 7C, 9C and 30C). Control mice were treated with the same hydroalcoholic (0.3%) solution used to dilute the medicines. Diazepam (1mg/kg) was the positive reference drug. Validated test models for locomotion and emotional response, the Open-Field (OF) and the Light-Dark (LD) tests, were employed. Five replications of the same protocol were carried out, in a randomised way using coded drugs/controls. RESULTS: In the OF the general locomotion of mice was slightly decreased by Ignatia 4C, but not by Ignatia 5C, 7C, 9C and 30C, indicating the absence of unspecific motor impairment or sedation by these dilutions/dynamizations. Ignatia and diazepam seemed to decrease the number of urine spots released in the OF during 10min, with borderline significance (P=0.083). In the LD the tested medicine showed anxiolytic-like activity (increase of time spent and distance travelled in the lit area), though to a lesser extent than diazepam. The highest and most significant difference with untreated controls (P<0.01) was observed with the 9C dilution/dynamization. Among the 5 replication experiments, the best drug effects were obtained where the baseline anxiety of mice was higher. CONCLUSIONS: Homeopathic Ignatia dilutions/dynamizations (peak at 9C) modify some emotion-related symptoms in laboratory mice without affecting locomotion.

Low-dose Drosera rotundifolia induces gene expression changes in 16HBE human bronchial epithelial cells.

Drosera rotundifolia has been traditionally used for the treatment of respiratory diseases in phytotherapy and homeopathy. The mechanisms of action recognized so far are linked to the known effects of specific components, such as flavonoids, but are not completely understood. In this study, the biological functions of D. rotundifolia were explored in vitro following the treatment of bronchial epithelial cells, which are the potential targets of the pharmacological effects of the herbal medicine. To do so, the whole plant ethanolic extract was 1000-fold diluted in water (D. rotundifolia 3×) and added to a 16HBE human cell line culture for 3 h or 6 h. The effects on gene expression of the treatments and corresponding controls were then investigated by RNA sequencing. The differentially expressed genes were validated through RT-qPCR, and the enriched biological functions involved in the effects of treatment were investigated. D. rotundifolia 3× did not impair cell viability and was shown to be a stimulant of cell functions by regulating the expression of dozens of genes after 3 h, and the effects were amplified after 6 h of treatment. The main differentially expressed genes encoded ligands of epithelial growth factor receptor, proteins involved in xenobiotic detoxification and cytokines, suggesting that D. rotundifolia 3× could stimulate self-repair systems, which are impaired in airway diseases. Furthermore, D. rotundifolia 3× acts on a complex and multifaceted set of genes and may potentially affect different layers of the bronchial mucosa.

Assays of homeopathic remedies in rodent behavioural and psychopathological models.

The first part of this paper reviews the effects of homeopathic remedies on several models of anxiety-like behaviours developed and described in rodents. The existing literature in this field comprises some fifteen exploratory studies, often published in non-indexed and non-peer-reviewed journals. Only a few results have been confirmed by multiple laboratories, and concern Ignatia, Gelsemium, Chamomilla (in homeopathic dilutions/potencies). Nevertheless, there are some interesting results pointing to the possible efficacy of other remedies, and confirming a statistically significant effect of high dilutions of neurotrophic molecules and antibodies. In the second part of this paper we report some recent results obtained in our laboratory, testing Aconitum, Nux vomica, Belladonna, Argentum nitricum, Tabacum (all 5CH potency) and Gelsemium (5, 7, 9 and 30CH potencies) on mice using ethological models of behaviour. The test was performed using coded drugs and controls in double blind (operations and calculations). After an initial screening that showed all the tested remedies (except for Belladonna) to have some effects on the behavioural parameters (light-dark test and open-field test), but with high experimental variability, we focused our study on Gelsemium, and carried out two complete series of experiments. The results showed that Gelsemium had several effects on the exploratory behaviour of mice, which in some models were highly statistically significant (p < 0.001), in all the dilutions/dynamizations used, but with complex differences according to the experimental conditions and test performed. Finally, some methodological issues of animal research in this field of homeopathy are discussed. The "Gelsemium model" - encompassing experimental studies in vitro and in vivo from different laboratories and with different methods, including significant effects of its major active principle gelsemine - may play a pivotal rule for investigations on other homeopathic remedies.

Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues.

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.

Arnica montana experimental studies: confounders and biases?

Arnica montana is a popular traditional remedy widely used in complementary and alternative medicine, in part for its wound-healing properties. The authors recently showed that this plant extract and several of its homeopathic dilutions are able to modify the expression of a series of genes involved in inflammation and connective tissue regeneration. Their studies opened a debate, including criticisms to the "errors" in the methods used and the "confounders and biases". Here the authors show that the criticisms raised on methodology and statistics are not consistent and cannot be considered pertinent. The present comment also updates and reviews information concerning the action of A. montana dilutions in human macrophage cells while summarizing the major experimental advances reported on this interesting medicinal plant.

Effects of Gelsemium sempervirens L. on pathway-focused gene expression profiling in neuronal cells.

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.

A dynamic network model of the similia principle.

The use of drugs in high dilutions and the principle of similarity (or "similia") are two basic tenets of homeopathy. However, the plausibility of both is a subject of debate. Although several models have been proposed to explain the similia principle, it can be best understood and appreciated in the framework of complexity science and dynamic systems theory. This work applies a five-node Boolean network to show how self-organization and adaptation are relevant to rationalizing this traditional medical principle. Simulating the trajectories and attractors of the network system in the energy state-space provides a rudimentary and qualitative illustration of how targeted external perturbations can have pathological effects, leading to permanent, self-sustaining alterations. Similarly, changes that conversely enable the system to find its way back to the original state can induce therapeutic effects, by causing specific shifts in attractors when suitable conditions are satisfied. Extrapolating these mechanisms to homeopathy, we can envisage how major changes in the evolution of homeodynamic systems (and, eventually, healing of the entire body) can be achieved through carefully selected remedies that reproduce the whole symptom pattern of the ill state.

Advances in homeopathy and immunology: a review of clinical research.

The present paper reviews the clinical research carried out over the past three decades to evaluate the effectiveness of homeopathy for the treatment of respiratory allergies, common upper respiratory tract infections, otorhinolaryngologic complaints, and rheumatic diseases. We include in the analysis both randomised and non-randomised trials, assigning them different weightings in the final balance of evidence, on the basis of semi-quantitative criteria. Overall, the literature concerning a total of 83 original studies suggests that homeopathy may have significant effects in some conditions, e.g. Galphimia glauca (low homeopathic dilutions/dynamizations) in allergic oculorhinitis, Anas barbariae (high homeopathic dilution/dynamization) in influenza-like syndromes, classical individualised homeopathy in otitis, in allergic complaints and in fibromyalgia, and a few low-potency homeopathic complexes in sinusitis, rhinoconjunctivitis, arthritis. The evidence for individualised homeopathic therapy in the field of upper respiratory tract infections and for homeopathic immunotherapy in respiratory allergies is more conflicting. Pragmatic equivalence trials suggest that, in primary care, homeopathic treatment is not inferior to conventional treatment. A larger number of observational studies and of clinical trials -- conducted in a methodologically correct manner without altering the treatment setting-- are needed before sure conclusions concerning the application of homeopathy for specific diseases can be drawn.

Hormesis and its relationship with homeopathy.

Homeopathy is an ancient and complex therapeutic method that is rediscovering its scientific foundations. Hormesis is a frequently observed phenomenon that has been rigorously reported with precise dose-response curves. The therapeutic method based on the principle of 'like cures like' should not be confused with hormesis, which has several different implications from those of homeopathy. Yet, because both these approaches to nature and medicine are very broad in scope, they do end up having some points of contact. Thus, the well-established and consolidated field of hormesis can help cast light, through its ideas and research methods, on the possible mechanisms of action of remedies in ultra-low doses.