Potentized homoeopathic drugs act through regulation of gene-expression: a hypothesis to explain their mechanism and pathways of action in vitro

doi:10.1016/S0965-2299(97)80090-8

Complementary Therapies in Medicine

Volume 5, Issue 1, March 1997, Pages 43-46

https://doi.org/10.1016/S0965-2299(97)80090-8 Get rights and content

Summary

A working hypothesis to explain the mechanism of action of potentized homoeopathic drugs in vivo has been proposed. The model is partly substantiated from our own research data on repair of chromosomal damages in X-irradiated or toxic chemical-treated mice by the oral administration of some potentized homoeopathic drugs, and partly from some of the unpublished and published works of other researchers in the field of homoeopathy. In this model, strong scientific arguments have been made to form the hypothesis that the potentized homoeopathic drugs act through regulation of gene-expression, presumably through hormone—hormone—protein complexes — the sensorgene-integrator gene-receptor gene-producer gene pathway of Britten and Davidson's model, or else through the regulator/mutator gene-operator gene-structural gene pathway of Jacob and Monod's model among some other independent mechanisms. Scientific details of some possible pathways, admittedly speculative for some steps, have also been provided to stimulate research in this direction to verify the correctness of the hypothesis.

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2017, Homeopathy
Citation Excerpt :
Since the nosode HIV 30c was diluted by a factor of 1060, the possibility of presence of even a single original drug molecule is extremely low, yet it showed its apparent ability to modulate the expression of well-known cancer bio-markers in a given time span, particularly noticeable in the cancer cells, though less so in the normal WRL-68 cells, while the succussed alcohol (“placebo”) without having any drug molecular imprints failed to do so in the initial control parameters tested. It seems that homeopathic potentized remedies may have the ability to trigger the “target”/“master gene(s)” and modulate precisely the action of some specific and relevant genes downstream in a “chain”, reaction, pushing them into either activation or inactivation, in a regulatory manner to restore their proper functional activities, as advocated by Khuda-Bukhsh34–40 and also supported recently by Paolo Bellavite and his colleagues.41,42 However, precise details of the mechanism by which this initial trigger is implemented needs further experimental elucidation.
To examine if HIV nosode in 30c dilution (HIV 30c) has therapeutic potential against lung cancer cells (A549) as compared to WRL-68 normal cells and to elucidate its possible molecular mechanism of action on DNA replication and apoptosis.
Effects of HIV 30c were thoroughly tested for its possible anticancer potential on A549 cells (lung cancer); WRL-68 normal liver cells served as control. Three doses, one at LD50 and two below LD-50, were used. Proliferation, migration and senescence assays were made and generation of reactive oxygen species (ROS) studied by routine techniques. The ability of HIV 30c to induce apoptosis in A549 cells and its possible signalling pathway were determined using immunoblots of relevant signal proteins and confocal microscopy, including studies on telomerase reverse transcriptase (TERT) and topoisomerase II (Top II) activities, intimately associated with cell division and DNA replication.
HIV 30c prevented cancer cell proliferation and migration, induced pre-mature senescence, enhanced pro-apoptotic signal proteins like p53, bax, cytochrome c, caspase-3 and inhibited anti-apoptotic signal proteins Bcl2, TERT and Top II, changed mitochondrial membrane potential and caused externalization of phosphatidyl serine. Thus, it induced apoptosis as also evidenced from increase in cells with distorted membrane morphology, nuclear condensation, DNA fragmentation, and ROS, typical of apoptosis in progress.
HIV 30c nosode has therapeutic potential for inducing cytotoxic effects on A549 cells as manifested by changes in nuclear condensation, DNA fragmentation, ROS generation and MMP, and for its inhibitory action on cell proliferation, cell migration, expression of telomerase reverse transcriptase and Top II genes, and increasing expression of pro-apoptotic genes.
A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase II activities as also by promoting apoptosis via intrinsic mitochondrial pathway
2016, Journal of Integrative Medicine
Homeopathic nosodes have seldom been scientifically validated for their anticancer effects. This study was conducted to examine if a recently developed hepatitis C nosode has demonstrable anticancer potential in cancer cells in vitro.
Anticancer effects of Hepatitis C 30C (Hep C 30), if any, were initially tested on three cancer cell lines, HepG2 (liver cancer), MCF-7 (breast cancer) and A549 (lung cancer) and one normal liver cell line WRL-68 cells and subsequently a more thorough study using further scientific protocols was undertaken on HepG2 cells (against WRL-68 cells as the normal control) as HepG2 cells showed better anticancer response than the other two. Three doses, one at 50% lethal dose (LD₅₀) and the other two below LD₅₀, were used on HepG2 cells subsequently. Protocols like apoptosis induction and its possible signaling mechanism were deployed using immunoblots of relevant signal proteins and confocal microscopy, with particular reference to telomerase and topoisomerase II (Top II) activities, two strong cancer biomarkers for their direct relationship with divisional activities of cells and DNAs.
Hep C 30 induced apoptosis, caused distorted cell morphology typical of apoptotic cells, increased reactive oxygen species generation and produced increased DNA nicks. Further it enhanced pro-apototic signal proteins like Bax, cytochrome c and inhibited anti-apoptotic signal proteins, Bcl-2, cytochrome c and caspase-3, changed mitochondrial membrane potential and caused externalization of phosphatidylserine. The drug also decreased expression of two cancer biomarkers, Top II and telomerase, consistent with its anticancer effect.
Hep C 30 has demonstrable anticancer effects against liver cancer cells in vitro.
Ultra-highly diluted plant extracts of Hydrastis canadensis and Marsdenia condurango induce epigenetic modifications and alter gene expression profiles in HeLa cells in vitro
2015, Journal of Integrative Medicine
Methylation-specific epigenetic process and gene expression profiles of HeLa cells treated with ultra-high dilutions (HDs) of two plant extracts, Hydrastis canadensis (HC-30) and Marsdenia condurango (Condu-30), diluted 10⁶⁰ times, were analyzed against placebo 30C (Pl-30) for alterations in gene profiles linked to epigenetic modifications.
Separate groups of cells were subjected to treatment of Condu-30, HC-30, and Pl-30 prepared by serial dilutions and succussions. Global microarray data recorded on Affymetrix platform, using 25-mer probes were provided by iLifeDiscoveries, India. Slides were scanned with 3000 7G microarray scanner and raw data sets were extracted from Cel (raw intensity) files. Analyses of global microarray data profile, differential gene expression, fold change and clusters were made using GeneSpring GX12.5 software and standard normalization procedure. Before microarray study, concentration of RNA (ng/µL), RIN value and rRNA ratio for all the samples were analysed by Agilant Bioanalyzer 2100. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RT-PCR were done for analyzing SMAD-4 expression. Fluorescence-activated cell sorting study was further made to elucidate fate of cells at divisional stages. Methylation-specific restriction enzyme assay was conducted for ascertaining methylation status of DNA at specific sites.
HDs of HC-30 and Condu-30 differentially altered methylation in specific regions of DNA and expression profiles of certain genes linked to carcinogenesis, as compared to Pl-30. Two separate cut sites were found in genomic DNA of untreated and placebo-treated HeLa cells when digested with McrBC, compared to a single cut observed in Condu-30-treated genomic DNA. SMAD-4 gene expression validated the expression pattern observed in microarray profile. Methylation-specific restriction enzyme assay elucidated differential epigenetic modifications in drug-treated and control cells.
HDs triggered epigenetic modifications and alterations in microarray gene expression profiles of many genes associated with carcinogenesis in HeLa cells in vitro.
Hormetic effects of extremely diluted solutions on gene expression
2015, Homeopathy
Citation Excerpt :
Some studies have been carried out using the microarray technique with the aim of supporting the claim that ultra-high diluted homeopathic remedies induce biological effects which thus affect the gene expression profiles. This hypothesis of Khuda-Bukhsh33,34 has been confuted by some studies of Thangapazham, Jonas et al.35,36 However this hypothesis seems to be consistent with the findings of several studies. Unfortunately these investigations used a single dilution of the homeopathic preparation and it is not possible to demonstrate the existence of hormetic effects.
This paper summarizes the results of investigations showing how molecular biological tools, such as DNA-microarrays, can provide useful suggestions about the behaviour of human organisms treated with microamounts of drugs or homeopathic medicines. The results reviewed here suggest firstly that the action of drugs is not quenched by ultra-high dilution and proceeds through modulation of gene expressions. The efficacy of drug solutions seems to be maintained in ultra-highly diluted preparations, a fact which constitutes a challenge to the dogma of quantization of matter.
The second and more important result is that the different gene expression profiles of cell systems treated with the same drugs at different dilutions suggest the existence of hormetic mechanisms. The gene expression profiles of cells treated with copper(II) sulfate, Gelsemium sempervirens and Apis mellifica, are characterized by the same common denominator of the concentration-dependent inversion of gene expression, which can justify at a molecular level the concept of simile adopted in homeopathy.
The main conclusion we draw from these results is that these procedures provide new kinds of information and a tool for disclosing the mechanisms involved in hormetic effects. The application of these effects to modern medicine may allow researchers to conceive unprecedented therapeutic applications or to optimize the currently used ones in the framework of a low-dose pharmacology based on a reliable experimental platform.
Modulation of inflammation response to murine cutaneous Leishmaniosis by homeopathic medicines: Thymulin 5cH
2014, Homeopathy
Citation Excerpt :
More than this, a re-arrangement of gene expression is expected in immune cells stimulated by thymulin 5cH, determining an organized epigenetic regulation involving the immune system and the parasite communication. This kind of epigenetic regulation by homeopathic medicines has been observed in recent studies in vitro and in plant models.51–56 Taken as a whole the data show that thymulin 5cH treatment is able to change the dynamic of local and systemic immune reaction of mice to Leishmania (L.) amazonensis, giving rise to modified organization of both, chronic local inflammation and systemic immune cells balance.
In previous studies, we observed that thymulin 5cH could modulate BCG (Bacillus Calmette-Guerin) induced chronic inflammation by increasing peritoneal B1 stem cells differentiation into phagocytes and improving phagocytosis efficiency.
We used the same protocol to study the effects of thymulin 5cH in the experimental murine Leishmaniasis, in order to elucidate some aspects of the parasite–host relation under this homeopathic treatment. Male Balb/c mice were orally treated with thymulin 5cH or vehicle during 60 days, after the subcutaneous inoculation of 2 × 10⁶ units of Leishmania (L.) amazonensis into the footpad. Washied inflammatory cell suspension from peritoneal cavity, spleen, local lymph node and infected subcutaneous tissue were harvested after 2 and 60 days from infection to quantify the inflammation cells by flow cytometry and histometry methods.
After a transitory increase of peritoneal T reg cells, treated mice presented, chronically, increase in the peritoneal and spleen B1 cells percentage (p = 0.0001) in relation to other cell types; more organized and exuberant inflammation response in the infection site, and decrease in the number of parasites per field inside the primary lesion (p = 0.05). No difference was seen in local lymph node histology.
Thymulin 5cH is able to improve B1 cell activation and Leishmania (L) amazonensis phagocytosis efficiency in mice, similarly to that observed previously in BCG experimental infection.
Two Homeopathic Remedies Used Intermittently Provide Additional Protective Effects Against Hepatotoxicity Induced by Carcinogens in Mice
2012, JAMS Journal of Acupuncture and Meridian Studies
The purpose of the study was to evaluate whether potentized cholesterinum (Chol) intermittently used with another homeopathic remedy, Natrum Sulphuricum (Nat Sulph) can provide additional benefits in combating hepatotoxicity generated by chronic feeding of carcinogens, p-dimethylaminoazobenzene (p-DAB), and phenobarbital (PB). Mice were categorized into subgroups: normal untreated (Gr-1); normal + alcohol “vehicle” (Alc) (Gr-2), 0.06% p-DAB +0.05% PB (Gr-3), p-DAB+PB+Alc (Gr-4), p-DAB+PB+Nat Sulph-30 (Gr-5), p-DAB+PB+Chol-200 (Gr-6), p-DAB+PB+Nat Sulph-30+Chol-200 (Gr-7), p-DAB+PB+Nat Sulph-200 (Gr-8), and DAB+PB+Nat Sulph-200+Chol-200 (Gr-9). Hepatotoxicity was assessed through biomarkers like aspartate and alanine aminotransferases (AST and ALT), acid and alkaline phosphatases (AcP and AlkP), reduced glutathione content (GSH), glucose 6-phosphate dehydrogenase (G6PD), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), and analysis of lipid peroxidation (LPO) at 30, 60, 90, and 120 days and antioxidant biomarkers like superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) were assayed. Electron microscopic studies (scanning and transmission) and gelatin zymography for matrix metalloproteinases were conducted in liver. The feeding of the homeopathic drugs showed intervention in regard to the increased activities of AST, ALT, AcP, AlkP, GGT, LDH, and LPO and decreased activities of G6PD, SOD, CAT, GR, and GSH noted in the intoxicated mice, more appreciable in Groups 7 and 9. Thus, combined therapy provided additional antihepatotoxic and anticancer effects.

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: This hypothesis was presented by the author in the Invited Symposium section of the VIIIth All India Congress of Cytology and Genetics held at the University of Berhampore, Orissa, 15–18 October 1993.

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Potentized homoeopathic drugs act through regulation of gene-expression: a hypothesis to explain their mechanism and pathways of action in vitro

Summary

Br Hom J

Br Hom J

Br Hom J

Br Hom J

Br Hom J

Research in homeopathy — a bibliography compiled and annotated by Dr. P. Fisher

Microdose paradox — a new concept

J Am Inst Hom

Physikalische Wirkungen hochverdunnter potenzierter Substanzen

Die Naturwissenchaften

Modern instrumentation for the evaluation of homeopathic drug structure

J Am Inst Hom

Nuclear magnetic resonance studies of succussed solutions — a preliminary report

J Am Hom Assoc

Dielectric strength testing of homeopathic dilutions of HgC12

J Am Inst Hom

Etude des dilutions homeopathiques par effect Raman-Laser

Ann Hom Franc

Etude de l'action de chaleurs sur les dilutions Hahnemanniennes par spectrometrie Raman

Ann Hom Franc

Physics Teacher

A working hypothesis for homeopathic microdiluted remedies

Berlin J Res Hom

Physico-chemico study of homoeopathic solutions

Coherent dynamics in water

A thermodynamic model of the organism conducive to homeopathy and a hypothesis on the wavelike behaviour of the homeopathic remedy

Increase in serotonin and dopamine metabolites in mouse hypothalamus following oral administration of Agaricus muscarius 12, a homeopathic drug

Sci Culture

Influence of dopamine agonists and an opiate antagonist induced catalepsy as tested by a new method

Arch Int Pharmacodyn Ther

Influence of homoeopathic drugs on neurotransmitter systems

Sci Culture