Courtesy : Oxford Journal

Although reports on the efficacy of homeopathic medicines inanimal models are limited, there are even fewer reports on thein vitro action of these dynamized preparations. In Amla Cancer Research Centre, Kerala , Ellanzhiyil Surendran Sunila, Ramadasan Kuttan, Korengath Chandran Preethi and Girija Kuttan have evaluatedthe cytotoxic activity of 30C and 200C potencies of ten dynamizedmedicines against Dalton's Lymphoma Ascites, Ehrlich's AscitesCarcinoma, lung fibroblast (L929) and Chinese Hamster Ovary(CHO) cell lines and compared activity with their mother tincturesduring short-term and long-term cell culture. The effect ofdynamized medicines to induce apoptosis was also evaluated andthey have studied how dynamized medicines affected genes expressedduring apoptosis. Mother tinctures as well as some dynamizedmedicines showed significant cytotoxicity to cells during shortand long-term incubation. Potentiated alcohol control did notproduce any cytotoxicity at concentrations studied. The dynamizedmedicines were found to inhibit CHO cell colony formation andthymidine uptake in L929 cells and those of Thuja, Hydrastisand Carcinosinum were found to induce apoptosis in DLA cells.Moreover, dynamized Carcinosinum was found to induce the expressionof p53 while dynamized Thuja produced characteristic ladderingpattern in agarose gel electrophoresis of DNA. These resultsindicate that dynamized medicines possess cytotoxic as wellas apoptosis-inducing properties.

Recently, limited investigations on the efficacy of dynamizedmedicines in animal models as well as clinical trials have reportedthat potentiated Lycopodium clavatum has protective action againstCCl₄-induced liver damage in rats (3) and that chelidonium 30Ccould ameliorate both p-dimethylaminoazobenzene and azodye-inducedhepatocarcinogenesis in mice (4,5). Anti-genotoxic effect ofdifferent dynamized medicines has also been reported (6,7):Arsenicum album was found to ameliorate arsenic-induced toxicityin mice as well as in clinical studies and could reduce theelevated antinuclear antibody titer and hematological toxicities(8,9). Homeopathic therapy for asymptomatic HIV carriers hasalso proven beneficial (10) and recently Rajendran (11) reportedhomeopathy as a supportive therapy in cancer. Pathak et al.(12) investigated Ruta 6 on regression of human glioma braincancer cell growth clinically and found that Ruta induces severetelomere erosion in MGRI brain cancer cells but has no effecton B-lymphoid cells and normal lymphocytes. Banerji and Banerji(13) reported that Ruta was effective for intracranial cysticercosis.

Very few investigations have explored the action of dynamizedmedicine in in vitro cell culture systems. Podophyllum has beenshown to inhibit adhesion of neutrophils to serum-coated microplates (14). Traumeen S, a homeopathic formulation used clinicallyto relieve trauma and inflammation has been shown to inhibitthe production of Interleukin-β, TNF- and Interleukin-8by human T cells and monocytes in culture (15). Many homeopathicdrugs at low potencies were found to potentiate oxidative metabolismin cultured cells (16).

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Although the healing potential of homeopathic drugs is widelyaccepted, the exact mechanism of action is still unclear. Inparagraphs 63–69 of Organon, Hahneman describes the mechanismof action through the ‘primary action’ of the medicine(dynamized or not) and the ‘secondary and curative reaction’of the organism: ‘Every agent that acts upon the vitality,every medicine, deranges more or less the vital force, and causesa certain alteration in the health of the individual for a longeror a shorter period. This is termed primary action. Althougha product of the medicinal and vital powers conjointly, it isprincipally due to the former power. To its action our vitalforce endeavors to oppose its own energy. This resistant actionis a property, is indeed an automatic action of our life-preservingpower, which goes by the name of secondary action or counteraction’.We have tried to explain the mechanism of action of the dynamizedpreparations taking into consideration the original propositionby Samuel Hahnemann and have approached this problem by investigatingthe action of dynamized drugs in various cultured cells in asystematic scientific manner.

Cytotoxic activity of a drug is often considered a first steptowards elucidating its possible use against cancer and allof the drugs selected are being used by homeopathic practionersagainst cancer. They have  found that in short-term cytotoxicity research,some of the dynamized preparations showed significant cytotoxicactions against cancer cell lines and at times the activitywas higher than that of the mother tinctures. For example, Coniumat 200C potency was more cytotoxic than its mother tinctureand that the cytotoxicity induced by Carcinosinum was higherat 200C than at 30C potency indicating that dynamization inducesthe cytotoxic potential of these medications. Results were morepronounced during MTT assay in which a longer period of incubationwas involved. Many dynamized preparations at potency of 200Cinhibited the growth of L929 cells. Clonogenic assay using CHOcells is a standard method to determine growth inhibitory activityof the drugs and we found that dynamized preparations of Thuja,Hydrastis, Carcinosinum and Podophyllum at 200C potency almostcompletely inhibited the CHO colony formation. As in other cases,Conium 200C was more active than 30C. We have confirmed thecytotoxic potential of dynamized preparations by thymidine uptake,for the marker of the inhibition DNA synthesis. As in the caseother experiments, DNA synthesis was significantly inhibitedby several dynamized preparations.

Cytotoxicity could be produced in cells either by necrosis orby apoptotic induction. Apoptosis, which is known as programmedcell death is highly regulated by events taking place withinthe cell and is highly relevant with respect to the destructionand removal of transformed cells from the body. The inductionof apoptosis could be an external agent and a cascade of reactionstaking place within the cell produces an ultimate cell death.Some of the events via occurring during apoptosis include morphologicalchanges in the cell, production of apoptotic bodies, damageto genetic material and finally induction of proteolytic enzymes,which produces cellular destruction. Apoptosis could be visualizedby morphology and DNA laddering. In the present study, dynamizedpreparations induced apoptosis as observed from their morphologyand DNA laddering. Moreover, dynamized preparation of Carcinosinumcould induce the p53, which is considered to be a proapoptoticprotein and involved in signal transduction pathway.

The mechanism of action of some of the homeopathic drugs hasbeen proposed. Potentiated preparation of Ruta possesses protectiveaction on normal B-lymphoid cells against H₂O₂-induced chromosomaldamage (13). Moreover, the telomere erosion was enhanced incancer cells by treatment with Ruta while normal cells showedno change. Thus, the telomeres that protect individual chromosomesof cancer cells are damaged by Ruta, which may be the mechanismof its therapeutic action in brain cancer (13).

The protective effect of Chelidonium against p-DAB-induced hepaticcancer may occur by the modulating effect of the drug on restorationof damage caused to several gene-regulated phenomena like enzymeactivities and chromosomal abnormalities. This gives insightinto the mechanism of action, which may be by means of interferingwith the process of carcinogenesis by actively modifying actionsof oncogenes or by activating tumor suppressor genes (5). Anothermechanism of actions of homeopathic drugs may occur throughimmune modification. Benveniste (17) has shown that human basophilsundergo degranulation not only at usual anti-IgE antibody dosesbut also at extremely high dilutions. Bastide (18)has shownthe therapeutic effect of high dilution of –β interferonand thymic hormones on cellular immunity and had good therapeuticeffect in immunodepressed patients. Similarly Bentwich et al.(19) revealed that small amounts of antigens are capable ofspecific antibody response. The role of immunity in the therapeuticefficacy of homeopathic medicines has also been reviewed (20).

There  results indicate that the dynamized preparation initiallyproduces a secondary action on cells that is in line with theoriginal proposition by Hahnemann on the mechanism of actionof medicines dynamized or not. However, limited knowledgein this area does not fully explain the mechanism of actionof all drugs . More scientific analysesare warranted to elucidate these interesting preparations ofultra dilutions.

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