Biological Actions, Electrical Conductance and Silicon-Containing Microparticles of Arsenicum Album Prepared in Plastic and Glass VialsFunding We thank the Brazilian Association of Homeopathic Pharmacists (Associação Brasileira de Farmacêuticos Homeopatas—ABFH) for funding the study and CAPES-PROSUP (number 1678566) for the PhD grant.
20 June 2017
06 August 2018
05 October 2018 (eFirst)
Introduction According to the “silica hypothesis” formulated to explain homeopathy, the information of starting materials would be transferred to cells by silica nanoparticles detached from the glassware walls by serial dilution and agitation through epitaxy. We compared the biological activity, electrical current and silicon microparticle content (by means of scanning electron microscopy/energy-dispersive X-ray spectroscopy) of high dilutions (HDs) of arsenic prepared in plastic and glass vials to investigate the role of silica in their biological effects in vitro.
Materials and Methods Co-cultures of macrophages and yeast (Saccharomyces cerevisiae) were treated with different HDs of arsenic prepared in plastic and glass vials. Macrophage morphology, phagocytosis index, nitric oxide (NO), and cytokine production were evaluated.
Results Measurable amounts of silicon microparticles were detected only in the HDs prepared in glass vials, but ultra-centrifugation eliminated them. Specific and non-specific results were observed. Non-specific pro-inflammatory effects were seen in all dilutions prepared in plastic vials, including elevation of pro-inflammatory cytokines, NO and macrophage phagocytic index. Only the 200th centesimal dilution of arsenic produced specific decrease in interleukin-6 production in macrophages, and it was independent of the vial type or the presence of microparticles of silica in the medicine samples. The nature of the vials had an impact on the electric flow in the respective fluids.
Conclusion The non-specific, pro-inflammatory effects might be attributed to organic residuals detached from the vials' plastic walls during manipulation. Instead, specific silica-independent effects of the homeopathic medicine can be attributed to the decrease of interleukin-6 after treatment with the 200th centesimal dilution of arsenic.
• Arsenicum album 200 cH decreases specifically IL-6 expression in macrophages in vitro.
• Silicon content in microparticles found in Arsenicum album has no relation to specific biological effects.
• Remedies prepared in plastic vials presented non-specific pro-inflammatory action.
• Decrease in IL-6 was independent of the material of the vials and/or of the silica microparticle content.
• The nature of the vials seems to influence the electric flow in the respective fluids.
- 1 Chikramane PS, Suresh AK, Bellare JR, Kane SG. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Homeopathy 2010; 99: 231-242
- 2 Rajendran ES. Homeopathy a material science! nanoparticle characterization of Aurum metallicum 6C, 30C, 200C, 1000C, 10000C, 50000C and 100000C. Int J Curr Res 2017; 9: 48923-48927
- 3 Bhattacharyya SS, Mandal SK, Biswas R. , et al. In vitro studies demonstrate anticancer activity of an alkaloid of the plant Gelsemium sempervirens. Exp Biol Med (Maywood) 2008; 233: 1591-1601
- 4 Ives JA, Moffett JR, Arun P. , et al. Enzyme stabilization by glass-derived silicates in glass-exposed aqueous solutions. Homeopathy 2010; 99: 15-24
- 5 Demangeat JL. NMR relaxation evidence for solute-induced nanosized superstructures in ultramolecular aqueous dilutions of silica-lactose. J Mol Liq 2010; 155: 71-79
- 6 Upadyhay RP, Nayak C. Homeopathy emerging as nanomedicine. Int J High Dilution Res. 2011; 10: 299-310
- 7 Perry CC, Tucker TK. Crystalline silica prepared at room temperature from aqueous solution in the presence of intrasilica bioextracts. Chem Commun (Camb) 1998; 23: 2587-2588
- 8 Perry CC, Tucker TK. Model studies of colloidal silica precipitation using biosilica extracts from Equisetum telmateia . Colloid Polym Sci 2003; 281: 652-664
- 9 Khripin CY, Pristinski D, Dunphy DR, Brinker CJ, Kaehr B. Protein-directed assembly of arbitrary three-dimensional nanoporous silica architectures. ACS Nano 2011; 5: 1401-1409
- 10 Wang DC, Chen GY, Chen KY, Tsai CH. DNA as a template in self-assembly of Au nano-structure. IET Nanobiotechnol 2011; 5: 132-135
- 11 Baca HK, Carnes EC, Ashley CE. , et al. Cell-directed-assembly: directing the formation of nano/bio interfaces and architectures with living cells. Biochim Biophys Acta 2011; 1810: 259-267
- 12 Neville F, Broderick MJ, Gibson T, Millner PA. Fabrication and activity of silicate nanoparticles and nanosilicate-entrapped enzymes using polyethyleneimine as a biomimetic polymer. Langmuir 2011; 27: 279-285
- 13 Bhattacharyya SS, Das J, Das S. , et al. Rapid green synthesis of silver nanoparticles from silver nitrate by a homeopathic mother tincture Phytolacca Decandra. Zhong Xi Yi Jie He Xue Bao 2012; 10: 546-554
- 14 Anick DJ, Ives JA. The silica hypothesis for homeopathy: physical chemistry. Homeopathy 2007; 96: 189-195
- 15 Hornung V, Bauernfeind F, Halle A. , et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 2008; 9: 847-856
- 16 Xynos ID, Edgar AJ, Buttery LDK, Hench LL, Polak JM. Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem Biophys Res Commun 2000; 276: 461-465
- 17 Holandino C, Oliveira AP, Homsani F. , et al. Structural and thermal analyses of zinc and lactose in homeopathic triturated systems. Homeopathy 2017; 106: 160-170
- 18 Caron V, Willart JF, Lefort R, Derollez P, Danède F, Descamps M. Solid state amorphization kinetic of alpha lactose upon mechanical milling. Carbohydr Res 2011; 346: 2622-2628
- 19 Das S, Das J, Samadder A, Bhattacharyya SS, Das D, Khuda-Bukhsh AR. Biosynthesized silver nanoparticles by ethanolic extracts of Phytolacca decandra, Gelsemium sempervirens, Hydrastis canadensis and Thuja occidentalis induce differential cytotoxicity through G2/M arrest in A375 cells. Colloids Surf B Biointerfaces 2013; 101: 325-336
- 20 Paul BK, Kar S, Bandyopadhyay P. , et al. Significant enhancement of dielectric and conducting properties of electroactive polymer polyvinylidene fluoride films: an innovative use of Ferrum metallicum at different concentrations. Indian J Res 2016; 10: 52-58
- 21 Verdel N, Jerman I, Krasovec R, Bukovec P, Zupancic M. Possible time-dependent effect of ions and hydrophilic surfaces on the electrical conductivity of aqueous solutions. Int J Mol Sci 2012; 13: 4048-4068
- 22 Boiron J, Cier A, VIngert C. Effets de quelques facteurs physiques sur l'activité pharmacologique de dilutions infinitésimales. Ann Homeopath Fr 1968; 10: 187-196
- 23 Witt CM, Lüdtke R, Weisshuhn TE, Quint P, Willich SN. The role of trace elements in homeopathic preparations and the influence of container material, storage duration, and potentisation. Forsch Komplement Med 2006; 13: 15-21
- 24 Ive EC, Couchman IM, Reddy L. Therapeutic effect of Arsenicum album on leukocytes. Int J Mol Sci 2012; 13: 3979-3987
- 25 de Santana FR, Dalboni LC, Nascimento KF. , et al. High dilutions of antimony modulate cytokines production and macrophage - Leishmania (L.) amazonensis interaction in vitro. Cytokine 2017; 92: 33-47
- 26 Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013; 496: 445-455
- 27 Marzotto M, Bonafini C, Olioso D. , et al. Arnica montana stimulates extracellular matrix gene expression in a macrophage cell line differentiated to wound-healing phenotype. PLoS One 2016; 11: e0166340
- 28 Brazilian Homeopathic Pharmacopoeia. 3rd ed, Brazil: Ministerio da Saúde 2011, pp 34. Available at: http://portal.anvisa.gov.br/documents/33832/259147/Farmacopeia+HOMEOPATICA+3a+EDICAO+INGLES+com+alerta.pdf/49a48a50-0d3e-4ab9-bc41-eb361c8afbb1
- 29 Verdel N, Jerman I, Krasovec R, Bukovec P, Zupancic M. Possible time-dependent effect of ions and hydrophilic surfaces on the electrical conductivity of aqueous solutions. Int J Mol Sci 2012; 13: 4048-4068
- 30 Bach C, Dauchy X, Severin I, Munoz JF, Etienne S, Chagnon MC. Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: chemical analysis and potential toxicity. Food Chem 2013; 139: 672-680
- 31 Grotenhuis N, De Witte SF, van Osch GJ, Bayon Y, Lange JF, Bastiaansen-Jenniskens YM. Biomaterials influence macrophage-mesenchymal stem cell interaction in vitro. Tissue Eng Part A 2016; 22: 1098-1107
- 32 Grotenhuis N, Vd Toom HFE, Kops N. , et al. In vitro model to study the biomaterial-dependent reaction of macrophages in an inflammatory environment. Br J Surg 2014; 101: 983-992
- 33 Bell IR, Muralidharan S, Schwartz GE. Nanoparticle characterization of traditional homeopathically - manufactured Gelsemium sempervirens medicines and placebo controls. J Nanomedicine Biotherapeutic Discov 2015; 5: 1-13
- 34 Demangeat JL. Gas nanobubbles and aqueous nanostructures: the crucial role of dynamization. Homeopathy 2015; 104: 101-115
- 35 Jäger T, Scherr C, Wolf U, Simon M, Heusser P, Baumgartner S. Investigation of arsenic-stressed yeast (Saccharomyces cerevisiae) as a bioassay in homeopathic basic research. Sci World J 2011; 11: 568-583
- 36 Olioso D, Marzotto M, Bonafini C, Brizzi M, Bellavite P. Arnica montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR. Homeopathy 2016; 105: 131-147
- 37 Mondal J, Das J, Shah R, Khuda-Bukhsh AR. 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. J Integr Med 2016; 14: 209-218
- 38 Mukherjee S, Ray M, Dutta MK, Acharya A, Mukhopadhyay SK, Ray S. Morphological alteration, lysosomal membrane fragility and apoptosis of the cells of Indian freshwater sponge exposed to washing soda (sodium carbonate). Ecotoxicol Environ Saf 2015; 122: 331-342
- 39 Köpf-Maier P. The phosphorus content of lysosomes in hepatocytes and Kupffer cells. A study using electron-spectroscopic imaging. Acta Anat (Basel) 1990; 139: 164-172
- 40 Kao JK, Wang SC, Ho LW. , et al. Chronic iron overload results in impaired bacterial killing of THP-1 derived macrophage through the inhibition of lysosomal acidification. PLoS One 2016; 11: e0156713
- 41 Temgire MK, Suresh AK, Kane SG, Bellare JR. Establishing the interfacial nano-structure and elemental composition of homeopathic medicines based on inorganic salts: a scientific approach. Homeopathy 2016; 105: 160-172
- 42 Chikramane PS, Suresh AK, Kane SG, Bellare JR. Metal nanoparticle induced hormetic activation: a novel mechanism of homeopathic medicines. Homeopathy 2017; 106: 135-144
- 43 Ullman D. Let's have a serious discussion of nanopharmacology and homeopathy. FASEB J 2006; 20: 2661 , author reply 2662
- 44 Cartwright SJ. Solvatochromic dyes detect the presence of homeopathic potencies. Homeopathy 2016; 105: 55-65
- 45 Cartwright SJ. Interaction of homeopathic potencies with the water soluble solvatochromic dye bis-dimethylaminofuchsone. Part 1: pH studies. Homeopathy 2017; 106: 37-46
- 46 Cartwright SJ. Degree of response to homeopathic potencies correlates with dipole moment size in molecular detectors: implications for understanding the fundamental nature of serially diluted and succussed solutions. Homeopathy 2018; 107: 19-31
- 47 Ynnon T. Very dilute aqueous solutions – structural and electromagnetic phenomena. Water 2017; 9: 28-66
- 48 Klein SD, Würtenberger S, Wolf U, Baumgartner S, Tournier A. Physicochemical investigations of homeopathic preparations: a systematic review and bibliometric analysis-Part 1. J Altern Complement Med 2018; 24: 409-421
- 49 Pollack GH. The Fourth Phase of Water – Beyond Solid, Liquid, and Vapor. Seattle: Ebner & Sons Publishers; 2013: 357
- 50 Bellavite P, Signorini A. The Emerging Science of Homeopathy. Complexity, Biodynamics and Nanopharmacology, 1st ed. Berkeley, CA: North Atlantic Books; 2002: 409
- 51 Guedes JRP, Bonamin LV, Capelozzi VL. Water-related mechanisms proposed for storing and transmitting homeopathic information: putative links with biological responses. Homeopathy 2018; 107: 172-180