The Nucleus

, Volume 57, Issue 1, pp 3–17 | Cite as

Current trends in high dilution research with particular reference to gene regulatory hypothesis

  • Anisur Rahman Khuda-BukhshEmail author
Review Article


In homeopathy, ultra-low doses of drugs at ultra-high dilutions are often used with great benefits to patients although at such dilutions physical existence of even a single molecule of the original drug substance is highly improbable. Despite serious challenges thrown by scientists and rationalists from time to time, homeopathy has managed to survive over 200 years now, and is no more considered a myth. Research activities on homeopathy in recent years, at clinical, physical, chemical, biological and medical levels with acceptable scientific norms and approach have paved the way for more rigorous research, particularly at the molecular level to understand the physico-chemical nature and mechanism of action of ultra-high dilutions. Although major breakthrough has been made in understanding many physical aspects and interactions between the “drug” and “aquatic ethanol” used as vehicle/solvent/diluents, certain aspects in regard to structure of water/aquatic ethanol and the latter’s changing structural organization still remain unclear. In recent years, the quest for understanding the mechanism of biological action of the ultra-high dilutions has made homeopathy a hot bed of research. Much progress has been made in understanding the molecular mechanism in the light of the “gene regulatory hypothesis” that can explain the action of the homeopathic high dilutions in all living organisms, both in higher and lower animals as well as in plants. The present review focuses mainly on research in support of the gene regulatory hypothesis, and mention has been made of some relevant physical and biological aspects at cellular and molecular levels.


Ultra-high dilution research Homeopathy Molecular mechanism of action Gene regulatory hypothesis 



The author is indebted to his research students and collaborators for their sincere work in this challenging field, and to the funding agencies, particularly to Boiron Laboratories, Lyon, France, and AYUSH, New Delhi, who sanctioned grant for the work.


  1. 1.
    Allegre CJ, Provost A, Jaupart C. Oscillatory zoning: a pathological case of crystal growth. Nature. 1989;294:223–8.Google Scholar
  2. 2.
    Anagnostatos GS. Small water clusters (clathrates) in the preparation process of homeopathy. In: Endler PC, Schulte J, editors. Ultra High Dilution: Physiology and Physics. Dordrecht: Kluwer Academic Publishers; 1994. p. 121–128.Google Scholar
  3. 3.
    Andersson PU, Tomsic A, Andersson MB, Petterson JBC. Emission of small fragments during water cluster collisions with graphite surface. Chem Phys Lett. 1997;279:100–6.Google Scholar
  4. 4.
    Anick DJ, Ives JA. The silica hypothesis for homeopathy: physical chemistry. Homeopathy. 2007;96:189–95.PubMedGoogle Scholar
  5. 5.
    Ball P. Water e an enduring mystery. Nature. 2008;452:291–2.PubMedGoogle Scholar
  6. 6.
    Banerjee P, Bhattacharyya SS, Pathak S, Naoual B, Belon P, Khuda-Bukhsh AR. Comparative efficacy of two microdoses of a potentized homeopathic drug, arsenicum album, to ameliorate toxicity induced by repeated sublethal injections of arsenic trioxide in mice. Pathobiology. 2008;75:156–70.PubMedGoogle Scholar
  7. 7.
    Banerjee P, Biswas SJ, Belon P, Khuda-Bukhsh AR. A potentized homeopathic drug, Arsenicum Album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice. J Vet Med A Physiol Pathol Clin Med. 2007;54:370–6.PubMedGoogle Scholar
  8. 8.
    Banerjee A, Chakrabarty SB, Karmakar SR, Chakrabarty A, Biswas SJ, Haque S, et al. Can homeopathy bring additional benefits to thalassemic patients on hydroxyurea therapy? Encouraging results of a preliminary study. Evid Based Complement Alternat Med. 2010;7:129–36. doi: 10.1093/ecam/nem161.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Banerjee A, Pathak S, Biswas SJ, Roy-Karmakar S, Boujedaini N, Belon P, et al. Chelidonium majus 30C and 200C in induced hepato-toxicity in rats. Homeopathy. 2010;99:167–76. doi: 10.1016/j.homp.2010.05.008.PubMedGoogle Scholar
  10. 10.
    Banik S, Khuda-Bukhsh AR. Alterations of cytogenetical and haematological effects by ultra-low doses of Ginseng in whole-body X-irradiated mice. Nucleus. 1996;49:28–35.Google Scholar
  11. 11.
    Banik S, Khuda-Bukhsh AR. Quantitative assessment of spermhead anomaly in X-irradiated mice and the alteration of frequency by the oral administration of a potentized homeopathic drug, Ginseng. Proc. Sym. “Zoological Research in Relation to Man and Environment”, Calcutta University, 1–4 March, 1992, In: Proc. Zool. Soc., Calcutta, 1992:45:243–248.Google Scholar
  12. 12.
    Bell IR, Schwartz GE. Adaptive network nanomedicine: an integrated model for homeopathic medicine. Front Biosci (Schol Ed). 2013;5:685–708.Google Scholar
  13. 13.
    Bellavite P, Conforti A, Pontarollo F, Ortolani R. Immunology and homeopathy. 2. Cells of the immune system and inflammation. Evid Based Complement Alternat Med. 2006;3:13–24.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Bellavite P, Magnani P, Marzotto M, Conforti A. Assays of homeopathic remedies in rodent behavioural and psychopathological models. Homeopathy. 2009;98:208–27.PubMedGoogle Scholar
  15. 15.
    Bellavite P, Marzotto M, Olioso D, Christofoleti M, Brizzi M, Tononi P, et al. Cellular and transcriptional responses of SH-SY5Y human neurocytes following in vitro exposure to Gelsemium sempervirens. Int J High Dilution Res. 2012;11:144–6.Google Scholar
  16. 16.
    Bellavite P, Marzotto M, Olioso D, Moratti E, Conforti A. High-dilution effects revisited. 1. Physicochemical aspects: review. Homeopathy. 2014;103:4–21.PubMedGoogle Scholar
  17. 17.
    Bellavite P, Marzotto M, Olioso D, Moratti E, Conforti A. High-dilution effects revisited. 2. Pharmacodynamic mechanisms: review. Homeopathy. 2014;103:22–43.PubMedGoogle Scholar
  18. 18.
    Bellavite P, Ortolani R, Conforti A. Immunology and homeopathy. 3. Experimental studies on animal models. Evid Based Complement Alternat Med. 2006;3:171–86.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Bellavite P, Ortolani R, Pontarollo F, Pitari G, Conforti A. Immunology and homeopathy. 5. The rationale of the ‘Simile’. Evid Based Complement Alternat Med. 2007;4:149–63.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Bellavite P, Signorini A. The emerging science of homeopathy. Berkeley: North Atlantic; 2002.Google Scholar
  21. 21.
    Belon P, Banerjee P, Choudhury SC, Banerjee A, Biswas SJ, Karmakar SR, et al. Can administration of potentized homeopathic remedy, Arsenicum album, alter antinuclear antibody (ANA) titer in people living in high-risk arsenic contaminated areas? I. A correlation with certain hematological parameters. Evid Based Complement Alternat Med. 2006;3:99–107.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Belon P, Banerjee A, Karmakar SR, Biswas SJ, Choudhury SC, Banerjee P, et al. Homeopathic remedy for arsenic toxicity?: evidence-based findings from a randomized placebo-controlled double blind human trial. Sci Total Environ. 2007;384:141–50.PubMedGoogle Scholar
  23. 23.
    Belon P, Cumps J, Ennis M, Mannaioni PF, Roberfroid M, Sainte-Laudy J, et al. Histamine dilutions modulate basophil activation. Inflamm Res. 2004;53:181–8.PubMedGoogle Scholar
  24. 24.
    Belon P, Cumps J, Ennis M, Mannaioni PF, Sainte-Laudy J, Roberfroid M, et al. Inhibition of human basophil degranulation by successive histamine dilutions: results of a European multi-centre trial. Inflamm Res. 1999;48(Supplement 1):S17–8.PubMedGoogle Scholar
  25. 25.
    Benveniste J, Guillonnet D. QED and digital biology. Riv Biol. 2004;97:169–72.PubMedGoogle Scholar
  26. 26.
    Bernardini S, Dei A. Hormesis may provide a central concept for homeopathy development. Toxicol Appl Pharmacol. 2006;211:84.PubMedGoogle Scholar
  27. 27.
    Betti L, Trebbi G, Olioso D, Marzotto M, Bellavite P. Basic research in homeopathy and ultra-high dilutions: what progress is being made? Homeopathy. 2013;102:151–4.PubMedGoogle Scholar
  28. 28.
    Bhattacharjee N, Banerjee P, Khuda-Bukhsh AR. Homeopathic drugs Natrum Sulphuricum and carcinosin prevent azo dye-induced hepatocarcinogenesis in mice. Indian J Biochem Biophys. 2009;46:307–18.PubMedGoogle Scholar
  29. 29.
    Bhattacharjee N, Khuda-Bukhsh AR. Two homeopathic remedies used intermittently provide additional protective effects against hepatotoxicity induced by carcinogens in mice. J Acupunct Meridian Stud. 2012;5:166–75. doi: 10.1016/j.jams.2012.05.004.PubMedGoogle Scholar
  30. 30.
    Bhattacharjee N, Pathak S, Khuda-Bukhsh AR. Amelioration of carcinogen induced toxicity in mice by administration of a potentized homeopathic drug, Natrum Sulphuricum 200. Evid Based Complement Alternat Med. 2009;6:65–75. doi: 10.1093/ecam/nem067.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Bhattacharyya SS, Das J, Das S, Samadder A, Das D, De A, 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;10:546–54.PubMedGoogle Scholar
  32. 32.
    Bhattacharyya SS, Mandal SK, Biswas R, Paul S, Pathak S, Boujedaini N, et al. In vitro studies demonstrate anticancer activity of an alkaloid of the plant Gelsemiumsempervirens. Exp Biol Med (Maywood). 2008;233:1591–601.Google Scholar
  33. 33.
    Bhattacharyya SS, Paul S, De A, Das D, Samadder A, Boujedai N, et al. Poly (lactide-co-glycolide) acid nanoencapsulation of a synthetic coumarin: cytotoxicity and bio-distribution in mice, in cancer cell line and interaction with calf thymus DNA as target. Toxicol Appl Pharmacol. 2011;253:270–81. doi: 10.1016/j.taap.2011.04.010.PubMedGoogle Scholar
  34. 34.
    Bhattacharyya SS, Paul S, Dutta S, Boujedani N, Khuda-Bukhsh AR. Anti-oncogenic potentials of a plant coumarin (7-hydroxy coumarin) against DMBA induced skin papilloma in mice: the possible role of several key signal proteins. J Chin Integr Med. 2010;8:645–54.Google Scholar
  35. 35.
    Bhattacharyya SS, Paul S, Khuda-Bukhsh AR. Encapsulated plant extract (Gelsemium semipervirens) poly (lactide-co-glycolide) nanoparticles enhance cellular uptake and increases bioactivity in vitro. Exp Biol Med (Maywood). 2010;235:678–88. doi: 10.1258/ebm.2010.009338.Google Scholar
  36. 36.
    Bishayee K, Chakraborty D, Ghosh S, Boujedaini N, Khuda-Bukhsh AR. Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: signalling cascade and drug-DNA interaction. Eur J Pharmacol. 2013;698:110–21.PubMedGoogle Scholar
  37. 37.
    Bishayee K, Ghosh S, Mukherjee A, Sadhukhan R, Mondal J, Khuda-Bukhsh AR. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction. Cell Prolif. 2013;46:153–63.PubMedGoogle Scholar
  38. 38.
    Bishayee K, Mukherjee A, Paul A, Khuda-Bukhsh AR. Homeopathic mother tincture of Conium initiates reactive oxygen species mediated DNA damage and makes HeLa cells prone to apoptosis. TANG Int J Genuine Tradit Med. 2012;2:e-26. doi: 10.5667/tang.2012.0018.Google Scholar
  39. 39.
    Bishayee K, Paul A, Ghosh S, Sikdar S, Mukherjee A, Biswas R, et al. Condurango-glycoside-A fraction of Gonolobus condurango induces DNA damage associated senescence and apoptosis via ROS-dependent p53 signalling pathway in HeLa cells. Mol Cell Biochem. 2013;382:173–83.PubMedGoogle Scholar
  40. 40.
    Bishayee K, Sikdar S, Khuda-Bukhsh AR. Ultra-highly diluted Gonolobus condurango extract inhibits histone De-Acetylase2 activity in cervix cancer cells in vitro: evidence of epigenetic modification in cell cycle arrest. J Pharmacopunct. 2013;16:7–13.Google Scholar
  41. 41.
    Biswas SJ, Bhattacharjee N, Khuda-Bukhsh AR. Efficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice. Food Chem Toxicol. 2008;46:1474–87.PubMedGoogle Scholar
  42. 42.
    Biswas SJ, Khuda-Bukhsh AR. Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice. BMC Complement Alternat Med. 2002;2:1–16.Google Scholar
  43. 43.
    Biswas SJ, Khuda-Bukhsh AR. Evaluation of protective potentials of a potentized homeopathic drug, Chelidoniummajus, during azo dye induced hepatocarcinogenesis in mice. Indian J Exp Biol. 2004;42:698–714.PubMedGoogle Scholar
  44. 44.
    Biswas R, Mandal SK, Dutta S, Bhattacharyya SS, Boujedani N, Khuda-Bukhsh AR. Thujone rich fraction of Thuja occidentalis demonstrates major anti-cancer potentials: evidences from in vitro studies on A375 cells. eCAM. 2011. doi: 10.1093/ecam/neq042.Google Scholar
  45. 45.
    Biswas SJ, Pathak S, Bhattacharjee N, Das JK, Khuda-Bukhsh AR. Efficacy of a potentized homeopathic drug, Carcinosin-200, fed alone and in combination with another drug, Chelidonium 200, in amelioration of p-DAB induced hepatocarcinogenesis in mice. J Altern Complement Med Mary Ann Liebert Pub. 2005;11:839–54.Google Scholar
  46. 46.
    Bonamin LV, Endler PC. Animal models for studying homeopathy and high dilutions: conceptual critical review. Homeopathy. 2010;99:37–50.PubMedGoogle Scholar
  47. 47.
    Calabrese EJ. Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem. 2008;27:1451–74.PubMedGoogle Scholar
  48. 48.
    Chakrabarti J, Biswas SJ, Khuda-Bukhsh AR. Cytogenetical effects of sonication in mice and their modulations by actinomycin D and a homeopathic dug., Arnica 30. Indian J Exp Biol. 2001;39:1235–42.PubMedGoogle Scholar
  49. 49.
    Chakraborty D, Ghosh S, Bishayee K, Mukherjee A, Sikdar S, Khuda-Bukhsh AR. Anti-hyperglycemic drug Gymnema sylvestre also shows anti-cancer potentials in human melanoma A375 cells via ROS generation and mitochondria-dependent caspase pathway. Integr Cancer Ther. 2013;12:433–41. doi: 10.1177/1534735413485419.PubMedGoogle Scholar
  50. 50.
    Chakraborty D, Sikdar S, Bishayee K, Mukherjee A, Khuda-Bukhsh AR. Combination of Helonias dioica extract and Metforminimproves insulin responsiveness by activating PI3K/AKT pathway signaling in obese hyperglycemic mice. Chinese Journal of Integrative Medicine, Springer, (In Press).Google Scholar
  51. 51.
    Chaplin MF. The memory of water: an overview. Homeopathy. 2007;96:143–50.PubMedGoogle Scholar
  52. 52.
    Chikramane PS, Kalita D, Suresh AK, Kane SG, Bellare JR. Why extreme dilutions reach non-zero asymptotes: a nanoparticulate hypothesis based on froth flotation. Langmuir. 2012;28:15864–75.PubMedGoogle Scholar
  53. 53.
    Chikramane PS, Suresh AK, Bellare JR, Kane SG. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Homeopathy. 2010;99:231–42.PubMedGoogle Scholar
  54. 54.
    Dantas F, Fisher P, Walach H, Wieland F, Rastogi DP, Teixeira H, et al. A systematic review of the quality of homeopathic pathogenetic trials published from 1945 to 1995. Homeopathy. 2007;96:4–16.PubMedGoogle Scholar
  55. 55.
    Das S, Das J, Paul A, Samadder A, Khuda-Bukhsh AR. Apigenin, a bioactive flavonoid from Lycopodium clavatum, stimulates nucleotide excision repair genes to protect skin keratinocytes from ultraviolet B-induced reactive oxygen species and DNA damage. J Acupunct Meridian Stud. 2013;6:252–62.PubMedGoogle Scholar
  56. 56.
    Das J, Das S, Samadder A, Bhadra K, Khuda-Bukhsh AR. Poly(lactide-co-glycolide) encapsulated extract of Phytolacca decandra demonstrates better intervention against induced lung adenocarcinoma in mice and on A549 cells. Eur J Pharm Sci. 2012;47:313–24. doi: 10.1016/j.ejps.2012.06.018.PubMedGoogle Scholar
  57. 57.
    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;101:325–36.PubMedGoogle Scholar
  58. 58.
    Das S, Das J, Samadder A, Boujedaini N, Khuda-Bukhsh AR. Apigenin induced apoptosis in A375 and A549 cells through selective action and dysfunction of mitochondria. Exp Biol Med (Maywood). 2012;237:1433–48.Google Scholar
  59. 59.
    Das S, Das J, Samadder A, Khuda-Bukhsh AR. Dihydroxy-isosteviol methyl ester from Pulsatilla nigricans induces apoptosis in HeLa cells: its cytoxicity and interaction with calf thymus DNA. Phytother Res. 2013;27:664–71. doi: 10.1002/ptr.4768.PubMedGoogle Scholar
  60. 60.
    Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR. Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: mitochondria mediated apoptotic signalling cascades. Food Chem Toxicol. 2013;62:670–80. doi: 10.1016/j.fct.2013.09.037.PubMedGoogle Scholar
  61. 61.
    Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR. Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro. Toxicol Lett. 2013;223:124–38.PubMedGoogle Scholar
  62. 62.
    Das D, De A, Dutta S, Biswas R, Boujedaini N, Khuda-Bukhsh AR. Potentized homeopathic drug Arsenicum Album 30C positively modulates protein biomarkers and gene expressions in Saccharomyces cerevisae exposed to arsenate. Zhong Xi Yi Jie He Xue Bao. 2011;9:752–60.PubMedGoogle Scholar
  63. 63.
    Das D, De A, Khuda-Bukhsh AR. A potentized homeopathic remedy, Arsenicum Album 6C can attenuate Sodium arsenite induced apoptosis in the budding yeast Saccharomyces cerevisiae. Proc. AICCG, Bodh Gaya, Nov. 21–23. 2011; 15:55–66.Google Scholar
  64. 64.
    Das S, Saha SK, De A, Das D, Khuda-Bukhsh AR. Potential of the homeopathic remedy, Arnica Montana 30C, to reduce DNA damage in Escherichia coli exposed to ultraviolet irradiation through up-regulation of nucleotide excision repair genes. Zhong Xi Yi Jie He Xue Bao. 2012;10:337–46.PubMedGoogle Scholar
  65. 65.
    Das J, Samadder A, Das S, Paul A, Boujedaini N, Khuda-Bukhsh AR. Potentized homeopathic drug, Phytolacca Decandra 15C, induces apoptosis in lung adenocarcinoma cells A549 through DNA damage and ROS generation. Chinese Journal of Integrated Medicine. (In Press).Google Scholar
  66. 66.
    Datta S, Biswas SJ, Khuda-Bukhsh AR. Comparative efficacy of pre-feeding, post-feeding and combined pre- and post-feeding of two microdoses of a potentized homeopathic drug, mercurius solubilis, in ameliorating genotoxic effects produced by mercuric chloride in mice. Evid Based Complement Alternat Med. 2004;1:291–300.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Datta S, Khuda-Bukhsh AR. Efficacy of a potentized homeopathic drug, Stannum 30, in modifying clastogenic effects of stannum chloride in mice. Perspect Cytol Genet. 1998;9:345–51.Google Scholar
  68. 68.
    Datta S, Mallick P, Khuda-Bukhsh AR. Efficacy of a potentized homeopathic drug (Arsenicum Album -30) in reducing genotoxic effects produced by arsenic trioxide in mice: comparative studies of pre-, post-, pre- and post-oral administration and comparative efficacy of two microdoses. Comp Ther Med. 1999;7:62–75.Google Scholar
  69. 69.
    Datta S, Mallick P, Khuda-Bukhsh AR. Comparative efficacy of two microdoses of a potentized homoeopathic drug, Cadmium Sulphoricum, in reducing genotoxic effects produced by cadmium chloride in mice: a time course study. BMC Complement Alternat Med. 2001;1:1–18.Google Scholar
  70. 70.
    Dayenas E, Beauvais F, Amara J, Oberbaum M, Robinzon B, Miadonna A, et al. Human basophil degranulation triggered by very dilute antiserum against IgE. Nature. 1988;333:816–8.Google Scholar
  71. 71.
    De A, Das D, Dutta S, Chakraborty D, Boujedaini N, Khuda-Bukhsh AR. Potentized homeopathic drug Arsenicum Album 30C inhibits intracellular reactive species generation and up-regulates expression of arsenic resistance gene in arsenic exposed bacteria Escherichia coli. Zhong Xi Yi Jie He Xue Bao. 2012;10:210–27.PubMedGoogle Scholar
  72. 72.
    Drost-Hansen W. The occurrence and extent of vicinal water. In: Franks F, Mathias S, editors. Biophysics of water. New York: Wiley; 1982. p. 163–8.Google Scholar
  73. 73.
    Drost-Hansen W. Temperature effects on cell-functioning e a critical role for vicinal water. Cell Mol Biol (Noisy-le-grand). 2001;47:865–83.Google Scholar
  74. 74.
    Druyan S, de Oliveira JE, Ashwell CM. Focused microarrays as a method to evaluate subtle changes in gene expression. Poult Sci. 2008;87:2418–29.PubMedGoogle Scholar
  75. 75.
    Elia V, Baiano S, Duro I, Napoli E, Niccoli M, Nonatelli L. Permanent physico-chemical properties of extremely diluted aqueous solutions of homeopathic medicines. Homeopathy. 2004;93:144–50.PubMedGoogle Scholar
  76. 76.
    Elia V, Marrari LA, Napoli E. Aqueous nanostructures in water induced by electromagnetic fields emitted by EDS. A conductometric study of fullerene and carbon nanotube EDS. J Therm Anal Calorim. 2012;107:843–51.Google Scholar
  77. 77.
    Elia V, Napoli E, Germano R. The “Memory of Water”: an almost deciphered enigma. Dissipative structures in extremely dilute aqueous solutions. Homeopathy. 2007;96:163–9.PubMedGoogle Scholar
  78. 78.
    Elia V, Napoli E, Niccoli M, Nonatelli L, Ramaglia A, Ventimiglia E. New physico-chemical properties of extremely diluted aqueous solutions. A calorimetric and conductivity study at 25 ° C. J Therm Anal Calorim. 2004;78:331–42.Google Scholar
  79. 79.
    Elia V, Niccoli M. Thermodynamics of extremely diluted aqueous solutions. Ann N Y Acad Sci. 1999;879:241–8.PubMedGoogle Scholar
  80. 80.
    Endler PC, Thieves K, Reich C, Matthiessen P, Bonamin L, Scherr C, et al. Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10(-23): a bibliometric study. Homeopathy. 2010;99:25–36.PubMedGoogle Scholar
  81. 81.
    Fuxreiter M, Mezei M, Simon I, Osmany R. Interfacial water as a ‘hydration fingerprint’ in the noncognate complex of BamHI. Biophys J. 2005;89:903–11.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Ghosh S, Bishayee K, Khuda-Bukhsh AR. Graveoline isolated from ethanolic extract of Ruta graveolens triggers apoptosis and autophagy in skin melanoma cells: a novel apoptosis-independent autophagic signaling pathway. Phytother Res. 2013. doi: 10.1002/ptr.5107.PubMedGoogle Scholar
  83. 83.
    Ghosh S, Bishayee K, Paul A, Mukherjee A, Sikdar S, Chakraborty D, et al. Homeopathic mother tincture of Phytolacca decandra induces apoptosis in skin melanoma cells by activating caspase mediated signaling via reactive oxygen species elevation. J Integr Med. 2013;11:116–24. doi: 10.3736/jintegrmed2013014.PubMedGoogle Scholar
  84. 84.
    Hahnemann CFS. In: Reves J, editor. Organon of medicine. 5 and 6th ed. Haifa: Homeopress Ltd; 1842. ed. 1994.Google Scholar
  85. 85.
    Kawakami AP, Sato C, Cardoso TN, Bonamin LV. Inflammatory process modulation by homeopathic Arnica montana 6CH: the role of individual variation. Evid Based Complement Alternat Med. 2011;2011:917541. doi: 10.1155/2011/917541.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Khesbak H, Savchuk O, Tsushima S, Fahmy K. The role of water H-bond imbalances in B-DNA substate transitions and peptide recognition revealed by time-resolved FTIR spectroscopy. J Am Chem Soc. 2011;133:5834–42.PubMedGoogle Scholar
  87. 87.
    Khuda-Bukhsh AR. Alteration of X-ray effects by homeopathic drugs: a new approach in radio-protection. In: Manna GK, Roy SC, editors. Perspectives in cytology and genetics, vol. 8. Calcutta: All India Congress of Cytology and Genetics; 1995. p. 649–63.Google Scholar
  88. 88.
    Khuda-Bukhsh AR. Potentized homeopathic drugs act through regulation of gene expression: a hypothesis to explain their mechanism and pathways of action in vivo. Comp Ther Med. 1997;5:43–6.Google Scholar
  89. 89.
    Khuda-Bukhsh AR. The efficacy of potentized homeopathic drug in combating arsenic poisioning: a suggestive scientific probe. Perspect Cytol Genet. 2001;10:231–9.Google Scholar
  90. 90.
    Khuda-Bukhsh AR. Towards understanding molecular mechanisms of action of homeopathic drugs: an overview. Mol Cell Biochem. 2003;253:339–45.PubMedGoogle Scholar
  91. 91.
    Khuda-Bukhsh AR. Laboratory research in homeopathy: pro. Integr Cancer Ther. 2006;5:320–32.PubMedGoogle Scholar
  92. 92.
    Khuda-Bukhsh AR. Mice as a model for homeopathy research. Homeopathy. 2009;98:267–79. doi: 10.1016/j.homp.2009.09.007.PubMedGoogle Scholar
  93. 93.
    Khuda-Bukhsh AR. Some homeopathic drugs as radio-protective agents in X-irradiated mice. In: Manna GK, Sinha U, editors. Persp. In Cytol. Genet, 1986; 5:407–12.Google Scholar
  94. 94.
    Khuda-Bukhsh AR, Banerjee A, Biswas SJ, Roy Karmakar S, Banerjee P, Pathak S, et al. An initial report on the efficacy of a millesmal potency Arsenicum Album LM 0/3 in ameliorating arsenic toxicity in humans living in a high risk arsenic village. Zhong Xi Yi Jie He Xue Bao. 2011;9:596–604.PubMedGoogle Scholar
  95. 95.
    Khuda-Bukhsh AR, Banik S. Assessment of cytogenetical damages in X-irradiated mice and their alterations by oral administrations of a potentized homeopathic drug, Ginseng 200. Berlin J Res Hom. 1991;1:254–63.Google Scholar
  96. 96.
    Khuda-Bukhsh AR, Bhattacharyya SS, Paul S, Boujedaini N. Polymeric nanoparticle encapsulation of a naturally occurring plant scopoletin and its effects on human melanoma cell A375. Zhong Xi Yi Jie He Xue Bao. 2010;8:853–62.PubMedGoogle Scholar
  97. 97.
    Khuda-Bukhsh AR, Bhattacharyya SS, Paul S, Dutta S, Boujedaini N, Belon P. Modulation of signal proteins: a plausible mechanism to explain how a potentized drug Secale Cor 30C diluted beyond Avogadro’s limit combats skin papilloma in mice. eCAM. 2011;2011:286320. doi: 10.1093/ecam/nep084.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Khuda-Bukhsh AR, De A, Das D, Dutta S, Boujedaini N. Analysis of the capability of ultra-highly diluted glucose to increase glucose uptake in arsenite-stressed bacteria Escherichia coli. Zhong Xi Yi Jie He Xue Bao. 2011;9:901–12.PubMedGoogle Scholar
  99. 99.
    Khuda-Bukhsh AR, Goswami S, Barat A, Sadhukhan G, Mukherjee A. X-ray induced chromosomal aberrations and their alterations by the oral administration of a homeopathic drug, Arnica Montanma, in mice. Proc. Sem on. the “Effects of Environmental Agents on Genetical Systems”, Calcutta University, 18–20 Oct., 1982, pp. 2–3.Google Scholar
  100. 100.
    Khuda-Bukhsh AR, Maity S. Alterations of cytogenetic effects by oral administration of a homeopathic drug, Ruta Graveolens, in mice exposed to sub-lethal X-irradiation. Berlin J Res Hom. 1990;1:264–74.Google Scholar
  101. 101.
    Khuda-Bukhsh AR, Pathak S. Homeopathic drug discovery: theory update and methodological aspect. Expert Opin Drug Dis. 2008;3:979–90.Google Scholar
  102. 102.
    Khuda-Bukhsh AR, Pathak S, Guha B, Karmakar SR, Das JK, Banerjee P, et al. Can homeopathic arsenic remedy combat arsenic poisoning in humans exposed to groundwater arsenic contamination?: a preliminary report on first human trial. Evid Based Complement Alternat Med. 2005;2:537–48.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Kitano H, Gemmei-Ide M. Structure of water in the vicinity of amphoteric polymers as revealed by vibrational spectroscopy. J Biomater Sci Polym Ed. 2010;21:1877–93.PubMedGoogle Scholar
  104. 104.
    Kolomytkin OV, Dunn S, Hart FX, Frilot C, Kolomytkin D, Marino AA. Glycoproteins bound to ion channels mediate detection of electric fields: a proposed mechanism and supporting evidence. Bioelectromagnetics. 2007;28:379–85.PubMedGoogle Scholar
  105. 105.
    Kundu SN, Mitra K, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing cytotoxic effects produced by of arsenic trioxide in mice. III. Tissue damage recovery, and enzymatic changes in liver. Comp Ther Med. 2000;8:76–81.Google Scholar
  106. 106.
    Kundu SN, Mitra K, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing cytotoxic effects produced by of arsenic trioxide in mice. IV. On certain pathological conditions, gel electrophoretic protein profiles, DNA and RNA. Comp Ther Med. 2000;8:157–65.Google Scholar
  107. 107.
    Lewin B. Genes VIII. New Jersy, USA: Pearson Prentice Hall, Pearson Education International; 2004.Google Scholar
  108. 108.
    Lo SY, Bonavida B. A book containing a dozen experiments using IE crystals. In: Lo SY, Bonavida B, editors. Proceedings of the First International Symposium on IE water clusters. Singapore: World Scientific; 1998. p. 81–90.Google Scholar
  109. 109.
    Luu C. Etude des Diluitions Homeopathiques par Spectroscopie Raman-Laser. Paris: Ed. Boiron; 1976.Google Scholar
  110. 110.
    Mallick P, Mallick JC, Guha B, Khuda-Bukhsh AR. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice. BMC Complement Alternat Med. 2003;22:3–7.Google Scholar
  111. 111.
    Mandal SK, Biswas R, Bhattacharyya SS, Paul S, Dutta S, Pathak S, et al. Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. Eur J Pharmacol. 2010;626:115–22.PubMedGoogle Scholar
  112. 112.
    Markovic N, Andersson PU, Nagard MB, Pettersson JBC. Scattering of water from graphite: simulations and experiments. Chem Phys. 1999;247:413.Google Scholar
  113. 113.
    Meyl K. DNA and cell resonance: magnetic waves enable cell communication. DNA Cell Biol. 2012;31:422–6.PubMedGoogle Scholar
  114. 114.
    Mitra K, Kundu SN, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing cytotoxic effects produced by of arsenic trioxide in mice. I. On rate of accumulation of arsenic in certain vital organs. Comp Ther Med. 1998;6:178–84.Google Scholar
  115. 115.
    Mitra K, Kundu SN, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing cytotoxic effects produced by of arsenic trioxide in mice.II. On alterations in body weight, tissue weight and total protein. Comp Ther Med. 1999;7:24–34.Google Scholar
  116. 116.
    Montagnier L, Aissa J, Del Giudice E, Lavallee C, Tedeschi A. DNA waves and water. J Phys Conf Ser. 2011;306:012007.Google Scholar
  117. 117.
    Montagnier L, Aissa J, Ferris S, Montagnier JL, Lavallee C. Electromagnetic signals are produced by aqueous nanostructures derived from bacterial DNA sequences. Interdiscip Sci Comput Life Sci. 2009;1:81–90.Google Scholar
  118. 118.
    Montagnier L, Aissa J, Lavallee C, Mbamy M, Varon J, Chenal H. Electromagnetic detection of HIV DNA in the blood of AIDS patients treated by antiretroviral therapy. Interdiscip Sci Comput Life Sci. 2009;1:245–53.Google Scholar
  119. 119.
    Mukherjee A, Boujedaini N, Khuda-Bukhsh AR. Homeopathic Thuja 30C ameliorates benzo(a)pyrene-induced DNA damage, stress and viability of perfused lung cells of mice in vitro. J Integr Med. 2013;11:397–404. doi: 10.3736/jintegrmed2013054.PubMedGoogle Scholar
  120. 120.
    Mukherjee A, Sikdar S, Bishayee K, Boujedaini N, Khuda-Bukhsh AR. Flavonol isolated from ethanolic leaf extract of Thuja occidentalis arrests the cell cycle at G2-M and induces ROS-independent apoptosis in A549 cells, targeting nuclear DNA. Cell Prolif. 2014;47:56–71. doi: 10.1111/cpr.12079.PubMedGoogle Scholar
  121. 121.
    Pathak S, Banerjee A, Khuda-Bukhsh AR. Efficacy of ethanolic spore extract of Lycopodium clavatum in reducing induced hepatotoxicity and genotoxicity in mice. Int J Biol Chem Sci. 2010;4:770–81.Google Scholar
  122. 122.
    Pathak S, Banerjee A, Paul S, Khuda-Bukhsh AR. Protective potentials of a plant extract (lycopodium clavatum) on mice chronically fed hepato-carcinogens. Indian J Exp Biol. 2009;47:602–7.PubMedGoogle Scholar
  123. 123.
    Pathak S, Bhattacharjee N, Das JK, Choudhury SC, Roy-Karmakar S, Banerjee P, et al. Supportive evidences for anti-cancerous potential of an alternative medicine in hepatocarcinogenesis of mice. Res Complement Med (Forsch Komplementarmed). 2007;14:148–56.Google Scholar
  124. 124.
    Pathak S, Das JK, Biswas SJ, Khuda-Bukhsh AR. Protective potentials of a potentized homeopathic drug, Lycopodium-30, in ameliorating azo dye induced hepatocarcinogenesis in mice. Mol Cell Biochem. 2006;285:121–31.PubMedGoogle Scholar
  125. 125.
    Paul S, Bhattacharyya SS, Boujedaini N, Khuda-Bukhsh AR. Anticancer potentials of root extract of polygala senega and its PLGA nanoparticles-encapsulated form. Evid Based Complement Alternat Med. 2011. doi: 10.1155/2011/517204.Google Scholar
  126. 126.
    Paul S, Bhattacharyya SS, Samaddar A, Boujedaini N, Khuda-Bukhsh AR. Further evidences of anti-cancer potentials of root extract of Polygala senega against benzo[a] pyrene induced lung cancer in mice. J Chin Integr Med. 2011;9:320–7.Google Scholar
  127. 127.
    Paul A, Bishayee K, Ghosh S, Mukherjee A, Sikdar S, Chakraborty D, et al. Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways. Zhong Xi Yi Jie He Xue Bao. 2012;10:1025–38.PubMedGoogle Scholar
  128. 128.
    Paul A, Das S, Das J, Samadder A, Bishayee K, Sadhukhan R, et al. Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anticancer effects on HeLa and PC3 cell lines: signalling pathway and drug-DNA interaction. J Integr Med. 2013;11:405–15.PubMedGoogle Scholar
  129. 129.
    Paul A, Das J, Das S, Samadder A, Khuda-Bukhsh AR. Anticancer potential of myricanone, a major bioactive component of Myrica cerifera: novel signaling cascade for accomplishing apoptosis. J Acupunct Meridian Stud. 2013;6:188–98.PubMedGoogle Scholar
  130. 130.
    Paul A, Das J, Das S, Samadder A, Khuda-Bukhsh AR. PLGA nano-encapsulation of chelidonine enhances the ameliorative potential against cadmium induced oxidative damage and hepatic injury in mice. Environ Toxicol Pharmacol. 2013;36:937–47.PubMedGoogle Scholar
  131. 131.
    Paul A, Das S, Das J, Samadder A, Khuda-Bukhsh AR. Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo. Toxicol Lett. 2013;222:10–22.PubMedGoogle Scholar
  132. 132.
    Poitevin B, Davenas E, Benveniste J. In vitro immunological degranulation of human basophils is modulated by lung histamine and Apis mellifica. Br J Clin Pharmacol. 1988;25:439–44.PubMedPubMedCentralGoogle Scholar
  133. 133.
    Preethi K, Ellanghiyil S, Kuttan G, Kuttan R. Induction of apoptosis of tumor cells by some potentiated homeopathic drugs: implications on mechanism of action. Integr Cancer Ther. 2012;11:172–82.PubMedGoogle Scholar
  134. 134.
    Rao ML, Roy R, Bell I. Characterization of the structure of ultra-dilute sols with remarkable biological properties. Mater Lett. 2008;62:1487.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Rey L. Thermoluminescence of ultra-high dilutions of lithium chloride and sodium chloride. Physica. 2003;323:67–74.Google Scholar
  136. 136.
    Rey L. Can low-temperature thermoluminescence cast light on the nature of ultra-high dilutions? Homeopathy. 2007;96:170–4.PubMedGoogle Scholar
  137. 137.
    Roy Karmakar S, Biswas SJ, Khuda-Bukhsh AR. Anti-carcinogenic potentials of a plant extract (Hydrastis canadensis): I. Evidence from in vivo studies in mice (Mus musculus). Asian Pac J Cancer Prev. 2010;11:545–51.Google Scholar
  138. 138.
    Saha SK, Das S, Khuda-Bukhsh AR. Phenotypic evidence of ultra-highly diluted homeopathic remedies to act at gene expression level: a novel probe on experimental phage infectivity in bacteria. Zhong Xi Yi Jie He Xue Bao. 2012;10:210–27.Google Scholar
  139. 139.
    Saha SK, Roy S, Khuda-Bukhsh AR. Evidence in support of gene regulatory hypothesis: gene expression profiling manifests homeopathy effect as more than placebo. Int J High Dilution Res. 2013;12:162–7.Google Scholar
  140. 140.
    Saha SK, Sikdar S, Mukherjee A, Bhadra K, Boujedaini N, Khuda-Bukhsh AR. Ethanolic extract of the Goldenseal, Hydrastis canadensis, has demonstrable chemopreventive effects on HeLa cells in vitro: drug-DNA interaction with calf thymus DNA as target. Environ Toxicol Pharmacol. 2013;36:202–14. doi: 10.1016/j.etap.2013.03.023.PubMedGoogle Scholar
  141. 141.
    Sainte-Laudy J, Boudjedaini N, Belon P. Differential effect of storage on molecular and ultra-molecular dilutions of histamine. Inflamm Res. 2009;58 Suppl 1:30–1.PubMedGoogle Scholar
  142. 142.
    Samadder A, Chakraborty D, De A, Bhattacharyya SS, Bhadra K, Khuda-Bukhsh AR. Possible signaling cascades involved in attenuation of alloxan-induced oxidative stress and hyperglycemia in mice by ethanolic extract of Syzygium jambolanum: drug-DNA interaction with calf thymus DNA as target. Eur J Pharm Sci. 2011;9(44):207–17. doi: 10.1016/j.ejps.2011.07.012.Google Scholar
  143. 143.
    Samadder A, Das J, Das S, Das D, De A, Bhadra K, et al. Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: its toxicity, drug-DNA interaction and signaling cascades. Zhong Xi Yi Jie He Xue Bao. 2012;10:1433–42.PubMedGoogle Scholar
  144. 144.
    Samadder A, Das J, Das S, De A, Saha SK, Bhattacharyya SS, et al. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: some novel findings. Toxicol Appl Pharmacol. 2013;15(267):57–73. doi: 10.1016/j.taap.2012.12.018.Google Scholar
  145. 145.
    Samadder A, Das J, Das S, Khuda-Bukhsh AR. Dihydroxy-isosteviol-methyl-ester, an active biological component of Pulsatilla nigricans, reduces arsenic induced cellular dysfunction in testis of male mice. Environ Toxicol Pharmacol. 2012;34:743–52. doi: 10.1016/j.etap.2012.09.013.PubMedGoogle Scholar
  146. 146.
    Samadder A, Das S, Das J, Khuda-Bukhsh AR. Relative efficacies of insulin and poly (lactic-co-glycolic) acid encapsulated nano-insulin in modulating certain significant biomarkers in arsenic intoxicated L6 cells. Colloids Surf B: Biointerfaces. 2013;109:10–9. doi: 10.1016/j.colsurfb.2013.03.028.PubMedGoogle Scholar
  147. 147.
    Samadder A, Das S, Das J, Paul A, Boujedaini N, Khuda-Bukhsh AR. The potentized homeopathic drug, Lycopodium clavatum (5C and 15C) has anti-cancer effect on hela cells in vitro. J Acupunct Meridian Stud. 2013;6:180–7.PubMedGoogle Scholar
  148. 148.
    Samadder A, Das S, Das J, Paul A, Khuda-Bukhsh AR. Ameliorative effects of Syzygium jambolanum extract and its poly(lactic-co-glycolic) acid nano-encapsulated form on arsenic induced hypoglycemic stress: a multiparametric evaluation. J Acupunct Meridian Stud. 2012;5:310–8.PubMedGoogle Scholar
  149. 149.
    Samal S, Geckeler KE. Unexpected solute aggregation in water on dilution. Chem Commun. 2001;21:2224–5.Google Scholar
  150. 150.
    Sikdar S, Khuda-Bukhsh AR. Post-cancer treatment of Condurango 30C, traditionally used in homeopathy, ameliorates tissue damage and stimulates reactive oxygen species in benzo[a]pyrene-induced lung cancer of rat. Humanitas Traditional Medicine (TANG), 2013, 3, e25.
  151. 151.
    Sikdar S, Mukherjee A, Bishayee K, Paul A, Saha S, Ghosh S, et al. Assessment of apoptotic and anticancer potentials of a potentized homeopathic drug, Condurango 30C, in Benzo[a]pyrene-induced lung cancer of rat: the signalling cascade. J Pharmacopunct. 2013;16:011–22.Google Scholar
  152. 152.
    Sikdar S, Mukherjee A, Ghosh S, Khuda-Bukhsh AR. Condurango glycoside-rich components stimulate DNA damage-induced cell cycle arrest and ROS-mediated caspase-3 dependent apoptosis through inhibition of cell-proliferation in lung cancer, in vitro and in vivo. Environ Toxicol Pharmacol. 2013;37:300–14.PubMedGoogle Scholar
  153. 153.
    Sikdar S, Saha SK, Khuda-Bukhsh AR. Relative apoptosis-inducing potential of homeopathic Condurango 6C and 30C in H460 lung cancer cells in vitro: the signaling cascade. Pharmacopuncture, 2014 February [In press].Google Scholar
  154. 154.
    Sukul NC, Sukul A. High dilution effects: physical and biochemical basis. Dordrecht: Kluwer; 2003.Google Scholar
  155. 155.
    Wiegant FA, Souren JEM, VanWijk R. Stimulation of survival capacity in heat shocked cells by subsequent exposure to minute amounts of chemical stressors; role of similarity in hsp-inducing effects. Hum Exp Toxicol. 1999;18:460–70.PubMedGoogle Scholar
  156. 156.
    Wisnieski ES, Folmer DE, Caselman AW Jr. Spectroscopic studies of clusters species. Final program 383, PHYS Fall 2000 Techincal program, 222nd ACS national meeting Chicago, ILL, Aug 2001, 26–30.Google Scholar
  157. 157.
    Witt CM, Bluth M, Albrecht H, Weisshuhn TE, Baumgartner S, Willich SN. The in vitro evidence for an effect of high homeopathic potencies : a systematic review of the literature. Complement Ther Med. 2007;15:128–38.PubMedGoogle Scholar
  158. 158.
    Wolf U, Wolf M, Heusser P, Thurneysen A, Baumgartner S. Homeopathic preparations of quartz, sulfur and copper sulfate assessed by UV-spectroscopy. Evid Based Complement Alternat Med. 2011;2011:692798.PubMedPubMedCentralGoogle Scholar

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© Archana Sharma Foundation of Calcutta 2014

Authors and Affiliations

  1. 1.Department of ZoologyUniversity of KalyaniKalyaniIndia

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