Subscribe to RSS
Exploring the effects of homeopathic Apis mellifica preparations on human gene expression profiles
Received24 July 2013
revised16 January 2014
accepted20 January 2014
18 December 2017 (online)
Background: Diluted preparations obtained from Apis mellifica are reported in the homeopathic literature to have anti-inflammatory activity. The present study was designed to explore the effects on global gene expression profiles of human cells by means of microarrays, using Apis mellifica mother tincture (TM) and its 3C, 5C, 7C dynamized dilutions; the technique employed allowed us to study the changes in gene expression at concentrations much lower than those associated with pharmacological responses.
Methods: An RWPE-1 cell line (human immortalized prostate epithelial cells) was used to study the effects on global gene expression by transcriptomic analysis.
Results: Apis mellifica TM and its 3C, 5C, 7C dynamized dilutions modulated hundreds of genes; using cluster analysis we observed groups of genes up- or down-regulated with similar expression profiles among treatments; other genes showed opposite regulation profiles at low and high dilutions of Apis mellifica, suggesting a hormetic response. In particular, genes involved in cytokine expression, inflammatory processes, anti-oxidative responses and proteasome degradation were differentially, and sometimes divergently expressed by the TM or by Apis mellifica 3C, 5C and 7C dilutions. We confirmed these data by RT-PCR analyses on 5 selected candidate genes (IL1β, CD46, ATF1, UBE2Q2 and MT1X).
Conclusions: Apis mellifica TM modifies gene expression in human cells and has inhibitory effects on regulatory processes of inflammation; in addition, extremely diluted dynamized dilutions (3C, 5C and 7C) still exert significant effects on genes involved in inflammation and oxidative stress.
- 1 Dunglison R.. New remedies: with formulae for their preparation and administration. 7th edn 1856. Blanchard & Lea; Philadelphia: 706-707.
- 2 Urtubey N.. Apitoxina Del Veneno De Abejas A La Apitoxina De Uso Médico. 2nd edn 2003. Santiago del Estero, Argentina
- 3 Hellner M., Winter D., von Georgi R., Münstedt K.. Apitherapy: usage and experience ion German bee keepers. Evid Based Complement Altern Med 5 (04) 2008; 475-479.
- 4 Kwon Y.B., Kim J.H., Yoon J.H.. et al. The analgesic efficacy of bee venom acupuncture for knee osteoarthritis: a comparative study with needle acupuncture. Am J Chin Med 29 (02) 2001; 187-199.
- 5 Liu X.D., Zhang J.L., Zheng H.G., Liu F.Y., Chen Y.. Clinical randomized study of bee-sting therapy for rheumatoid arthritis. Zhen Ci Yan Jiu 33 (03) 2008; 197-200.
- 6 Park H.J., Lee S.H., Son D.J.. et al. Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis Rheum 50 (11) 2004; 3504-3515.
- 7 Kim H.Y., Kwon T., Ham D.. et al. General pharmacological profiles of bee venom and its water soluble fractions in rodent models. J Vet Sci 5 (04) 2004; 309-318.
- 8 Baek Y.H., Huh J.E., Lee J.D., Choi do Y., Park D.S.. Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: mediation by alpha2-adrenoceptors. Brain Res 35 (10) 2006; 1073-1074.
- 9 Kwon Y.B., Ham T.W., Kim H.W., Roh D.H., Yoon S.Y., Han H.J.. et al. Water soluble fraction (<10 kDa) from bee venom reduces visceral pain behavior through spinal alpha 2-adrenergic activity in mice. Pharmacol Biochem Behav 80 (01) 2005; 181-187.
- 10 Son D.J., Kang J., Kim T.J.. et al. Melittin, a major bioactive component of bee venom toxin, inhibits PDGF receptor beta-tyrosine phosphorylation and downstream intracellular signal transduction in rat aortic vascular smooth muscle cells. J Toxicol Environ Health 70 15–16 2007; 1350-1355.
- 11 Hahnemann CFS. In: Organon of Medicine. Joseph Reves (ed.) from the 5th and 6th edn (1842). Haifa: Homeopress Ltd, 1994.
- 12 Bigagli E., Luceri C., Bernardini S., Dei A., Dolara P.. Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact 188 (01) 2010; 214-219.
- 13 Poitevin B., Davenas E., Benveniste J.. In vitro immunological degranulation of human basophils is modulated by Lung histamine and Apis mellifica. Brit J Clin Pharm 1988; 25: 439-444.
- 14 Bildet J., Guyot M., Bonini F., Grignon M.C., Poitevin B., Quilichini R.. The effect of dilutions of Apis mellifica and Apium virus on ultraviolet light-induced erythema in the guinea pig. Ann Pharm Fr 1989; 47: 24-32.
- 15 Conforti A., Bellavite P., Bertani S., Chiarotti F., Menniti-Ippolito F., Raschetti R.. Rat models of acute inflammation: a randomized controlled study on the effects of homeopathic remedies. BMC Complement Altern Med 2007; 7: 1
- 16 Yang E.J., Jiang J.H., Lee S.M.. et al. Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models. J Neuroinflammation 2010; 7: 69
- 17 Calabrese E., Iavicoli I., Calabrese V.. Hormesis: Its impact on medicine and health. Hum Exp Toxicol 2 (02) 2013; 120-152.
- 18 Murphy G., Caplice N., Molloy M.. Fractalkine in rheumatoid arthritis: a review to date. Rheumatology (Oxford) 47 (10) 2008; 0
- 19 Tang D., Kang R., Zeh 3rd H.J., Lotze M.T.. High-mobility group box 1, oxidative stress, and disease. Antioxid Redox Signal 14 (07) 2011; 1315-1335.
- 20 Nasti T.H., Timares L.. Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage. Photochem Photobiol 88 (05) 2012; 1111-1125.
- 21 Matsui K., Tsutsui H., Nakanishi K.. Pathophysiological roles for IL-18 in inflammatory arthritis. Expert Opin Ther Targets 7 (06) 2003; 701-724.
- 22 Deramaudt T.B., Dill C., Bonay M.. Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases. Med Mal Infect 43 (03) 2013; 100-107.
- 23 Thomas A.H., Edelman E.R., Stultz C.M.. Collagen fragments modulate innate immunity. Exp Biol Med (Maywood) 232 (03) 2007; 406-411.
- 24 Etienne-Manneville S., Hall A.. Rho GTPases in cell biology. Nature 2002; 420: 629-635.
- 25 Minamino K., Takahara K., Adachi T.. et al. IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms. Int Immunol 24 (09) 2012; 573-581.
- 26 El Kebir D., Filep J.G.. Modulation of neutrophil apoptosis and the resolution of inflammation through β2 integrins. Front Immunol 2013; 4: 60