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Professor Leoni Villano Bonamin is one of the leading researchers studying ultra-high dilutions (UHDs) of biologically active substances and their effects on living systems. Professor Bonamin is currently heading several research projects on this subject at Paulista University (UNIP) in São Paulo, Brazil [1-3].
Leoni Villano Bonamin was born in São Paulo, Brazil, in 1965. In 1987, she graduated from the University of São Paulo with a degree in veterinary science [2-3]. Leoni continued her studies there, receiving a master's degree in 1990 and a doctorate in experimental and comparative pathology in 1995. Her doctoral dissertation was partly completed at the National School of Veterinary Research in Lyon, France (1992–1993) [2-3]. Since 1991, Leoni Bonamin has been a professor at Paulista University in her native São Paulo. From 2002 to 2014 she was president and vice-president of Groupe International de Recherché sur l'Infenitésimal (GIRI) – the International community of researchers of ultra-low doses and the effect of high dilutions, and currently sits on its Executive Committee.
Professor Bonamin became interested in the subject of ultra-high dilutions in her first year at University and decided to devote her academic career to it [4]. In 1994-1995, she completed her specialisation at the Faculty of Health Sciences of São Paulo.
Paulista University. Source: https://www.unip.br/
Leoni Bonamin is undertaking research into the effects of UHDs of various substances on the development of infectious diseases in animal models. Thus, studies of Phosphorus UHDs were carried out on an in vivo model of Chagas disease [5] and an in vitro infection of a cell culture with microsporidia [6].
Chagas disease is caused by protozoa of the species Trypanosoma cruzi and is quite common in South America. The disease can become chronic, accompanied by a constant inflammatory process, which can lead to heart failure and damage to the digestive organs. By infecting experimental animals with the parasite, scientists found that the drug Phosphorus affect the pathogenicity of Trypanosoma cruzi. There was no mortality in the group of mice that was given Phosphorus 20 days after infection, however, at the same time, the parasitic load and the duration of apparent parasitaemia increased, and the number of lymphocytes fell [5]. When Phosphorus was introduced into a macrophage culture infected with the pathogenic fungus Encephalitozoon cuniculi, which causes microsporidiosis in animals and humans, the rate of macrophage apoptosis decreased, whereas their lysosomal activity [which aids the 'digestion' of parasites] increased. There was also an increase in the level of RANTES chemokine (CCL5), attracting lymphocytes to the site of the inflammation [6]. It is worth noting that some other changes, such as a decrease in the number of invading parasites and an increase in the level of certain cytokines, were also observed for a 'positive' control - the administration of a similarly prepared ethanol solution instead of Phosphorus [6].
A large series of Professor Bonamin's works was devoted to studying the action of a UHD of the hormone thymulin, an endogenous peptide that has an immunoregulatory function involved in T-lymphocyte maturation, as well as some neuroendocrine and neuroprotective functions. A group led by Bonamin showed that thymulin in 5C dilutions can be effective in combatting chronic viral and bacterial inflammation in birds [7] and rodents [8, 9]. Broiler chickens fed with thymulin in their drinking water for 42 days showed better survival and weight gain (although only in females]) as well as fewer pro-inflammatory cells [7]. In a mouse study, 5C dilutions of thymulin modulated chronic inflammation caused by the introduction of Bacillus Calmette-Guérin (BCG) into the animal's paw by means of increased B1 peritoneal stem cell differentiation in phagocytes and increased phagocytosis efficiency [8].
Thymulin also had a mild immunomodulatory effect (an increase in the T/B lymphocyte ratio) when the mice were infected with the influenza virus [9]. Based on the results [7, 8], the scientists decided to test the efficacy of thymulin UHDs in the treatment of cutaneous leishmaniasis, a disease common in Asia and South America caused by Leishmania protozoa, which leads to skin damage. Once in the human body, Leishmania parasitise in macrophages, turning from extracellular promastigotes into intracellular amastigotes – a kind of 'Trojan horse'. While inside the macrophages, they are protected from the host immune system and continue to multiply and infect the body. To simulate this disease, scientists injected laboratory mice subcutaneously into the paw with Leishmania amazonensis, and then assessed the damage and the immune response. 60 days after leishmania infection, the number of parasites at the site of injury was reduced in the mice, which had received thymulin in drinking water, and the proportion of peritoneal and splenic B1 cells increased, as did the efficiency of phagocytosis. This may indicate a more effective containment of the infection in this experimental group [10].
Leishmaniasis model experiments were also carried out with other drugs in vivo and in vitro [11-14]. Administering a UHD of Antimonium crudum two days after infection led to an increase in the parasitic load and the local and systemic number of B-lymphocytes. However, two months after infection, inflammation severity decreased, and the systemic and local B-lymphocytic response began to prevail, associated with a decrease in the level of phagocyte migration to the site of injury. There was also an increase in the number of free forms of amastigotes [non-phagocytic parasites] at the infection site. Such a context may be favourable for halting the parasitic cycle inside the body, due to the violation of the Trojan horse effect [11].
The immunomodulatory effect of Antimonium crudum has also been shown in the systemic infection of mice with another parasite, Leishmania infantum. The number of Th1-type cytokines increased in the mice, which is typical for resistance to infection [12]. To study the effect of Antimonium crudum on leishmaniasis in more detail, scientists conducted in vitro experiments on a macrophage culture – the ultimate goal of the parasite inside the host organism [13]. It was shown that this drug helps to reduce the level of certain chemokines and cytokines, which have been increased by parasitic infection [13]. The M1 complex, consisting of a mixture of 15 different UHD preparations of varying dilutions, was also shown to be effective against Leishmania amazonensis [both in vivo and in vitro]. M1 reduced the intensity of leishmaniasis development due to a decrease in the parasitic load and number of infected macrophages, as well as an increase in the intensity of the Th1 response and in the level of interleukin 10 [14].
Another series of works by Professor Bonamin is dedicated to the effect of UHD drugs on inflammatory processes. A model of artificially induced edema in the paws of rats was used to study the effect of UHDs of the synthetic glucocorticosteroid dexamethasone [15-16] as well as the drugs Causticum [17] and Arnica montana [18]. Administering a UHD of dexamethasone to rats together with the usual dose led to a significant decrease in the severity of dexamethasone's anti-inflammatory effect [15]. In rats whose mothers were given UHDs of dexamethasone during pregnancy and lactation, the nature of the inflammatory reaction changed somewhat, but no macro-changes in edema were observed [16]. Administering Causticum orally at various dilutions 24 hours or 30 minutes before injecting a pro-inflammatory agent significantly reduced the severity of subsequent edema [17], and with the administration of Arnica montana after the pro-inflammatory agent, the reaction depended on the individual characteristics of the animals. Edema decreased only in rats whose inflammation developed later, probably due to an increase in the diameter of blood vessels and an improvement in lymph outflow [18].
In E. coli-induced peritonitis [19] and cystitis [20] models, UHD preparations also influenced the development of the inflammatory process. Thus, Atropa belladonna, Echinacea angustifolia, and a mixture of the two modulated the inflammatory response in peritonitis and exerted a cytoprotective effect [19]. Use of the drug Cantharis also led to a change in the balance of inflammatory cells and cytokines in the bladder mucosa and renal pelvis towards a more subtle and local inflammatory response, which can likely contribute to remission of the infection [20].
Studying the effects of UHD drugs on carcinogenesis is a relevant and important area of research. A group led by Bonamin showed that the administration of the aforementioned thymulin in an ultra-low dose leads to a change in the tumour microenvironment without affecting the growth of Ehrlich carcinoma and the systemic immune response, contributing to the apoptosis of cancer cells [25]. Symphytum Officinale extract has a protective effect in the early stages of induced liver cancer in standard concentration [26]. In addition to experimental work on UHDs and carcinogenesis, Bonamin also conducts meta-analyses of existing publications on this topic [27].
Mention may be made of some more positive effects of UHD drugs that have been shown in studies, which Leoni Bonamin has led or participated in. For example, Dolichos pruriens is efficacious for pruritus, skin damage, and thinning of fur in rats in high-temperature conditions [28], Chamomilla normalises the behaviour of mice subjected to stressful conditions [29], and UHDs of the triiodothyronine hormone influence apoptosis in tadpole tail explants [30-31].
Professor Bonamin also conducts research in the field of so-called biotherapy. UHDs of infectious agents are used as a therapeutic agent in biotherapy [5, 9, 12, 22]. This approach produced a positive effect in Chagas disease [a UHD of Trypanosoma cruzi] [5], influenza (a UHD of H3N2 influenza virus) [9], and leishmaniasis models (a UHD of Leishmania infantum) [12].
Bonamin and her colleagues also evaluate the physicochemical and biological properties of the drugs they use in UHDs [32, 33]. Thus, it was shown that UHDs of arsenic prepared in plastic and glass have different properties [33].
Leoni Bonamin is also the chief editor of the International Journal of High Dilution Research [3]. In addition, she is the author of books Signals and Images: Contributions and Contradictions about High Dilution Research [34] and Discovering How Homeopathy Works.
References
1. https://www.researchgate.net/profile/Leoni_Bonamin
2. https://orcid.org/0000-0002-9850-9491
3. http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728342Y6
4. https://researchinhomeopathy.org/interview-lb/
5. de Almeida LR, Campos MC, Herrera HM, Bonamin LV, da Fonseca AH. (2008). Effects of homeopathy in mice experimentally infected with Trypanosoma cruzi. Homeopathy. 97 (2): 65-9.
6. Nagai MY, Dalboni LC, Cardoso TN, Correia MS, Pinto SAG, Pinto AAG, Coelho CP, Alvarez-Saraiva A, Peres GB, Lallo MA, Bonamin LV. 2019. Effects of Homeopathic Phosphorus on Encephalitozoon cuniculi-Infected Macrophages in vitro. Homeopathy. 108 (3): 188-200.
7. Sato C, Listar VG, Bonamin LV. 2012. Development of broiler chickens after treatment with thymulin 5cH: a zoo technical approach. Homeopathy. 101 (1): 68-73.
8. Bonamin LV, Sato C, Zalla Neto R, Morante G, Cardoso TN, de Santana FR, Coelho Cde P, Osugui L, Popi AF, Hurtado EC, Mariano M. (2013). Immunomodulation of Homeopathic Thymulin 5CH in a BCG-Induced Granuloma Model. Evid Based Complement Alternat Med. 2013: 686018.
9. Siqueira CM, Motta PD, Cardoso TN, de Paula Coelho C, Popi AF, Couceiro JN, Bonamin LV, Holandino C. (2016). Homeopathic treatments modify inflammation but not behavioral response to influenza antigen challenge in BALB/c mice. Homeopathy. 105(3): 257-264.
10. Rodrigues de Santana F, Coelho Cde P, Cardoso TN, Laurenti MD, Perez Hurtado EC, Bonamin LV. 2014. Modulation of inflammation response to murine cutaneous Leishmaniosis by homeopathic medicines: thymulin 5cH. Homeopathy. 103 (4): 275-84.
11. Rodrigues de Santana F, de Paula Coelho C, Cardoso TN, Perez Hurtado EC, Roberti Benites N, Dalastra Laurenti M, Villano Bonamin L. (2014). Modulation of inflammation response to murine cutaneous Leishmaniasis by homeopathic medicines: Antimonium crudum 30cH. Homeopathy. 103 (4): 264-74.
12. Cajueiro APB, Goma EP, Dos Santos HAM, Almeida Rodrigues I, Toma HK, Araújo SM, Bonamin LV, Gomes NBN, Castelo-Branco MTL, de Souza Dias EP, Dos Santos Pyrrho A, Holandino C. (2017). Homeopathic medicines cause Th1 predominance and induce spleen and megakaryocytes changes in BALB/c mice infected with Leishmania infantum. Cytokine. 95: 97-101.
13. de Santana FR, Dalboni LC, Nascimento KF, Konno FT, Alvares-Saraiva AM, Correia MS, Bomfim MD, Casarin RC, Perez EC, Lallo MA, Peres GB, Laurenti MD, Benites NR, Buchi DF, Bonamin LV. 2017. High dilutions of antimony modulate cytokines production and macrophage - Leishmania (L.) amazonensis interaction in vitro. Cytokine. 92: 33-47.
14. Nascimento KF, de Santana FR, da Costa CRV, Kaplum V, Volpato H, Nakamura CV, Bonamin LV, de Freitas Buchi D. (2017). M1 homeopathic complex trigger effective responses against Leishmania (L) amazonensis in vivo and in vitro. Cytokine. 99: 80-90.
15. Bonamin LV, Martinho KS, Nina AL, Caviglia F, Do Rio RG. 2001. Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo. Br Homeopath J. 90(4): 198-203.
16. Bonamin LV, de Moraes CL, Sanches F, Cardoso TN, Sato C, Duran Filho C, Martini LC. 2012. Rats Born to Mothers Treated with Dexamethasone 15 cH Present Changes in Modulation of Inflammatory Process. Evid Based Complement Alternat Med. 2012: 710923.
17. Prado Neto Jde A, Perazzo FF, Cardoso LG, Bonamin LV, Carvalho JC. 2004. Action of Causticum in inflammatory models. Homeopathy. 93 (1): 12-6.
18. Kawakami AP, Sato C, Cardoso TN, Bonamin LV. 2011. Inflammatory Process Modulation by Homeopathic Arnica montana 6CH: The Role of Individual Variation. Evid Based Complement Alternat Med. 2011: 917541.
19. Pedalino CM, Perazzo FF, Carvalho JC, Martinho KS, Massoco Cde O, Bonamin LV. 2004. Effect of Atropa belladonna and Echinacea angustifolia in homeopathic dilution on experimental peritonitis. Homeopathy. 93 (4): 193-8.
20. de Paula Coelho C, Motta PD, Petrillo M, de Oliveira Iovine R, Dalboni LC, Santana FR, Correia MS, Casarin RC, Carvalho VM, Bonamin LV. 2017. Homeopathic medicine Cantharis modulates uropathogenic E. coli (UPEC)-induced cystitis in susceptible mice. Cytokine. 92: 103-109.
21. Soto FR, Vuaden ER, Coelho Cd, Benites NR, Bonamin LV, de Azevedo SS. (2008). A randomized controlled trial of homeopathic treatment of weaned piglets in a commercial swine herd. Homeopathy. 97 (4): 202-5.
22. de Paula Coelho, C., Vuaden, ER, Soto, FRM, Melville, PA, de Oliveira, FCS, Bonamin, LV, Moreno AM, Tahan P., Benites, NR (2014). Evaluation of homeopathic treatment of Escherichia coli infected swine with indetification of virulence factors involved: Pilot study. International Journal of High Dilution Research. 13(49), 197-206.
23. Soto, F.R., Vuaden, E.R., Coelho, C.D., Bonamin, L.V., Azevedo, S.S., Benites, N.R., Visintin, J.A., Barros, F.R., Goissis, M.D., Assumpção, M.E., Marques, M.G. (2010). Reproductive performance of sows inseminated with diluted semen treated with homeopathic medicine. International Journal of High Dilution Research-ISSN 1982-6206, 9(30), 51-57.
24. Soto FR, Vuaden ER, de Paula Coelho C, Bonamin LV, de Azevedo SS, Benites NR, de Barros FR, Goissis MD, Ortiz D'Ávila Assumpção ME, Visintin JA, Marques MG. 2011. Effects of the utilization of homeopathic elements in commercial diluent on swine sperm viability. Vitro Cell Dev Biol Anim. 47 (3): 205-9.
25. Amaral, J. G., Cardoso, T. N., de Carvalho, A. C., de Paula Coelho, C., Waisse, S., Perez, E. C., Bonamin, L. V. (2018). High-diluted thymulin on Ehrlich tumor growth in mice and the importance of tumor microenvironment. International Journal of High Dilution Research-ISSN 1982-6206, 17(3-4), 20-20.
26. Gomes MF, de Oliveira Massoco C, Xavier JG, Bonamin LV. 2010. Comfrey (Symphytum Officinale. l.) and Experimental Hepatic Carcinogenesis: A Short-term Carcinogenesis Model Study. Evid Based Complement Alternat Med. 7 (2): 197-202.
27. Bonamin LV, de Carvalho AC, Waisse S. (2017). Viscum album (L.) in experimental animal tumors: A meta-analysis. Exp Ther Med. 13 (6): 2723-2740.
28. de Paula Coelho C, D'Almeida V, Pedrazzolli-Neto M, Duran-Filho C, Florio JC, Zincaglia LM, Bonamin LV. (2006). Therapeutic and pathogenetic animal models for Dolichos pruriens. Homeopathy. 95 (3): 136-43.
29. Pinto SA, Bohland E, Coelho Cde P, Morgulis MS, Bonamin LV. (2008). An animal model for the study of Chamomilla in stress and depression: pilot study. Homeopathy. 97 (3): 141-4.
30. Guedes JR, Carrasco S, Ferreira CM, Bonamin LV, Souza W, Goldenstein-Schainberg C, Parra ER, Capelozzi VL. 2011. Ultra high dilution of triiodothyronine modifies cellular apoptosis in Rana catesbeiana tadpole tail in vitro. Homeopathy. 100 (4): 220-7.
31. Guedes JRP, Carrasco S, Ferreira CM, Bonamin LV, Goldenstein-Schainberg C, Martins V, Capelozzi VL. (2016). A morphometric and molecular study of the apoptosis observed on tadpoles' tail explants under the exposition of triiodothyronine in different homeopathic dilutions. Homeopathy. 105 (3): 250-256.
32. Holandino C, Oliveira AP, Homsani F, de Paiva JP, Barbosa GM, de Lima Zanetti MR, de Barros Fernandes T, Siqueira CM, da Veiga VF, Coli Louvisse de Abreu L, Marzotto M, Bernardi P, Bonamin LV, Bellavite P, Rossi AL, Picciani PHS. 2017. Structural and thermal analyses of zinc and lactose in homeopathic triturated systems. Homeopathy. 106 (3): 160-170.
33. Dalboni LC, Coelho CP, Palombo Pedro RR, Correia MS, de Santana FR, Cardoso TN, Pinto SAG, Alvares-Saraiva AM, Dutra-Correa M, Peres GB, Holandino C, Rossi A, César AT, Waisse S, Bonamin LV. 2019. Biological Actions, Electrical Conductance and Silicon-Containing Microparticles of Arsenicum Album Prepared in Plastic and Glass Vials. Homeopathy. 108 (1): 12-23.
34. L. Bonamin (Ed.). (2008). Signals and Images. Contributions and Contradictions about High Dilution Research. Springer Netherlands. p. 222.
35. Bonamin, LV. 2018. Discovering How Homeopathy Works. Kindle Edition. p. 94.