期刊论文详细信息
BMC Complementary and Alternative Medicine
Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers
Dorly de F Buchi1  Edvaldo da S Trindade1  Jenifer P Gonçalves1  Eneida J Da Lozzo1  Diogo Kuczera1  Ediely L de O Coletto1  Raffaello P Di Bernardi1  Lucas F de Andrade1  Fernando de SF Guimarães1  Simone M de Oliveira1  Ana Paula R Abud1  Carolina C de Oliveira1 
[1] Laboratório de Estudos de Células Inflamatórias e Neoplásicas, Departamento de Biologia Celular, SCB, Centro Politecnico, Universidade Federal do Paraná - Curitiba, CEP 81531-980, PR - Brazil
关键词: macrophages;    lymph node cells;    bone marrow cells;    immune cells;    highly diluted tinctures;    drug discovery;   
Others  :  1232947
DOI  :  10.1186/1472-6882-11-101
 received in 2011-06-16, accepted in 2011-10-26,  发布年份 2011
PDF
【 摘 要 】

Background

In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system.

Methods

We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment.

Results

None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity.

Conclusions

Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

【 授权许可】

   
2011 de Oliveira et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20151116163924758.pdf 649KB PDF download
Figure 5. 32KB Image download
Figure 4. 65KB Image download
Figure 3. 45KB Image download
Figure 2. 46KB Image download
Figure 1. 57KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Parkin J, Cohen B: An overview of the immune system. Lancet 2001, 357(9270):1777-1789.
  • [2]de Oliveira CC, de Oliveira SM, Godoy LM, Gabardo J, Buchi Dde F: Canova, a Brazilian medical formulation, alters oxidative metabolism of mice macrophages. The Journal of infection 2006, 52(6):420-432.
  • [3]Cesar B, Abud AP, de Oliveira CC, Cardoso F, Bernardi RP, Guimaraes FS, Gabardo J, de Freitas Buchi D: Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation. Evidence-based complementary and alternative medicine: eCAM 2009.
  • [4]Guimaraes FS, Andrade LF, Martins ST, Abud AP, Sene RV, Wanderer C, Tiscornia I, Bollati-Fogolin M, Buchi DF, Trindade ES: In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8) treatment in a murine melanoma model. BMC cancer 2010, 10:113. BioMed Central Full Text
  • [5]Borenfreund E, Puerner JA: A simple quantitative procedure using monolayer culture for toxicity assays. Journal of Tissue Culture Methods 1984, 9:7-9.
  • [6]Johnston RB, Godzik CA, Cohn ZA: Increased superoxide anion production by immunologically activated and chemically elicited macrophages. Journal of Experimental Medicine 1978, 148:115-27.
  • [7]Pick E, Mizel D: Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods 1981, 46:211-26.
  • [8]Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS: Analysis of nitrate, nitrite, and [15N ]-nitrate in biological fluids. Analytical Biochemistry 1982, 126:131-8.
  • [9]Nooz-Zadeh J, Tajaddini-Sarmadi J, Wolff SP: Measurement of plasma hydroperoxide concentrations by the ferrous oxidatio-xylenol orange assay in conjunction with triphenylphosphine. Analytical Biochemistry 1994, 220:403-409.
  • [10]Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, Green DR: Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. The Journal of experimental medicine 1995, 182(5):1545-1556.
  • [11]Fotakis G, Timbrell JA: In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 2006, 160(2):171-177.
  • [12]Naser B, Bodinet C, Tegtmeir M, Lindequist U: Thuja occidentalis (Arbor vitae): A review of its pharmaceutical, pharmacological and clinical properties. Evidence-based complementary and alternative medicine 2005, 2(1):69-78.
  • [13]Bellavite P, Conforti A, Pontarollo F, Ortolani R: Immunology and Homeopathy. 2. Cells of the Immune System and Inflammation. eCAM 2006, 3(1):13-24.
  • [14]Karin M, Lin A: NF-kappaB at the crossroads of life and death. Nat Immunol 2002, 3(3):221-227.
  • [15]Ghosh S, Karin M: Missing pieces in the NF-kappaB puzzle. Cell 2002, 109(Suppl):S81-96.
  • [16]Tang X, Fenton MJ, Amar S: Identification and functional characterization of a novel binding site on TNF-alpha promoter. Proc Natl Acad Sci USA 2003, 100(7):4096-4101.
  • [17]Nauseef WM: Assembly of the phagocyte NADPH oxidase. Histochem Cell Biol 2004, 122:277-291.
  • [18]Miller RA, Britigan BE: Role of oxidants in microbial pathophysiology. Clin Microbiol Rev 1997, 10(1):1-18.
  • [19]Wink DA, Mitchell JB: Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 1998, 25(4-5):434-456.
  • [20]Storz G, Imlay JA: Oxidative stress. Current Opinion in Microbiology 1999, 2:188-194.
  • [21]Yang Y, Sharma R, Sharma A, Awasthi S, Awasthi YC: Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling. Acta Biochim Pol 2003, 50(2):319-336.
  • [22]Sharma R, Sharma A, Chaudhary P, Pearce V, Vatsyayan R, Singh SV, Awasthi S, Awasthi YC: Role of lipid peroxidation in cellular responses to D,L-sulforaphane, a promising cancer chemopreventive agent. Biochemistry 2010, 49(14):3191-3202.
  文献评价指标  
  下载次数:45次 浏览次数:20次