BMC Complementary and Alternative Medicine | |
Effect of Uncaria tomentosa extract on purinergic enzyme activities in lymphocytes of rats submitted to experimental adjuvant arthritis model | |
Daniela B. R. Leal3  Jamile F. Gonçalves3  Margareth L. Athayde2  Juliano Ferreira3  Ritiel Corrêa da Cruz2  Emerson André Casalli1  Mariane A. da Silva3  Mateus F. Rossato3  Pedro H. Doleski4  Josiane B. Schlemmer3  Jeandre A. dos S. Jaques3  Maria Luiza Thorstenberg3  Jader B. Ruchel3  João F. P. Rezer3  Lívia G. Castilhos4  | |
[1] Laboratório de Enzimologia Aplicada ao Sistema Purinérgico, Departamento de Bioquímica, Instituto deCiências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil;Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima, Santa Maria, 97105-900, RS, Brazil;Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Av. Roraima, Santa Maria, 97105-900, RS, Brazil;Departamento de Microbiologia e Parasitologia, Centro de Ciências da Saúde, Universidade Federal deSanta Maria, Av. Roraima, Prédio 20 – Sala 4102, Santa Maria, 97105-900, RS, Brazil | |
关键词: Adenosine deaminase; E-NTPDase; lymphocytes; Uncaria tomentosa; Adjuvant arthritis; | |
Others : 1217070 DOI : 10.1186/s12906-015-0694-4 |
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received in 2014-04-14, accepted in 2015-05-27, 发布年份 2015 | |
【 摘 要 】
Background
Considering that adjuvant arthritis is an experimental model of arthritis widely used for preclinical testing of numerous anti-arthritic agents, which were taken by a large number of patients worldwide, it is of great interest to investigate the therapeutic action of compounds with anti-inflammatory properties, such as Uncaria tomentosa extract. Moreover, there are no studies demonstrating the effect of U. tomentosa on the metabolism of adenine nucleotides published so far. Thus, the purpose of the present study is to investigate the effects of U. tomentosa extract on E-NTPDase and E-ADA activities in lymphocytes of Complete Freund’s Adjuvant (CFA) arthritis induced rats.
Methods
To evaluate the effect of U. tomentosa extract on the activity of E-NTPDase and ADA in lymphocytes, the rats were submitted to an experimental adjuvant arthritis model. Peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Data were analyzed by a one- or two-way ANOVA. Post hoc analyses were carried out by the Student-Newman-Keuls (SNK) Multiple Comparison Test.
Results
E-NTPDase activity was increased in arthritic untreated. Arthritic rats which received U. tomentosa extract, presented similar results to the control group. However, results obtained for adenosine hydrolysis by E-ADA were not altered in arthritic rats. U. tomentosa extract did not alter E-NTPDase and E-ADA activity in healthy animals.
Conclusions
The present investigation supports the hypothesis that the increased E-NTPDase activity verified in arthritic rats might be an attempt to maintain basal levels of ATP and ADP in the extracellular medium, since the arthritis induction causes tissue damage and, consequently, large amounts of ATP are released into this milieu. Also, it highlights the possibility to use U. tomentosa extract as an adjuvant to treat arthritis.
【 授权许可】
2015 Castilhos et al.
【 预 览 】
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【 参考文献 】
- [1]Reinhard KH. Uncaria tomentosa (Willd.) D.C.: Cat’s claw, uña de gato, or saventaro. J Altern Complement Med. 1999; 5:143-51.
- [2]Patidar A, Birla D, Patel V, Chaturvedi M, Manocha N. A review of on advantages of natural analgesics over conventional synthetic analgesics. Int J Pharm Life Sci. 2014; 5:3534-9.
- [3]Rojas-Durana R, Gonza’lez-Aspajoa G, Ruiz-Martel C, Bourdy G, Doroteo-Ortega VH, Alban-Castillo J, Robert G, Auberger P, Deharo E. Anti-inflammatory activity of Mitraphylline isolated from Uncaria tomentosa bark. J Ethnopharmacol. 2012; 143:801-4.
- [4]Wagner H, Kreutzkamp B, Jurcic K. Die Alkaloide von Uncaria tomentosa ihre phagozytosesteigernde wirkung. Planta Med. 1985; 51:419-23.
- [5]Aquino R, De Simone F, Pizza C, Conti C, Stein ML. Plant Metabolites structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda. J Nat Prod. 1989; 52:679-85.
- [6]Aquino R, Vicenzo F, Francesco S. Plant Metabolites. New compounds and anti inflamatory activity of Uncaria tomentosa. J Nat Prod. 1991; 52:679-85.
- [7]Yoshimoto K, Sato H, Ohtake M, Laus G, Brössner D, Keplinger K. Alkaloids of Peruvian Uncaria tomentosa. Phytochemistry. 1997; 45:855-60.
- [8]Falkiewicz B, Łukasiak J. Vilcacora [Uncaria tomentosa (Willd.) DC. and Uncaria guianensis (Aublet) Gmell.]—a review of published scientific literature. Case Rep Clin Pract Rev. 2001; 2:305-16.
- [9]Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001; 344:907-16.
- [10]MacGregor AJ, Silman AJ et al.. Rheumatoid arthritis and other synovial disorders: Classification and epidemiology. Rheumatology. Hochberg MC, editor. Mosby Publications, London; 2004.
- [11]Bush KA, Kirkham BW, Walker JS. The in vivo effects of tumor necrosis factor blockade on the early cell mediated immune events and syndrome expression in rat adjuvant arthritis. Clin Exp Immunol. 2002; 127:423-9.
- [12]Hegen M, Keith JC, Collins M, Nickerson-Nutter CL. Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann Rheum Dis. 2008; 67:1505-15.
- [13]Iain BM, Georg S. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007; 7:429-42.
- [14]Luttikhuizen DT, Harmsen MC, de Leij LFMH, van Luyn MJA. Expression of P2 receptors at site of chronic inflammation. Cell Tissue Res. 2004; 317:289-98.
- [15]Ralevic V, Burnstock G. Involvement of purinergic signaling in cardiovascular diseases. Drug News Perspect. 2003; 16:133-40.
- [16]Bours M, Swennen E, Di Virgilio F, Cronstein BN, Dagnelie PC. Adenosine 5′ triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther. 2006; 112:358-404.
- [17]Langston H, Ke Y, Gewirtz A, Dombrowski K, Kapp J. Secretion of IL-2 and IFN-y, but not IL-4, by antigen-speci.c T cells requires extracellular ATP. J Immunol. 2003; 170:2962-70.
- [18]Robson SC, Sévigny J, Zimmermann H. The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal. 2006; 2:409-30.
- [19]Zimmermann H, Mishra S, Shukla V, Langer D, Gampe K, Grimm I, Delic J, Braun N. Ecto-nucleotidases, molecular properties and functional impact. An R Acad Nac Farm. 2007; 73:537-66.
- [20]Yegutkin GG. Nucleotide and nucleoside converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophs Acta. 2008; 1783:673-94.
- [21]Pulte E, Broekman M, Olson K, Drosopoulos JHF, Kizer JR, Islam N, Marcus AJ. CD39/NTPDase-1 activity and expression in normal leucocytes. Thromb Res. 2007; 121:309-17.
- [22]Barankiewicz J, Dosch HM, Cohen A. Extracellular nucleotide catabolism in human B and T lymphocytes. The source of adenosine production. J Biol Chem. 1988; 263:7094-8.
- [23]Franco R, Casadó V, Ciruela F, Saura C, Canela EI, Lluis C. Cell surface adenosine deaminase: much more than an ectoenzyme. Prog Neurobiol. 1997; 52:283-94.
- [24]Bota A, Javier Gella F, Profilis C, Férard G, Hadjivassiliou AG, Hørder M, Schiele F, Segura R, Canalias F. Production and certification of an enzyme reference material for adenosine deaminase 1 (BCR 647). Clin Chim Acta. 2001; 306:79-89.
- [25]Antonioli L, Fornai M, Colucci R, Ghisu N, Tuccori M, Del Tacca M, Blandizzi C. Pharmacological modulation of adenosine system: novel options for treatment of inflammatory bowel diseases. Inflamm Bowel Dis. 2008; 14:566-74.
- [26]Sociedade Brasileira de Ciências em Animais de Laboratório. Cuidado e Manejo de Animais de Laboratório, Brasil; 2009.
- [27]Sauzem PD, Sant’Anna GS, Machado P, Duarte MM, Ferreira J, Mello CF, Beck P, Bonacorso HG, Zanatta N, Martins MA, Rubin MA. Effect of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles on chronic inflammatory pain model in rats. Eur J Pharmacol. 2009; 616:91-100.
- [28]Bertol G, Franco L, Oliveira BH. HPLC Analysis of Oxindole Alkaloids in Uncaria tomentosa: Sample Preparation and Analysis Optimisation by Factorial Design. Phytochem Anal. 2012; 23:143-51.
- [29]Cao YQ, Mantyh PW, Carlson EJ, Gillespie A, Epstein CJ, Basbaum A. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 1998; 392:390-3.
- [30]Dixon WJ. Efficient analysis of experimental observations. Ann Rev Pharmacol Toxicol. 1980; 20:441-62.
- [31]Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem. 1983; 132:345-52.
- [32]Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968; 97:77-89.
- [33]Jaques JA, Peres Rezer JF, Ruchel JB, Gutierres J, Bairros AV, Gomes Farias IL, da Luz SC A, Mello Bertoncheli C, Chitolina Schetinger MR, Morsch VM, Leal DB. A method for isolation of rat lymphocyte-rich mononuclear cells from lung tissue useful for determination of nucleoside triphosphate diphosphohydrolase activity. Anal Biochem. 2011; 410:34-9.
- [34]Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54.
- [35]Leal DBR, Streher CA, Neu TN, Bitencourt FP, Leal CAM, Silva JEP, Morsch VM, Schetinger MRC. Characterization of NTPDase (NTPDase1; ecto-apyrase; ecto-diphosphohydrolase; CD39; E.C. 3.6.1.5) activity in humans lymphocytes. Biochim Biophys Acta. 2005; 1721:9-15.
- [36]Chan KM, Delfert D, Junger KD. A direct colorimetric assay for Ca2+ stimulated ATPase activity. Anal Biochem. 1986; 157:375-80.
- [37]Giusti G, Galanti B. Colorimetric Method. In: Methods of enzymatic analysis. Bergmeyer HU, editor. Verlag Chemie, Weinheim; 1984: p.315-23.
- [38]Voelter W, Zech K, Arnold P, Ludwig G. Determination of selected pyrimidines, purines and their metabolites in serum and urine by reverse-phase ion-pair chromatography. J Chromatogr. 1980; 199:345-54.
- [39]Akesson C, Lindgren H, Pero RW, Leanderson T, Ivars F. Quinic acid is a biologically active component of the Uncaria tomentosa extract C-Med 100. Int Immunopharmacol. 2005; 5:219-29.
- [40]Jurgensen S, Dalbó S, Angers P, Santos AR, Ribeiro do Valle RM. Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa. Pharmacol Biochem Behav. 2005; 81:466-77.
- [41]Pilarski R, Zieliński H, Ciesiołka D, Gulewicz K. Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC. J Ethnopharmacol. 2006; 104:18-23.
- [42]Aquino R, De Simone F, Pizza C, Vincieri F, Gacs BE. New polyhydroxylated triterpenes from Uncaria tomentosa. J Nat Prod. 1990; 53:559-64.
- [43]Laus G, Brossner D, Keplinger K. Alkaloids of peruvian Uncaria tomentosa. Phytochemistry. 1997; 45:855-60.
- [44]Aguilar JL, Rojas P, Marcelo A, Plaza A, Bauer R, Reininger E, Klaas CA, Merfort I. Anti-inflamatory activity of two extracts of Uncaria tomentosa (Rubiaceae). J Ethnopharmacol. 2002; 81:271-6.
- [45]Joe B, Griffiths MM, Remmers EF, Wilder RL. Animal models of rheumatoid arthritis and related inflammation. Cur Rheumat R. 1999; 1:139-48.
- [46]Keplinger K, Laus G, Wurm M, Dierich MP, Teppner H. Uncaria tomentosa (Wild). Ethnomedicinal Uses and new pharmacological, toxicological and botanical results. J Ethnopharmacol. 1999; 64:23-34.
- [47]Castañeda O, León G, León D, Calvoh A, Chávez J, Escalante J, Luza A, Quevedo H, Sedano O, Vega E. Uña de Gato en Artritis Reumatóide: Estúdio doble cego, en comparación com placebo. Rev Peru Reumatol. 1998; 4:15-21.
- [48]Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M. Efficacy and safety of freeze-dried cat’s claw in osteoarthritis knee: mechanism of actions of the species Uncaria guianensis. Inflamm Res. 2001; 50:442-8.
- [49]Mur E, Hartig F, Eibl G, Schirmer M. Randized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002; 29:678-81.
- [50]Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 2007; 13:108-16.
- [51]la Sala A, Ferrari D, Di Virgilio F, Idzko M, Norgauer J, Girolomoni G. Alerting and tuning the immune response by extracellular nucleotides. J Leukoc Biol. 2003; 73:339-43.
- [52]Gordon JL. Extracellular ATP: effects, sources and fate. Biochem J. 1986; 233:309-19.
- [53]Becker LV, Rosa CS, Souza VCG, Bagatini MD, Casali EA, Leal CAM, Silva JCN, Moretto MB, Pinheiro FV, Morsch VM, Schetinger MRC, Leal DBR. Activities of enzymes that hydrolyze adenine nucleotides in platelets from patients with rheumatoid arthritis. Clin Biochem. 2010; 43:1096-100.
- [54]Jaques JAS, Becker LV, Souza VCG, Leal CAM, Bertoldo TMD, Pinheiro KV, Morsch VM, Schetinger MRC, Leal DBR. Activities of enzymes that hydrolyze adenine nucleotides in lymphocytes from patients with rheumatoid arthritis. Cell Biochem Funct. 2013; 31:395-9.
- [55]Loza MJ, Anderson AS, O’Rourke KS, Wood J, Khan IU. T-cell specific defect in expression of the NTPDase CD39 as a biomarker for lupus. Cell Immunol. 2011; 271:110-7.
- [56]Schmatz R, Schetinger MR, Spanevello RM, Mazzanti CM, Stefanello N, Maldonado PA, Gutierres J, Correa Mde C, Girotto E, Moretto MB, Morsch VM. Effects of resveratrol on nucleotide degrading enzymes in streptozotocin-induced diabetic rats. Life Sci. 2009; 84:345-50.
- [57]Spanevello RM, Mazzanti CM, Schmatz R, Thome G, Bagatini M, Correa M, Rosa C, Stefanello N, Belle LP, Moretto MB, Oliveira L, Morsch VM, Schetinger MR. The activity and expression of NTPDase is altered in lymphocytes of multiple sclerosis patients. Clin Chim Acta. 2010; 411:210-4.
- [58]Di Virgilio F. The P2Z purinoreceptor: intriguing role in immunity, inflammation and cell death. Immunol Today. 1995; 16:524-8.
- [59]Gessi S, Varani K, Merighi S, Fogli E, Sacchetto V, Benini A, Leung E, Mac-Lennan S, Borea PA. Adenosine and lymphocyte regulation. Purinergic Signal. 2007; 3:109-16.
- [60]Di Virgilio F, Ferrari D, Idzko M, Panther E, Norgauer J, La Sala A, Extracellular GG. P2 receptors, and inflammation. Drug Devel R. 2003; 59:171-4.
- [61]Di Virgilio F, Boeynaems JM, Robson SC. Extracellular nucleotides as negative modulators of immunity. Cur Op Pharmacol. 2009; 9:507-13.
- [62]Heitzman ME, Neto CC, Winiarz E, Vaisberg AJ, Hammond GB. Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry. 2005; 66:5.
- [63]Erowele GI, Kalejaiye AO. Pharmacology and therapeutic uses of cat’s claw. Am J Health Syst Pharm. 2009; 66:992-5.
- [64]Urdanibia I, Estrada O, Ibarra C, Michelangeli F, Milano B, Taylor P. Anti-inflammatory and anti-tumour effects of two species of Cat’s claw (Uncaria). Planta Med. 2013; 79:PF11.
- [65]Urdanibia I, Estrada O, Ibarra C, Michelangeli F, Ruiz MC, Taylor P. Anti-inflammatory effects of different preparations of cat’s claw. Planta Med. 2012; 78:PI131.
- [66]Yegutkin GG, Henttinen T, Samburski SS, Spychala J, Jalkanen S. The evidence for two opposite, ATP-generating and ATP-consuming, extracellular pathways on endothelial and lymphoid cells. Biochem J. 2002; 367:121-8.