Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity

Particle and Fibre Toxicology

Davis Ferreira¹  Márcia R Soares³  Marcelo DF de Meneses⁴  Renata Campos⁴  Tiago S Salles³  Kristie A Yamamoto³  Ricardo M Kuster²  Alda E dos Santos² 

[1] National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, Brazil;Natural Product Research Institute, Center of Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Chemistry Institute, Biochemistry Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Microbiology Institute, Virology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

关键词: MAYV;    Antiviral;    Quercetin derivatives;    Flavonoids;    Bauhinia longifolia;   

Others  :  807725
DOI  :  10.1186/1756-3305-7-130

 received in 2014-01-20, accepted in 2014-03-12,  发布年份 2014

【 摘 要 】

Background

The arthropod-borne Mayaro virus (MAYV) causes ‘Mayaro fever’, a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud.

Methods

Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay.

Results

The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC₉₀ = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity.

Conclusions

B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus.

【 授权许可】

   
2014 dos Santos et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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【 参考文献 】

• [1]Figueiredo LTM: Emergent arboviruses in Brazil. Rev Soc Bras Med Trop 2007, 40:224-229.
• [2]Rosa APAT, Vasconcelos PFC, Rosa JFST: An Overview Of Arbovirology In Brazil And Neighbouring Countries. Belém: Instituto Evandro Chagas; 1998.
• [3]Anderson CR, Downs WG, Wattley GH, Ahin NW, Reese AA: Mayaro virus: a new human disease agent. II. Isolation from blood of patients in Trinidad. Am J Trop Med Hyg 1957, 6:1012-1016.
• [4]Pinheiro FP, Freitas RB, Rosa JFT, Gabbay YB, Mello WA, LeDuc JW: An outbreak of Mayaro virus disease in Belterra, Brazil. I. Clinical and virological findings. Am J Trop Med Hyg 1981, 30:674-681.
• [5]Tesh RB, Watts DM, Russell KL, Damodaran C, Calampa C, Cabezas C, Ramirez G, Vasquez B, Hayes CG, Rossi CA, Powers AM, Hice CL, Chandler LJ, Cropp BC, Karabatsos N, Roehrig JT, Gubler DJ: Mayaro virus disease: an emerging mosquito-borne zoonosis in tropical South America. Clin Infect Dis 1999, 28:67-73.
• [6]Causey OR, Maroja OM: Mayaro virus: a new human disease agent. III. Investigation of an epidemic of acute febrile illness on the River Guana in Pará, Brazil, and isolation of Mayaro virus as causative agent. Am J Trop Med Hyg 1957, 6:1017-1023.
• [7]Schaeffer M, Gajdusek DC, Lema AB, Eichenwald H: Epidemic jungle fevers among Okinawan colonists in the Bolivian rain forest. I. Epidemiology. Am J Trop Med Hyg 1959, 8:372-396.
• [8]Leduc JW, Pinheiro FP, Rosa APAT: An outbreak of Mayaro virus disease in Belterra, Brazil. II. Epidemiology. Am J Trop Med Hyg 1981, 30:683-688.
• [9]Groot H, Kerr JA, Sanmartin C, Vidales H: Antibodies to yellow fever and other arthropod-borne viruses in human residents of San Vicente de Chucuri, Santander, Colombia. Am J Trop Med Hyg 1959, 8:175-189.
• [10]Pinheiro FP, LeDuc JW: Mayaro Virus Disease. In The Arboviruses, Epidemiology And Ecology. Edited by Monath T. Boca Raton: CRC Press; 1998:138-148.
• [11]Tavares-Neto J, Freitas-Carvalho J, Nunes MR, Rocha G, Rodrigues SG, Damasceno E, Darub R, Viana S, Vasconcelos PFC: Serologic survey for yellow fever and other arboviruses among inhabitants of Rio Branco, Brazil, before and three months after receiving the yellow fever 17D vaccine. Rev Soc Bras Med Trop 2004, 37:1-6.
• [12]Torres JR, Russell KL, Vasquez C, Barrera R, Tesh RB, Salas R, Watts DM: Family cluster of Mayaro fever, Venezuela. Emerg Infect Dis 2004, 10:1304-1306.
• [13]Navarrete-Espinoza J, Gomez-Dantes H: Arbovirus causing hemorrhagic fever at IMSS. Rev Med Inst Mex Seguro Soc 2006, 44:347-353.
• [14]Mourão MPG, Bastos MS, Figueiredo RP, Gimaque JBL, Galusso ES, Kramer VM, Oliveira CMC, Naveca FG, Figueiredo LTM: Mayaro Fever in the city of Manaus, Brazil, 2007–2008. Vector Borne and Zoonotic Dis 2012, 12:42-46.
• [15]Neumayr A, Gabriel M, Fritz J, Gunther S, Hatz C, Schimidt-Chanasit J, Blum J: Mayaro virus infection in traveler returning from Amazon Basin, Northern Peru. Emerg Infect Dis 2012, 18:695-696.
• [16]Cortez LP, Burlandy FM, Rebello MA: Efeito da tunicamicina sobre a replicação do vírus Mayaro em células de Aedes albopictus. Rev Ciênc Méd Biol 2003, 1:5-11.
• [17]Vasconcelos PFC, Rosa APAT, Pinheiro FP, Shope RE, Rosa JFST, Rodrigues SG, Dégallier N, da Rosa ES T: Arboviruses Pathogenic For Man In Brazil. In An Overview Of Arbovirology In Brazil And Neighbouring Countries. Edited by Rosa APAT, Vasconcelos PFC, Rosa JFST. Belém: Instituto Evandro Chagas; 1998:72-99.
• [18]Coimbra TLM, Santos CLS, Suzuki A, Petrella SMC, Bisordi I, Nagamori AH, Marti AT, Santos RN, Fialho DM, Lavigne S, Buzzar MR, Rocco IM: Mayaro virus: imported cases of human infection in São Paulo state, Brazil. Rev Inst Med Trop Sao Paulo 2007, 4:221-224.
• [19]Receveur MC, Grandadam M, Pistone T, Malvy D: Infection with Mayaro virus in a French traveller returning from the Amazon region, Brazil. Euro Surveill 2010, 18:1-4.
• [20]Fischer D, Thomas SM, Suk JE, Sudre B, Hess A, Tjaden NB, Beierkuhnlein C, Semenza JC: Climate change effects on Chikungunya transmission in Europe: geospatial analysis of vector’s climatic suitability and virus’ temperature requirements. Int J Health Geogr 2013, 12:1-12.
• [21]Schaffner F, Bellini R, Petric D, Scholte EJ, Zeller H, Rakotoarivony LM: Development of guidelines for the surveillance of invasive mosquitoes in Europe. Paras Vectors 2013, 6:209-219.
• [22]Kampen H, Werner D: Out of the bush: the Asian bush mosquito Aedes japonicus japonicus (Theobald, 1901) (Diptera, Culicidae) becomes invasive. Paras Vectors 2014, 7:59-69.
• [23]Yasuhara-Bell J, Yuanan L: Marine compounds and their antiviral activities. Antiviral Res 2010, 86:231-240.
• [24]Newman DJ, Cragg GM: Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012, 75:311-335.
• [25]George DR, Finn RD, Graham KM, Sparagano OAE: Present and future potential of plant-derived products to control arthropods of veterinary and medical significance. Parasit Vectors 2014, 7:1-12.
• [26]Politi FAS, Figueira GMF, Araújo AM, Sampieri BR, Mathias MIC, Szabó MPJ, Bechara GH, Santos LC, Vilegas W, Pietro RCLR: Acaricidal activity of ethanolic extract from aerial parts of Tagetes patula L. (Asteraceae) against larvae and engorged adult females of Rhipicephalus sanguineus (Latreille, 1806). Parasit Vectors 2012, 5:295-306.
• [27]Cechinel-Filho V: Chemical composition and biological potential of plants from the genus Bauhinia. Phytother Res 2009, 23:1347-1354.
• [28]Almeida ER, Guedes MC, Albuquerque JFC, Xavier H: Hypoglycemic effect of Bauhinia cheilandra in rats. Fitoterapia 2006, 77:276-278.
• [29]Pizzolatti MG, Cunha Junior A, Szpoganicz B, Sousa E, Braz-Filho R, Schripsema J: Flavonóides glicosilados das folhas e flores de Bauhinia forficata (Leguminosae). Quim Nova 2003, 26:466-469.
• [30]Nijveldt RJ, van Nood EV, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM: Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001, 74:418-425.
• [31]Borenfreund E, Puerner JA: Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 1985, 24:119-124.
• [32]Kalegari M, Miguel MD, Dias JFG, Lordello ALL, Lima CP, Miyazaki CMS, Zanin SMW, Verdam MCS, Miguel OG: Phytochemical constituents and preliminary toxicity evaluation of leaves from Rourea induta Planch. (Connaraceae). Braz J Pharm Sci 2011, 3:635-642.
• [33]Fossen T, Andersen OM: Spectroscopic Techniques Applied To Flavonoids. In Flavonoids: Chemistry, Biochemistry and Applications. Edited by Andersen OM, Markham KR. Boca Raton: Taylor & Francis Group; 2006:37-142.
• [34]Piccinelli AL, Veneziano A, Passi S, Simone F, Rastrelli L: Flavonoids glycosides from whole cottonseed by product. Food Chem 2007, 100:344-349.
• [35]Rodrigues ED, Silva DB, Oliveira DCR, Silva GVJ: DOSY NMR applied to analysis of flavonoid glycosides from Bidens sulphurea. Magn Reson Chem 2009, 47:1095-1100.
• [36]Davies KM, Schwinn KE: Molecular Biology and Biotechnology of Flavonoid Biosynthesis. In Flavonoids: Chemistry, Biochemistry and Applications. Edited by Andersen OM, Markham KR. Boca Raton: Taylor & Francis Group; 2006:168-169.
• [37]Elia G, Belloli C, Cirone F, Lucente MS, Caruso M, Martella V, Decaro N, Buonavoglia C, Ormas P: In vitro efficacy of ribavirin against canine distemper virus. Antiviral Res 2008, 77:108-113.
• [38]Yarmolinsky L, Huleihel M, Zaccai M, Ben-Shabat S: Potent antiviral flavone glycosides from Ficus benjamina leaves. Fitoterapia 2012, 83:362-367.
• [39]Gould KS, Lister C: Flavonoids Functions In Plants. In Flavonoids: Chemistry, Biochemistry and Applications. Edited by Andersen OM, Markham KR. Boca Raton: Taylor & Francis Group; 2006:416-417.
• [40]Orhan DD, Ozçelik B, Ozgen S, Ergun F: Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiol Res 2010, 165:496-504.
• [41]Fan D, Zhou X, Zhao C, Chen H, Zhao Y, Gong X: Anti-inflammatory, antiviral and quantitative study of quercetin-3-O-β-D-glucuronide in Polygonum perfoliatum L. Fitoterapia 2011, 82:805-810.
• [42]Zandi K, Teoh B, Sam SS, Wong PF, Mustafa MR, Abubakar S: Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J 2011, 8:560.
• [43]Thapa M, Kim Y, Desper J, Chang KO, Hua DH: Synthesis and antiviral activity of substituted quercetins. Bioorg Med Chem Lett 2012, 22:353-356.
• [44]Wagoner J, Negash A, Kane OJ, Martinez LE, Nahmias Y, Bourne N, Owen DM, Grove J, Brimacombe C, McKeating JA, Pécheur EI, Graf TN, Oberlies NH, Lohmann V, Cao F, Tavis JE, Polyak SJ: Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology 1912–1921, 2010:51.
• [45]Zhang T, Wu Z, Du J, Hu Y, Liu L, Yang F, Jin Q: Anti- Japanese-encephalitis-viral effects of kaempferol and daidzin and their RNA-Binding characteristics. PLoS One 2012, 7:e30259.