{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:01:36Z","timestamp":1791403296385,"version":"4.3.3"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1P20 GM103641"],"award-info":[{"award-number":["1P20 GM103641"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant global human disease and mortality. One approach to develop treatments for DENV infection and the prevention of severe disease is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during DENV infection. Studies have proposed that the oxidative stress response may be one mechanism responsible for triggering inflammation during DENV infection. Thus, blocking the oxidative stress response could reduce inflammation and the development of severe disease. Garlic has been shown to both reduce inflammation and affect the oxidative stress response. Here, we show that the garlic active compounds diallyl disulfide (DADS), diallyl sulfide (DAS) and alliin reduced inflammation during DENV infection and show that this reduction is due to the effects on the oxidative stress response. These results suggest that garlic could be used as an alternative treatment for DENV infection and for the prevention of severe disease development.<\/jats:p>","DOI":"10.3390\/v9070159","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T08:16:18Z","timestamp":1498205778000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Garlic Organosulfur Compounds Reduce Inflammation and Oxidative Stress during Dengue Virus Infection"],"prefix":"10.3390","volume":"9","author":[{"given":"Alex","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Troupin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-5274","authenticated-orcid":false,"given":"Berlin","family":"Londono-Renteria","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonya","family":"Colpitts","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2174\/18715206113136660370","article-title":"The immunomodulation and anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention","volume":"14","author":"Schafer","year":"2014","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1032S","DOI":"10.1093\/jn\/131.3.1032S","article-title":"Garlic and cancer: A critical review of the epidemiologic literature","volume":"131","author":"Fleischauer","year":"2001","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0955-2863(99)00021-2","article-title":"Antioxidant effects of fructosyl arginine, a Maillard reaction product in aged garlic extract","volume":"10","author":"Ide","year":"1999","journal-title":"J. Nutr. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s10495-006-0024-x","article-title":"Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells","volume":"12","author":"Karmakar","year":"2007","journal-title":"Apoptosis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.3945\/jn.110.121277","article-title":"Ajoene, a stable garlic by-product, has an antioxidant effect through Nrf2-mediated glutamate-cysteine ligase induction in HepG2 cells and primary hepatocytes","volume":"140","author":"Kay","year":"2010","journal-title":"J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.3945\/jn.109.105452","article-title":"1,2-vinyldithiin from garlic inhibits differentiation and inflammation of human preadipocytes","volume":"139","author":"Keophiphath","year":"2009","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1089\/jmf.2012.2275","article-title":"Anti-inflammatory activity of sulfur-containing compounds from garlic","volume":"15","author":"Li","year":"2012","journal-title":"J. Med. Food"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Beatty, M.E., Stone, A., Fitzsimons, D.W., Hanna, J.N., Lam, S.K., Vong, S., Guzman, M.G., Mendez-Galvan, J.F., Halstead, S.B., and Letson, G.W. (2010). Best practices in dengue surveillance: A report from the Asia-Pacific and Americas Dengue Prevention Boards. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000890"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1097\/PEC.0b013e31828ed30e","article-title":"A review of Dengue fever: A resurging tropical disease","volume":"29","author":"Mangold","year":"2013","journal-title":"Pediatr. Emerg. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1136\/bmj.324.7353.1563","article-title":"Dengue: An escalating problem","volume":"324","author":"Gibbons","year":"2002","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0966-842X(01)02288-0","article-title":"Epidemic dengue\/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century","volume":"10","author":"Gubler","year":"2002","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Flasche, S., Jit, M., Rodriguez-Barraquer, I., Coudeville, L., Recker, M., Koelle, K., Milne, G., Hladish, T.J., Perkins, T.A., and Cummings, D.A. (2016). The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002181"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fagundes, C.T., Costa, V.V., Cisalpino, D., Amaral, F.A., Souza, P.R., Souza, R.S., Ryffel, B., Vieira, L.Q., Silva, T.A., and Atrasheuskaya, A. (2011). IFN-\u03b3 production depends on IL-12 and IL-18 combined action and mediates host resistance to dengue virus infection in a nitric oxide-dependent manner. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001449"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Costa, V.V., Fagundes, C.T., Valadao, D.F., Cisalpino, D., Dias, A.C., Silveira, K.D., Kangussu, L.M., Avila, T.V., Bonfim, M.R., and Bonaventura, D. (2012). A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-\u03b3 in host resistance to infection. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001663"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1086\/340822","article-title":"Dengue-specific T cell responses in peripheral blood mononuclear cells obtained prior to secondary dengue virus infections in Thai schoolchildren","volume":"185","author":"Mangada","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/(SICI)1096-9071(199811)56:3<280::AID-JMV18>3.0.CO;2-I","article-title":"Elevated levels of IL-8 in dengue hemorrhagic fever","volume":"56","author":"Raghupathy","year":"1998","journal-title":"J. Med. Virol."},{"key":"ref_17","first-page":"187","article-title":"Interleukin-10 as a Marker of Disease Progression in Dengue Hemorrhagic Fever","volume":"26","author":"Tauseef","year":"2016","journal-title":"J. Coll. Phys. Surg. Pak."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/1743-422X-6-211","article-title":"The relationship of interacting immunological components in dengue pathogenesis","volume":"6","author":"Nielsen","year":"2009","journal-title":"Virol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1160\/TH09-03-0208","article-title":"Plasma leakage in dengue haemorrhagic fever","volume":"102","author":"Srikiatkhachorn","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.arcmed.2005.04.007","article-title":"Innate immune responses to dengue virus","volume":"36","author":"Despres","year":"2005","journal-title":"Arch. Med. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.canlet.2006.05.009","article-title":"Cancer chemoprevention with garlic and its constituents","volume":"247","author":"Shukla","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11060-013-1165-8","article-title":"Multi-targeted DATS prevents tumor progression and promotes apoptosis in ectopic glioblastoma xenografts in SCID mice via HDAC inhibition","volume":"114","author":"Wallace","year":"2013","journal-title":"J. Neuro-Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/cncr.22888","article-title":"Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells","volume":"110","author":"Das","year":"2007","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/09537100802155284","article-title":"Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation","volume":"19","author":"Soundravally","year":"2008","journal-title":"Platelets"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.freeradbiomed.2009.04.035","article-title":"Oxidative damage in dengue fever","volume":"47","author":"Seet","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s12038-008-0062-3","article-title":"Dengue and dengue haemorrhagic fever: Indian perspective","volume":"33","author":"Chaturvedi","year":"2008","journal-title":"J. Biosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ijid.2013.09.022","article-title":"Association between proinflammatory cytokines and lipid peroxidation in patients with severe dengue disease around defervescence","volume":"18","author":"Soundravally","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/jmf.2014.3214","article-title":"Aged Red Garlic Extract Suppresses Nitric Oxide Production in Lipopolysaccharide-Treated RAW 264.7 Macrophages Through Inhibition of NF-\u03baB","volume":"18","author":"Ryu","year":"2015","journal-title":"J. Med. Food"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/ars.2010.3190","article-title":"Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activation","volume":"14","author":"Han","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/BF01317418","article-title":"A comparative study of O\u2019nyong nyong virus with Chikungunya virus and plaque variants","volume":"59","author":"Chanas","year":"1979","journal-title":"Arch. Virol."},{"key":"ref_31","first-page":"310","article-title":"Role of garlic (Allium sativum L.) in human and plant diseases","volume":"39","author":"Singh","year":"2001","journal-title":"Indian J. Exp. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/mnfr.201300617","article-title":"Diallyl sulfide as a potential dietary agent to reduce TNF-\u03b1- and histamine-induced proinflammatory responses in A7r5 cells","volume":"58","author":"Ho","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/toxsci\/kfu255","article-title":"Radiation-induced lung injury and inflammation in mice: Role of inducible nitric oxide synthase and surfactant protein D","volume":"144","author":"Malaviya","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/infdis\/jiv122","article-title":"Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults","volume":"212","author":"Thein","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3201\/eid0102.952004","article-title":"Dengue\/dengue hemorrhagic fever: The emergence of a global health problem","volume":"1","author":"Gubler","year":"1995","journal-title":"Emerg. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1086\/499282","article-title":"Antibody-dependent enhancement in dengue virus infections","volume":"193","author":"Burke","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1038\/nm1144","article-title":"Emerging flaviviruses: The spread and resurgence of Japanese encephalitis, West Nile and dengue viruses","volume":"10","author":"Mackenzie","year":"2004","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1038\/nrmicro2460","article-title":"Dengue: A continuing global threat","volume":"8","author":"Guzman","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1089\/vbz.2013.1413","article-title":"Identification of dengue fever cases in Houston, Texas, with evidence of autochthonous transmission between 2003 and 2005","volume":"13","author":"Murray","year":"2013","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"652","DOI":"10.3201\/eid1904.121295","article-title":"Genetic relatedness of dengue viruses in Key West, Florida, USA, 2009\u20132010","volume":"19","author":"Santiago","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1128\/CMR.11.3.480","article-title":"Dengue and dengue hemorrhagic fever","volume":"11","author":"Gubler","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1574-695X.2003.tb00646.x","article-title":"Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection","volume":"35","author":"Atrasheuskaya","year":"2003","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.chom.2010.01.004","article-title":"Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease","volume":"7","author":"Zellweger","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11418","DOI":"10.1128\/JVI.01257-06","article-title":"Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis","volume":"80","author":"Clyde","year":"2006","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.cyto.2011.01.013","article-title":"Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability","volume":"54","author":"Chuang","year":"2011","journal-title":"Cytokine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1096\/fj.09-139469","article-title":"Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection","volume":"24","author":"Amaral","year":"2010","journal-title":"FASEB J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/nri3014","article-title":"Immunity to dengue virus: A tale of original antigenic sin and tropical cytokine storms","volume":"11","author":"Rothman","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bozza, F.A., Cruz, O.G., Zagne, S.M., Azeredo, E.L., Nogueira, R.M., Assis, E.F., Bozza, P.T., and Kubelka, C.F. (2008). Multiplex cytokine profile from dengue patients: MIP-1\u03b2 and IFN-\u03b3 as predictive factors for severity. BMC Infect. Dis., 8.","DOI":"10.1186\/1471-2334-8-86"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Guabiraba, R., Marques, R.E., Besnard, A.G., Fagundes, C.T., Souza, D.G., Ryffel, B., and Teixeira, M.M. (2010). Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015680"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/9\/7\/159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:40:10Z","timestamp":1760208010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/9\/7\/159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,23]]},"references-count":49,"aliases":["10.3390\/v9060159","10.3390\/v9060159"],"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["v9070159"],"URL":"https:\/\/doi.org\/10.3390\/v9070159","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,23]]}}}