{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:05:05Z","timestamp":1791421505721,"version":"4.3.3"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM072866"],"award-info":[{"award-number":["R01 GM072866"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008637","name":"Center for Strategic Scientific Initiatives, National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA012197"],"award-info":[{"award-number":["P30 CA012197"]}],"id":[{"id":"10.13039\/100008637","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for Molecular Signaling","award":["Wake Forest University Microscopic Imaging Core"],"award-info":[{"award-number":["Wake Forest University Microscopic Imaging Core"]}]},{"name":"Wake Forest Center for Redox Biology and Medicine","award":["Pilot Funds"],"award-info":[{"award-number":["Pilot Funds"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Chlamydia trachomatis (Ct) is a bacterial intracellular pathogen responsible for a plethora of diseases ranging from blindness to pelvic inflammatory diseases and cervical cancer. Although this disease is effectively treated with antibiotics, concerns for development of resistance prompt the need for new low-cost treatments. Here we report the activity of spilanthol (SPL), a natural compound with demonstrated anti-inflammatory properties, against Ct infections. Using chemical probes selective for imaging mitochondrial protein sulfenylation and complementary assays, we identify an increase in mitochondrial oxidative state by SPL as the underlying mechanism leading to disruption of host cell F-actin cytoskeletal organization and inhibition of chlamydial infection. The peroxidation product of SPL (SPL endoperoxide, SPLE), envisioned to be the active compound in the cellular milieu, was chemically synthesized and showed more potent anti-chlamydial activity. Comparison of SPL and SPLE reactivity with mammalian peroxiredoxins, demonstrated preferred reactivity of SPLE with Prx3, and virtual lack of SPL reaction with any of the reduced Prx isoforms investigated. Cumulatively, these findings support the function of SPL as a pro-drug, which is converted to SPLE in the cellular milieu leading to inhibition of Prx3, increased mitochondrial oxidation and disruption of F-actin network, and inhibition of Ct infection.<\/jats:p>","DOI":"10.3390\/antiox9121220","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T11:15:43Z","timestamp":1606994143000},"page":"1220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Discovery of Spilanthol Endoperoxide as a Redox Natural Compound Active against Mammalian Prx3 and Chlamydia trachomatis Infection"],"prefix":"10.3390","volume":"9","author":[{"given":"Rosine","family":"Dushime","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhuang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Saez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1789-4990","authenticated-orcid":false,"given":"Kirtikar","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-2345","authenticated-orcid":false,"given":"Heather","family":"Brown-Harding","sequence":"additional","affiliation":[{"name":"Department of Biology, Wake Forest University, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maique W.","family":"Biavatti","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade, Departamento de Ci\u00eancias Farmac\u00eauticas, Bloco J\/K, Universidade Federal de Santa Catarina, Florian\u00f3polis 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly J.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B.","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-1295","authenticated-orcid":false,"given":"William T.","family":"Lowther","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina M.","family":"Furdui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Newman, L., Rowley, J., Vander Hoorn, S., Wijesooriya, N.S., Unemo, M., Low, N., Stevens, G., Gottlieb, S., Kiarie, J., and Temmerman, M. (2015). Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143304"},{"key":"ref_2","first-page":"303","article-title":"Genital Chlamydia trachomatis: An update","volume":"138","author":"Malhotra","year":"2013","journal-title":"Indian J. Med. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Buckner, L.R., Amedee, A.M., Albritton, H.L., Kozlowski, P.A., Lacour, N., McGowin, C.L., Schust, D.J., and Quayle, A.J. (2016). Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146663"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/(SICI)1097-0215(20000101)85:1<35::AID-IJC6>3.0.CO;2-A","article-title":"Chlamydia trachomatis infection as a risk factor for invasive cervical cancer","volume":"85","author":"Koskela","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1093\/aje\/kwi262","article-title":"Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents","volume":"162","author":"Samoff","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Patel, A.L., Chen, X., Wood, S.T., Stuart, E.S., Arcaro, K.F., Molina, D.P., Petrovic, S., Furdui, C.M., and Tsang, A.W. (2014). Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development. BMC Microbiol., 14.","DOI":"10.1186\/s12866-014-0277-4"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a010256","DOI":"10.1101\/cshperspect.a010256","article-title":"Chlamydial intracellular survival strategies","volume":"3","author":"Bastidas","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11430","DOI":"10.1073\/pnas.0703218104","article-title":"Mechanisms of host cell exit by the intracellular bacterium Chlamydia","volume":"104","author":"Hybiske","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1128\/iai.39.2.898-907.1983","article-title":"Inhibition of onset of overt multiplication of Chlamydia psittaci in persistently infected mouse fibroblasts (L cells)","volume":"39","author":"Moulder","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.4049\/jimmunol.86.4.382","article-title":"Effect of antiserum and antibiotics on persistent infection of HeLa cells with meningopneumonitis virus","volume":"86","author":"Galasso","year":"1961","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Poston, T.B., Gottlieb, S.L., and Darville, T. (2017). Status of vaccine research and development of vaccines for Chlamydia trachomatis infection. Vaccine, 7289\u20137294.","DOI":"10.1016\/j.vaccine.2017.01.023"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1086\/315372","article-title":"Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure","volume":"181","author":"Somani","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.3390\/molecules20034180","article-title":"Natural products for the treatment of trachoma and Chlamydia trachomatis","volume":"20","author":"Potroz","year":"2015","journal-title":"Molecules"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/pro.3536","article-title":"Sulforaphane promotes chlamydial infection by suppressing mitochondrial protein oxidation and activation of complement C3","volume":"28","author":"Saez","year":"2019","journal-title":"Protein Sci."},{"key":"ref_15","first-page":"2987","article-title":"Spilanthol inhibits TNFalphainduced ICAM1 expression and proinflammatory responses by inducing heme oxygenase1 expression and suppressing pJNK in HaCaT keratinocytes","volume":"18","author":"Huang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1007\/s10753-018-0837-0","article-title":"Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-\u03baB and MAPK Signaling in Interleukin-1\u03b2-Stimulated Human Lung Epithelial Cells","volume":"41","author":"Huang","year":"2018","journal-title":"Inflammation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/tx0502138","article-title":"Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane","volume":"18","author":"Hong","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"ref_18","first-page":"510298","article-title":"The genus spilanthes ethnopharmacology, phytochemistry, and pharmacological properties: A review","volume":"2013","author":"Paulraj","year":"2013","journal-title":"Adv. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/ptr.3395","article-title":"The traditional medicine Spilanthes acmella, and the alkylamides spilanthol and undeca-2e-ene-8, 10-diynoic acid isobutylamide, demonstrate in vitro and in vivo antimalarial activity","volume":"25","author":"Spelman","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_20","first-page":"291","article-title":"High therapeutic potential of Spilanthes acmella: A review","volume":"12","author":"Prachayasittikul","year":"2013","journal-title":"EXCLI J."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Silveira, N., Saar, J., Santos, A.D., Barison, A., Sandjo, L.P., Kaiser, M., Schmidt, T.J., and Biavatti, M.W. (2016). A New Alkamide with an Endoperoxide Structure from Acmella ciliata (Asteraceae) and Its in Vitro Antiplasmodial Activity. Molecules, 21.","DOI":"10.3390\/molecules21060765"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1158\/0008-5472.CAN-07-1998","article-title":"Paxillin is a target for somatic mutations in lung cancer: Implications for cell growth and invasion","volume":"68","author":"Jagadeeswaran","year":"2008","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6946","DOI":"10.1021\/ja043002i","article-title":"One-pot regio- and stereoselective cyclization of 1,2,n-triols","volume":"127","author":"Zheng","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1021\/ol061383u","article-title":"Sequencing of three-component olefin metatheses: Total synthesis of either (+)-gigantecin or (+)-14-deoxy-9-oxygigantecin","volume":"8","author":"Hoye","year":"2006","journal-title":"Org. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1039\/B615487E","article-title":"Stereoselective synthesis, natural occurrence and CB(2) receptor binding affinities of alkylamides from herbal medicines such as Echinacea sp.","volume":"5","author":"Matovic","year":"2007","journal-title":"Org. Biomol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fchem.2020.00187","article-title":"An Improved and Practical Method for Synthesizing of alpha-Sanshools and Spilanthol","volume":"8","author":"Nakamura","year":"2020","journal-title":"Front. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Julien, S.G., Kim, S.Y., Brunmeir, R., Sinnakannu, J.R., Ge, X., Li, H., Ma, W., Yaligar, J., Kn, B.P., and Velan, S.S. (2017). Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle. PLoS Biol., 15.","DOI":"10.1371\/journal.pbio.1002597"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6635","DOI":"10.1038\/s41598-018-24493-x","article-title":"Mitochondria-targeted Probes for Imaging Protein Sulfenylation","volume":"8","author":"Holmila","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11901","DOI":"10.1074\/jbc.RA117.001690","article-title":"Novel hyperoxidation resistance motifs in 2-Cys peroxiredoxins","volume":"293","author":"Bolduc","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29714","DOI":"10.1074\/jbc.M113.473470","article-title":"Molecular basis for the resistance of human mitochondrial 2-Cys peroxiredoxin 3 to hyperoxidation","volume":"288","author":"Haynes","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nature06415","article-title":"Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace","volume":"451","author":"Jonsson","year":"2008","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4300\/JGME-D-12-00156.1","article-title":"Using Effect Size-or Why the P Value Is Not Enough","volume":"4","author":"Sullivan","year":"2012","journal-title":"J. Grad. Med. Educ."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Forshaw, T.E., Holmila, R., Nelson, K.J., Lewis, J.E., Kemp, M.L., Tsang, A.W., Poole, L.B., Lowther, W.T., and Furdui, C.M. (2019). Peroxiredoxins in Cancer and Response to Radiation Therapies. Antioxidants, 8.","DOI":"10.3390\/antiox8010011"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/j.str.2005.07.021","article-title":"Bovine mitochondrial peroxiredoxin III forms a two-ring catenane","volume":"13","author":"Cao","year":"2005","journal-title":"Structure"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/intimm\/dxt067","article-title":"Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production","volume":"26","author":"Kimura","year":"2014","journal-title":"Int. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1093\/infdis\/jit830","article-title":"Protecting against post-influenza bacterial pneumonia by increasing phagocyte recruitment and ROS production","volume":"209","author":"Subramaniam","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S1201-9712(00)90066-3","article-title":"Generation of reactive oxygen species and formation and membrane lipid peroxides in cells infected with Chlamydia trachomatis","volume":"4","author":"Azenabor","year":"2000","journal-title":"Int. J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1128\/IAI.00725-09","article-title":"Production of reactive oxygen species is turned on and rapidly shut down in epithelial cells infected with Chlamydia trachomatis","volume":"78","author":"Boncompain","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3389\/fcimb.2017.00499","article-title":"Growth of Chlamydia pneumoniae Is Enhanced in Cells with Impaired Mitochondrial Function","volume":"7","author":"Kading","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"41637","DOI":"10.1074\/jbc.M110.137885","article-title":"Enhancement of reactive oxygen species production and chlamydial infection by the mitochondrial Nod-like family member, NLRX1","volume":"285","author":"Lam","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e01924","DOI":"10.1128\/mBio.01924-14","article-title":"Developmental stage oxidoreductive states of Chlamydia and infected host cells","volume":"5","author":"Wang","year":"2014","journal-title":"mBio"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1139\/O10-027","article-title":"Higher expression of ferritin protects Chlamydia trachomatis infected HeLa 229 cells from reactive oxygen species mediated cell death","volume":"88","author":"Vardhan","year":"2010","journal-title":"Biochem. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.3390\/ijms9122724","article-title":"Vasorelaxant and antioxidant activities of Spilanthes acmella Murr","volume":"9","author":"Wongsawatkul","year":"2008","journal-title":"Int. J. Mol. Sci"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1042\/BJ20150572","article-title":"Kinetic analysis of structural influences on the susceptibility of peroxiredoxins 2 and 3 to hyperoxidation","volume":"473","author":"Poynton","year":"2016","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S0140-6736(88)91339-6","article-title":"\u201cDrug dumping\u201d in donations to Sudan","volume":"1","author":"Ali","year":"1988","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1056\/NEJM199712183372512","article-title":"Inappropriate drug-donation practices in Bosnia and Herzegovina, 1992 to 1996","volume":"337","author":"Berckmans","year":"1997","journal-title":"New Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(81)90129-X","article-title":"Marketing of obsolete antibiotics in Central America","volume":"1","author":"Gustafsson","year":"1981","journal-title":"Lancet"},{"key":"ref_49","unstructured":"WHO Executive Board (1994). Implementation of the global strategy for health for all by the year 2000. Second evaluation. Eighth report on the world health situation. WHO Reg. Publ. Eur. Ser., 52, 1\u2013289."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0140-6736(96)90333-5","article-title":"The infected metropolis","volume":"347","author":"Horton","year":"1996","journal-title":"Lancet"},{"key":"ref_51","first-page":"428","article-title":"Strategies to maintain health in the Third World. Tropical medicine and parasitology: Official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ)","volume":"42","author":"Korte","year":"1991","journal-title":"Eur. PMC"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/12\/1220\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:40:56Z","timestamp":1760179256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/12\/1220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["antiox9121220"],"URL":"https:\/\/doi.org\/10.3390\/antiox9121220","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,3]]}}}