{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:38:36Z","timestamp":1758807516481,"version":"3.41.2"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:00:00Z","timestamp":1696032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100012725","name":"Tecnol\u00f3gico Nacional de M\u00e9xico","doi-asserted-by":"publisher","award":["13881.22-P"],"award-info":[{"award-number":["13881.22-P"]}],"id":[{"id":"10.13039\/100012725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Leishmania mexicana is one of the causal agents of cutaneous leishmaniasis. Current antileishmanial chemotherapeutics have demonstrated adverse side effects; thus, alternative treatments are needed. In this study, we performed in silico and in vitro analyses of the leishmanicidal potential of the most abundant phenolic compounds identified in black sesame sprouts biostimulated with Bacillus clausii. The molecular docking analysis showed strong interactions (binding free energies between \u22126.5 and \u22129.5\u2009kcal\/mol) of sesaminol 2-O-triglucoside, pinoresinol dihexoside, isoverbascoside, and apigenin with the arginase, leishmanolysin, cysteine peptidase B, and pyruvate kinase leishmanial enzymes. Furthermore, almost all phenolic compounds interacted with the active site residues of L. mexicana enzymes. In vitro, the B. clausii-biostimulated sprout phenolic extracts and apigenin inhibited the growth of promastigotes with IC50 values of 0.08\u2009mg gallic acid equivalent\/mL and 6.42\u2009\u03bcM (0.0017\u2009mg\/mL), respectively. Additionally, in the macrophage infection model, cells treated with B. clausii-biostimulated sprout phenolic extracts and infected with L. mexicana exhibited significantly (P\u00a0&amp;lt;\u00a00.05) reduced nitric oxide production and decreased parasite burden. Altogether, our study provides important data related to high efficacy and less toxic natural antileishmanial candidates against promastigotes of L. mexicana.<\/jats:p>","DOI":"10.1093\/lambio\/ovad115","type":"journal-article","created":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T05:50:21Z","timestamp":1696139421000},"source":"Crossref","is-referenced-by-count":1,"title":["Biostimulated-sesame sprout extracts as potential agents against <i>Leishmania mexicana<\/i>"],"prefix":"10.1093","volume":"76","author":[{"given":"Karime G","family":"Gardu\u00f1o-F\u00e9lix","sequence":"first","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Molecular y Bioactivos, Tecnol\u00f3gico Nacional de M\u00e9xico-Instituto Tecnol\u00f3gico de Culiac\u00e1n , 80220 Culiac\u00e1n , M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4731-2792","authenticated-orcid":false,"given":"Jes\u00fas J","family":"Roch\u00edn-Medina","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Molecular y Bioactivos, Tecnol\u00f3gico Nacional de M\u00e9xico-Instituto Tecnol\u00f3gico de Culiac\u00e1n , 80220 Culiac\u00e1n , M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina C","family":"Murua-L\u00f3pez","sequence":"additional","affiliation":[{"name":"CAC BB-UAS-264. Posgrados de la Facultad de Ciencias Qu\u00edmico-Biol\u00f3gicas, Universidad Auton\u00f3ma de Sinaloa , 80030 Culiac\u00e1n , M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-205X","authenticated-orcid":false,"given":"H\u00e9ctor S","family":"L\u00f3pez-Moreno","sequence":"additional","affiliation":[{"name":"CAC BB-UAS-264. Posgrados de la Facultad de Ciencias Qu\u00edmico-Biol\u00f3gicas, Universidad Auton\u00f3ma de Sinaloa , 80030 Culiac\u00e1n , M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0138-992X","authenticated-orcid":false,"given":"Karina","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Molecular y Bioactivos, Tecnol\u00f3gico Nacional de M\u00e9xico-Instituto Tecnol\u00f3gico de Culiac\u00e1n , 80220 Culiac\u00e1n , M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"key":"2023100412152468500_bib1","first-page":"527","article-title":"Discovery of novel pyruvate kinase inhibitors in Leishmania major among FDA approved drugs through a system biology and molecular docking approach","volume":"18","author":"Amiri-Dashatan","year":"2021","journal-title":"Turkish J Pharm Sci"},{"key":"2023100412152468500_bib2","doi-asserted-by":"crossref","first-page":"e0007206","DOI":"10.1371\/journal.pntd.0007206","article-title":"In vitro activity and mode of action of phenolic compounds on Leishmania donovani","volume":"13","author":"Antwi","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"2023100412152468500_bib3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.idc.2018.10.004","article-title":"Cutaneous leishmaniasis: updates in diagnosis and management","volume":"33","author":"Aronson","year":"2019","journal-title":"Infect Dis Clin North Am"},{"key":"2023100412152468500_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.ppat.1005658","article-title":"Cysteine peptidase B regulates leishmania mexicana virulence through the modulation of GP63 expression","volume":"12","author":"Casgrain","year":"2016","journal-title":"PLoS Pathog"},{"key":"2023100412152468500_bib5","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.3390\/molecules27165183","article-title":"Mexican Oregano (Lippia berlandieri Schauer and Poliomintha longiflora Gray) essential oils induce cell death by apoptosis in Leishmania ( Leishmania) mexicana promastigotes","volume":"27:","author":"Chac\u00f3n-Vargas","year":"2022","journal-title":"Molecules"},{"key":"2023100412152468500_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12639-010-0006-3","article-title":"Drug targets in Leishmania","volume":"34","author":"Chawla","year":"2010","journal-title":"J Parasit Dis"},{"key":"2023100412152468500_bib7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00726-010-0630-3","article-title":"Polyamine metabolism in Leishmania: from arginine to trypanothione","volume":"40","author":"Colotti","year":"2011","journal-title":"Amino Acids"},{"key":"2023100412152468500_bib8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/cbdd.13391","article-title":"Cinnamic acids derived compounds with antileishmanial activity target leishmania amazonensis arginase","volume":"93","author":"da\u00a0Silva","year":"2019","journal-title":"Chem Biol Drug Des"},{"key":"2023100412152468500_bib9","first-page":"103","article-title":"Proteins and proteomics of leishmania and trypanosoma","volume-title":"Subcellular Biochemistry","author":"da\u00a0Silva","year":"2014"},{"key":"2023100412152468500_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2023.1066407","article-title":"Apigenin is a promising molecule for treatment of visceral leishmaniasis","volume":"13","author":"Emiliano","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"2023100412152468500_bib11","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s11030-016-9693-8","article-title":"Synthesis of new quinazolin-2,4-diones as anti-Leishmania mexicana agents","volume":"20","author":"Enciso","year":"2016","journal-title":"Mol Divers"},{"key":"2023100412152468500_bib12","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1021\/acs.jnatprod.5b00011","article-title":"Effect of Apigenin on Leishmania amazonensis is associated with reactive oxygen species production followed by mitochondrial dysfunction","volume":"78","author":"Fonseca-Silva","year":"2015","journal-title":"J Nat Prod"},{"key":"2023100412152468500_bib13","doi-asserted-by":"crossref","first-page":"e14666","DOI":"10.1371\/journal.pone.0014666","article-title":"Reactive oxygen species production and mitochondrial dysfunction contribute to Quercetin induced death in Leishmania amazonensis","volume":"6","author":"Fonseca-Silva","year":"2011","journal-title":"PLoS One"},{"key":"2023100412152468500_bib14","doi-asserted-by":"crossref","first-page":"e0004442","DOI":"10.1371\/journal.pntd.0004442","article-title":"Oral efficacy of apigenin against cutaneous leishmaniasis: involvement of reactive oxygen species and autophagy as a mechanism of action","volume":"10","author":"Fonseca-Silva","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"2023100412152468500_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/2603730","article-title":"Cutaneous leishmaniasis: the complexity of host's effective immune response against a polymorphic parasitic disease","volume":"2019","author":"Gabriel","year":"2019","journal-title":"J Immunol Res"},{"key":"2023100412152468500_bib16","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1007\/s11694-021-01115-1","article-title":"Phenolic profile in black sesame sprouts biostimulated with Bacillus clausii","volume":"15","author":"Gardu\u00f1o-F\u00e9lix","year":"2021","journal-title":"Food Measure"},{"key":"2023100412152468500_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/molecules21050589","article-title":"Arginase flavonoid anti-leishmanial in silico inhibitors flagged against anti-targets","volume":"21","author":"Glisic","year":"2016","journal-title":"Molecules"},{"key":"2023100412152468500_bib18","doi-asserted-by":"crossref","first-page":"6893","DOI":"10.1074\/jbc.M805861200","article-title":"The Leishmania surface protease GP63 cleaves multiple intracellular proteins and actively participates in p38mitogen-activated protein kinase inactivation","volume":"284","author":"Hall\u00e9","year":"2009","journal-title":"J Biol Chem"},{"key":"2023100412152468500_bib19","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.3390\/molecules27217579","article-title":"Antileishmanial activities of medicinal herbs and phytochemicals in vitro and in vivo: an update for the years 2015 to 2021","volume":"27","author":"Hassan","year":"2022","journal-title":"Molecules"},{"key":"2023100412152468500_bib20","doi-asserted-by":"crossref","first-page":"e18724","DOI":"10.1371\/journal.pone.0018724","article-title":"Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function","volume":"6","author":"Hassani","year":"2011","journal-title":"PLoS One"},{"key":"2023100412152468500_bib21","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1002\/iub.2129","article-title":"Leishmania species-dependent functional duality of toll-like receptor 2","volume":"71","author":"Jafarzadeh","year":"2019","journal-title":"IUBMB Life"},{"key":"2023100412152468500_bib22","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1002\/jsfa.10306","article-title":"Increase in phenolic compounds of coriandrum sativum L. after the application of a Bacillus halotolerans biofertilizer","volume":"100","author":"Jim\u00e9nez-G\u00f3mez","year":"2020","journal-title":"J Sci Food Agric"},{"key":"2023100412152468500_bib23","doi-asserted-by":"crossref","first-page":"0","DOI":"10.1111\/pim.12520","article-title":"Olive (Olea europaea) leaf extract alters the cytokine profile of Leishmania major-infected macrophages: new insight into the underlying mechanism","volume":"40","author":"Kheirandish","year":"2018","journal-title":"Parasite Immunol"},{"key":"2023100412152468500_bib24","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1111\/j.1365-2958.2006.05459.x","article-title":"the major surface-metalloprotease of the parasitic protozoan, Leishmania, protects against antimicrobial peptide-induced apoptotic killing","volume":"62","author":"Kulkarni","year":"2006","journal-title":"Mol Microbiol"},{"key":"2023100412152468500_bib25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fcimb.2012.00083","article-title":"The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response","volume":"2","author":"Liu","year":"2012","journal-title":"Front Cell Inf Microbio"},{"key":"2023100412152468500_bib26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41401-019-0228-6","article-title":"CB-Dock: a web server for cavity detection-guided protein\u2013ligand blind docking","volume":"41","author":"Liu","year":"2020","journal-title":"Acta Pharmacol Sin"},{"key":"2023100412152468500_bib27","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/j.foodchem.2013.05.025","article-title":"Dietary flavonoids fisetin, luteolin and their derived compounds inhibit arginase, a central enzyme in Leishmania (Leishmania) amazonensis infection","volume":"141","author":"Manjolin","year":"2013","journal-title":"Food Chem"},{"key":"2023100412152468500_bib28","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0166-6851(99)00204-2","article-title":"Comparative study of Leishmania mexicana and Trypanosoma brucei NAD- dependent glycerol-3-phosphate dehydrogenase","volume":"106","author":"March\u00e9","year":"2000","journal-title":"Mol Biochem Parasitol"},{"key":"2023100412152468500_bib29","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jmgm.2012.08.003","article-title":"Homology modeling, docking and molecular dynamics of the Leishmania mexicana arginase: a description of the catalytic site useful for drug design","volume":"38","author":"M\u00e9ndez-Cuesta","year":"2012","journal-title":"J Mol Graphics Modell"},{"key":"2023100412152468500_bib30","doi-asserted-by":"crossref","first-page":"14741","DOI":"10.1021\/acsomega.0c01584","article-title":"Homology modeling of Leishmanolysin (gp63) from Leishmania panamensis and molecular docking of flavonoids","volume":"5","author":"Mercado-Camargo","year":"2020","journal-title":"ACS Omega"},{"key":"2023100412152468500_bib31","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/ejlt.200700057","article-title":"Lignan contents in sesame seeds and products","volume":"109","author":"Moazzami","year":"2007","journal-title":"Eur J Lipid Sci Technol"},{"key":"2023100412152468500_bib32","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jcs.2010.08.010","article-title":"Phenolic content and antioxidant activity of tortillas produced from pigmented maize processed by conventional nixtamalization or extrusion cooking","volume":"52","author":"Mora-Rochin","year":"2010","journal-title":"J Cereal Sci"},{"key":"2023100412152468500_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2017.02682","article-title":"Arginine and polyamines fate in Leishmania infection","volume":"8","author":"Muxel","year":"2018","journal-title":"Front Microbiol"},{"key":"2023100412152468500_bib34","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jmgm.2013.12.010","article-title":"Antileishmanial phytochemical phenolics: molecular docking to potential protein targets","volume":"48","author":"Ogungbe","year":"2014","journal-title":"J Mol Graphics Modell"},{"key":"2023100412152468500_bib35","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.4155\/fmc.13.114","article-title":"Interactions of antiparasitic alkaloids with Leishmania protein targets: a molecular docking analysis","volume":"5","author":"Ogungbe","year":"2013","journal-title":"Future Med Chem"},{"key":"2023100412152468500_bib36","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1007\/s00436-020-06736-x","article-title":"An overview of biochemically characterized drug targets in metabolic pathways of Leishmania parasite","volume":"119","author":"Raj","year":"2020","journal-title":"Parasitol Res"},{"key":"2023100412152468500_bib37","doi-asserted-by":"crossref","first-page":"110429","DOI":"10.1016\/j.lwt.2020.110429","article-title":"Effect of Bacillus clausii-fermented spent coffee ground extract on Salmonella-infected macrophages","volume":"137","author":"Roch\u00edn-Medina","year":"2021","journal-title":"LWT"},{"key":"2023100412152468500_bib38","doi-asserted-by":"crossref","first-page":"111688","DOI":"10.1016\/j.ejmech.2019.111688","article-title":"Synthesis of cinnamic acid derivatives and leishmanicidal activity against Leishmania braziliensis","volume":"183","author":"Rodrigues","year":"2019","journal-title":"Eur J Med Chem"},{"key":"2023100412152468500_bib39","doi-asserted-by":"crossref","first-page":"e77460","DOI":"10.1371\/journal.pone.0077460","article-title":"Identification of semicarbazones, thiosemicarbazones and triazine nitriles as inhibitors of Leishmania mexicana cysteine protease CPB","volume":"8","author":"Schr\u00f6der","year":"2013","journal-title":"PLoS One"},{"key":"2023100412152468500_bib40","doi-asserted-by":"crossref","first-page":"4970","DOI":"10.1021\/jf100335j","article-title":"Comprehensive profiling of isoflavones, phytosterols, tocopherols, minerals, crude protein, lipid, and sugar during soybean (Glycine max) germination","volume":"58","author":"Shi","year":"2010","journal-title":"J Agric Food Chem"},{"key":"2023100412152468500_bib41","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.2174\/1389557522666220404090429","article-title":"Bioactivity of natural polyphenols as antiparasitic agents and their biochemical targets","volume":"22","author":"Soto-S\u00e1nchez","year":"2022","journal-title":"MRMC"},{"key":"2023100412152468500_bib42","doi-asserted-by":"crossref","first-page":"A3.B.1","DOI":"10.1002\/0471142735.ima03bs111","article-title":"Trypan blue exclusion test of cell viability","volume":"111","author":"Strober","year":"2015","journal-title":"CP Immunol"},{"key":"2023100412152468500_bib43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1389557517666170425105129","article-title":"Limitations of current therapeutic options, possible drug targets and scope of natural products in control of leishmaniasis","volume":"18","author":"Tiwari","year":"2017","journal-title":"MRMC"},{"key":"2023100412152468500_bib44","first-page":"8040","article-title":"Caryocar coriaceum wittm. Fruit extracts as Leishmania inhibitors: in-vitro and in-silico approaches","author":"Tomiotto-Pellissier","year":"2021","journal-title":"J Biomol Struct Dyn"},{"key":"2023100412152468500_bib45","article-title":"Number of cases of cutaneous leishmaniasis reported [WWW Document]","author":"WHO","year":"2023","journal-title":"Glob Heal Obs"},{"key":"2023100412152468500_bib46","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.exppara.2010.07.014","article-title":"Regulation of the expression of nitric oxide synthase by Leishmania mexicana amastigotes in murine dendritic cells","volume":"126","author":"Wilkins-Rodr\u00edguez","year":"2010","journal-title":"Exp Parasitol"},{"key":"2023100412152468500_bib47","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s11130-005-6931-0","article-title":"Isoflavone contents in germinated soybean seeds","volume":"60","author":"Zhu","year":"2005","journal-title":"Plant Foods Hum Nutr"},{"key":"2023100412152468500_bib48","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1111\/ijfs.14158","article-title":"Effects of probiotic L. plantarum 299v on consumer quality, accumulation of phenolics, antioxidant capacity and biochemical changes in legume sprouts","volume":"54","author":"Z\u0142otek","year":"2019","journal-title":"Int J Food Sci Technol"}],"container-title":["Letters in Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/lambio\/advance-article-pdf\/doi\/10.1093\/lambio\/ovad115\/51822361\/ovad115.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lambio\/article-pdf\/76\/10\/ovad115\/51849136\/ovad115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lambio\/article-pdf\/76\/10\/ovad115\/51849136\/ovad115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T12:37:52Z","timestamp":1696423072000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/lambio\/article\/doi\/10.1093\/lambio\/ovad115\/7287372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,30]]},"references-count":48,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10,4]]}},"URL":"https:\/\/doi.org\/10.1093\/lambio\/ovad115","relation":{},"ISSN":["1472-765X"],"issn-type":[{"type":"electronic","value":"1472-765X"}],"subject":[],"published-other":{"date-parts":[[2023,10]]},"published":{"date-parts":[[2023,9,30]]},"article-number":"ovad115"}}