{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:18:44Z","timestamp":1790965124868,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008802","name":"Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy","doi-asserted-by":"publisher","award":["Z.28015\/252\/2016-HPC (EMR)-AYUSH-C)"],"award-info":[{"award-number":["Z.28015\/252\/2016-HPC (EMR)-AYUSH-C)"]}],"id":[{"id":"10.13039\/501100008802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP 2021\/132"],"award-info":[{"award-number":["RSP 2021\/132"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Visceral leishmaniasis (VL), caused by the protozoan parasite <jats:italic>Leishmania donovani<\/jats:italic> (<jats:italic>L. donovani<\/jats:italic>), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance. Therefore, it is time to search for cheap and effective antileishmanial agents. In the present work, we evaluated the antileishmanial potential of sesamol against promastigotes as well as intracellular amastigotes. Further, we tried to work out its mechanism of antileishmanial action on parasites through different assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> antileishmanial assays were performed to evaluate the antileishmanial potential of sesamol on <jats:italic>L. donovani<\/jats:italic>. Cytotoxicity was determined by MTT assay on human THP-1-derived macrophages. Sesamol-induced morphological and ultrastructural changes were determined by electron microscopy. H<jats:sub>2<\/jats:sub>DCFDA staining, JC-1dye staining, and MitoSOX red staining were performed for reactive oxygen assay (ROS), mitochondrial membrane potential, and mitochondrial superoxide, respectively. Annexin V\/PI staining for apoptosis, TUNEL assay, and DNA laddering for studying sesamol-induced DNA fragmentation were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sesamol inhibited the growth and proliferation of <jats:italic>L. donovani<\/jats:italic> promastigotes in a dose-dependent manner. It also reduced the intracellular parasite load without causing significant toxicity on host-macrophages. Overall, it showed antileishmanial effects through induction of ROS, mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death to parasites. Our results suggested the possible use of sesamol for the treatment of leishmaniasis after further <jats:italic>in vivo<\/jats:italic> validations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.749420","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T08:11:46Z","timestamp":1635408706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Sesamol Induces Apoptosis-Like Cell Death in Leishmania donovani"],"prefix":"10.3389","volume":"11","author":[{"given":"Rahat","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shams","family":"Tabrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjadul Kadir","family":"Akand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazlur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atahar","family":"Husein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd","family":"Arish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali S.","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Z.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Husain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdur","family":"Rub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007227","article-title":"Cinnamomum Cassia Exhibits Antileishmanial Activity Against Leishmania Donovani Infection In Vitro and In Vivo","volume":"13","author":"Afrin","year":"2019","journal-title":"PloS NTDs."},{"key":"B2","doi-asserted-by":"publisher","first-page":"8548","DOI":"10.1021\/acsomega.1c00366","article-title":"Antileishmanial Evaluation of Bark Methanolic Extract of Acacia Nilotica: In Vitro and In Silico Studie","volume":"6","author":"Ali","year":"2021","journal-title":"ACS Omega"},{"key":"B3","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.micpath.2016.07.004","article-title":"Mechanistic Insights Into the Mode of Action of Anticandidal Sesamol","volume":"98","author":"Ansari","year":"2017","journal-title":"Microbial pathogenesis."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007206","article-title":"In Vitro Activity and Mode of Action of Phenolic Compounds on Leishmania Donovan","author":"Antwi","year":"2019","journal-title":"PloS NTDs."},{"key":"B5","article-title":"Drugs for Neglected Diseases Initiative (DNDi)","year":"2018"},{"key":"B6","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1007\/s10495-016-1259-9","article-title":"Plumbagin, a Plant-Derived Naphthoquinone Metabolite Induces Mitochondria-Mediated Apoptosis-Like Cell Death in Leishmania Donovani: An Ultrastructural and Physiological Study","volume":"21","author":"Awasthi","year":"2016","journal-title":"Apop"},{"key":"B7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ejmech.2018.10.022","article-title":"Leishmania Treatment and Prevention: Natural and Synthesized Drugs","volume":"160","author":"Bekhit","year":"2018","journal-title":"Euro.J Of Med. 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