{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:24:51Z","timestamp":1792272291687,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010221","name":"Higher Education Commision, Pakistan","doi-asserted-by":"publisher","award":["5192\/KPK\/NRPU\/R&D\/HEC\/2016"],"award-info":[{"award-number":["5192\/KPK\/NRPU\/R&D\/HEC\/2016"]}],"id":[{"id":"10.13039\/501100010221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Natural products from plants contain many interesting biomolecules. Among them, quercetin (Q), gallic acid (GA), and rutin (R) all have well-reported antileishmanial activity; however, their exact mechanisms of action are still not known. The current study is a step forward towards unveil the possible modes of action of these compounds against Leishmania donovani (the causative agent of visceral leishmaniasis). The selected compounds were checked for their mechanisms of action against L. donovani using different biological assays including apoptosis and necrosis evaluation, effects on genetic material (DNA), quantitative testing of nitric oxide production, ultrastructural modification via transmission electron microscopy, and real-time PCR analysis. The results confirmed that these compounds are active against L. donovani, with IC50 values of 84.65 \u00b5g\/mL, 86 \u00b5g\/mL, and 98 \u00b5g\/mL for Q, GA, and R, respectively. These compounds increased nitric oxide production and caused apoptosis and DNA damage, which led to changes in the treated cells\u2019 ultrastructural behavior and finally to the death of L. donovani. These compounds also suppressed essential enzymes like trypanothione reductase and trypanothione synthetase, which are critical for leishmanial survival. The selected compounds have high antileishmanial potentials, and thus in-vivo testing and further screening are highly recommended.<\/jats:p>","DOI":"10.3390\/molecules26195843","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T21:40:30Z","timestamp":1632778830000},"page":"5843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Bioflavonoid-Induced Apoptosis and DNA Damage in Amastigotes and Promastigotes of Leishmania donovani: Deciphering the Mode of Action"],"prefix":"10.3390","volume":"26","author":[{"given":"Shaila","family":"Mehwish","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Varikuti","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-4244","authenticated-orcid":false,"given":"Mubarak","family":"Ali Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9194-9240","authenticated-orcid":false,"given":"Tariq","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biological Sciences, University of Malakand, Chakdara 18800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-0246","authenticated-orcid":false,"given":"Imdad Ullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Satoskar","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed Abdelhamid","family":"Elsayed Elserehy","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyad 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazif","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/qjmed\/hct116","article-title":"Leishmaniasis: Clinical syndromes and treatment","volume":"107","author":"McGwire","year":"2013","journal-title":"QJM Int. 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