{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:29:06Z","timestamp":1792805346571,"version":"4.5.0"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hypericin, a natural compound from\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Hypericum perforatum<\/jats:named-content>\n            (St. John's wort), has been identified as a specific inhibitor of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n            spermidine synthase (LdSS) using integrated computational and biochemical approaches. Hypericin showed\n            <jats:italic>in vitro<\/jats:italic>\n            inhibition of recombinant LdSS enzyme activity. The\n            <jats:italic>in vivo<\/jats:italic>\n            estimation of spermidine levels in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>\n            promastigotes after hypericin treatment showed significant decreases in the spermidine pools of the parasites, indicating target specificity of the inhibitor molecule. The inhibitor, hypericin, showed significant antileishmanial activity, and the mode of death showed necrosis-like features. Further, decreased trypanothione levels and increased glutathione levels with elevated reactive oxygen species (ROS) levels were observed after hypericin treatment. Supplementation with trypanothione in the medium with hypericin treatment restored\n            <jats:italic>in vivo<\/jats:italic>\n            trypanothione levels and ROS levels but could not prevent necrosis-like death of the parasites. However, supplementation with spermidine in the medium with hypericin treatment restored\n            <jats:italic>in vivo<\/jats:italic>\n            spermidine levels and parasite death was prevented to a large extent. The data overall suggest that the parasite death due to spermidine starvation as a result of LdSS inhibition is not related to elevated levels of reactive oxygen species. This suggests the involvement of spermidine in processes other than redox metabolism in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>\n            parasites. Moreover, the work provides a novel scaffold, i.e., hypericin, as a potent antileishmanial molecule.\n          <\/jats:p>","DOI":"10.1128\/aac.04169-14","type":"journal-article","created":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T03:23:42Z","timestamp":1413257022000},"page":"15-24","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Probing the Molecular Mechanism of Hypericin-Induced Parasite Death Provides Insight into the Role of Spermidine beyond Redox Metabolism in Leishmania donovani"],"prefix":"10.1128","volume":"59","author":[{"given":"Shalini","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamali","family":"Sarma","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Indian Institute of Technology 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