{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:02:12Z","timestamp":1780084932235,"version":"3.54.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The efficacy of 18\u03b2-glycyrrhetinic acid (GRA), a pentacyclic triterpene belonging to the \u03b2-amyrin series of plant origin, was evaluated in experimental visceral leishmaniasis. GRA is reported to have antitumor and immunoregulatory activities, which may be attributable in part to the induction of NO. Indeed, an 11-fold increase in NO production was observed with 20 \u03bcM GRA in mouse peritoneal macrophages infected with Leishmania donovani promastigotes. In addition to having appreciable inhibitory effects on amastigote multiplication within macrophages (IC50, 4.6 \u03bcg\/ml), complete elimination of liver and spleen parasite burden was achieved by GRA at a dose of 50 mg\/kg\/day, given three times, 5 days apart, in a 45-day mouse model of visceral leishmaniasis. GRA treatment resulted in reduced levels of IL-10 and IL-4, but increased levels of IL-12, IFN-\u03b3, TNF-\u03b1, and inducible NO synthase, reflecting a switch of CD4+ differentiation from Th2 to Th1. This treatment is likely to activate immunity, thereby imparting resistance to reinfection. GRA induced NF-\u03baB migration into the nucleus of parasite-infected cells and caused a diminishing presence of I\u03baB in the cytoplasm. The lower level of cytoplasmic I\u03baB\u03b1 in GRA-treated cells resulted from increased phosphorylation of I\u03baB\u03b1 and higher activity of I\u03baB kinase (IKK). Additional experiments demonstrated that GRA does not directly affect IKK activity. These results suggest that GRA exerts its effects at some level upstream of IKK in the signaling pathway and induces the production of proinflammatory mediators through a mechanism that, at least in part, involves induction of NF-\u03baB activation.<\/jats:p>","DOI":"10.4049\/jimmunol.175.2.1161","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T22:40:18Z","timestamp":1398206418000},"page":"1161-1169","source":"Crossref","is-referenced-by-count":57,"title":["18\u03b2-Glycyrrhetinic Acid Triggers Curative Th1 Response and Nitric Oxide Up-Regulation in Experimental Visceral Leishmaniasis Associated with the Activation of NF-\u03baB"],"prefix":"10.1093","volume":"175","author":[{"given":"Anindita","family":"Ukil","sequence":"first","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology , Calcutta ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna","family":"Biswas","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology , Calcutta ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapasi","family":"Das","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology , Calcutta ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pijush K","family":"Das","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology , Calcutta ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,7,15]]},"reference":[{"key":"2026020212132240100_R1","first-page":"37","volume-title":"Ann. 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