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ROS and mitochondrial membrane potential were measured by H2DCFDA- and JC-1-based fluorometric analysis. ELISA was performed for various Th1 and Th2 cytokines in both in vitro and in vivo infected conditions to evaluate the type of immunological responses. The role of UCP2 was assessed by lipofectamine-mediated transfection and overexpression in macrophages and short hairpin RNA-mediated knockdown of UCP2 in infected animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genipin reduced the infection-induced UCP2 levels in macrophages, with optimum effect at 100\u2009\u03bcM. Genipin reversed parasite-induced ROS suppression and mitochondrial membrane potential disruption. It has no inhibitory effect on promastigote or axenic amastigote forms, but markedly suppressed amastigote multiplication within macrophages, which was reversed by the ROS scavenger N-acetyl cysteine. Genipin administration (30\u2009mg\/kg\/day) in infected mice showed significant suppression of liver and spleen parasite burdens with an enhanced host-favourable cytokine balance in a ROS\u2013p38 mitogen-activated protein kinase-dependent manner. Co-treatment with genipin plus a sublethal dose of sodium antimony gluconate (SAG50) showed almost a curative reduction in spleen and liver parasite burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest the effectiveness of genipin as a synergistic agent for the front-line antileishmanial drug SAG in circumventing the resistance and toxicity problems associated with its high curative dose.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkaa406","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T11:09:49Z","timestamp":1599649789000},"page":"135-145","source":"Crossref","is-referenced-by-count":14,"title":["Antileishmanial effect of the natural immunomodulator genipin through suppression of host negative regulatory protein UCP2"],"prefix":"10.1093","volume":"76","author":[{"given":"Anand Kumar","family":"Gupta","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Roy","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pijush K","family":"Das","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"2020121103534610400_dkaa406-B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/00034983.1995.11813013","article-title":"New developments in the chemotherapy of leishmaniasis","volume":"89 Suppl 1","author":"Chance","year":"1995","journal-title":"Ann Trop Med Parasitol"},{"key":"2020121103534610400_dkaa406-B2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0169-4758(93)90231-4","article-title":"Practical progress and new drugs for changing patterns of leishmaniasis","volume":"9","author":"Olliaro","year":"1993","journal-title":"Parasitol Today"},{"key":"2020121103534610400_dkaa406-B3","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1126\/science.284.5416.951","article-title":"Requirement for type 2 NO synthase for IL-12 signaling in innate immunity","volume":"284","author":"Diefenbach","year":"1999","journal-title":"Science"},{"key":"2020121103534610400_dkaa406-B4","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<669::AID-IMMU669>3.0.CO;2-N","article-title":"Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani","volume":"28","author":"Engwerda","year":"1998","journal-title":"Eur J Immunol"},{"key":"2020121103534610400_dkaa406-B5","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.4049\/jimmunol.148.4.1188","article-title":"Stimulus\u2013response coupling in monocytes infected with Leishmania. 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