Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis

Abstract Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Saptarshi Roy, Devawati Dutta, Eswara M. Satyavarapu, Pawan K. Yadav, Chhabinath Mandal, Susanta Kar, Chitra Mandal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80716169997740029d4fce07680fcce7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:80716169997740029d4fce07680fcce7
record_format	dspace
spelling	oai:doaj.org-article:80716169997740029d4fce07680fcce72021-12-02T12:30:53ZMahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis10.1038/s41598-017-03943-y2045-2322https://doaj.org/article/80716169997740029d4fce07680fcce72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03943-yhttps://doaj.org/toc/2045-2322Abstract Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination.Saptarshi RoyDevawati DuttaEswara M. SatyavarapuPawan K. YadavChhabinath MandalSusanta KarChitra MandalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saptarshi Roy Devawati Dutta Eswara M. Satyavarapu Pawan K. Yadav Chhabinath Mandal Susanta Kar Chitra Mandal Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
description	Abstract Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination.
format	article
author	Saptarshi Roy Devawati Dutta Eswara M. Satyavarapu Pawan K. Yadav Chhabinath Mandal Susanta Kar Chitra Mandal
author_facet	Saptarshi Roy Devawati Dutta Eswara M. Satyavarapu Pawan K. Yadav Chhabinath Mandal Susanta Kar Chitra Mandal
author_sort	Saptarshi Roy
title	Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
title_short	Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
title_full	Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
title_fullStr	Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
title_full_unstemmed	Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
title_sort	mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/80716169997740029d4fce07680fcce7
work_keys_str_mv	AT saptarshiroy mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis AT devawatidutta mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis AT eswaramsatyavarapu mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis AT pawankyadav mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis AT chhabinathmandal mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis AT susantakar mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis AT chitramandal mahanineexertsinvitroandinvivoantileishmanialactivitybymodulationofredoxhomeostasis
_version_	1718394287586017280

Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis

Ejemplares similares