Serine protease inhibitors rich Coccinia grandis (L.) Voigt leaf extract induces protective immune responses in murine visceral leishmaniasis
Autor: | Pijush Kanti Pramanik, Asmita Pramanik, Tapati Chakraborti, Dibyendu Paik |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Serine Proteinase Inhibitors Leishmania donovani Spleen RM1-950 Pharmacology Immunomodulation Mice 03 medical and health sciences 0302 clinical medicine Immune system In vivo medicine Animals Visceral leishmaniasis Immunity Cellular Mice Inbred BALB C Coccinia grandis (L.) Voigt Serine protease inhibitor biology Plant Extracts Effector Leishmaniasis General Medicine Antileishmanial activity biology.organism_classification medicine.disease Immunity Humoral Plant Leaves Cucurbitaceae 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Toxicity Leishmaniasis Visceral Female Therapeutics. Pharmacology |
Zdroj: | Biomedicine & Pharmacotherapy, Vol 111, Iss, Pp 224-235 (2019) |
ISSN: | 0753-3322 |
Popis: | Leishmaniasis is a parasite-mediated tropical disease affecting millions of individuals worldwide. The available antileishmanial chemotherapeutic modalities exhibit adverse toxicity, exorbitant price and advent of drug-resistant parasites. Hence, plant-derived products are an alternative preference for the emergence of novel and effective antileishmanial agents that rejuvenate the host immunity with limited toxicity. The present work is complementary to our previous report that revealed the in vitro antileishmanial and immunomodulatory activity of Coccinia grandis (L.) Voigt leaf extract (Cg-Ex) rich in serine protease inhibitors. Thus, preliminary objectives of the study were to elucidate the leishmanicidal activity and host effector mechanism in Leishmania donovani infected BALB/c mice treated with Cg-Ex. Oral administration of Cg-Ex significantly reduced the spleen and liver parasite burden at dose-dependently. The parasite elimination was associated with generation of ROS and NO that are interrelated with up-regulation of disease-suppressing Th1 cytokines and down-regulation of disease-promoting Th2 cytokines at both protein and mRNA level. Moreover, Cg-Ex augmented the delayed-type hypersensitivity (DTH) response and serum IgG2a level which are correlated with the diminution of parasite burden with no hepatic and renal toxicity. Additionally, histological analysis of spleen depicted the improvement of structural disorganization of white and red pulp after Cg-Ex treatment. Therefore, our intriguing findings have presented the first indication of in vivo antileishmanial efficacy through activation of pro-inflammatory immune responses of the host by a natural plant leaf extract (Cg-Ex) containing serine protease inhibitors which could have a role as a potential immunomodulator against visceral leishmaniasis. |
Databáze: | OpenAIRE |
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