Withania somnifera chemotype NMITLI 101R significantly increases the efficacy of antileishmanial drugs by generating strong IFN-γ and IL-12 mediated immune responses in Leishmania donovani infected hamsters

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• 作者：Chandra Dev Pati Tripathi^a ; Pramod Kumar Kushawaha^a ; ^d ; Rajender Singh Sangwan^b ; Chitra Mandal^c ; Shailja Misra-Bhattacharya^a ; Anuradha Dube^a ; ^{anuradhadube@gmail.com} ; ^{anuradha_dube@rediffmail.com} ; ^{anuradha_dube@hotmail.com}
• 关键词：Withania somnifera ; Chemotype NMITLI 101R ; Leishmania donovani ; Th1 response ; Delayed type hypersensitivity (DTH)
• 刊名：Phytomedicine
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：24
• 期：Complete
• 页码：87-95
• 全文大小：1753 K
• 卷排序：24

文摘

Withania somnifera (L.) Dunal (Solanaceae), commonly known as Ashwagandha, is one of the most important medicinal plant in the traditional Indian medical systems. Pharmacological studies have established that root extracts of W. somnifera contain several bioactive constituents called withanolides. The plant has long been used for its several beneficial properties and recently as an immunomodulator.Hypothesis/PurposeA combination therapy including a potential and safe immunostimulant with lower doses of effective drug, which can reduce the parasitic burden and simultaneously can produce an enhancement of adaptive immunity, has proven to be significantly a more effective approach than immunotherapy or drug therapy alone.Study designEvaluation of the immunostimulatory effect of W. somnifera chemotype NMITLI 101R when used in combination with ED50 doses of antileishmanial drugs in Leishmania donovani infected hamsters.MethodsInfected animals were administered with chemotype 101R(30 mg/kg × 15 days) either alone or in combination with ED50 doses of miltefosine (10 mg/kg × 5 days), paromomycin (30 mg/kg × 5 days) or amphotericin B (0.5 mg/kg × 5 days). The treated animals were euthanized on days 30 and 60 post-treatment (p.t.) and checked for parasite clearance, delayed type hypersensitivity (DTH) response, cytokine and inducible nitric oxide synthase levels by real-time PCR, nitric oxide (NO) production, reactive oxygen species (ROS) generation, lymphoproliferative and antibody responses.ResultsThe group of animals that received 101R and ED50 dose of miltefosine showed optimum inhibition of parasite multiplication (∼98%) by day 60 p.t. followed by the group that received 101R plus paromomycin (∼94%) and 101R plus amphotericin B (∼93%). The efficacy was well supported by the increased inducible NO synthase mRNA transcript, strong IFN-γand IL-12 mediated Th1 immune responses and significantly suppressed levels of Th2 cytokines (IL-4, IL-10 and TGF-β). Additionally, same therapy also induced significant increase in the level of NO production, ROS generation, Leishmania specific IgG2 antibody along with profound DTH and strong T-cell responses as compared with all the other treated groups.ConclusionOur results suggest that combination of chemotype 101R with ED50 doses of antileishmanial drugs may provide a promising alternative for the cure of visceral leishmaniasis with significant restoration of the host immune response.