Tiwari Brajendra, Pahuja Richa, Kumar Pradeep, Rath Srikanta Kumar, Gupta Kailash Chand, Goyal Neena
Division of Biochemistry, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India.
Nucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Antimicrob Agents Chemother. 2017 Feb 23;61(3). doi: 10.1128/AAC.01169-16. Print 2017 Mar.
Leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. Combination therapies (CT) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. CT are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite In the present study, we investigated the effect of a combination of a traditional Indian medicine (ayurveda), a natural product curcumin and miltefosine, the only oral drug for visceral leishmaniasis (VL) using a -hamster model. We developed an oral nanoparticle-based formulation of curcumin. Nanoformulation of curcumin alone exhibited significant leishmanicidal activity both and In combination with miltefosine, it exhibited a synergistic effect on both promastigotes and amastigotes under conditions. The combination of these two agents also demonstrated increased leishmanicidal activity accompanied by increased production of toxic reactive oxygen/nitrogen metabolites and enhanced phagocytic activity. The combination also exhibited increased lymphocyte proliferation. The present study thus establishes the possible use of nanocurcumin as an adjunct to antileishmanial chemotherapy.
由于药物成本高昂、伴有毒性以及会随着时间产生耐药性，利什曼病的化疗仍然极具挑战性。联合疗法（CT）目前被用于治疗许多疾病，如癌症和疟疾，因为它比单一疗法更有效且更经济实惠。联合疗法被认为是治疗利什曼病的一种新的可探索策略，利什曼病是一种由专性细胞内寄生虫引起的被忽视的热带疾病。在本研究中，我们使用仓鼠模型研究了一种传统印度医学（阿育吠陀）、天然产物姜黄素与米替福新（唯一用于治疗内脏利什曼病的口服药物）联合使用的效果。我们开发了一种基于纳米颗粒的姜黄素口服制剂。单独的姜黄素纳米制剂在体外和体内均表现出显著的杀利什曼原虫活性。与米替福新联合使用时，在体外条件下，它对前鞭毛体和无鞭毛体均表现出协同作用。这两种药物的联合使用还显示出增强的杀利什曼原虫活性，同时伴随着有毒活性氧/氮代谢产物生成增加以及吞噬活性增强。联合使用还表现出淋巴细胞增殖增加。因此，本研究确定了纳米姜黄素作为抗利什曼化疗辅助药物的潜在用途。
