Chandrasekaran Sambamurthy, Veronica Jalaja, Sundar Shyam, Maurya Radheshyam
Department of Animal Biology, University of Hyderabad, Hyderabad, India.
Infectious Disease Research Laboratory, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Front Med (Lausanne). 2017 May 12;4:55. doi: 10.3389/fmed.2017.00055. eCollection 2017.
Visceral leishmaniasis (VL) causes fatal life-threatening disease, if left untreated. The current drugs have various limitations; hence, natural products from medicinal plants are being focused in search of new drugs to treat leishmaniasis. The aim of the present study was to evaluate the antileishmanial and immunomodulatory activities of F5 and F6 alcoholic fractions from leaves and purified withaferin-A in -infected peritoneal macrophages and BALB/c mice. We observed that F5 (15 µg/mL), F6 (10 µg/mL), and withaferin-A (1.5 µM) reduce amastigote count in peritoneal macrophages and induce reactive oxygen species and significant decrease in IL-10 mRNA expression compared to control upon treatment. Subsequently, study mice were treated with F5 (25 and 50 mg/kg b.wt.), F6 (25 and 50 mg/kg b.wt.) orally, and withaferin-A (2 mg/kg b.wt.) intraperitoneally for 10 consecutive days and a drastic reduction in parasite burden in both spleen and liver were observed. The treatment resulted in the reduction in IL-10, IL-4, and TGF-β mRNA expression and a significant increase in IFN-γ/IL-10 expression ratio in the treated group compared to control. The humoral response of these alcoholic fractions and withaferin-A shows increased IgG2a levels when compared with IgG1 in treated mice. Taken together, our result concludes that withanolides in alcoholic fractions demonstrate a potent antileishmanial and immunomodulatory activities in experimental VL.
内脏利什曼病（VL）若不治疗会导致致命的危及生命的疾病。目前的药物有各种局限性；因此，药用植物中的天然产物正成为寻找治疗利什曼病新药的重点。本研究的目的是评估从叶片中提取并经纯化的阿魏酸A的F5和F6乙醇提取物在感染的腹腔巨噬细胞和BALB/c小鼠中的抗利什曼原虫和免疫调节活性。我们观察到，与对照组相比，F5（15μg/mL）、F6（10μg/mL）和阿魏酸A（1.5μM）可减少腹腔巨噬细胞中的无鞭毛体数量，诱导活性氧产生，并显著降低IL-10 mRNA表达。随后，对研究小鼠连续10天口服F5（25和50mg/kg体重）、F6（25和50mg/kg体重），腹腔注射阿魏酸A（2mg/kg体重），观察到脾脏和肝脏中的寄生虫负荷均大幅降低。与对照组相比，治疗导致治疗组中IL-10、IL-4和TGF-β mRNA表达降低，IFN-γ/IL-10表达比值显著升高。与治疗小鼠中的IgG1相比，这些乙醇提取物和阿魏酸A的体液反应显示IgG2a水平升高。综上所述，我们的结果表明，乙醇提取物中的醉茄内酯在实验性VL中表现出强大的抗利什曼原虫和免疫调节活性。
