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马铃薯块茎提取物对内脏利什曼病的保护性炎症反应:成功治疗的新方法。

Protective inflammatory response against visceral leishmaniasis with potato tuber extract: A new approach of successful therapy.

作者信息

Paik Dibyendu, Das Partha, Naskar Kshudiram, Pramanik Pijush Kanti, Chakraborti Tapati

机构信息

Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India.

Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, Kolkata 700032, India.

出版信息

Biomed Pharmacother. 2016 Oct;83:1295-1302. doi: 10.1016/j.biopha.2016.08.046. Epub 2016 Aug 25.

Abstract

The increasing number of drug resistance issue of Leishmania donovani strain to common drugs compels to develop new therapeutics against leishmaniasis with minimal toxicity. In this regard, bioactive phytocomponents may lead to the discovery of new medicines with appropriate efficiency. The important roles of Leishmania proteases in the virulence of Leishmania parasite make them very hopeful targets for the improvement of current remedial of leishmaniasis. As part of a hunt for new drugs, we have evaluated in vivo anti-leishmanial activity of serine protease inhibitor rich fraction (PTEx), isolated by sodium bisulfite extraction from potato tuber. The amastigote load of 25mg/kg body weight/day treated BALB/c mice showed 86.9% decrease in liver and 88.7% in case of spleen. This anti-leishmanial effect was also supported by PTEx induced immunomodulatory activity like acute formation of ROS and prolonged NO generation. The Th1/Th2 cytokine balance in splenocytes of PTEx treated animals was estimated and evaluated by ELISA assay as well as by mRNA expression using RT-PCR. Furthermore, significant survival rate (80%) was observed in PTEx treated hamsters. Thus, from the present observations we could accentuate the potential of PTEx to be employed as a new therapeutics from natural source against L. donovani. This might also provide a novel perception of natural serine protease inhibitor from potato tuber as an alternate approach for the treatment of visceral leishmaniasis.

摘要

杜氏利什曼原虫菌株对常用药物的耐药性问题日益严重,这促使人们开发毒性最小的新型利什曼病治疗药物。在这方面,生物活性植物成分可能会带来具有适当疗效的新药发现。利什曼原虫蛋白酶在利什曼原虫毒力中发挥的重要作用使其成为改善当前利什曼病治疗方法的极具潜力的靶点。作为新药研发工作的一部分,我们评估了通过亚硫酸氢钠从马铃薯块茎中提取得到的富含丝氨酸蛋白酶抑制剂的组分(PTEx)的体内抗利什曼原虫活性。以25mg/kg体重/天的剂量处理BALB/c小鼠后,其肝脏中的无鞭毛体负荷降低了86.9%,脾脏中的降低了88.7%。PTEx诱导的免疫调节活性,如活性氧的急性形成和一氧化氮的持续产生,也支持了这种抗利什曼原虫作用。通过ELISA检测以及使用RT-PCR的mRNA表达评估和估计了PTEx处理动物脾细胞中的Th1/Th2细胞因子平衡。此外,在PTEx处理的仓鼠中观察到了显著的存活率(80%)。因此,从目前的观察结果来看,我们可以强调PTEx作为一种来自天然来源的针对杜氏利什曼原虫的新型治疗药物的潜力。这也可能为将马铃薯块茎中的天然丝氨酸蛋白酶抑制剂作为治疗内脏利什曼病的替代方法提供新的认识。

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