Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India.
Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India.
Int Immunopharmacol. 2020 Aug;85:106623. doi: 10.1016/j.intimp.2020.106623. Epub 2020 Jun 5.
To overcome the drug toxicity and frequent resistance of parasites against the conventional drugs for the healing of human visceral leishmaniasis, innovative plant derived antileishmanial components are very imperative. Fuelled by the complications of clinically available antileishmanial drugs, a novel potato serine protease inhibitor was identified with its efficacy on experimental visceral leishmaniasis (VL). The serine protease inhibitors from potato tuber extract (PTEx) bearing molecular mass of 39 kDa (PTF1), 23 kDa (PTF2) and 17 kDa (PTF3) were purified and identified. Among them, PTF3 was selected as the most active inhibitor (IC 143.5 ± 2.4 µg/ml) regarding its antileishmanial property. Again, intracellular amastigote load was reduced upto 83.1 ± 1.7% in pre-treated parasite and 88.5 ± 0.5% in in vivo model with effective dose of PTF3. Protective immune response by PTF3 was noted with increased production of antimicrobial substances and up-regulation of pro-inflammatory cytokines. Therapeutic potency of PTF3 is also followed by 80% survival in infected hamster. The peptide mass fingerprint (MALDI-TOF) results showed similarity of PTF3 with serine protease inhibitors database. Altogether, these results strongly propose the effectiveness of PTF3 as potent immunomodulatory therapeutics for controlling VL.
为了克服治疗人类内脏利什曼病的传统药物的毒性和寄生虫频繁耐药性,非常需要创新的植物来源的抗利什曼原虫成分。由于临床可用的抗利什曼病药物存在并发症,因此鉴定了一种新型马铃薯丝氨酸蛋白酶抑制剂,其对实验性内脏利什曼病(VL)有效。从马铃薯块茎提取物(PTEx)中分离出具有 39 kDa(PTF1)、23 kDa(PTF2)和 17 kDa(PTF3)分子量的丝氨酸蛋白酶抑制剂,并对其进行了鉴定。其中,PTF3 被选为最有效的抑制剂(IC 143.5±2.4μg/ml),因为它具有抗利什曼原虫特性。此外,在预处理寄生虫中,细胞内无鞭毛体负荷减少了 83.1±1.7%,在体内模型中减少了 88.5±0.5%,有效剂量为 PTF3。PTF3 还能引起保护性免疫反应,增加抗菌物质的产生和促炎细胞因子的上调。PTF3 的治疗效果还表现为感染仓鼠的 80%存活率。肽质量指纹(MALDI-TOF)结果表明 PTF3 与丝氨酸蛋白酶抑制剂数据库具有相似性。总之,这些结果有力地证明了 PTF3 作为有效的免疫调节治疗药物控制 VL 的有效性。