de Carvalho Lara Soares Aleixo, de Souza Vinícius Carius, Rodrigues Vinícius C, Ribeiro Aline Correa, Nascimento Jorge Willian Leandro, Capriles Priscila V S Z, Pinto Priscila de F, de Moraes Josué, da Silva Filho Ademar Alves
Faculdade de Farmácia, Departamento de Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, Juiz de Fora 36036-900, MG, Brazil.
Programa de Pós-Graduação em Modelagem Computacional, Departamento de Ciência da Computação, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, MG, Brazil.
Pharmaceutics. 2022 May 17;14(5):1071. doi: 10.3390/pharmaceutics14051071.
Schistosomiasis, caused by parasites of the genus , is a neglected disease with high global prevalence, affecting more than 240 million people in several countries. Praziquantel (PZQ) is the only drug currently available for the treatment. NTPDases (known as SmNTPDases, ATP diphosphohydrolases or -apyrases) are potential drug targets for the discovery of new antischistosomal drugs. In this study, we screen NTPDases inhibitors from (Apiaceae) using an ultrafiltration combined UHPLC-QTOF-MS method and potato apyrase, identifying asiaticoside as one of the apyrase-binding compounds. After isolation of asiaticoside from extract, we assessed its in vivo antischistosomal activities against worms and its in vitro enzymatic apyrase inhibition. Also, molecular docking analysis of asiaticoside against potato apyrase, NTPDases 1 and 2 were performed. Asiaticoside showed a significant in vitro apyrase inhibition and molecular docking studies corroborate with its possible actions in potato apyrase and NTPDases. In mice harboring a patent infection, a single oral dose of asiaticoside (400 mg/kg. p.o.) showed significantly in vivo antischistosomal efficacy, markedly decreasing the total worm load and egg burden, giving support for further exploration of apyrase inhibitors as antischistosomal agents.
血吸虫病由血吸虫属寄生虫引起，是一种全球流行率高但被忽视的疾病，在多个国家影响着超过2.4亿人。吡喹酮（PZQ）是目前唯一可用于治疗的药物。NTPD酶（称为SmNTPD酶、ATP二磷酸水解酶或 - 腺苷三磷酸双磷酸酶）是发现新型抗血吸虫药物的潜在药物靶点。在本研究中，我们使用超滤结合UHPLC - QTOF - MS方法和马铃薯腺苷三磷酸双磷酸酶从积雪草（伞形科）中筛选NTPD酶抑制剂，鉴定出积雪草苷是与腺苷三磷酸双磷酸酶结合的化合物之一。从积雪草提取物中分离出积雪草苷后，我们评估了其对曼氏血吸虫的体内抗血吸虫活性及其体外酶促腺苷三磷酸双磷酸酶抑制作用。此外，还进行了积雪草苷对马铃薯腺苷三磷酸双磷酸酶、曼氏血吸虫NTPD酶1和2的分子对接分析。积雪草苷显示出显著的体外腺苷三磷酸双磷酸酶抑制作用，分子对接研究证实了其在马铃薯腺苷三磷酸双磷酸酶和曼氏血吸虫NTPD酶中的可能作用。在患有明显曼氏血吸虫感染的小鼠中，单次口服剂量的积雪草苷（400 mg/kg，口服）显示出显著的体内抗血吸虫功效，显著降低了虫体总数和虫卵负荷，为进一步探索腺苷三磷酸双磷酸酶抑制剂作为抗血吸虫药物提供了支持。
