Schistosomiasis, caused by parasites of the genus Schistosoma, 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. S. mansoni NTPDases (known as SmNTPDases, ATP diphosphohydrolases or ecto-apyrases) are potential drug targets for the discovery of new antischistosomal drugs. In this study, we screen NTPDases inhibitors from Centella erecta (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 C. erecta extract, we assessed its in vivo antischistosomal activities against Schistosoma mansoni worms and its in vitro enzymatic apyrase inhibition. Also, molecular docking analysis of asiaticoside against potato apyrase, S. mansoni 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 S. mansoni NTPDases. In mice harboring a patent S. mansoni 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.

中文翻译：

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UF-UHPLC-MS 鉴定积雪草（伞形科）中积雪草苷作为潜在的腺苷三磷酸双磷酸酶抑制剂及其体内抗血吸虫活性

由血吸虫属寄生虫引起的血吸虫病是一种被忽视的疾病，在全球范围内具有很高的流行率，影响了多个国家的 2.4 亿多人。吡喹酮（PZQ）是目前唯一可用于治疗的药物。S. mansoni NTPDases（称为 SmNTPDases、ATP 二磷酸水解酶或ecto -apyrases）是发现新的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筛选积雪草（伞形科）中的NTPDases 抑制剂，确定积雪草苷是一种腺苷三磷酸双磷酸酶结合化合物。从直立叶中分离积雪草苷后提取物，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。此外，进行了积雪草苷对马铃薯腺苷三磷酸双磷酸酶、曼氏沙门氏菌 NTPDases 1 和 2 的分子对接分析。Asiaticoside 显示出显着的体外 apyrase 抑制作用，分子对接研究证实了它在马铃薯 apyrase 和S. mansoni NTPDases 中的可能作用。在感染曼氏沙门氏菌的小鼠中，单次口服积雪草苷（400 mg/kg. po）显示出显着的体内抗血吸虫功效，显着降低了总蠕虫负荷和卵负荷，支持进一步探索腺苷三磷酸双磷酸酶抑制剂作为抗血吸虫剂。