Abstract：
BACKGROUND: Roots of Pothomorphe umbellata (L.) Miq. are used in traditional medicine of Africa and South America for the treatment of malaria and helminthiasis. However, neither P. umbellata nor its isolated compounds have been evaluated against Schistosoma species.
OBJECTIVE: To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis.
METHODS: The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni. PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound.
RESULTS: PuE (EC50: 18.7 μg/mL) and PuH (EC50: 9.2 μg/mL) kill adult schistosomes ex vivo. The UHPLC-HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC50 of 2.9 μM (0.91 μg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans. In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly. 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni, decreasing worm burden in 52.4%.
CONCLUSIONS: This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics.
OBJECTIVE: To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis.
METHODS: The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni. PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound.
RESULTS: PuE (EC50: 18.7 μg/mL) and PuH (EC50: 9.2 μg/mL) kill adult schistosomes ex vivo. The UHPLC-HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC50 of 2.9 μM (0.91 μg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans. In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly. 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni, decreasing worm burden in 52.4%.
CONCLUSIONS: This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics.
摘要：
背景：Pothomorpheumbellata的根（L.）Miq。在非洲和南美的传统医学中用于治疗疟疾和蠕虫病。然而,均未对其分离的化合物进行过针对血吸虫物种的评估。
目的：研究山葵根提取物和分离的化合物4-nerolidyl儿茶酚（4-NC）在体外和小鼠血吸虫病模型中对曼氏血吸虫的抗血吸虫作用。
方法:制备伞形假单胞菌根的粗水醇(PuE)和己烷(PuH)提取物,并首先进行针对成年曼氏链球菌的离体表型筛选。通过HPLC-DAD分析PuH,UHPLC-HRMS/MS,并接受色谱分馏，导致4-NC的隔离。针对成年血吸虫和血吸虫病的小鼠模型，对4-NC的驱虫特性进行了离体分析，以治疗专利和专利曼氏链球菌感染。吡喹酮(PZQ)用作参考化合物。
结果：PuE（EC50：18.7μg/mL）和PuH（EC50：9.2μg/mL）离体杀死成年血吸虫。UHPLC-HRMS/MS分析PuH,最活跃的提取物，揭示了4-NC的存在，peltatolA,和peltatolB或C.从PuH隔离后，4-NC具有显着的体外杀血吸虫活性，EC50为2.9μM（0.91μg/mL），对Vero哺乳动物细胞的选择性指数高于68，不影响线虫秀丽隐杆线虫的生存能力。在专利曼森尼感染中，4-NC口服治疗减少了52.1%和52.3%的蠕虫负担和产蛋量，分别,也减少脾肿大和肝肿大。4-NC,与PZQ不同,显示了对幼年曼索尼的体内功效，蠕虫负担减少52.4%。
结论：本研究表明，伞形根具有抗血吸虫活性，支持这种植物对寄生虫的药用。4-NC被鉴定为有效的体外和体内抗血吸虫化合物之一，并且是开发新型驱虫药的潜在线索。
目的：研究山葵根提取物和分离的化合物4-nerolidyl儿茶酚（4-NC）在体外和小鼠血吸虫病模型中对曼氏血吸虫的抗血吸虫作用。
方法:制备伞形假单胞菌根的粗水醇(PuE)和己烷(PuH)提取物,并首先进行针对成年曼氏链球菌的离体表型筛选。通过HPLC-DAD分析PuH,UHPLC-HRMS/MS,并接受色谱分馏，导致4-NC的隔离。针对成年血吸虫和血吸虫病的小鼠模型，对4-NC的驱虫特性进行了离体分析，以治疗专利和专利曼氏链球菌感染。吡喹酮(PZQ)用作参考化合物。
结果：PuE（EC50：18.7μg/mL）和PuH（EC50：9.2μg/mL）离体杀死成年血吸虫。UHPLC-HRMS/MS分析PuH,最活跃的提取物，揭示了4-NC的存在，peltatolA,和peltatolB或C.从PuH隔离后，4-NC具有显着的体外杀血吸虫活性，EC50为2.9μM（0.91μg/mL），对Vero哺乳动物细胞的选择性指数高于68，不影响线虫秀丽隐杆线虫的生存能力。在专利曼森尼感染中，4-NC口服治疗减少了52.1%和52.3%的蠕虫负担和产蛋量，分别,也减少脾肿大和肝肿大。4-NC,与PZQ不同,显示了对幼年曼索尼的体内功效，蠕虫负担减少52.4%。
结论：本研究表明，伞形根具有抗血吸虫活性，支持这种植物对寄生虫的药用。4-NC被鉴定为有效的体外和体内抗血吸虫化合物之一，并且是开发新型驱虫药的潜在线索。
