Antiparasitic properties of 4-nerolidylcatechol from Pothomorphe umbellata (L.) Miq. (Piperaceae) in vitro and in mice models with either prepatent or patent Schistosoma mansoni infections

• Published in: Journal of ethnopharmacology Vol. 313; p. 116607
• Main Authors: Costa, Danilo de Souza, Leal, Carla Monteiro, Cajas, Rayssa A., Gazolla, Matheus Coutinho, Silva, Lívia Mara, Carvalho, Lara Soares Aleixo de, Lemes, Bruna L., Moura, Renato Oliveira de, Almeida, Juliana de, de Moraes, Josué, da Silva Filho, Ademar A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.09.2023
• Subjects: Animals; Anthelminthic; Anthelmintics - pharmacology; Anthelmintics - therapeutic use; Antiparasitic Agents - pharmacology; Antischistosomal; Mammals; Mice; Natural products; Piper umbellata; Piperaceae - chemistry; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Praziquantel - pharmacology; Schistosoma mansoni; Schistosomiasis - drug therapy; Schistosomiasis mansoni - drug therapy; Schistosomiasis mansoni - parasitology; Schistosomicidal; Piper umbellata; Antischistosomal; Natural products; Schistosomicidal; Anthelminthic
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2023.116607

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. 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. 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. 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%. 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. [Display omitted] •P. umbellata root extracts showed in vitro schistosomicidal properties.•4-nerolidylcatechol, with high in vitro antischistosomal effects, was isolated.•4-nerolidylcatechol was not toxic to mammalian cells or Caenorhabditis elegans.•4-nerolidylcatechol was in vivo active against juvenile and adult S. mansoni.•The activity supports the medicinal use of P. umbellata roots in treating parasites.