de Mello Leonardo Luiz O, Leal Carla M, Amaro Monique C, Andrade-de-Siqueira Allan I, de Moraes Josué, da Silva Filho Ademar A, Amarante Giovanni W
Núcleo de Identificação e Pesquisa em Princípios Ativos Naturais (NIPPAN), Faculdade de Farmácia, Departamento de Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, Juiz de Fora, MG 36036-900, Brazil.
Grupo de Pesquisas em Metodologias Sintéticas (GPMS), Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, Juiz de Fora, MG 36036-900, Brazil.
ACS Omega. 2025 Jul 9;10(28):30773-30784. doi: 10.1021/acsomega.5c03005. eCollection 2025 Jul 22.
Schistosomiasis, a neglected tropical disease (NTD) caused by flatworms of the genus , affects more than 250 million people globally. Praziquantel (PZQ) remains the sole therapeutic option, underscoring the need for novel treatments. This study investigates the antischistosomal activity of DC. MacLeish (Asteraceae) extracts, and their isolated compounds are against . assays revealed that the rinsed extract (LEE) exhibited a significantly lower EC (18.1 μg/mL) compared to that of the ethanolic extract (EEE) (191.5 μg/mL), with no cytotoxicity observed at concentrations up to 500 μg/mL. UHPLC-ESI-MS/MS analysis annotated 16 metabolites, including sesquiterpene lactones (STLs) and pentacyclic triterpenoids. From LEE, friedelin (), betulinic acid (), and acacetin () were isolated, with the latter two being reported in for the first time. Among them, only betulinic acid () demonstrated significant antischistosomal activity (EC = 36.8 μM, SI > 15.5), while friedelin () and acacetin () were inactive (EC > 50 μM). In -infected mice, the oral administration of betulinic acid () (400 mg/kg) reduced the worm burden by 41.9%, whereas LEE (400 mg/kg) achieved a substantial reduction in both the worm (∼86%) and egg burden (∼81%), also decreasing immature egg deposition by ∼87%. These findings highlight the promising antischistosomal potential of , particularly LEE, warranting further studies to optimize the isolation and characterization of bioactive compounds.
血吸虫病是一种由血吸虫属扁虫引起的被忽视的热带病(NTD),全球有超过2.5亿人受其影响。吡喹酮(PZQ)仍然是唯一的治疗选择,这凸显了对新型治疗方法的需求。本研究调查了DC. MacLeish(菊科)提取物及其分离化合物对血吸虫的抗血吸虫活性。实验表明,与乙醇提取物(EEE)(191.5μg/mL)相比,冲洗提取物(LEE)的半数有效浓度(EC)显著更低(18.1μg/mL),在浓度高达500μg/mL时未观察到细胞毒性。超高效液相色谱-电喷雾串联质谱(UHPLC-ESI-MS/MS)分析鉴定出16种代谢物,包括倍半萜内酯(STLs)和五环三萜类化合物。从LEE中分离出了木栓酮()、桦木酸()和刺槐素(),后两者首次在该植物中被报道。其中,只有桦木酸()表现出显著的抗血吸虫活性(EC = 36.8μM,选择性指数>15.5),而木栓酮()和刺槐素()无活性(EC>50μM)。在感染血吸虫的小鼠中,口服桦木酸()(400mg/kg)使虫负荷降低了41.9%,而LEE(400mg/kg)使虫负荷(约86%)和卵负荷(约81%)大幅降低,还使未成熟卵沉积减少了约87%。这些发现突出了DC. MacLeish,特别是LEE的抗血吸虫潜力,值得进一步研究以优化生物活性化合物的分离和表征。