血吸虫病,一种潜在致命的慢性疾病,其病因是血吸虫属的血吸虫蠕虫。,是最普遍和最令人衰弱的被忽视疾病之一。血吸虫病的治疗完全依赖于吡喹酮(PZQ),一种自20世纪70年代以来一直使用的药物,已经有治疗功效降低的报道,与血吸虫耐药或耐药菌株的发展有关。因此,迫切需要寻找新的治疗替代方案。铅球(PLUM),从Plumbago属植物的根部分离的萘醌,由于其对原生动物和蠕虫的抗寄生虫特性,引起了人们对研究的兴趣。这里,我们评估了PLUM对曼氏血吸虫的体内杀血吸虫潜力和计算机药代动力学参数。使用PkCSM和SwissADME平台评估ADMET参数和口服生物利用度,分别。该研究是用五组感染的小鼠进行的,分为以下几组:未经处理的对照组,用PZQ治疗的对照组,三组口服8、16或32mg/kg的PLUM。治疗后,采用Kato-Katz技术评估粪便中的蛋数量(EPG).对动物实施安乐死以恢复蠕虫,收集肠道样本以评估产卵模式,在肝和肠组织上确定卵的负荷,并对组织和肝肉芽肿进行组织病理学和组织形态学评估。PLUM将EPG降低了65.27、70.52和82.49%,减少了总蜗杆载荷46.7、55.25和72.4%,女性蠕虫负荷分别为44.01、52.76和71.16%,对于8、16和32mg/kg的剂量,分别。PLUM还显着减少了未成熟卵的数量,并增加了照片中死亡卵的数量。肝组织中的卵减少36.11、46.46和64.14%,在8、16和32mg/kg的剂量下,在肠组织中也观察到57.22、65.18和80.5%,分别。在所有剂量下,PLUM对肝肉芽肿的组织病理学和组织形态学参数有影响,肉芽肿的数值密度减少了41.11、48.47和70.55%,体积减少了49.56、57.63和71.21%,分别。PLUM是一种有前途的体内抗寄生虫候选药物,不仅对寄生虫学参数起作用,而且对肝肉芽肿也起作用。此外,在硅,通过ADMET,PLUM显示出良好的预测药代动力学特征。
Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus Schistosoma spp., is one of the most prevalent and debilitating neglected diseases. The treatment of schistosomiasis depends exclusively on praziquantel (PZQ), a drug that has been used since the 1970s and that already has reports of reduced therapeutic efficacy, related with the development of Schistosoma-resistant or -tolerant strains. Therefore, the search for new therapeutic alternatives is an urgent need. Plumbagin (PLUM), a naphthoquinone isolated from the roots of plants of the genus Plumbago, has aroused interest in research due to its antiparasitic properties against protozoa and helminths. Here, we evaluated the in vivo
schistosomicidal potential of PLUM against Schistosoma mansoni and the in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The study was carried out with five groups of infected mice and divided as follows: an untreated control group, a control group treated with PZQ, and three groups treated orally with 8, 16, or 32 mg/kg of PLUM. After treatment, the Kato-Katz technique was performed to evaluate a quantity of eggs in the feces (EPG). The animals were euthanized for worm recovery, intestine samples were collected to evaluate the oviposition pattern, the load of eggs was determined on the hepatic and intestinal tissues and for the histopathological and histomorphometric evaluation of tissue and hepatic granulomas. PLUM reduced EPG by 65.27, 70.52, and 82.49%, reduced the total worm load by 46.7, 55.25, and 72.4%, and the female worm load by 44.01, 52.76, and 71.16%, for doses of 8, 16, and 32 mg/kg, respectively. PLUM also significantly reduced the number of immature eggs and increased the number of dead eggs in the oogram. A reduction of 36.11, 46.46, and 64.14% in eggs in the hepatic tissue, and 57.22, 65.18, and 80.5% in the intestinal tissue were also observed at doses of 8, 16, and 32 mg/kg, respectively. At all doses, PLUM demonstrated an effect on the histopathological and histomorphometric parameters of the hepatic granuloma, with a reduction of 41.11, 48.47, and 70.55% in the numerical density of the granulomas and 49.56, 57.63, and 71.21% in the volume, respectively. PLUM presented itself as a promising in vivo antiparasitic candidate against S. mansoni, acting not only on parasitological parameters but also on hepatic granuloma. Furthermore, in silico, PLUM showed good predictive pharmacokinetic profiles by ADMET.