寻求一种新型的抗雪鬼药物

Echinococcosis is an often fatal zoonotic disease caused by infection with the larval stage of tapeworms from the genus Echinococcus. These parasitic worms are found across much of the globe and are particularly prevalent in the northern hemisphere, such as Europe, Central and Eastern Asia, and North America.

这life cycle of Echinococcus is a relatively complex one, involving a (usually) herbivorous mammal as an intermediate host and a carnivorous mammal, such as dogs or foxes, as the definitive host.

人类是echinococcus的意外中间宿主,感染通过ingestion of food or water containing parasite eggs,通过直接接触被污染的土壤,或与感染的动物宿主接触。

这two main types of Echinococcosis that appear in humans are the cystic form (CE) caused byE.颗粒,以及由E. multilocularis

Life cycle of Echinococcus multilocularis, the tapeworm responsible for Alveolar Echinococcosis. Source:CDC,,,,Public Domain

Upon infection withE. multiolcularis,寄生虫迁移到肝脏并发展为幼虫形式(元模),可无限期增殖。增殖会导致寄生肿瘤样质量增加,这些肿瘤样肿块可以侵入其他组织,例如肺和大脑。AE对公共卫生构成了极大的威胁,被认为是最致命的蠕虫病,如果未经治疗,则在10年内死亡率> 90%。

Unfortunately, once patients are diagnosed the disease has often progressed to the advanced stage and requires invasive surgery to remove the malignant parasitic mass, or prolonged chemotherapy withbenzimidazoles。这se drugs areparasitostatic,因此疗效有限,通常需要重复治疗。因此,需要新的药物来克服这些缺陷,并改善对AE的治疗。

番红花鳄鱼鳄鱼鳄鱼是鳄鱼的来源。资源:Wikimedia Commons,由Kenpei,CC BY-SA 3.0

A recent study by刘和同事调查使用复合鳄鱼治疗AE的情况,已经返回了一些有希望的发现。

Crocus sativus& Crocin

Crocin是在植物中发现的一种天然的类胡萝卜素Crocus sativus(或藏红花),主要负责植物/香料生动的颜色。刘等人研究了鳄鱼作为可能的抗雪球球菌化合物,原因是其证明的抗氧化剂,antitumour, antiangiogenic,,,,anti-inflammatory,抗菌和抗寄生虫作用,,,,as well as its liver, gallbladder and neural protective properties.

Assessment of crocin activity againstE. multilocularis

测试了鳄鱼的抗球球菌作用,以针对元素,生发细胞层和原生体E. multilocularisin vitro,,,,as well as its体内被感染小鼠的疗效。这三种寄生虫tissues were targeted due to their role in the proliferation and survival of the parasite.

体外

体外analyses revealed that crocin was significantly toxic to the protoscoleces and germinal cells ofE. multiocularis元模具。在10μM浓度下,鳄鱼会显着抑制生发细胞的增殖,使细胞活力降低〜45%,并导致生发细胞层从肠系统上脱离,从而造成实质性的结构损伤。

Across a 7-day treatment at the same concentration, crocin was also shown to have killed ~60% of protoscoleces, thereby demonstrating a promisingparasiticidaleffect. Overall, crocin was determined to have a median effective concentration (EC50)of 11.36μM againstE. multilocularis元模具。

In vivo

在感染的小鼠中,通过分析治疗前后的寄生虫的体重来确定鳄鱼的有效性,并在100mg/kg的剂量下显示出显着降低(68%)。再次证明鳄鱼处理对元模的生发细胞层造成了相当大的结构损害。

此外,揭示了用鳄鱼治疗显着提高表达水平白介素2(IL-2)andIL-4,,,,as well as inhibiting the expression ofmatrix metalloproteinases (MMPs)并促进寄生虫周围宿主组织中的胶原蛋白沉积。

An increase in IL-4 has been先前显示的为了限制AE元库的生长,而IL-2的增加was revealed增强免疫反应E. multilocularis,并降低寄生虫逃脱宿主的免疫系统的能力。此外,MMP的作用是降解宿主的细胞外基质,从而允许元模具生长和增殖。因此,MMP的抑制以及胶原蛋白的沉积增加,限制了元模化的生长和涂鸦,并促进了更大的Agranulomatous responseto contain the parasite.

in vitroand体内assessment of crocin highlighted its considerable therapeutic efficacy againstEchinoccocus multilocularis

鳄鱼作用在肠膜片上的图形表示。资源:Liu等,2021

评估鳄鱼毒性

In addition to being highly effective at killing the parasite, drugs must also be safe for the patient/host. The researchers tested its toxicity against Human foreskin fibroblast (HFFs) and Reuber rat hepatoma (RH) cells (in vitro),,,,as well as after 6 weeks in the crocin-treated mice (体内)。

体外,鳄鱼被认为是对HFF和RH细胞系的毒性的一半,而不是E. multilocularismetacestodes and germinal cells. As for its体内毒性,在治疗过程中未观察到不良反应,也没有改变blood indices,经过组织学分析,在经鳄鱼处理的小鼠的肝脏或肾脏中未见损害。

鳄鱼:有希望的新驱虫?

In this work Liu and colleagues demonstrated the considerable parasiticidal activity of crocin againstE. multilocularis体外和体内,及其对哺乳动物细胞系和治疗小鼠的有限毒性。特别是,鳄鱼对AE诱导的肝脏和肾脏纤维化具有积极作用。

作者认为,AE的鳄鱼治疗的免疫作用需要进一步研究,但是,鳄鱼似乎是一种需要进一步研究和开发的AE治疗的高度有希望的替代药物。

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