体内和体外西红花酸抗泡球蚴的疗效。

In vivo and in vitro efficacy of crocin against Echinococcus multilocularis.

机构信息

Qinghai University Affiliated Hospital, Xining, 810001, Qinghai, People's Republic of China.

Research Center for High Altitude Medicine, Qinghai University, Xining, 810001, Qinghai, People's Republic of China.

出版信息

Parasit Vectors. 2021 Jul 13;14(1):364. doi: 10.1186/s13071-021-04866-4.

DOI:10.1186/s13071-021-04866-4

PMID:34256821

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8278753/

Abstract

BACKGROUND

Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larvae of Echinococcus multilocularis. However, current chemotherapy treatment options are based on benzimidazoles [albendazole (ABZ) and mebendazole], which have limited efficacy. Therefore, novel drugs are necessary for the treatment of this disease.

METHODS

The anthelmintic effects of crocin were tested on E. multilocularis metacestodes, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFFs) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. The in vivo efficacy of crocin was investigated in mice following secondary infection with E. multilocularis. Furthermore, collagen deposition and degradation in host tissues around the metacestodes were evaluated.

RESULTS

In vitro, crocin had a median effective concentration of 11.36 μM against cultured E. multilocularis metacestodes, while it reduced germinal cell viability at a median inhibitory concentration of 10.05 μM. Crocin was less toxic to HFFs and RH mammalian cell lines than to metacestodes. Transmission electron microscopy revealed that crocin treatment resulted in structural damage in the germinal layer. In addition, 60.33 ± 3.06% of protoscoleces were killed by treatment with 10 μM crocin for 7 days, indicating that crocin has a parasiticidal effect. In vivo, the metacestode weight was significantly reduced after the administration of crocin at 50 mg/kg and 100 mg/kg (55.1 and 68.1%, respectively). Metacestode pathology showed structural disruption of the germinal and laminated layers after crocin treatment. The crocin- and ABZ-treated groups presented significant increases in the levels of interleukin (IL)-2 and IL-4. Furthermore, crocin inhibited the expression of matrix metalloproteinases (MMPs) (MMP2 and MMP9) and promoted collagen deposition in the metacestode.

CONCLUSIONS

Crocin was demonstrated to exert parasiticidal activity against E. multilocularis in vitro and in vivo, and can be developed as a novel drug for the treatment of AE.

摘要

背景

泡型包虫病（AE）是一种由细粒棘球绦虫幼虫引起的致命人畜共患病。然而，目前的化疗治疗选择基于苯并咪唑类药物（阿苯达唑和甲苯达唑），其疗效有限。因此，需要新型药物来治疗这种疾病。

方法

在体外测试了藏红花酸对多房棘球蚴原头蚴、生殖细胞和Protoscoleces 的驱虫作用。用人包皮成纤维细胞（HFFs）和 Reuber 大鼠肝癌（RH）细胞评估细胞毒性。通过继发性感染多房棘球蚴在小鼠体内研究藏红花酸的疗效。此外，评估了宿主组织中包虫周围胶原的沉积和降解。

结果

在体外，藏红花酸对培养的多房棘球蚴原头蚴的半数有效浓度为 11.36 μM，而对生殖细胞的抑制浓度为 10.05 μM。藏红花酸对 HFFs 和 RH 哺乳动物细胞系的毒性低于原头蚴。透射电镜显示，藏红花酸处理导致生殖层结构损伤。此外，用 10 μM 藏红花酸处理 7 天，有 60.33±3.06%的Protoscoleces 被杀死，表明藏红花酸具有杀寄生虫作用。在体内，用 50mg/kg 和 100mg/kg 藏红花酸治疗后，原头蚴的重量分别显著减少了 55.1%和 68.1%。包虫病病理学显示，藏红花酸处理后生殖层和层状层的结构破坏。藏红花酸和阿苯达唑治疗组白细胞介素（IL）-2 和 IL-4 水平显著升高。此外，藏红花酸抑制基质金属蛋白酶（MMPs）（MMP2 和 MMP9）的表达并促进包虫内胶原沉积。