In vivo and in vitro efficacy of crocin against Echinococcus multilocularis

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. Graphical abstract

Effect of Sunitinib against Echinococcus multilocularis through inhibition of VEGFA-induced angiogenesis

“…IL-4 is a pleiotropic Th2 lymphocyte-derived cytokine, and high IL-5 levels may contribute to the immune escape of E. multilocularis [56] . In our in vivo experiment, the serum IL-4 levels were signi cantly decreased in the control group, compared to the blank group, which was in line with the results of previous studies [21,31,57] ; however, after treatment, the serum IL-4 content in the ABZ and SU11248 groups were not signi cantly different from those in the control groups, which is in contrast to previous results [21,31] . This discrepancy was probably due to previous studies using BALB/c mice, which differ genetically from C57BL/6 mice, thus leading to different pathological immune responses.…”

A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice

“…The animal model was established by intraperitoneal injection of protoscoleces in this study, which is consistent with previous studies (25). However, it should be noted that this differs substantially from natural infection because the failure rate is higher than that of natural infection, and most E. multilocularis grows in the abdominal cavity and liver rather than in a single organ.…”

Antiparasitic Effects of Asteraceae Species Extracts on Echinococcus granulosus s.s

“…In this extract terpenoid and phenolic compounds have been detected [ 51 ]. On the other hand, the terpenoid crocin exerted in vitro and in vivo activity against E. multilocularis [ 52 ].…”