Purpose

At present, the chemotherapy for alveolar echinococcosis (AE) is mainly based on albendazole (ABZ). However, more than 20% of patients fail chemotherapy. Therefore, new and more effective treatments are urgently needed. Allicin has been reported to have antibacterial and antiparasitic effects. The objectives of the present study were to investigate the in vivo and in vitro efficacy of allicin against Echinococcus multilocularis (E. multilocularis).

Methods

The effects of allicin on protoscolex survival and structural changes were evaluated in vitro. The 4-week-old BALB/c male mice used for in vivo modelling underwent inoculation of E. multilocularis protoscoleces by intraperitoneal injection, followed by intragastric administration of allicin for 6 weeks. Then, the effects of allicin on lymphocyte subsets, metacestode growth and host tissue matrix metalloproteinase 2 (MMP2)/MMP9 expression around metacestodes in mice were evaluated. The toxicity of allicin was further evaluated in vivo and in vitro.

Results

Att 40 μg/mL, allicin showed a killing effect on protoscoleces in vitro and treatment resulted in the destruction of protoscolex structure. Molecular docking showed that allicin could form hydrogen bonds with E. multilocularis cysteine enzymes. After 6 weeks of in vivo allicin treatment, the spleen index of mice was increased and the weight of metacestodes was reduced. Allicin increased the proportion of CD4⁺ T cells and decreased the proportion of CD8⁺ T cells in the peripheral blood and spleen. Pathological analysis of the metacestodes showed structural disruption of the germinal and laminated layers after allicin treatment. In addition, allicin inhibited the expression of MMP2 and MMP9 in metacestode-surrounding host tissues. At 160 μg/mL, allicin had no significant toxicity to normal hepatocytes but could inhibit hepatoma cell proliferation. At 30 mg/kg, allicin had no significant hepatorenal toxicity in vivo.

Conclusion

These results suggest that allicin exerts anti-E. multilocularis effects in vitro and in vivo and can enhance immune function in mice, with the potential to be developed as a lead compound against echinococcosis.

中文翻译：

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大蒜素在体外和小鼠模型中对肺泡包虫病的评价

目的

目前治疗肺泡包虫病（AE）的化疗主要以阿苯达唑（ABZ）为主。然而，超过 20% 的患者化疗失败。因此，迫切需要新的更有效的治疗方法。据报道，大蒜素具有抗菌和抗寄生虫作用。本研究的目的是研究大蒜素对多房棘球绦虫（E. multilocularis）的体内和体外功效。

方法

在体外评估了大蒜素对原头节存活和结构变化的影响。用于体内建模的 4 周龄 BALB/c 雄性小鼠通过腹膜内注射接种多房大肠杆菌，然后灌胃大蒜素 6 周。然后，评估了大蒜素对小鼠淋巴细胞亚群、后绦虫生长和宿主组织基质金属蛋白酶 2 (MMP2)/MMP9 表达的影响。在体内和体外进一步评估大蒜素的毒性。

结果

Att 40 μg/mL，大蒜素在体外对原头节表现出杀伤作用，处理导致原头节结构的破坏。分子对接表明大蒜素可以与E. multilocularis半胱氨酸酶形成氢键。大蒜素体内处理6周后，小鼠脾指数增加，后绦虫重量减轻。大蒜素增加CD4 ⁺ T细胞比例，降低CD8 ^+比例外周血和脾脏中的 T 细胞。后绦虫的病理学分析显示大蒜素处理后生发层和层压层的结构破坏。此外，大蒜素还抑制了metacetode周围宿主组织中MMP2和MMP9的表达。在160 μg/mL时，大蒜素对正常肝细胞无明显毒性，但能抑制肝癌细胞增殖。在 30 mg/kg 时，大蒜素在体内没有明显的肝肾毒性。

结论

这些结果表明，大蒜素在体外和体内都发挥抗多房棘球绦虫的作用，并且可以增强小鼠的免疫功能，有可能被开发为抗棘球蚴病的先导化合物。