Evaluation of Allicin Against Alveolar Echinococcosis In Vitro and in a Mouse Model.

ABSTRACT

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.