Abstract
PurposeAt 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).MethodsThe 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.ResultsAtt 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.ConclusionThese 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.
Highlights
Alveolar echinococcosis (AE) is a rare zoonotic parasitic disease caused by Echinococcus multilocularis, the larva of E. multilocularis, parasitizing the human body, which is characterized by a growth pattern of malignant tumours and can extend to distant organs, such as the lungs, brain, and kidneys, through the blood circulation [1, 2]; and the disease is only endemic to Northern Hemisphere [3, 4]
We evaluated the in vitro efficacy of allicin using different concentrations of allicin applied to E. multilocularis protoscoleces for 7 days
Allicin down-regulated the expression of matrix metalloproteinase 2 (MMP2) and MMP9 proteins in metacestodesurrounding host tissues (Fig. 6b, c). These results demonstrate that allicin may affect the growth of metacestodes by inhibiting the expression of MMP2 and MMP9
Summary
Alveolar echinococcosis (AE) is a rare zoonotic parasitic disease caused by Echinococcus multilocularis, the larva of E. multilocularis, parasitizing the human body, which is characterized by a growth pattern of malignant tumours and can extend to distant organs, such as the lungs, brain, and kidneys, through the blood circulation [1, 2]; and the disease is only endemic to Northern Hemisphere [3, 4]. At the time of diagnosis, most patients are in the late stage of the disease and may have more obvious complications, such as abdominal pain, jaundice, weight loss and even liver failure [5]. The treatment of echinococcosis is based on radical surgery [7], but drug chemotherapy, as an adjuvant treatment for echinococcosis, is used preoperatively to reduce lesions and inhibit parasitic activity and postoperatively to prevent the recurrence of echinococcosis. Albendazole (ABZ) only inhibits the progression of parasitic granulomas rather than cures this disease, which means that patients must receive chemotherapy over a long period of time, posing the risk of high costs and side effects. The search for more effective drugs or lead compounds for the treatment of echinococcosis has been a hot topic in anti-echinococcosis research
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