Efficacy of osthole for Echinococcus granulosus in vitro and Echinococcus multilocularis in vivo

Vet Parasitol. 2016 Aug 15:226:38-43. doi: 10.1016/j.vetpar.2016.05.016. Epub 2016 Jun 23.

Abstract

Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus; in addition, this zoonosis has long been neglected as a parasitic disease and has limited treatment options. Clinical drugs such as benzimidazole derivatives have limited treatment efficacy. The current study evaluated a novel drug, osthole, with low toxicity and high activity against Echinococcus in vitro and in vivo. The results in vitro indicated that the viability of Echinococcus granulosus protoscoleces in the group treated with osthole (120μM) decreased by 100% within 3days. In vivo experiments were conducted using parasite-infected mice. For this purpose, three groups of infected mice were treated daily for 6 weeks with albendazole (ABZ, 100mg/kg, positive control group), osthole (100mg/kg, experimental group), or honey/PBS (100mg/kg, negative control group), respectively. The osthole- and ABZ-treated groups presented a significant reduction in wet weight of metacestodes, increase in the level of interleukin (IL)-4 and the percentage of eosinophils compared with the control group. Osthole exhibited a high activity against echinococcosis in vivo. In addition, the toxicity of osthole was evaluated via an in vitro 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, as well as via morphological observation and calculation of liver and kidney function indexes in vivo. No obvious toxic effects of osthole were observed in our study. Therefore, this novel drug may be a promising alternative to benzimidazole in anti-echinococcosis chemotherapy.

Keywords: Echinococcosis; Efficacy; Osthole; Toxicity.

MeSH terms

  • Albendazole / pharmacology
  • Albendazole / therapeutic use
  • Albendazole / toxicity
  • Animals
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / therapeutic use
  • Antiprotozoal Agents / toxicity
  • Blood Chemical Analysis
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channel Blockers / toxicity
  • Cell Line
  • Coumarins / pharmacology*
  • Coumarins / therapeutic use
  • Coumarins / toxicity
  • Echinococcosis / drug therapy*
  • Echinococcus granulosus / drug effects*
  • Echinococcus multilocularis / drug effects*
  • Eosinophils / drug effects
  • Female
  • Hep G2 Cells
  • Humans
  • Interleukin-4 / metabolism
  • Kidney / drug effects
  • Kidney / physiology
  • Leukocyte Count
  • Liver / cytology
  • Liver / drug effects
  • Liver / physiology
  • Mice
  • Mice, Inbred BALB C
  • Random Allocation
  • Sheep

Substances

  • Antiprotozoal Agents
  • Calcium Channel Blockers
  • Coumarins
  • Interleukin-4
  • Albendazole
  • osthol