Impact of Wortmannilactone F and G31P on Clonorchis Sinensis-infected mice

Int Immunopharmacol. 2020 Aug:85:106512. doi: 10.1016/j.intimp.2020.106512. Epub 2020 May 23.

Abstract

Clonorchis sinensis could induce inflammation, epithelial hyperplasia and fibrosis in the intrahepatic bile duct as a food-borne parasite, which was associated with the development of cholangiocarcinoma (CCA). Praziquantel was the most effective drug on treatment of this kind of parasite. However, new drugs with minimal toxicity to the host were urgently needed due to the side effects of Praziquantel and its CCA risk. In this study, helminth mitochondria respiratory chain blocker Wortmannilatone F (WF) and IL-8 analogue CXCL8 (3-72) K11R/G31P were used to treat BALB/C mice infected by Clonorchis sinensis. We investigated the gross and histopathological morphology of the liver, inflammation-associated cytokine IL-6, lipid peroxidation-related proteins cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), collagen fiber accumulation and fibroblast-specific protein 1 (FSP1), malignant markers proliferating cell nuclear antigen (PCNA) and cytokeratin 19 (CK19), as well as the disinfection effect on these parasites in vitro. WF inhibited and killed the worms dramatically, and the combination of WF with G31P improved the condition of the hepatobiliary duct tissue greatly. These outcomes indicated that the combination of WF and G31P was a potential therapeutic method to treat the Clonorchis sinensis infection.

Keywords: Clonorchiasis; Clonorchis sinensis; G31P; Praziquantel; Wortmannilatone F.

MeSH terms

  • Animals
  • Anthelmintics / pharmacology
  • Anthelmintics / therapeutic use*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Clonorchiasis / drug therapy*
  • Clonorchiasis / metabolism
  • Clonorchiasis / parasitology
  • Clonorchiasis / pathology
  • Clonorchis sinensis / drug effects
  • Collagen / metabolism
  • Cyclooxygenase 2 / metabolism
  • Interleukin-6 / blood
  • Interleukin-8 / pharmacology
  • Interleukin-8 / therapeutic use*
  • Keratin-19 / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Macrolides / pharmacology
  • Macrolides / therapeutic use*
  • Male
  • Mice, Inbred BALB C
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use*
  • Proliferating Cell Nuclear Antigen / metabolism
  • S100 Calcium-Binding Protein A4 / metabolism

Substances

  • Anthelmintics
  • CXCL8(3-72)K11R,G31P, human
  • Interleukin-6
  • Interleukin-8
  • Keratin-19
  • Macrolides
  • Peptide Fragments
  • Proliferating Cell Nuclear Antigen
  • S100 Calcium-Binding Protein A4
  • S100a4 protein, mouse
  • interleukin-6, mouse
  • wortmannilactone F
  • Collagen
  • Arachidonate 5-Lipoxygenase
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2