Molecular Targets Implicated in the Antiparasitic and Anti-Inflammatory Activity of the Phytochemical Curcumin in Trichomoniasis

Molecules. 2020 Nov 14;25(22):5321. doi: 10.3390/molecules25225321.

Abstract

Trichomoniasis, is the most prevalent non-viral sexually transmitted disease worldwide. Although metronidazole (MDZ) is the recommended treatment, several strains of the parasite are resistant to MDZ, and new treatments are required. Curcumin (CUR) is a polyphenol with anti-inflammatory, antioxidant and antiparasitic properties. In this study, we evaluated the effects of CUR on two biochemical targets: on proteolytic activity and hydrogenosomal metabolism in Trichomonas vaginalis. We also investigated the role of CUR on pro-inflammatory responses induced in RAW 264.7 phagocytic cells by parasite proteinases on pro-inflammatory mediators such as the nitric oxide (NO), tumor necrosis factor α (TNFα), interleukin-1beta (IL-1β), chaperone heat shock protein 70 (Hsp70) and glucocorticoid receptor (mGR). CUR inhibited the growth of T. vaginalis trophozoites, with an IC50 value between 117 ± 7 μM and 173 ± 15 μM, depending on the culture phase. CUR increased pyruvate:ferredoxin oxidoreductase (PfoD), hydrogenosomal enzyme expression and inhibited the proteolytic activity of parasite proteinases. CUR also inhibited NO production and decreased the expression of pro-inflammatory mediators in macrophages. The findings demonstrate the potential usefulness of CUR as an antiparasitic and anti-inflammatory treatment for trichomoniasis. It could be used to control the disease and mitigate the associated immunopathogenic effects.

Keywords: Trichomonas vaginalis; curcumin; hydrogenosomal enzymes; proinflammatory cytokines; proteinases.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antiparasitic Agents / pharmacology
  • Antiparasitic Agents / therapeutic use*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Membrane Potentials / drug effects
  • Mice
  • Molecular Targeted Therapy*
  • Nitric Oxide / biosynthesis
  • Parasites / drug effects
  • Phytochemicals / pharmacology
  • Phytochemicals / therapeutic use*
  • Proteolysis / drug effects
  • Pyruvate Synthase / genetics
  • Pyruvate Synthase / metabolism
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trichomonas Infections / drug therapy*
  • Trichomonas Infections / parasitology
  • Trichomonas vaginalis / drug effects
  • Trichomonas vaginalis / enzymology
  • Trichomonas vaginalis / genetics

Substances

  • Anti-Inflammatory Agents
  • Antiparasitic Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Phytochemicals
  • RNA, Messenger
  • Nitric Oxide
  • Pyruvate Synthase
  • Curcumin