Caffeic acid has antipromastigote activity by apoptosis-like process; and anti-amastigote by TNF-α/ROS/NO production and decreased of iron availability

Phytomedicine. 2019 Apr:57:262-270. doi: 10.1016/j.phymed.2018.12.035. Epub 2018 Dec 31.

Abstract

Background: Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus whose current treatment has high cost, highly toxic, and difficult administration, which makes it very important to find alternative natural compounds of high efficiency and low cost.

Purpose: This study assessed the in vitro effect of caffeic acid (CA) on promastigotes and L. amazonensis-infected macrophages.

Methods: Evaluation of the in vitro leishmanicidal activity of CA against promastigotes and L. amazonensis infected peritoneal macrophages, as well its microbicide mechanisms.

Results: CA 12.5-100 µg/ml were able to inhibit promastigotes proliferation at all tested periods. The IC50, 12.5 µg/ml, also altered promastigote cell morphology and cell volume accompanied by loss of mitochondrial integrity, increase in reactive oxygen species (ROS) production, phosphatidylserine exposure, and loss of plasma membrane integrity - characterizing the apoptosis-like process. Moreover, CA reduced the percentage of infected macrophages and the number of amastigotes per macrophages increasing TNF-α, ROS, NO and reducing IL-10 levels as well as iron availability.

Conclusion: CA showed in vitro antipromastigote and antiamostigote by increasing oxidant and inflammatory response important to eliminate the parasite.

Keywords: Apoptosis-like; Caffeic acid (CA); Cytotoxity; Iron; Phenolic compound; TNF-α.

MeSH terms

  • Animals
  • Antiprotozoal Agents / pharmacology*
  • Apoptosis / drug effects
  • Caffeic Acids / pharmacology*
  • Iron / metabolism
  • Leishmania / drug effects*
  • Leishmania / pathogenicity
  • Leishmania / physiology
  • Leishmaniasis / drug therapy
  • Leishmaniasis / parasitology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / parasitology
  • Mice, Inbred BALB C
  • Mitochondria / drug effects
  • Phosphatidylserines / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antiprotozoal Agents
  • Caffeic Acids
  • Phosphatidylserines
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Iron
  • caffeic acid