Antileishmanial Activity of Urtica Dioica Extract Against Zoonotic Cutaneous Leishmaniasis

PLoS Negl Trop Dis. 2020 Jan 13;14(1):e0007843. doi: 10.1371/journal.pntd.0007843. eCollection 2020 Jan.

Abstract

Background: Neglected parasitic diseases (NTDs) like cutaneous leishmaniasis (CL) have caused high mortality and morbidity rate in developing countries. This disease is considered as one of the six major tropical diseases, and has a great importance in HIV infected individuals as an opportunistic infection in those areas that both infections are endemic. This study evaluated the therapeutic effects of the Urtica dioica L (U. dioica) aqueous extract as an anti-leishmanial herbal drug in-vitro and in-vivo, and in addition to that, evaluated two vital immune system cytokines including gamma interferon (IFN-γ) and interleukin-4 (IL-4) plus nitric oxide (NO) and arginase activity against Leishmania major (L. major) infected mice.

Methodology/principal findings: In-vitro anti-leishmanial activity of U. dioica aqueous extract was determined using MTT method and also Parasite Rescue Transformation Assay. Also, the footpad lesion size and parasite load in BALB/c mice infected with L. major were quantified for in-vivo assessment. Furthermore, for evaluating the immune responses, the levels of IFN-γ, IL-4, NO and arginase were measured in the BALB/c mice. These results indicated that U. dioica extract significantly reduced the L. major promastigotes viability. According to the in-vitro cytotoxicity assay of the extract on Leishmania parasites (CC50) and infected macrophages (EC50), the extract had no toxicity to the macrophages, however it efficiently killed the L. major amastigotes. In addition, the lesion size, parasite load, IL-4, and ARG were decreased in the treated infected mice, however IFN-γ and NO were significantly increased.

Conclusions/significance: This study established satisfactory results in Leishmania parasite clearing both in-vivo and in-vitro. Therefore, U. dioica extract can be considered as an effective and harmless herbal compound for killing the parasite without toxicity to the host macrophages. Furthermore, it also can treat the CL by switching the mouse immune response towards a cell-mediated response (Th1); hence, it may be identified as a perfect therapeutic herbal drug for CL treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / pharmacology
  • Arginase / metabolism
  • Cell Line
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Leishmania major / drug effects*
  • Leishmaniasis, Cutaneous / drug therapy
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Parasite Load
  • Plant Extracts / pharmacology*
  • Plant Extracts / toxicity
  • Urtica dioica / chemistry*
  • Urtica dioica / toxicity

Substances

  • Antiprotozoal Agents
  • Plant Extracts
  • Interleukin-4
  • Nitric Oxide
  • Interferon-gamma
  • Arginase

Grant support

This work was financially supported by Shahid Beheshti University of Medical Sciences with grant number 12020 and ethical code IR.SBMU.MSP.REC.1397.515 to Vahid Fallah-Omrani and Dr. Hossein Dabiri. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.