The protective effects of Ziziphora tenuior L. against chlorpyrifos induced toxicity: Involvement of inflammatory and cell death signaling pathway

J Ethnopharmacol. 2021 May 23:272:113959. doi: 10.1016/j.jep.2021.113959. Epub 2021 Feb 24.

Abstract

Ethnopharmacological relevance: Ziziphora tenuior L. is used as a medicinal plant in treatment of various diseases such as gastric disorders, stomach ache, dysentery, uterus infection, gut inflammation and menstruation.

Aim of the study: In the present study, the protective effects of Ziziphora tenuior extract against chlorpyrifos (CPF), the most commonly or popularly used insecticide in Asia and Africa were investigated in liver and lung tissues with emphasis in apoptotic and inflammatory pathways in rat model.

Materials and methods: The experiments were performed by gavage of male rats for 8 weeks. The extract of Z. tenuior was administrated at three different doses (40, 80, 160 mg/kg). 6.75 mg/kg CPF was administrated as the maximum tolerable dose based on our previous study.

Results: Our data indicated that CPF can increase the expression of some inflammatory genes (IL-6, TLR-2, IL-1β, TNF-α, and NLPR3) and apoptosis genes (Caspase 3, Caspase 9, Caspase 8 and Bax). On the other hand, it can down regulate Bcl-2 gene expression. Post-treatment of Z. tenuior extract in CPF- treated rats showed significant decrease in apoptotic and inflammatory gene expression in the liver and lung due to its anti-apoptotic effects which confirmed by Bcl-2 gene overexpression.

Conclusion: The present study suggested that Z. tenuior extract, as a traditional treatment can be able to moderate CPF toxicity via significant effect on inflammatory and apoptotic cell death signaling pathway. Also, based on our preliminary data, it is suggested that Z. tenuior extract can prevent the adverse effects of CPF in liver and lung tissues.

Keywords: Apoptosis; Chlorpyrifos; Gene expression; Inflammation; Liver; Lung; Oxidative stress; Ziziphora tenuior.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Death / drug effects*
  • Chlorpyrifos / toxicity
  • Disease Models, Animal
  • Genes, bcl-2 / genetics
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lamiaceae / chemistry*
  • Liver / drug effects
  • Liver / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • IL1B protein, rat
  • Il6 protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • Nod-like receptor protein 3 inflammasome, rat
  • Plant Extracts
  • Protective Agents
  • Receptors, Cell Surface
  • Tlr2 protein, rat
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Caspases
  • Chlorpyrifos