In Vitro Studies on the Immunomodulatory Effects of Pulicaria crispa Extract on Human THP-1 Monocytes

Oxid Med Cell Longev. 2020 Sep 25:2020:7574606. doi: 10.1155/2020/7574606. eCollection 2020.

Abstract

Background: Pulicaria crispa (P. crispa) is a plant from the Compositae family that exhibits antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities.

Objective: The current study aimed at investigating the immunomodulatory effects of P. crispa extract in lipopolysaccharide- (LPS-) stimulated human monocytic THP-1 cells.

Methods: To induce macrophage differentiation, THP-1 cell lines were treated with phorbol-12-myristate 13-acetate, followed by exposure to LPS with or without 50 or 100 μg/ml of P. crispa extract. The following tests were employed to test the immunomodulatory effects of the extract: MTT assay, ELISA, Western blotting analysis, cell migration and phagocytosis assays, and Annexin V staining method.

Results: Exposure to 100 μg/ml P. crispa extract significantly reduced THP-1 cell proliferation, migration, and phagocytosis (in LPS-stimulated cells, but not in unstimulated cells). Moreover, the extract alone significantly reduced the rate of THP-1 cell apoptosis, while it increased the rate of late apoptosis. Molecular investigations showed that treatment with P. crispa extract significantly upregulated the expression of ERK1, p-MAPK, P-P38, and Bcl2, while it significantly reduced the expression of ERK5, Bax, NF-κB, P-NF-κB, CCL1, CCL2, CCL5, CCL22, CXCL1, and CXCL10.

Conclusion: Pulicaria crispa extract exhibited anti-inflammatory, antiproliferative, antimigratory, and antiphagocytic effects in LPS-stimulated THP-1 cells. Future studies should investigate these mechanisms in animal models with chronic inflammatory diseases.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CXCL1 / metabolism
  • Chemokines, CC / metabolism
  • Down-Regulation
  • Humans
  • Immunomodulation / drug effects*
  • Lipopolysaccharides / pharmacology
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Monocytes / drug effects*
  • NF-kappa B / metabolism
  • Phagocytosis / drug effects
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pulicaria / chemistry*
  • Pulicaria / metabolism
  • THP-1 Cells
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology
  • Up-Regulation
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • BCL2 protein, human
  • Chemokine CXCL1
  • Chemokines, CC
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • phorbolol myristate acetate
  • MAPK7 protein, human
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 7
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate