Astragalus and Baicalein Regulate Inflammation of Mesenchymal Stem Cells (MSCs) by the Mitogen-Activated Protein Kinase (MAPK)/ERK Pathway

Med Sci Monit. 2017 Jul 1:23:3209-3216. doi: 10.12659/msm.902441.

Abstract

BACKGROUND Mesenchymal stem cells (MSCs) have emerged as an attractive alternative to modulating immune response after transplantation. Recent studies have shown that systemically administered MSCs enter the inflamed intestine. In the present study, we propose a strategy to improve the efficacy of MSC-based cellular therapy for inflammation using Astragaloside and Baicalein to enhance cell survival, inhibit apoptosis, and modulate inflammatory response in vitro. MATERIAL AND METHODS MSCs were induced with lipopolysaccharide (LPS) as an inflammatory model before being treated for 48 h with Astragaloside, Baicalein, and the combination of both. MSCs proliferation was determined using the MTT method. The cell cycle situation was monitored using flow cytometry, and the apoptosis ability of MSCs was detected with Annexin-V flow cytometry. The levels of cytokine IL-1β, IL-8, and TNF-α, and their relations with the ERK pathway were measured using ELISA, RT-PCR, and Western blot. RESULTS Compared to the control groups (containing no drug), each drug-treated group showed the ability to promote epithelial differentiation and cell growth and to inhibit apoptosis. The combination group had reduced levels of IL-1β, IL-8, and TNF-α in LPS-induced MSCs, much more than in the other 2 groups. Compared with the other groups, the combination of Astragaloside and Baicalin more efficiently reduced IL-1β, IL-8, and TNF-α levels in the LPS-induced MSCs model, and ERK inhibitor was capable of recovering the inflammatory effect. CONCLUSIONS The results demonstrated that Astragaloside and Baicalin can promote epithelial differentiation and proliferation, inhibit apoptosis, and reduce inflammatory effects.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Separation
  • Cytokines / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Inflammation / drug therapy*
  • Inflammation / enzymology*
  • Inflammation / pathology
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / enzymology
  • Mesenchymal Stem Cells / pathology*
  • Rats, Sprague-Dawley
  • Saponins / therapeutic use*

Substances

  • Cytokines
  • Flavanones
  • Saponins
  • baicalein
  • Extracellular Signal-Regulated MAP Kinases