Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways

Int J Mol Sci. 2019 Nov 30;20(23):6039. doi: 10.3390/ijms20236039.

Abstract

Inflammation is a common feature of many neurodegenerative diseases. The treatment of stem cells as a therapeutic approach to repair damage in the central nervous system represents a valid alternative. In this study, using Next-Generation Sequencing (NGS) technology, we analyzed the transcriptomic profile of human Gingival Mesenchymal Stem Cells (hGMSCs) treated with Moringin [4-(α-l-ramanosyloxy)-benzyl isothiocyanate] (hGMSCs-MOR) or with Cannabidiol (hGMSCs-CBD) at dose of 0.5 or 5 µM, respectively. Moreover, we compared their transcriptomic profiles in order to evaluate analogies and differences in pro- and anti-inflammatory pathways. The hGMSCs-MOR selectively downregulate TNF-α signaling from the beginning, reducing the expression of TNF-α receptor while hGMSCs-CBD limit its activity after the process started. The treatment with CBD downregulates the pro-inflammatory pathway mediated by the IL-1 family, including its receptor while MOR is less efficient. Furthermore, both the treatments are efficient in the IL-6 signaling. In particular, CBD reduces the effect of the pro-inflammatory JAK/STAT pathway while MOR enhances the pro-survival PI3K/AKT/mTOR. In addition, both hGMSCs-MOR and hGMSCs-CBD improve the anti-inflammatory activity enhancing the TGF-β pathway.

Keywords: Cannabidiol; Moringin; human gingival mesenchymal stem cells; inflammation; transcriptome analysis.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cannabidiol / pharmacology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gingiva / cytology
  • Gingiva / drug effects
  • Gingiva / immunology
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Isothiocyanates / pharmacology*
  • Janus Kinases / genetics
  • Janus Kinases / immunology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / immunology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / immunology
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / immunology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / immunology
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology
  • Transcriptome / drug effects*
  • Transcriptome / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • IL6 protein, human
  • Interleukin-1
  • Interleukin-6
  • Isothiocyanates
  • Receptors, Interleukin-1
  • STAT Transcription Factors
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • moringin
  • Cannabidiol
  • MTOR protein, human
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases