Anti-aging effects exerted by Tetramethylpyrazine enhances self-renewal and neuronal differentiation of rat bMSCs by suppressing NF-kB signaling

Biosci Rep. 2019 Jun 25;39(6):BSR20190761. doi: 10.1042/BSR20190761. Print 2019 Jun 28.

Abstract

In order to improve the therapeutic effects of mesenchymal stem cell (MSC)-based therapies for a number of intractable neurological disorders, a more favorable strategy to regulate the outcome of bone marrow MSCs (bMSCs) was examined in the present study. In view of the wide range of neurotrophic and neuroprotective effects, Tetramethylpyrazine (TMP), a biologically active alkaloid isolated from the herbal medicine Ligusticum wallichii, was used. It was revealed that treatment with 30-50 mg/l TMP for 4 days significantly increased cell viability, alleviated senescence by suppressing NF-κB signaling, and promoted bMSC proliferation by regulating the cell cycle. In addition, 40-50 mg/l TMP treatment may facilitate the neuronal differentiation of bMSCs, verified in the present study by presentation of neuronal morphology and expression of neuronal markers: microtubule-associated protein 2 (MAP-2) and neuron-specific enolase (NSE). The quantitative real-time polymerase chain reaction (qRT-PCR) revealed that TMP treatment may promote the expression of neurogenin 1 (Ngn1), neuronal differentiation 1 (NeuroD) and mammalian achaete-scute homolog 1 (Mash1). In conclusion, 4 days of 40-50 mg/l TMP treatment may significantly delay bMSC senescence by suppressing NF-κB signaling, and enhancing the self-renewal ability of bMSCs, and their potential for neuronal differentiation.

Keywords: Mesenchymal stem cells; NF-κB signaling; Tetramethylpyrazine; neuronal differentiation; proliferation; senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Self Renewal / drug effects*
  • Cells, Cultured
  • Cellular Senescence / drug effects
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • NF-kappa B / metabolism
  • Neurogenesis / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Pyrazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Pyrazines
  • tetramethylpyrazine