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

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.

Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration

“…Cholinergic neurons hADSCs [190] BME + NGF Neurons mBMSCs [196] e-CSF β-tubulin III neurite outgrowth assay Neuronal-like cells m-ADSCs [197] AP-g-CH/GL/AG scaffold, chitosan-graft-aniline pentamer, gelatin, agarose; hOE-MSCs, human olfactory ecto-mesenchymal stem cells; hADSC, human adipose tissue-derived stem cells; NSE, neuron specific enolase; EN1, engriled homebox 1; GLI1, GLI family zinc finger 1; NURR1, nuclear receptor-related factor 1; VMAT2, vesicular monoaminetransporter 2; GIRK2, G-protein-regulated inward-rectifier potassium channel 2; PVA/SA, polyvinyl alcohol/sulphated alginate; hBMSCs, human bone marrow stem cells; PEMF, used electromagnetic field; hDPSCs, human dental pulp stem cells; PDGF-BB, platelet-derived growth factor BB; hUSCs, human urine-derived stem cells; RA, retinoic acid; mESC, mouse embryonic stem cell; NPCs, neural precursor cells; mBMSCs, murine bone marrow stem cells; BME, β-mercaptoethanol; NGF, nerve growth factor; ChAT, choline acetyl transferase; DAT, dopamine transporter; TMP, tetramethylpyrazine; MAP-2, microtubule-associated protein 2; NSE, neuron-specific enolase; Ngn1, neurogenin 1; NeuroD, neuronal differentiation 1; Mash1, mammalian achaete-scute homolog 1; e-CSF, embryonic cerebrospinal fluid. hADSC, human adipose-derived stem cell; NPs, neuronal precursors; ESCs, embryonic stem cells; MSCs, mesenchymal stem cells; hUCB-MSCs, human umbilical cord blood-derived mesenchymal stem cells; GSH, glutathione; SOD, superoxide dismutase.…”

Exploring the mechanism of Danggui Buxue Decoction in regulating atherosclerotic disease network based on integrated pharmacological methods

“…Current studies have found that some natural active ingredients can inhibit the cascade of inflammatory reactions, inhibit inflammatory stress and counter-inflammatory adverse events. For example, ligustrazine can inhibit endothelial cell inflammation and leukocyte adhesion response induced by oxidized low density lipoprotein (ox-LDL), and inhibit the activation of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways, which can inhibit the inflammatory response in the initial stage of inflammatory response [76][77][78]. Quercetin [79], emodin [80], triptolide Huang et al [86] used immunoblotting to detect the effect of DGBXD on the expression of p38 MAPK in RAW264.7 cells activated by ox-LDL.…”

Herb-Derived Products: Natural Tools to Delay and Counteract Stem Cell Senescence

“…Additional evidence in support of an antisenescence action of TMP can be inferred by the finding that TMP treatment (40–50 mg/L) can facilitate the neuronal differentiation of BMSCs, as it is highlighted by the presentation of a neuronal morphology, the expression of neuronal markers, such as microtubule-associated protein 2 (MAP-2) and neuron-specific enolase, and the enhanced expression of neurogenin 1 ( Ngn1 ), neuronal differentiation 1 ( NeuroD ), and mammalian achaete–scute homolog 1 ( Mash1 ) genes [ 228 ].…”