Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis

Kumar, Vivek; Pandey, Ankita; Jahan, Sadaf; Shukla, Rohit; Kumar, Durgesh; Srivastav, Ajeet K.; Singh, Sudhir; Rajpurohit, Chetan Singh; Yadav, Sanjay; Khanna, Vinay K.; Pant, Aditya B.

doi:10.1038/srep28142

Cited by 57 publications

(41 citation statements)

References 68 publications

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“…Our study demonstrated that RESV at 15 µM did not affect cell viability after LPS stimulation. Cell proliferation was observed in the presence of RESV at 10 and 20 µM, but at higher concentrations, a decrease in cell viability was seen [49]. A previous study using HCE7, Fig.…”

Section: Discussionmentioning

confidence: 59%

Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

Pinheiro

Oliveira

Coutinho

et al. 2019

Free Radical Biology and Medicine

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Oxidative stress generated during inflammation is associated with a wide range of pathologies. Resveratrol (RESV) displays anti-inflammatory and antioxidant activities, being a candidate for the development of adjuvant therapies for several inflammatory diseases. Despite this potential, the cellular responses induced by RESV are not well known. In this work, transcriptomic analysis was performed following lipopolysaccharide (LPS) stimulation of monocyte cultures in the presence of RESV. Induction of an inflammatory response was observed after LPS treatment and the addition of RESV led to decreases in expression of the inflammatory mediators, tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), without cytotoxicity. RNA sequencing revealed 823 upregulated and 2098 downregulated genes (cutoff ≥2.0 or ≤−2.0) after RESV treatment. Gene ontology analysis showed that the upregulated genes were associated with metabolic processes and the cell cycle, consistent with normal cell growth and differentiation under an inflammatory stimulus. The downregulated genes were associated with inflammatory responses, gene expression, and protein modification. The prediction of master regulators using the iRegulon tool showed nuclear respiratory factor 1 (NRF1) and GA-binding protein alpha subunit (GABPA) as the main regulators of the downregulated genes. Using immunoprecipitation and protein expression assays, we observed that RESV was able to decrease protein acetylation patterns, such as acetylated apurinic/apyrimidinic endonuclease-1/reduction-oxidation factor 1 (APE1/Ref-1), and increase histone methylation. In addition, reductions in p65 (nuclear factor-kappa B (NF-κB) subunit) and lysine-specific histone demethylase-1 (LSD1) expression were observed. In conclusion, our data indicate that treatment with RESV caused significant changes in protein acetylation and methylation patterns, suggesting the induction of deacetylase and reduction of demethylase activities that mainly affect regulatory cascades mediated by NF-кB and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. NRF1 and GABPA seem to be the main regulators of the transcriptional profile observed after RESV treatment.

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Section: Discussionmentioning

confidence: 59%

Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

Pinheiro

Oliveira

Coutinho

et al. 2019

Free Radical Biology and Medicine

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“…The authors suggested that enhanced proliferation was mediated by increased phosphorylation of extracellular signal-regulated kinases (ERKs) and p 38 kinases. Higher RES concentrations significantly reduced the activation of these molecules [49].…”

Section: Resveratrolmentioning

confidence: 92%

“…Proliferative activity of low phytoestrogens concentrations was generally explained on the basis of transactivation of the estrogen receptor [9][10][11][12][13][14][15][16][17][18][19][21][22][23]29,[37][38][39][40]44]. In more recent articles, some molecular aspects involving the induction of genes expression or activation by phytochemicals of various signaling pathways, for example, MAPK/ERK1/2 and PI3K/AKT were revealed [48,49,57,60,63,72,74,78,79]. In the Caenorhabditis elegans model, the increased expression of some genes involved in lifespan or stress response was associated with extended lifespan [34,86,87].…”

Section: Commentsmentioning

confidence: 99%

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Jodynis‐Liebert

Kujawska

2020

JCM

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Many phytochemicals demonstrate nonmonotonic dose/concentration-response termed biphasic dose-response and are considered to be hormetic compounds, i.e., they induce biologically opposite effects at different doses. In numerous articles the hormetic nature of phytochemicals is declared, however, no experimental evidence is provided. Our aim was to present the overview of the reports in which phytochemical-induced biphasic dose-response is experimentally proven. Hence, we included in the current review only articles in which the reversal of response between low and high doses/concentrations of phytochemicals for a single endpoint was documented. The majority of data on biphasic dose-response have been found for phytoestrogens; other reports described these types of effects for resveratrol, sulforaphane, and natural compounds from various chemical classes such as isoquinoline alkaloid berberine, polyacetylenes falcarinol and falcarindiol, prenylated pterocarpan glyceollin1, naphthoquinones plumbagin and naphazarin, and panaxatriol saponins. The prevailing part of the studies presented in the current review was performed on cell cultures. The most common endpoint tested was a proliferation of tumor and non-cancerous cells. Very few experiments demonstrating biphasic dose-response induced by phytochemicals were carried out on animal models. Data on the biphasic dose-response of various endpoints to phytochemicals may have a potential therapeutic or preventive implication.

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“…Moreover, resveratrol has an e ciently therapeutic effect on in vivo models, including enhancing liver regeneration (37), cardiogenic differentiation in cardiomyopathy (38). Interestingly, oral administration trans-resveratrol 20 mg/kg body weight for 45 days into aged rat has recovery the number of newly generated neurons in the hippocampus with positively Nissl substance (speci c granule of neurons), and BrdU (Proliferative marker) labelling (39). Moreover, resveratrol treatment improved learning, memory, and enhanced neurogenesis in Alzheimer's disease (AD) mouse model (40).…”

Section: Discussionmentioning

confidence: 99%

Potential of resveratrol in enrichment of neural progenitor-like cells induction of human stem cells from apical papilla

Songsaad

Gonmanee

Ruangsawasdi

et al. 2020

Preprint

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Introduction: Stem cell transplantation of exogenous neural progenitor cells (NPCs) derived from mesenchymal stem cells (MSCs) has emerged as a promising approach of neurodegenerative disease. Human stem cells from apical papilla (hSCAPs) are derived from migratory neural crest stem cells, and exhibit a potential of neuronal differentiation. However, their neuronal differentiation is low and unpredictable. Resveratrol has been described as a sirtuin 1 (SIRT1) activator which plays an important role in enhancing neuronal differentiation. In this study, we investigate the potential of resveratrol as an enhancer on neuronal differentiation through NPCs induction of hSCAPs.Methods: Stem cells were isolated from human apical papilla, and characterized as MSCs. The cellular toxicity of resveratrol treatment to the characterized hSCAPs was investigated by MTT assay. The non-cellular toxicity concentrations of resveratrol were assessed with various pre-treatment times to select the optimal condition that highly expressed the neural progenitor gene, NES. Consequently, the optimal condition of resveratrol pre-treatment was synergistically performed with a neuronal induction medium to trigger neuronal differentiation. The differentiated cells were visualized, the genes profiling was quantified, and the percentage of neuronal differentiation was calculated. Moreover, the intracellular calcium oscillation was demonstrated. Results: The cellular toxicity of resveratrol was not observed for up to 50 µM for 12 hours. Interestingly, hSCAPs pre-treated with 10 µM resveratrol for 12 hours (RSV-hSCAPs) significantly expressed NES, which is determined as the optimal condition. Under neuronal induction, both of hSCAPs and RSV-hSCAPs were differentiated (d-hSCAPs, and RSV-d-hSCAPs) as they exhibited neuronal-like appearances with Nissl substance staining. The highest expression of NES, and SOX1 was observed in RSV-d-hSCAPs. Additionally, the percentage of neuronal differentiation of RSV-d-hSCAPs was significantly higher than d-hSCAPs for 4 times. Importantly, the neuronal-like cells exhibited slightly increasing pattern of calcium intensity.Conclusion: This study demonstrated that pre-treatment of resveratrol strongly induces neural progenitor marker gene expression which synergistically enhances neural progenitor-like cells’ induction with neuronal induction medium.

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Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis

Cited by 57 publications

References 68 publications

Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Potential of resveratrol in enrichment of neural progenitor-like cells induction of human stem cells from apical papilla

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