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13 pages, 4121 KiB

Open AccessArticle

Regulatory Effects and Mechanism of Action of Green Tea Polyphenols on Osteogenesis and Adipogenesis in Human Adipose Tissue-Derived Stem Cells

by Weiguo Lao, Yi Zhao, Yi Tan, Michael Johnson, Yan Li, Linda Xiao, Jing Cheng, Yiguang Lin and Xianqin Qu

Curr. Issues Mol. Biol. 2022, 44(12), 6046-6058; https://doi.org/10.3390/cimb44120412 - 30 Nov 2022

Cited by 1 | Viewed by 1980

Abstract

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O [...] Read more.

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O staining and triglycerides synthesis measurement. Osteoporosis of hADSC was measured using alkaline phosphatase assays and intracellular calcium levels. Immunofluorescence staining and qRT-PCR were used to detect PPARγ-CEBPA regulated adipogenic pathway regulated by PPAR-CEBPA and the osteogenic pathway mediated by RUNX2-BMP2. We found that GTPs treatment significantly decreased lipid accumulation and cellular triglyceride synthesis in mature adipocytes and attenuated pioglitazone-induced adipogenesis in a dose-dependent manner. GTPs downregulated protein and mRNA expression of Pparγ and attenuated pioglitazone-stimulated-Cebpa expression. GTPs treatment significantly enhanced hADSCs differentiation into osteoblasts compared to control and pioglitazone-treated cells. GTPs upregulated RunX2 and Bmp2 proteins and mRNA expression compared to control and significantly attenuated decreased RunX2 and Bmp2 mRNA expression by pioglitazone. In conclusion, our data demonstrates GTPs possesses great ability to facilitate osteogenesis and simultaneously inhibits hADSC differentiation into adipogenic lineage by upregulating the RUNX2-BMP2 mediated osteogenic pathway and suppressing PPARγ-induced signaling of adipogenesis. These findings highlight GTPs’ potential to combat osteoporosis associated with obesity. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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15 pages, 2370 KiB

Open AccessArticle

Antioxidant Activity of New Sulphur- and Selenium-Containing Analogues of Potassium Phenosan against H₂O₂-Induced Cytotoxicity in Tumour Cells

by Lyubov S. Klyushova, Natalya V. Kandalintseva and Alevtina Y. Grishanova

Curr. Issues Mol. Biol. 2022, 44(7), 3131-3145; https://doi.org/10.3390/cimb44070216 - 07 Jul 2022

Cited by 2 | Viewed by 1453

Abstract

Among known phenolic antioxidants, the overwhelming majority of compounds have lipophilic properties and the number of known water-soluble compounds is very small. The list of hydrophilic phenolic antioxidants can be expanded via the synthesis of a structurally related series of polyfunctional compounds for [...] Read more.

Among known phenolic antioxidants, the overwhelming majority of compounds have lipophilic properties and the number of known water-soluble compounds is very small. The list of hydrophilic phenolic antioxidants can be expanded via the synthesis of a structurally related series of polyfunctional compounds for further research on their biological activity in vitro. New sulphur- and selenium-containing analogues of antioxidant potassium phenosan were synthesised. In vitro cytotoxicity and cytostaticity as well as antioxidant activity against H₂O₂-induced cytotoxicity to human cell lines (HepG2, Hep-2 and MCF-7) were investigated by high-content analysis. A selenium-containing analogue showed higher biological activity than did a sulphur-containing one. As compared to the activity of potassium phenosan, the selenium-containing analogue had a cell line-dependent antioxidant effect against H₂O₂-induced cytotoxicity: comparable in HepG2 cells and greater in Hep-2 cells. The selenium-containing analogue significantly increased the death of MCF-7 cells at concentrations above 50 µM. The sulphur-containing analogue has lower biological activity as compared to potassium phenosan and the selenium-containing analogue. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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14 pages, 1782 KiB

Open AccessArticle

Effect of Aqueous Extract of Phenolic Compounds Obtained from Red Wine in Experimental Model of Colitis in Mice

by Vanessa Mateus, João Estarreja, Inês Silva, Fernando Gonçalves, Edite Teixeira-Lemos and Rui Pinto

Curr. Issues Mol. Biol. 2022, 44(6), 2745-2758; https://doi.org/10.3390/cimb44060188 - 18 Jun 2022

Cited by 4 | Viewed by 1795

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder represented by Crohn’s disease and ulcerative colitis. Currently, there is no cure and pharmacological treatment aims to induce and maintain remission on patients. Because the therapy reveals a relatively high toxicity, during [...] Read more.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder represented by Crohn’s disease and ulcerative colitis. Currently, there is no cure and pharmacological treatment aims to induce and maintain remission on patients. Because the therapy reveals a relatively high toxicity, during a long-term utilization, it is essential to investigate new pharmacological approaches. Polyphenols, commonly present on red wine, have shown health-beneficial effects related to their antioxidant and anti-inflammatory effects through the inhibition of NF-kB activation, COX-2 and iNOS induction. In this sense, it would be interesting to study their effects in an IBD context. Therefore, this study aims to evaluate the effects of an aqueous extract of phenolic compounds in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced model of colitis. Method: Experimental colitis was induced in mice through an intrarectal administration of TNBS and then the mice were treated with an aqueous extract of phenolic compounds intraperitoneally for four days. Results and Discussion: The extract demonstrated an anti-inflammatory effect, reducing TNF-α levels in the colon, and had a beneficial effect on the extraintestinal manifestations related to IBD, without any significant side effects. The extract of phenolic compounds demonstrated to be a valuable object of study for the management of IBD in the future. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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9 pages, 1447 KiB

Open AccessArticle

Resveratrol Downregulates Granulocyte-Macrophage Colony-Stimulating Factor-Induced Oncostatin M Production through Blocking of PI3K/Akt/NF-κB Signal Cascade in Neutrophil-like Differentiated HL-60 Cells

by Na-Ra Han, Hi-Joon Park and Phil-Dong Moon

Curr. Issues Mol. Biol. 2022, 44(2), 541-549; https://doi.org/10.3390/cimb44020037 - 22 Jan 2022

Cited by 1 | Viewed by 3425

Abstract

Oncostatin M (OSM) is essential in a wide range of inflammatory responses, and most OSM is produced by neutrophils in respiratory diseases. While resveratrol (RES) is regarded as an anti-inflammatory agent in a variety of conditions, the mechanism of OSM inhibition by RES [...] Read more.

Oncostatin M (OSM) is essential in a wide range of inflammatory responses, and most OSM is produced by neutrophils in respiratory diseases. While resveratrol (RES) is regarded as an anti-inflammatory agent in a variety of conditions, the mechanism of OSM inhibition by RES in neutrophils remains to be elucidated. In this study, we investigated whether RES could inhibit OSM production in neutrophil-like differentiated (d)HL-60 cells. The effects of RES were measured by means of an enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Increases in production and mRNA expression of OSM resulted from the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) in neutrophil-like dHL-60 cells; however, these increases were downregulated by RES treatment. Exposure to GM-CSF led to elevations of phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-kB. Treatment with RES induced downregulation of the phosphorylated levels of PI3K, Akt, and NF-κB in neutrophil-like dHL-60 cells. These results suggest that RES could be applicable to prevent and/or treat inflammatory disorders through blockade of OSM. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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21 pages, 7810 KiB

Open AccessArticle

Gigantol Improves Cholesterol Metabolism and Progesterone Biosynthesis in MA-10 Leydig Cells

by Audrey Basque, Ha Tuyen Nguyen, Mohamed Touaibia and Luc J. Martin

Curr. Issues Mol. Biol. 2022, 44(1), 73-93; https://doi.org/10.3390/cimb44010006 - 23 Dec 2021

Cited by 7 | Viewed by 2911

Abstract

In aging males, androgen production by testicular Leydig cells decreases at a rate of approximately 1% per year. Phenolic compounds may enhance testosterone biosynthesis and delay the onset of male hypogonadism. Gigantol is a bibenzyl compound isolated from several types of orchids of [...] Read more.

In aging males, androgen production by testicular Leydig cells decreases at a rate of approximately 1% per year. Phenolic compounds may enhance testosterone biosynthesis and delay the onset of male hypogonadism. Gigantol is a bibenzyl compound isolated from several types of orchids of the genus Dendrobium. This compound has various biological activities, including antioxidant activity. However, its capacity to regulate gene expression and steroid production in testicular Leydig cells has never been evaluated. We investigated the effect of gigantol on MA-10 Leydig cells’ gene expression using an RNA-Seq approach. To further investigate the structure-function relationship of the hydroxy-methoxyphenyl moiety of gigantol, experiments were also performed with ferulic acid and isoferulic acid. According to transcriptomic analysis, all genes coding for cholesterol biosynthesis-related enzymes are increased in response to gigantol treatment, resulting in increased lipid droplets accumulation. Moreover, treatments with 10 μM gigantol increased StAR protein levels and progesterone production from MA-10 Leydig cells. However, neither ferulic acid nor isoferulic acid influenced StAR protein synthesis and progesterone production in MA-10 Leydig cells. Thus, our findings indicate that gigantol improves cholesterol and steroid biosynthesis within testicular Leydig cells. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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Review

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12 pages, 2440 KiB

Open AccessReview

Aromatic Polyphenol π-π Interactions with Superoxide Radicals Contribute to Radical Scavenging and Can Make Polyphenols Mimic Superoxide Dismutase Activity

by Francesco Caruso, Sandra Incerpi, Jens Pedersen, Stuart Belli, Sarjit Kaur and Miriam Rossi

Curr. Issues Mol. Biol. 2022, 44(11), 5209-5220; https://doi.org/10.3390/cimb44110354 - 26 Oct 2022

Cited by 11 | Viewed by 1550

Abstract

Polyphenols are valuable natural antioxidants present in our diet that likely mitigate aging effects, neurodegenerative conditions, and other diseases. However, because of their poor absorption in the gut and consequent low concentration in biological fluids (µM range), reservations about polyphenol antioxidant efficiency have [...] Read more.

Polyphenols are valuable natural antioxidants present in our diet that likely mitigate aging effects, neurodegenerative conditions, and other diseases. However, because of their poor absorption in the gut and consequent low concentration in biological fluids (µM range), reservations about polyphenol antioxidant efficiency have been raised. In this review, it is shown that after scavenging superoxide radicals, coumarin, chalcone, and flavonoid polyphenols can reform themselves, becoming ready for additional cycles of scavenging, similar to the catalytic cycle in superoxide dismutase (SOD) action. The π-π interaction between one polyphenol ring and superoxide is associated with oxidation of the latter due to transfer of its unpaired electron to a polyphenolic aromatic ring, and consequent formation of a molecule of O₂ (one product of SOD action). Mechanistically, it is very difficult to establish if this π-π interaction proceeds before or after the most common mode of scavenging superoxide, e.g., abstraction of an aromatic polyphenol H(hydroxyl), which then is used to form H₂O₂ (the other molecule produced by SOD action). At the end of this cycle of superoxide scavenging, 4-methyl-7,8-di-hydroxy-coumarin and the flavonoid galangin reform themselves. An alternative mechanistic pathway by galangin forms the η-(H₂O₂)-galangin-η-O₂ complex that includes additional H₂O₂ and O₂ molecules. Another mode of action is seen with the chalcone butein, in which the polyphenol system incorporates a molecule of O₂, e.g., a η-O₂-butein complex is formed, ready for additional scavenging. Of the several families of polyphenols analyzed in this review, only butein was able to circumvent an initial π-π interaction, directing the superoxide towards H(hydroxyl) in position 4, e.g., acting as a typical polyphenol scavenger of superoxide. This fact did not impede an additional superoxide to later react with the aromatic ring in π-π fashion. It is concluded that by mimicking SOD enzyme action, the low concentration of polyphenols in biological fluids is not a limiting factor for effective scavenging of superoxide. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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15 pages, 1012 KiB

Open AccessReview

Polyphenols and Small Phenolic Acids as Cellular Metabolic Regulators

by Mark Obrenovich, Yi Li, Moncef Tayahi and V. Prakash Reddy

Curr. Issues Mol. Biol. 2022, 44(9), 4152-4166; https://doi.org/10.3390/cimb44090285 - 09 Sep 2022

Cited by 10 | Viewed by 2068

Abstract

Polyphenols and representative small phenolic acids and molecules derived from larger constituents are dietary antioxidants from fruits, vegetables and largely other plant-based sources that have ability to scavenge free radicals. What is often neglected in polyphenol metabolism is bioavailability and the role of [...] Read more.

Polyphenols and representative small phenolic acids and molecules derived from larger constituents are dietary antioxidants from fruits, vegetables and largely other plant-based sources that have ability to scavenge free radicals. What is often neglected in polyphenol metabolism is bioavailability and the role of the gut microbiota (GMB), which has an essential role in health and disease and participates in co-metabolism with the host. The composition of the gut microbiota is in constant flux and is modified by multiple intrinsic and extrinsic factors, including antibiotics. Dietary or other factors are key modulators of the host gut milieu. In this review, we explore the role of polyphenols and select phenolic compounds as metabolic or intrinsic biochemistry regulators and explore this relationship in the context of the microbiota–gut–target organ axis in health and disease. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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23 pages, 9556 KiB

Open AccessReview

Putative Mechanisms Underlying the Beneficial Effects of Polyphenols in Murine Models of Metabolic Disorders in Relation to Gut Microbiota

by Yoshimi Niwano, Hidetsugu Kohzaki, Midori Shirato, Shunichi Shishido and Keisuke Nakamura

Curr. Issues Mol. Biol. 2022, 44(3), 1353-1375; https://doi.org/10.3390/cimb44030091 - 18 Mar 2022

Cited by 5 | Viewed by 2663

Abstract

The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in [...] Read more.

The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in relation to the gut microbiota in murine models of metabolic disorders. We analyzed the effects of polyphenols on three murine models of metabolic disorders, namely, models of a high-fat diet (HFD)-induced metabolic disorder, dextran sulfate sodium (DSS)-induced colitis, and a metabolic disorder not associated with HFD or DSS. Regardless of the model, polyphenols ameliorated the effects of metabolic disorders by alleviating intestinal oxidative stress, improving inflammatory status, and improving intestinal barrier function, as well as by modulating gut microbiota, for example, by increasing the abundance of short-chain fatty acid-producing bacteria. Consequently, polyphenols reduce circulating lipopolysaccharide levels, thereby improving inflammatory status and alleviating oxidative imbalance at the lesion sites. In conclusion, polyphenols likely act by regulating intestinal functions, including the gut microbiota, and may be a safe and suitable therapeutic agent for various metabolic disorders. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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