Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells

Abstract Diabetes mellitus (DM) is characterized by impaired glucose and insulin metabolism, resulting in chronic hyperglycemia. Hyperglycemia-induced inflammation is linked to the onset and progression of diabetes. Resveratrol (RES), a polyphenol phytoalexin, is studied in diabetes therapeutics res...

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Main Authors: Abegail Mukhethwa Tshivhase, Tandi Matsha, Shanel Raghubeer
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-50084-6
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author Abegail Mukhethwa Tshivhase
Tandi Matsha
Shanel Raghubeer
author_facet Abegail Mukhethwa Tshivhase
Tandi Matsha
Shanel Raghubeer
author_sort Abegail Mukhethwa Tshivhase
collection DOAJ
description Abstract Diabetes mellitus (DM) is characterized by impaired glucose and insulin metabolism, resulting in chronic hyperglycemia. Hyperglycemia-induced inflammation is linked to the onset and progression of diabetes. Resveratrol (RES), a polyphenol phytoalexin, is studied in diabetes therapeutics research. This study evaluates the effect of RES on inflammation and glucose metabolism in HepG2 cells exposed to high glucose. Inflammation and glucose metabolism-related genes were investigated using qPCR. Further, inflammatory genes were analyzed by applying ELISA and Bioplex assays. High glucose significantly increases IKK-α, IKB-α, and NF-kB expression compared to controls. Increased NF-kB expression was followed by increased expression of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-β, and COX2. RES treatment significantly reduced the expression of NF-kB, IKK-α, and IKB-α, as well as pro-inflammatory cytokines. High glucose levels reduced the expression of TGFβ1, while treatment with RES increased the expression of TGFβ1. As glucose levels increased, PEPCK expression was reduced, and GCK expression was increased in HepG2 cells treated with RES. Further, HepG2 cells cultured with high glucose showed significant increases in KLF7 and HIF1A but decreased SIRT1. Moreover, RES significantly increased SIRT1 expression and reduced KLF7 and HIF1A expression levels. Our results indicated that RES could attenuate high glucose-induced inflammation and enhance glucose metabolism in HepG2 cells.
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spelling doaj.art-2869789dff8d43dd9672ea91a4a51d282024-01-14T12:23:13ZengNature PortfolioScientific Reports2045-23222024-01-0114111310.1038/s41598-023-50084-6Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cellsAbegail Mukhethwa Tshivhase0Tandi Matsha1Shanel Raghubeer2SAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of TechnologySAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of TechnologySAMRC/CPUT Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of TechnologyAbstract Diabetes mellitus (DM) is characterized by impaired glucose and insulin metabolism, resulting in chronic hyperglycemia. Hyperglycemia-induced inflammation is linked to the onset and progression of diabetes. Resveratrol (RES), a polyphenol phytoalexin, is studied in diabetes therapeutics research. This study evaluates the effect of RES on inflammation and glucose metabolism in HepG2 cells exposed to high glucose. Inflammation and glucose metabolism-related genes were investigated using qPCR. Further, inflammatory genes were analyzed by applying ELISA and Bioplex assays. High glucose significantly increases IKK-α, IKB-α, and NF-kB expression compared to controls. Increased NF-kB expression was followed by increased expression of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-β, and COX2. RES treatment significantly reduced the expression of NF-kB, IKK-α, and IKB-α, as well as pro-inflammatory cytokines. High glucose levels reduced the expression of TGFβ1, while treatment with RES increased the expression of TGFβ1. As glucose levels increased, PEPCK expression was reduced, and GCK expression was increased in HepG2 cells treated with RES. Further, HepG2 cells cultured with high glucose showed significant increases in KLF7 and HIF1A but decreased SIRT1. Moreover, RES significantly increased SIRT1 expression and reduced KLF7 and HIF1A expression levels. Our results indicated that RES could attenuate high glucose-induced inflammation and enhance glucose metabolism in HepG2 cells.https://doi.org/10.1038/s41598-023-50084-6
spellingShingle Abegail Mukhethwa Tshivhase
Tandi Matsha
Shanel Raghubeer
Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
Scientific Reports
title Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
title_full Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
title_fullStr Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
title_full_unstemmed Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
title_short Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
title_sort resveratrol attenuates high glucose induced inflammation and improves glucose metabolism in hepg2 cells
url https://doi.org/10.1038/s41598-023-50084-6
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AT tandimatsha resveratrolattenuateshighglucoseinducedinflammationandimprovesglucosemetabolisminhepg2cells
AT shanelraghubeer resveratrolattenuateshighglucoseinducedinflammationandimprovesglucosemetabolisminhepg2cells