Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells

Objective: High glucose (HG)-induced oxidative stress is a metabolic stimulus for hepatic impairment in diabetes. Naturalphytochemicals may alleviate HG-induced complications. We aimed to examine the impact of citronellol (CT) on oxidativestress and inflammation in the human hepatocellular liver car...

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Main Authors: Razieh Choghakhori, Mojgan Azadpour, Amir Abbasnezhad, Farzad Ebrahimzadeh, Hassan Ahmadvand
Format: Article
Language:English
Published: Royan Institute (ACECR), Tehran 2024-10-01
Series:Cell Journal
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Online Access:https://www.celljournal.org/article_721279_d41d8cd98f00b204e9800998ecf8427e.pdf
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author Razieh Choghakhori
Mojgan Azadpour
Amir Abbasnezhad
Farzad Ebrahimzadeh
Hassan Ahmadvand
author_facet Razieh Choghakhori
Mojgan Azadpour
Amir Abbasnezhad
Farzad Ebrahimzadeh
Hassan Ahmadvand
author_sort Razieh Choghakhori
collection DOAJ
description Objective: High glucose (HG)-induced oxidative stress is a metabolic stimulus for hepatic impairment in diabetes. Naturalphytochemicals may alleviate HG-induced complications. We aimed to examine the impact of citronellol (CT) on oxidativestress and inflammation in the human hepatocellular liver carcinoma (HepG2) cell line under HG conditions.Materials and Methods: In this experimental study, the HepG2 cells were exposed to HG concentrations of 50 mM andco-treated with or without CT at concentrations of 10, 20, and 40 μg/ml for 48 hours. The impact of treatments on the levelsof malondialdehyde (MDA), glutathione (GSH), and the enzyme’s activity of glutathione peroxidase (GPx), catalase (CAT),and superoxide dismutase (SOD) was explored. We used quantitative reverse transcription polymerase chain reaction (qRTPCR)to evaluate the gene expression of nuclear factor-κβ (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6),and dipeptidyl peptidase-4 (DPP-4).Results: Co-treatment with CT (20 and 40 μg/ml) significantly reduced (P<0.05) HG-induced cell death (9.73 and10.56%, respectively) and MDA production (16 and 26.78%, respectively) compared to untreated HG control group.Meanwhile, CT (10, 20, and 40 μg/ml) substantially increased (P<0.05) GSH content (35.61, 55.24, and 69.75%,respectively), GPx (48.32, 61.75, and 75.10%, respectively), and CAT activity (20.25, 25.09, 30.16%, respectively)dose-dependently comparison to untreated ones. TNF-α and IL-6 gene expression were also modulated significantly(P<0.05) by 40 μg/ml CT (47.75 and 32.44%, respectively) as compared to the HG control group. Moreover, CT at 20and 40 μg/ml attenuated (P<0.05) NF-κB gene expression (30.41 and 39.93%, respectively), and at all doses, made aconsiderable reduction (P<0.05) in DPP-4 gene expression (18.77, 18.78, and 44.61%, respectively) dose-dependentlycomparison to untreated ones.Conclusion: Our research suggested that CT with greater effectiveness at 40 μg/ml might shield hepatocytes exposedto HG by lowering oxidative stress and inhibiting inflammatory reactions; however, more research is needed.
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institution OA Journals
issn 2228-5806
2228-5814
language English
publishDate 2024-10-01
publisher Royan Institute (ACECR), Tehran
record_format Article
series Cell Journal
spelling doaj-art-9114e98ee8ff4497a814212283dcd2222025-08-20T02:03:38ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142024-10-01261060261010.22074/cellj.2025.2026976.1554721279Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 CellsRazieh Choghakhori0Mojgan Azadpour1Amir Abbasnezhad2Farzad Ebrahimzadeh3Hassan Ahmadvand4Razi Herbal Medicines Research Center, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, IranRazi Herbal Medicines Research Center, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, IranNutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, IranNutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, IranRazi Herbal Medicines Research Center, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, IranObjective: High glucose (HG)-induced oxidative stress is a metabolic stimulus for hepatic impairment in diabetes. Naturalphytochemicals may alleviate HG-induced complications. We aimed to examine the impact of citronellol (CT) on oxidativestress and inflammation in the human hepatocellular liver carcinoma (HepG2) cell line under HG conditions.Materials and Methods: In this experimental study, the HepG2 cells were exposed to HG concentrations of 50 mM andco-treated with or without CT at concentrations of 10, 20, and 40 μg/ml for 48 hours. The impact of treatments on the levelsof malondialdehyde (MDA), glutathione (GSH), and the enzyme’s activity of glutathione peroxidase (GPx), catalase (CAT),and superoxide dismutase (SOD) was explored. We used quantitative reverse transcription polymerase chain reaction (qRTPCR)to evaluate the gene expression of nuclear factor-κβ (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6),and dipeptidyl peptidase-4 (DPP-4).Results: Co-treatment with CT (20 and 40 μg/ml) significantly reduced (P<0.05) HG-induced cell death (9.73 and10.56%, respectively) and MDA production (16 and 26.78%, respectively) compared to untreated HG control group.Meanwhile, CT (10, 20, and 40 μg/ml) substantially increased (P<0.05) GSH content (35.61, 55.24, and 69.75%,respectively), GPx (48.32, 61.75, and 75.10%, respectively), and CAT activity (20.25, 25.09, 30.16%, respectively)dose-dependently comparison to untreated ones. TNF-α and IL-6 gene expression were also modulated significantly(P<0.05) by 40 μg/ml CT (47.75 and 32.44%, respectively) as compared to the HG control group. Moreover, CT at 20and 40 μg/ml attenuated (P<0.05) NF-κB gene expression (30.41 and 39.93%, respectively), and at all doses, made aconsiderable reduction (P<0.05) in DPP-4 gene expression (18.77, 18.78, and 44.61%, respectively) dose-dependentlycomparison to untreated ones.Conclusion: Our research suggested that CT with greater effectiveness at 40 μg/ml might shield hepatocytes exposedto HG by lowering oxidative stress and inhibiting inflammatory reactions; however, more research is needed.https://www.celljournal.org/article_721279_d41d8cd98f00b204e9800998ecf8427e.pdfcitronellolhepg2 cellshyperglycemiainflammationoxidative stress
spellingShingle Razieh Choghakhori
Mojgan Azadpour
Amir Abbasnezhad
Farzad Ebrahimzadeh
Hassan Ahmadvand
Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells
Cell Journal
citronellol
hepg2 cells
hyperglycemia
inflammation
oxidative stress
title Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells
title_full Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells
title_fullStr Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells
title_full_unstemmed Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells
title_short Citronellol Attenuates High Glucose-Induced Oxidative Stress and Inflammatory Responses in HepG2 Cells
title_sort citronellol attenuates high glucose induced oxidative stress and inflammatory responses in hepg2 cells
topic citronellol
hepg2 cells
hyperglycemia
inflammation
oxidative stress
url https://www.celljournal.org/article_721279_d41d8cd98f00b204e9800998ecf8427e.pdf
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AT amirabbasnezhad citronellolattenuateshighglucoseinducedoxidativestressandinflammatoryresponsesinhepg2cells
AT farzadebrahimzadeh citronellolattenuateshighglucoseinducedoxidativestressandinflammatoryresponsesinhepg2cells
AT hassanahmadvand citronellolattenuateshighglucoseinducedoxidativestressandinflammatoryresponsesinhepg2cells