Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu

Mesenchymal stem cells (MSCs) exhibit great promise for treatment applications because of their immunosuppressive properties. The aryl hydrocarbon receptor (AHR), which is a transcription factor that is activated via ligand, has a pivotal role in regulating the immune system and is involved in a ran...

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Main Authors: Thi Sam Nguyen, Thi Thuy Ngan Nguyen, Thi Phuong Anh Nguyen, Tran Bao Chau Ha, Manh Cuong Nguyen, Syed Shadab Raza, Vinh Truong Do, Hoang Ha Chu
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/sci/6612312
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author Thi Sam Nguyen
Thi Thuy Ngan Nguyen
Thi Phuong Anh Nguyen
Tran Bao Chau Ha
Manh Cuong Nguyen
Syed Shadab Raza
Vinh Truong Do
Hoang Ha Chu
author_facet Thi Sam Nguyen
Thi Thuy Ngan Nguyen
Thi Phuong Anh Nguyen
Tran Bao Chau Ha
Manh Cuong Nguyen
Syed Shadab Raza
Vinh Truong Do
Hoang Ha Chu
author_sort Thi Sam Nguyen
collection DOAJ
description Mesenchymal stem cells (MSCs) exhibit great promise for treatment applications because of their immunosuppressive properties. The aryl hydrocarbon receptor (AHR), which is a transcription factor that is activated via ligand, has a pivotal role in regulating the immune system and is involved in a range of immune-related disorders. However, hyperglycemia, the defining biochemical hallmark of diabetes, creates a chronically pro-inflammatory microenvironment that impairs the immunoregulatory effects of MSCs. In this study, we explored the potential of kynurenic acid (KYNA) and quercetin, two naturally derived compounds, to modulate the immune response of MSCs through the regulation of AHR signaling under hyperglycemic conditions. We assessed the immunophenotyping and differentiation capacity of cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) in a high-glucose medium and quantified the mRNA expression rate of AHR, CYP1A1, CYP1B1, and IL-6 using real time PCR. Our study is the first to reveal that KYNA and quercetin enhance mRNA expression levels of AHR and CYP1B1, while reducing IL-6 expression in hUC-MSCs, suggesting their potential as immunomodulators. These findings highlight the compounds’ promise as drug candidates for immune-mediated diseases through stem cell therapy, particularly due to their modulation of AHR.
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spelling doaj-art-4d84de8a7e504e16a2edbfa9d07d88292025-08-20T03:31:27ZengWileyStem Cells International1687-96782025-01-01202510.1155/sci/6612312Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic MilieuThi Sam Nguyen0Thi Thuy Ngan Nguyen1Thi Phuong Anh Nguyen2Tran Bao Chau Ha3Manh Cuong Nguyen4Syed Shadab Raza5Vinh Truong Do6Hoang Ha Chu7Graduate University of Science and TechnologyStem Cell and Gene Therapy Applied Research CenterStem Cell and Gene Therapy Applied Research CenterStem Cell and Gene Therapy Applied Research CenterInstitute of Natural Products ChemistryLaboratory for Stem Cell and Restorative NeurologyStem Cell and Gene Therapy Applied Research CenterStem Cell and Gene Therapy Applied Research CenterMesenchymal stem cells (MSCs) exhibit great promise for treatment applications because of their immunosuppressive properties. The aryl hydrocarbon receptor (AHR), which is a transcription factor that is activated via ligand, has a pivotal role in regulating the immune system and is involved in a range of immune-related disorders. However, hyperglycemia, the defining biochemical hallmark of diabetes, creates a chronically pro-inflammatory microenvironment that impairs the immunoregulatory effects of MSCs. In this study, we explored the potential of kynurenic acid (KYNA) and quercetin, two naturally derived compounds, to modulate the immune response of MSCs through the regulation of AHR signaling under hyperglycemic conditions. We assessed the immunophenotyping and differentiation capacity of cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) in a high-glucose medium and quantified the mRNA expression rate of AHR, CYP1A1, CYP1B1, and IL-6 using real time PCR. Our study is the first to reveal that KYNA and quercetin enhance mRNA expression levels of AHR and CYP1B1, while reducing IL-6 expression in hUC-MSCs, suggesting their potential as immunomodulators. These findings highlight the compounds’ promise as drug candidates for immune-mediated diseases through stem cell therapy, particularly due to their modulation of AHR.http://dx.doi.org/10.1155/sci/6612312
spellingShingle Thi Sam Nguyen
Thi Thuy Ngan Nguyen
Thi Phuong Anh Nguyen
Tran Bao Chau Ha
Manh Cuong Nguyen
Syed Shadab Raza
Vinh Truong Do
Hoang Ha Chu
Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu
Stem Cells International
title Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu
title_full Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu
title_fullStr Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu
title_full_unstemmed Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu
title_short Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu
title_sort immunoregulation of quercetin and kynurenic acid on human umbilical cord mesenchymal stem cells through gene expression of aryl hydrocarbon receptor and interleukin 6 in hyperglycemic milieu
url http://dx.doi.org/10.1155/sci/6612312
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