Potential of Orally Administered Quercetin, Hesperidin, and p-Coumaric Acid in Suppressing Intra-/Extracellular Advanced Glycation End-Product-Induced Cytotoxicity in Proximal Tubular Epithelial Cells

Takanobu Takata ^1,2, Junji Moriya ^3,4, Katsuhito Miyazawa ⁵

¹Division of Molecular and Genetic Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan.
²Department of Pharmacy, Kanazawa Medical University Hospital, Uchinada 920-0293, Ishikawa, Japan.
³Department of General Internal Medicine, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan.
⁴General Medical Center, Kanazawa Medical University Hospital, Uchinada 920-0293, Ishikawa, Japan.
⁵Department of Urology, Kanazawa Medical University Hospital, Uchinada 920-0393, Ishikawa, Japan.
⁶Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan.
⁷Department of Pathology, Kanazawa Medical University Hospital, Uchinada 920-0293, Ishikawa, Japan.
⁸Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050011, China.
⁹Hebei Key Laboratory of Turbidity Toxin Syndrome, Shijiazhuang 050011, China.
¹⁰Research Center, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050011, China.
¹¹Inoue Iin Clinic, Kusatsu 525-0034, Shiga, Japan.
¹²Department of Internal Medicine, Fukui Saiseikai Hospital, Wadanaka 918-8503, Fukui, Japan.

⁰Division of Molecular and Genetic Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan.

International Journal of Molecular Sciences +

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September 27, 2025

View abstract on PubMed

Summary

Japanese folk medicine compounds like quercetin and hesperidin may protect kidney cells from damage caused by advanced glycation end-products (AGEs). These compounds and p-coumaric acid show potential in preventing AGE-related kidney dysfunction.

Area Of Science

Nephrology
Pharmacology
Natural Products Chemistry

Background

Advanced glycation end-products (AGEs) contribute to proximal tubular epithelial (PTE) cell dysfunction in lifestyle diseases.
Urinary stones cause cytotoxicity in PTE cells, necessitating therapeutic interventions.
Japanese folk medicine utilizes *Quercus salicina*/*Q. stenophylla* leaves, known to contain bioactive compounds.

Purpose Of The Study

To review the effects of quercetin, hesperidin, and p-coumaric acid on PTE cells.
To investigate the metabolism of these compounds after oral administration.
To explore their role in mitigating AGE-induced cytotoxicity and generation in PTE cells.

Main Methods

Literature review of existing preclinical and clinical studies.
Analysis of metabolic pathways of quercetin, hesperidin, and p-coumaric acid.
Assessment of their impact on AGEs and PTE cell cytotoxicity.

Main Results

Non-metabolized quercetin and p-coumaric acid may suppress AGE-induced cytotoxicity in PTE cells.
Metabolites of quercetin and hesperidin show potential in inhibiting AGE generation.
The combined effect of these compounds may offer collective protection against AGEs in PTE cells.

Conclusions

Quercetin, hesperidin, and p-coumaric acid from *Q. salicina*/*Q. stenophylla* show promise in managing AGE-related PTE cell damage.
Further preclinical and clinical research is warranted to validate these findings.
Understanding the metabolism of these compounds is crucial for therapeutic development.

Keywords:

Quercus salicina Blume Quercus stenophylla Makino advanced glycation end-product hesperidin metabolism p-coumaric acid proximal tubular epithelial cell quercetin traditional Japanese medicine