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Pinoresinol Diglucoside Potentiates α-lipoic Acid-mediated Attenuation of ROS-induced Cell Injury by Affecting Oxidative and ER Stress in NIH-3T3 Fibroblasts.

Created on 27 Jul 2026

Authors

Yan Zhang, Lian Yang, Han Wang, Ximao Cui, Dawei Deng, Yili Yang, Xin Xu

Published in

Combinatorial chemistry & high throughput screening. May 21, 2026. Epub May 21, 2026.

Abstract

A Large amount of ROS generated by radiotherapy leads to radiationinduced skin injury (RISI), but drugs that can treat RISI are still limited in the clinic.
An oxidative-stress model was established by inducing NIH-3T3 cells with H2O2, and the protective effects of α-lipoic acid (α-LA) combined with pinoresinol diglucoside (PDG) on H2O2-induced cell injury were evaluated. Cell viability was assessed by the CCK-8 assay. Oxidative stress was evaluated by detecting the expressions of oxidative and antioxidant factors. Endoplasmic reticulum (ER) stress was evaluated by detecting ER stress-associated biomarkers. A Western blot was performed to assess the expression of the indicated proteins.
Co-administration of α-LA and PDG significantly abolished H2O2-induced cell death and oxidative stress in NIH-3T3 fibroblasts, including changes in cell viability, ROS generation, and the expressions of oxidative and antioxidant factors. Mechanistically, PDG enhanced the ability of α-LA to suppress H2O2-induced JNK activation and PARP cleavage. PDG also potentiated α-LA-mediated upregulation of AKT activation, as well as the expression of Nrf2 in H2O2- treated NIH-3T3 fibroblasts. Moreover, PDG strengthened the inhibitory effect of α-LA on H2O2-induced ER stress in these cells.
The present study investigated the protective effects of α-LA and PDG against ROSinduced injury in NIH-3T3 fibroblasts, and further investigations using in vivo models of RISI will be performed in future studies.
This study revealed that co-administration of α-LA and PDG exerted the protective effects on H2O2-induced cell injury by reducing oxidative stress and ER stress, suggesting a promising therapeutic strategy for the treatment of RISI in the future.

PMID:
42504717
Bibliographic data and abstract were imported from PubMed on 27 Jul 2026.

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