Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation

Abstract

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.

Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway

“…In in vitro experiments, we studied the effect of probucol on MSCs under oxidative stress. The secondary injury following H 2 O 2 represents consecutive pathological processes including oxidative stress and apoptosis [24]. Oxidants and their dericatives generated by H 2 O 2 enhance the generation of ROS and exhaust antioxidant defense enzymes.…”

Gastrodin Inhibits H₂O₂-Induced Ferroptosis through Its Antioxidative Effect in Rat Glioma Cell Line C6

“…39) GSH depletion activates lipoxygenase, inhibits GPX4 activity and triggers lipid peroxidation. 40) Our results show that gastrodin increased the level of GSH and the activity of GPX. Further, the oxidation of endogenous lipids was determined by measuring MDA in C6 cells treated with gastrodin or H 2 O 2 .…”

Gastrodin Alleviates Oxidative Stress-Induced Apoptosis and Cellular Dysfunction in Human Umbilical Vein Endothelial Cells via the Nuclear Factor-Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway and Accelerates Wound Healing In Vivo

“…This phenomenon may be due partly to the insufficient activation of the Nrf2 /HO-1 pathway to prevent toxicity under TBHP stimulation. It has been reported that GAS can ameliorate oxidative stress-induced damage through the Nrf2 /HO-1 pathway in particular cell types (Zhang et al, 2018). Indeed, the results of our study demonstrated that GAS significantly increased Nrf2 accumulation in the nucleus and HO-1 expression in TBHP-treated HUVECs.…”