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

Hongbin Zhang,Shikun Yang,Zhong Zeng,Hanfei Huang,Siming Qu,Bo Yuan

doi:10.1590/1414-431x20187439

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.

Highlights

Gastrodin (GSTD) is an active compound isolated from the roots of a plant used in ancient Chinese traditional medicine, Rhizoma gastrodiae, more commonly known as Tianma
We speculated that the protective effects of GSTD treatment on cell viability was associated with the Nuclear factor erythroid-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway
Oxidative stress is a common pathological mechanism involved in several types of liver disease, including nonalcoholic fatty liver disease (NAFLD), IR, drug- and non-drug-induced liver injury, and hepatic fibrosis [10,11,12]

Summary

Introduction

Gastrodin (GSTD) is an active compound isolated from the roots of a plant used in ancient Chinese traditional medicine, Rhizoma gastrodiae, more commonly known as Tianma. GSTD was found to be effective against several types of liver disease, including drug- and non-drug-induced liver injury, nonalcoholic fatty liver disease (NAFLD), and hepatic fibrosis [5,6,7]. These studies indicated that GSTD protected liver cells as the disease progressed. In line with the current understanding of IR, our study revealed that efficacy of GSTD treatment was mainly attributed to antioxidant and anti-inflammatory activities. GSTD treatment may help patients with liver disease recover more rapidly through the antioxidant and antiinflammatory properties of the compound

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