Activation of the Nrf2/HO-1 Signaling Pathway Contributes to the Protective Effects of Baicalein Against Oxidative Stress-induced DNA Damage and Apoptosis in HEI193 Schwann Cells

Overview

Journal Int J Med Sci

Specialty General Medicine

Date 2019 Jan 22

PMID 30662338

Citations 37

Authors

Jae Yeob Jeong

Hee-Jae Cha

Eun Ok Choi

Cheol Hong Kim

Gi-Young Kim

Young Hyun Yoo

Hye-Jin Hwang

Hwan Tae Park

Hyun Min Yoon

Yung Hyun Choi

Affiliations

Soon will be listed here.

Abstract

Baicalein, a flavonoid extracted from the roots of Georgi., has various pharmacological effects due to its high antioxidant activity. However, no study has yet been conducted on the protective efficacy of baicalein against oxidative stress in Schwann cells. In this study, we evaluated the protective effect of baicalein on DNA damage and apoptosis induced by hydrogen peroxide (HO) in HEI193 Schwann cells. For this purpose, HEI193 cells exposed to HO in the presence or absence of baicalein were applied to cell viability assay, immunoblotting, Nrf2-specific small interfering RNA (siRNA) transfection, comet assay, and flow cytometry analyses. Our results showed that baicalein effectively inhibited HO-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Baicalein also weakened HO-induced mitochondrial dysfunction, increased the Bax/Bcl-2 ratio, activated caspase-9 and -3, and degraded poly(ADP-ribose) polymerase. In addition, baicalein increased not only the expression but also the phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and promoted the expression of heme oxygenase-1 (HO-1), a critical target enzyme of Nrf2, although the expression of kelch-like ECH-associated protein-1 was decreased. However, the inhibition of Nrf2 expression by transfection with Nrf2-siRNA transfection abolished the expression of HO-1 and antioxidant potential of baicalein. These results demonstrate that baicalein attenuated HO-induced apoptosis through the conservation of mitochondrial function while eliminating ROS in HEI193 Schwann cells, and the antioxidant efficacy of baicalein implies at least a Nrf2/HO-1 signaling pathway-dependent mechanism. Therefore, it is suggested that baicalein may have a beneficial effect on the prevention and treatment of peripheral neuropathy induced by oxidative stress.

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