Baicalein protects C6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the Nrf2 signaling pathway

Choi,Eun-Ok; Jeong,Jin-Woo; Park,Cheol; Hong,Su  Hyun; Kim,Gi-Young; Hwang,Hye-Jin; Cho,Eun-Ju; Choi,Yung  Hyun

doi:10.3892/ijmm.2016.2460

Baicalein protects C6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the Nrf2 signaling pathway

Authors:
- Eun-Ok Choi
- Jin-Woo Jeong
- Cheol Park
- Su Hyun Hong
- Gi-Young Kim
- Hye-Jin Hwang
- Eun-Ju Cho
- Yung Hyun Choi
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Affiliations: Department of Food and Nutrition, College of Human Ecology, Pusan National University, Busan 609-735, Republic of Korea, Anti-Aging Research Center and Blue-Bio Industry RIC, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea, Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea, Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea
Published online on: January 20, 2016 https://doi.org/10.3892/ijmm.2016.2460
Pages: 798-806

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Abstract

Baicalein, a flavonoid originally obtained from the roots of Scutellaria baicalensis Georgi, has been reported to possess various biological properties. Although several studies have demonstrated the anti-oxidative activity of baicalein, its neuroprotective mechanisms have not been clearly established. The present study aimed to detect the effects of baicalein against hydrogen peroxide (H2O2)-induced neuronal damage in C6 glial cells and to investigate the molecular mechanisms involved in this process. The results demonstrated that baicalein effectively inhibited H2O2-induced growth and reactive oxygen species (ROS) generation. We noted that Baicalein also attenuated the H2O2‑induced formation of comet tail, phosphorylation of p-γH2A.X, loss of mitochondrial membrane potential (MMP or ΔΨm), and changes to apoptosis‑related protein expression, which suggests that it can prevent H2O2‑induced cellular DNA damage and apoptotic cell death. Furthermore, treatment with baicalein effectively induced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TrxR1) in a concentration and time-dependent manner. Moreover, the protective effects of baicalein against H2O2‑induced DNA damage and apoptosis were abolished by zinc protoporphyrin (ZnPP) IX, a HO-1 inhibitor, and auranofin, a TrxR inhibitor. In addition, we noted that the cytoprotective effects of baicalein were attenuated by transient transfection with Nrf2-specific small interfering RNA (siRNA). The findings of our present study suggest that baicalein enhances cellular antioxidant defense capacity through the inhibition of ROS generation and the activation of the Nrf2 signaling pathway, thus protecting C6 cells from H2O2-induced neuronal damage.

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