Baicalein Decreases Hydrogen Peroxide-Induced Damage to NG108-15 Cells via Upregulation of Nrf2

Abstract

Baicalein is a flavonoid inhibitor of 12-lipoxygenase. Here, we investigated its effect on hydrogen peroxide-induced damage to NG108-15 cells. Hydrogen peroxide activated the mitochondrial apoptotic pathway, decreased Nrf2 expression, increased reactive oxygen species (ROS) levels, reduced viability, and increased cell death after 2-24 h treatment of NG108-15 cells. Co-treatment with hydrogen peroxide and baicalein completely suppressed the activation of mitochondrial apoptotic pathway by upregulating Nrf2 expression and reducing ROS stress and partially inhibited the effects on cell viability and cell death. Silencing of 12-lipoxygenase had a similar protective effect to baicalein on hydrogen peroxide-induced damage by blocking the hydrogen peroxide-induced decrease in Nrf2 expression and increase in ROS levels. Neither protective effect was altered by addition of 12-hydroxyeicosatetraenoic acid, the product of 12-lipoxygenase, suggesting that hydrogen peroxide induced damage via 12-lipoxygenase by another, as yet unknown, mechanism, rather than activating it. Co-treatment of cells with hydrogen peroxide and N-acetylcysteine or the Nrf2 inducer sulforaphane reduced hydrogen peroxide-induced damage in a similar fashion to baicalein, while the Nrf2 inhibitor retinoic acid blocked the protective effect of baicalein. Silencing Nrf2 also inhibited the protective effects of baicalein, sulforaphane, and N-acetylcysteine and resulted in high ROS levels, suggesting ROS elimination was mediated by Nrf2. Taken together our results suggest that baicalein protects cells from hydrogen peroxide-induced activation of the mitochondrial apoptotic pathway by upregulating Nrf2 and inhibiting 12-lipoxygenase to block the increase in ROS levels. Hydrogen peroxide also activates a second mitochondrial dysfunction independent death pathway which is resistant to baicalein.

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

“…In the present study, we found that baicalein increased Nrf2 protein expression and decreased Keap1 in a concentration-and time-dependent manner in C6 cells. These results are consistent with those of previous studies (42)(43)(44), and were associated with the induction of HO-1 and TrxR1. However, the inhibition of HO-1 function using ZnPP significantly weakened the inhibitory effects of baicalein on H 2 O 2 -induced MMP loss, growth inhibition, and apoptosis by blocking PARP cleavage, XIAP inhibition, and γH2A.X phosphorylation.…”

Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes

“…Interestingly, we found that their expression levels were inhibited in 3-AT-treated adipocytes. First, our results agree with a recent study that found that H 2 O 2 lowers NRF2 expression [ 46 ]. Moreover, the inflammatory response present in adipocytes treated with 3-AT could also explain the reduced NRF2 expression because it has been widely demonstrated that Nrf2 and NF-κB behave antagonistically [ 47 ].…”

The Fascinating Effects of Baicalein on Cancer: A Review

“…The chemical structure and properties of baicalein are shown in Figure 1. Emerging evidence has demonstrated that baicalein exerts multiple pharmacological effects including anti-inflammatory [17], antioxidant [18], and antiviral [19] properties, as well as protection against cardiovascular illness [20]. In the past decade, there has been great progress in exploring the target mechanisms and signaling pathways of baicalein’s anti-cancer potential.…”