Orientin-mediated Nrf2/HO-1 signal alleviates H(2)O(2)-induced oxidative damage via induction of JNK and PI3K/AKT activation.

Oxidative stress is closely associated with the pathogenesis of various diseases. Orientin (Ori), a flavonoid component isolated from natural plants, possesses antioxidant activity. Accordingly, we focused on exploring the potential therapeutic effects of Ori on hydrogen peroxide (H2O2)-induced oxidative impairment in RAW 264.7 cells and the underlying antioxidative mechanisms. Our findings suggested that Ori exposure effectively alleviated H2O2-stimulated cytotoxicity, inhibited reactive oxygen species (ROS) generation, and glutathione (GSH) depletion, which were involved in induction of heme oxygenase-1 (HO-1) by enhancing the nuclear factor-erythroid 2-related factor 2 (Nrf2) translocation, decreasing the Keap1 protein expression, and increasing the antioxidant response element (ARE) activity. However, knockdown of Nrf2 and HO-1 with siRNA mostly abolished the cytoprotective effects against H2O2-induced cell oxidative injury, reduced the expression of Nrf2 and HO-1, respectively. Moreover, Ori exposure significantly induced a c-Jun NH2-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT) phosphorylation, but JNK and PI3K/AKT inhibitors treatment effectively reduced levels of Ori-enhanced Nrf2 nuclear translocation and HO-1 protein expression, and blocked Ori-inhibited cytotoxicity and ROS accumulation triggered by H2O2 respectively. Taken together, Ori might exhibit a protective role against H2O2-stimulated oxidative damage by the induction of HO-1 expression through the activation of the JNK- and PI3K/AKT-Nrf2 signaling pathways.

Xiao Q ，Piao R ，Wang H ，Li C ，Song L ... -  《-》

Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway.

Han D ，Chen W ，Gu X ，Shan R ，Zou J ，Liu G ，Shahid M ，Gao J ，Han B ... -  《Oncotarget》

The cytoprotective effects of 7,8-dihydroxyflavone against oxidative stress are mediated by the upregulation of Nrf2-dependent HO-1 expression through the activation of the PI3K/Akt and ERK pathways in C2C12 myoblasts.

Kang JS ，Choi IW ，Han MH ，Kim GY ，Hong SH ，Park C ，Hwang HJ ，Kim CM ，Kim BW ，Choi YH ... -  《-》

Lico A Enhances Nrf2-Mediated Defense Mechanisms against t-BHP-Induced Oxidative Stress and Cell Death via Akt and ERK Activation in RAW 264.7 Cells.

Lv H ，Ren H ，Wang L ，Chen W ，Ci X ... -  《-》

Rhein from Rheum rhabarbarum Inhibits Hydrogen-Peroxide-Induced Oxidative Stress in Intestinal Epithelial Cells Partly through PI3K/Akt-Mediated Nrf2/HO-1 Pathways.

Zhuang S ，Yu R ，Zhong J ，Liu P ，Liu Z ... -  《-》