Hemistepsin A protects human keratinocytes against hydrogen peroxide-induced oxidative stress through activation of the Nrf2/HO-1 signaling pathway.

Hemistepsin A, a sesquiterpene lactone compound isolated from Hemistepta lyrata, has been identified a variety of pharmacological actions including anti-hepatotoxic, anti-inflammatory and anti-cancer activities. Nevertheless, the antioxidant effects of hemistepsin A and the underlying mechanisms have not been investigated properly. Therefore, in the present study, we investigated the protective effect of hemistepsin A against oxidative stress in HaCaT human keratinocytes. The results demonstrated that hemistepsin A suppressed 500 μM hydrogen peroxide (H2O2)-induced cytotoxicity and DNA damage by blocking ROS accumulation. 10 μM Hemistepsin A also prevented apoptosis by preventing the mitochondrial dysfunction and the cytosolic release of cytochrome c, reducing the rate of Bax/Bcl-2 expression, and decreasing the activation of caspase-9 and caspase-3, suggesting that hemistepsin A protected cells from H2O2-induced mitochondria-mediated apoptosis. In addition, hemistepsin A markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression and activity of heme oxygenase-1 (HO-1) in the presence of 500 μM H2O2. However, inhibiting the expression of HO-1 by artificially blocking the expression of Nrf2 or HO-1 using siRNA significantly eliminated the protective effect of hemistepsin A, indicating that hemistepsin A activates the Nrf2/HO-1 signaling pathway in HaCaT cells to protect against oxidative stress. Therefore, these results suggest that hemistepsin A may be useful as a potential therapeutic agent against various oxidative stress-related skin diseases.

Park C ，Lee H ，Noh JS ，Jin CY ，Kim GY ，Hyun JW ，Leem SH ，Choi YH ... -  《-》

Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes.

Park C ，Cha HJ ，Hong SH ，Kim GY ，Kim S ，Kim HS ，Kim BW ，Jeon YJ ，Choi YH ... -  《Marine Drugs》

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes.

Choi YH 《GENERAL PHYSIOLOGY AND BIOPHYSICS》

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.

Jeong JY ，Cha HJ ，Choi EO ，Kim CH ，Kim GY ，Yoo YH ，Hwang HJ ，Park HT ，Yoon HM ，Choi YH ... -  《International Journal of Medical Sciences》

trans-Cinnamaldehyde Prevents Oxidative Stress-Induced Apoptosis in V79-4 Chinese Hamster Lung Fibroblasts through the Nrf2-Mediated HO-1 Activation.

Choi YH 《-》