Calycosin alleviates<scp>H<sub>2</sub>O<sub>2</sub></scp>‐induced astrocyte injury by restricting oxidative stress through the Akt/Nrf2/<scp>HO</scp>‐1 signaling pathway
Cheng‐You Lu, Cecilia Hsuan Day, Chia‐Hua Kuo, Tso‐Fu Wang, Tsung‐Jung Ho, Pei‐Fang Lai, Ray‐Jade Chen, Chun‐Hsu Yao, Vijaya Padma Viswanadha, Wei‐Wen Kuo, Chih‐Yang Huang
Abstract
Abstract Oxidative stress‐induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)‐associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi ( Radix Astragali Mongolici ), is a potential therapeutic candidate with anti‐inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H 2 O 2 . The results revealed that H 2 O 2 significantly induced ROS and inflammatory factor (tumor necrosis factor [TNF]‐α and interleukin [IL]‐1β) production, whereas post‐treatment with calycosin dramatically and concentration‐dependently suppressed H 2 O 2 ‐induced damage by enhancing cell viability, repressing ROS and inflammatory factor production, and increasing superoxide dismutase (SOD) expression. Additionally, we found that calycosin facilitated nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of antioxidant molecules (heme oxygenase [HO]‐1 and SOD) following H 2 O 2 treatment. Moreover, calycosin did not attenuated H 2 O 2 ‐induced astrocyte damage and ROS production in the presence of the ML385 (a Nrf2‐specific inhibitor) and following Nrf2 silencing. Furthermore, calycosin failed to increase Akt phosphorylation and mitigate H 2 O 2 ‐induced astrocyte damage in the presence of the LY294002 (a selective phosphatidylinositol 3‐kinase inhibitor), indicating that calycosin‐mediated regulation of oxidative‐stress homeostasis involved Akt/Nrf2/HO‐1 signaling. These findings demonstrated that calycosin protects against oxidative injury in brain astrocytes by regulating oxidative stress through the AKT/Nrf2/HO‐1 signaling pathway.