In:
Environmental Toxicology, Wiley, Vol. 37, No. 4 ( 2022-04), p. 858-867
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.
Type of Medium:
Online Resource
ISSN:
1520-4081
,
1522-7278
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2027534-1
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