Abstract
Andrographolide (ANDRO) has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains) were subjected to 3 and 21% of O2 for various times (0–12 h) to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.
Highlights
Traumatic brain injury (TBI) is a major cause of death or disability worldwide, especially in young people
These results suggested that cell apoptosis and autophagy were significantly increased after 8 h of hypoxic incubation in astrocytes
After treatment with JNK inhibitor, ANDRO treatment did not lead to increases in the expressions of LC3-II, Beclin-1, and S100B, or a decline in p62 expression. These results suggested that the promotion of autophagy and S100B expression by ANDRO might be through activating JNK signaling pathways in hypoxic astrocytes
Summary
Traumatic brain injury (TBI) is a major cause of death or disability worldwide, especially in young people. After severe TBI, many people are killed by secondary injury, which is a complex set of cellular processes following trauma [1]. These secondary processes can worsen the damage and account for the greatest number of TBI deaths [2]. Brain hypoxia is a common cause of secondary injury. Brain hypoxia initiates a sequence of biochemical events to induce neuronal cell apoptosis, resulting in a hypoxic brain injury and dysfunction [3]. Brain hypoxia can aggravate TBI and is regarded as an independent predictor or a marker of disease severity [4]
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