Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

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.

Andrographolide exerts anti-inflammatory effects in Mycobacterium tuberculosis-infected macrophages by regulating the Notch1/Akt/NF-κB axis

“…Many HDT candidates were designed to activate autophagy and overcome Mtb resistance. Consistent with the findings by Juan Du, et al who have reported that Andro promotes cell autophagy and S100B expression in mouse astrocytes, 42 we found that Andro induces autophagy in Mtb‐infected macrophages. But Andro‐induced autophagy has another effect which acts as a negative regulator of NLRP3 inflammasome.…”

“…Andrographolide (Andro) is the major bioactive component of Andrographis paniculata , which is considered to be responsible for the majority of the biological effects of herbal medicine. Andro is a small‐molecule that possesses many biological properties such as anti‐inflammatory, anti‐bacterial, anti‐diabetic, anti‐allergic, hepato‐protective and anti‐cancer bioactivities 40–44 . Andro plays its biologic functions through diverse mechanisms, including an anti‐oxidant ability, modulation of prostaglandin production, modulation of immune cells, and so on.…”

“…Andro is a small-molecule that possesses many biological properties such as anti-inflammatory, anti-bacterial, anti-diabetic, anti-allergic, hepato-protective and anticancer bioactivities. [40][41][42][43][44] Andro plays its biologic functions through diverse mechanisms, including an anti-oxidant ability, modulation of prostaglandin production, modulation of immune cells, and so on. Several reports have shown anti-microbial effects of Andro in human lung epithelial cells by up-regulation of -defensin-2 through regulating p38 MAPK and NF-B pathways.…”

Cortical interlaminar astrocytes across the therian mammal radiation

“…AntiS100 β: Immunogen: Synthetic peptide within Human S100 beta aa 50 to the C-terminus (C terminal). The exact sequence is proprietary; Host: rabbit; Antibody type: monoclonal, clone (EP1576Y); Manufacturer and Catalogue#: Abcam ab52642; Concentration: 1:300; Characterization reference: WB astrocytes cell culture, band size 11 kDa (Du et al, 2018). RRID:AB_882426.…”

Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids

“…Andrographolide increased Beclin-1 expression, together with other markers of autophagy such as LC3II, and, in parallel, decreased the formation of autophagosomes. As for the autophagy regulation, the neurotrophic effect was mediated by the JNK pathway [79].…”