Annals of translational medicine · 2020
Asiaticoside attenuates neonatal hypoxic-ischemic brain damage through inhibiting TLR4/NF-κB/STAT3 pathway.
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Zhou Yu, Wang Si, Zhao Jing, Fang Ping
Аннотация
BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) is currently a leading cause of neonatal death. Asiaticoside (AT), a bioactive constituent isolated from Centella asiatica, possesses numerous biological properties. For instance, previous studies showed that AT could protect ischemia hypoxia neurons by mediating BCL-2 protein. However, the roles and underlying mechanisms of AT in neonatal HIE have not been clarified.
METHODS: Rice-Vannucci was applied to construct a hypoxic-ischemic brain damage (HIBD) model. Pathological damage of brain neuron tissue was determined by hematoxylin-eosin (HE) staining, while apoptosis was evaluated by terminal-deoxynucleoitidyl transferase nick end labeling (TUNEL) staining. Western blot and immunohistochemistry were applied to monitor related proteins levels. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the expression levels of inflammatory cytokines.
RESULTS: The present study indicated that AT dose-dependently ameliorated histologic damage and inhibited apoptosis induced by hypoxic ischemia (HI) (P<0.01). AT also dose-dependently alleviated oxidative damage and reduced the levels of proinflammatory cytokines (ICAM-1, IL-18, and IL-1β) and TLR4 level. In terms of mechanism, decrease of TLR and IL-18 suppressed NF-κB phosphorylation and reduced the levels of TNFα, IL-6, and p-STAT3, leading to the inactivation of NF-κB/STAT3 pathway. Interestingly, with the addition of lipopolysaccharide (LPS), the increase of TLR4 activated NF-κB/STAT3 pathway again.
CONCLUSIONS: Collectively, the data provide insight into a novel mechanism by which AT may be an effective agent for HIE via the TLR4/NF-κB/STAT3 pathway.
METHODS: Rice-Vannucci was applied to construct a hypoxic-ischemic brain damage (HIBD) model. Pathological damage of brain neuron tissue was determined by hematoxylin-eosin (HE) staining, while apoptosis was evaluated by terminal-deoxynucleoitidyl transferase nick end labeling (TUNEL) staining. Western blot and immunohistochemistry were applied to monitor related proteins levels. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the expression levels of inflammatory cytokines.
RESULTS: The present study indicated that AT dose-dependently ameliorated histologic damage and inhibited apoptosis induced by hypoxic ischemia (HI) (P<0.01). AT also dose-dependently alleviated oxidative damage and reduced the levels of proinflammatory cytokines (ICAM-1, IL-18, and IL-1β) and TLR4 level. In terms of mechanism, decrease of TLR and IL-18 suppressed NF-κB phosphorylation and reduced the levels of TNFα, IL-6, and p-STAT3, leading to the inactivation of NF-κB/STAT3 pathway. Interestingly, with the addition of lipopolysaccharide (LPS), the increase of TLR4 activated NF-κB/STAT3 pathway again.
CONCLUSIONS: Collectively, the data provide insight into a novel mechanism by which AT may be an effective agent for HIE via the TLR4/NF-κB/STAT3 pathway.