Luteolin alleviates neuroinflammation via downregulating the TLR4/TRAF6/NF-?B pathway after intracerebral hemorrhage - 19/04/20
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Graphical abstract |
Potential mechanisms of luteolin to improve ICH-induced SBI.
Luteolin can engage with TRAF6 and inhibit TLR4/TRAF6/NF-κB signaling pathway activation, finally improving the neuroinflammation induced by ICH.
Highlights |
• | Luteolin alleviates intracerebral hemorrhage induced secondary brain injury. |
• | Luteolin inhibits the activation of microglia and inflammatory response induced by ICH. |
• | Luteolin downregulates TLR4/TRAF6/NF-κB pathway activation. |
• | Luteolin targets TRAF6 and prevents the ubiquitination of TRAF6. |
Abstract |
The activation of microglia and inflammatory responses is essential for the process of intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we investigated the effects of luteolin on ICH-induced SBI and the potential mechanisms. Autologous blood was injected to establish the ICH model in vivo, and oxyhemoglobin (OxyHb) was used to mimic the ICH model in vitro. We found that the administration of luteolin significantly improved motor and sensory impairments and inhibited neuronal cell degeneration in vivo. In the in vitro study, the decrease of the neuronal cell viability induced by activated microglia was alleviated by luteolin treatment. Furthermore, by antagonizing the activation of the Toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-κB (NF-κB) signaling pathway, the ICH-induced elevation of cytokine release was decreased after treatment with luteolin, which was confirmed both in vivo and in vitro. Additionally, we found that luteolin engaged with TRAF6 and inhibited the ubiquitination of TRAF6. Taken together, our findings demonstrate the neuroprotective effects of luteolin after ICH and the potential mechanisms, which suggest that luteolin is a potential therapeutic candidate for ICH treatment.
Le texte complet de cet article est disponible en PDF.Abbreviations : ICH, SBI, TLR, TRAF6, PPRs, DAMPs, PAMPs, LPS, Nrf2, PVDF, PBST, CETSA, CO-IP, FBS, rCTRP9, OxyHb, NF-κB, SD, FJB, ELISA, PBS, ECL, RT, BBB
Keywords : Intracerebral hemorrhage, Luteolin, TRAF6, NF-κB, Neuroinflammation
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