Eupatilin attenuates the inflammatory response induced by intracerebral hemorrhage through the TLR4/MyD88 pathway

et al. 2022

J Neuroinflammation

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Background Inflammation induced by intracerebral hemorrhage (ICH) is one of the main causes of the high mortality and poor prognosis of patients with ICH. A1 astrocytes are closely associated with neuroinflammation and neurotoxicity, whereas A2 astrocytes are neuroprotective. Homer scaffolding protein 1 (Homer1) plays a protective role in ischemic encephalopathy and neurodegenerative diseases. However, the role of Homer1 in ICH-induced inflammation and the effect of Homer1 on the phenotypic conversion of astrocytes remain unknown. Methods Femoral artery autologous blood from C57BL/6 mice was used to create an ICH model. We use the A1 phenotype marker C3 and A2 phenotype marker S100A10 to detect astrocyte conversion after ICH. Homer1 overexpression/knock-down mice were constructed by adeno-associated virus (AAV) infection to explore the role of Homer1 and its mechanism of action after ICH. Finally, Homer1 protein and selumetinib were injected into in situ hemorrhage sites in the brains of Homer1flox/flox/Nestin-Cre+/− mice to study the efficacy of Homer1 in the treatment of ICH by using a mouse cytokine array to explore the potential mechanism. Results The expression of Homer1 peaked on the third day after ICH and colocalized with astrocytes. Homer1 promotes A1 phenotypic conversion in astrocytes in vivo and in vitro. Overexpression of Homer1 inhibits the activation of MAPK signaling, whereas Homer1 knock-down increases the expression of pathway-related proteins. The Homer1 protein and selumetinib, a non-ATP competitive MEK1/2 inhibitor, improved the outcome in ICH in Homer1flox/flox/Nestin-Cre+/− mice. The efficacy of Homer1 in the treatment of ICH is associated with reduced expression of the inflammatory factor TNFSF10 and increased expression of the anti-inflammatory factors activin A, persephin, and TWEAK. Conclusions Homer1 plays an important role in inhibiting inflammation after ICH by suppressing the A1 phenotype conversion in astrocytes. In situ injection of Homer1 protein may be a novel and effective method for the treatment of inflammation after ICH.

Section: Methodsmentioning

confidence: 99%

Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage

Fei

Dou

et al. 2022

J Neuroinflammation

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“…The TLR4 signal pathway is associated with inflammation in many disease conditions such as colitis (Feng et al, 2014), and intracerebral hemorrhage (Fei et al, 2019). Growing evidence suggests that the TLR4 signal pathway is involved in inflammation during development of AS (Ha et al, 2018;Shinohara et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Salvia Miltiorrhiza Extract Prevents Atherosclerosis Development via TLR4/ NF-κB Pathway

Zhao

et al. 2021

Preprint

Aim of the Study Aqueous extract from Salvia Miltiorrhiza has been traditionally used to treat cardiovasulcar diseases. This study aims to explore the anti-inflammatory mechanisms underlying attenuation of atherosclerosis development by aqueous extract from Salvia Miltiorrhiza. Materials and methods Male ApoE-/- mice were randomly allocated into the model, the SABP, and the rosuvastatin calcium groups (RC). After 8-wk-treatment, the lipid profiles in serum, the lactate dehydrogenase (LDH), and creatine kinase (CK) in heart tissue were measured and the morphology alterations of thoracic aorta and heart were assessed. The protein expression of Toll-like receptor 4 (TLR4), TGF beta-activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the heart tissue were determined by western blotting analysis. The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels were increased and the high-density lipoprotein cholesterol (HDL-C) level was decreased in ApoE-/- mice. Results SABP significantly decreased the serum lipid levels and improved histopathology in the thoracic aorta. In addition, SABP treatment reduced the expression of TLR4, TAK1, NF-κB, IL-6, and TNF-α, and inhibited the expression and activation of NF-κB in the heart of ApoE-/- mice. The LDH and CK in the heart did not differ significantly among different groups, and the heart did not have obvious pathological changes. Conclusions These findings indicated that SABP may exert an anti-atherosclerotic effect by lowering blood lipids and inhibiting inflammatory response via TLR4/ NF-κB signaling pathway.

“…In accordance with previous studies, herein, our results showed that eupatilin inhibited the activation of NF-κB, STAT3, and AKT signaling pathways caused by TGF-β1 induction. Recently, Fei et al [26] showed that eupatilin inhibited inflammatory response through the TLR4/MyD88 pathway in erythrocyte lysis stimulation-induced mouse microglia BV2. Whether eupatilin can attenuate the inflammatory response in asthma will require further studies.…”

Section: Discussionmentioning

confidence: 99%

Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

Ren

et al. 2020

Bioscience Reports

Childhood asthma is a common chronic airway disease, and its severe form remains a challenge. Eupatilin is a bioactive natural flavone that has been found to possess potential anti-asthma activity. However, the roles of eupatilin in asthma remain to be elucidated. In the present study, airway smooth muscle cells (ASMCs) were applied for the in vitro investigation since their phenotype plasticity make great contribution to airway remodeling during asthma pathogenesis. Our results showed that eupatilin suppressed the transforming growth factor β1 (TGF-β1)-induced proliferation and migration of ASMCs. Exposure of ASMCs to eupatilin increased the expressions of contractile markers smooth muscle α-actin (α-SMA) and myocardin, whereas expressions of extracellular matrix (ECM) proteins type I collagen (Coll I) and fibronectin were reduced. Furthermore, eupatilin treatment reversed the activation of nuclear factor-κ B (NF-κB), signal transducer and activator of transcription 3 (STAT3) and AKT pathways caused by TGF-β1 in ASMCs. These findings suggested that eupatilin might attenuate airway remodeling via regulating phenotype plasticity of ASMCs.