Syringaresinol mitigates cerebral ischemia-induced brain injury via NF-κB pathway inhibition and glial cell deactivation

Background: It is vital to clarify the pathogenesis and develop new effective therapies for the treatment of cerebral ischemia-reperfusion injury (CIRI). Syringaresinol (Syr), a furan lignan found in various medicinal herbs, may play a significant role in the treatment of CIRI. This study aims to investigate the effects of Syr on the progression of CIRI and to uncover the underlying mechanisms involved. Methods: A middle cerebral artery occlusion (MCAO) mouse model was developed to investigate CIRI. Mice were administered Syr at concentrations of 20 mg/kg and 40 mg/kg for 48 hours. The effects of Syr on cerebral infarction in the mice were evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) assays. Immunostaining was conducted to detect Ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), while enzyme-linked immunosorbent assays (ELISA) were utilized to quantify levels of Interleukin (IL)-1β, Tumor Necrosis Factor (TNF)-α, IL-10 and IL-6. Furthermore, Terminal Deoxynucleotidyl Transferase (TdT)-mediated 2′-deoxyuridine 5′-triphosphate (dUTP) nick end labeling (TUNEL) assays were performed to assess the effects on the activation of cerebral glial cells, inflammation, and apoptosis in the brain tissues of Middle Cerebral Artery Occlusion Model (MCAO) mice. Immunoblotting was further performed to confirm the mechanism. Results: Syr was found to alleviate cerebral infarction in MCAO mice. Additionally, it reduces the activation of cerebral glial cells in these models. Our findings further demonstrate that Syr decreases inflammation within the brain tissues of MCAO mice. It also inhibits apoptosis in these tissues. Mechanistically, Syr suppresses the Nuclear Factor kappa-B (NF-κB) pathway, thereby alleviating CIRI. Conclusions: In summary, Syr mitigates CIRI by blocking glial activation and inhibiting the inflammatory response.

Cerebral ischemia-reperfusion injury (CIRI); Syringaresinol; Cerebral infarction; Apoptosis; NF-κB pathway

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