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Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation.
Acta Pharmacologica Sinica ( IF 8.2 ) Pub Date : 2018-Nov-01 , DOI: 10.1038/s41401-018-0160-1
Jun-rong Zhu , Hai-dan Lu , Chao Guo , Wei-rong Fang , Hong-dong Zhao , Jun-shan Zhou , Feng Wang , Yan-li Zhao , Yun-man Li , Ying-dong Zhang , Chang-qing Yang , Jian-guo Sun

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.

中文翻译:

小ber碱通过抑制HMGB1释放和NF-κB核易位来减轻缺血再灌注损伤。

炎性损害在脑缺血性发病机制中起着重要作用,并且代表了治疗中风的新靶标。小ber碱是具有多种有益生物活性的天然药物。在这项研究中,我们探讨了黄连素对短暂性大脑中动脉闭塞(tMCAO)小鼠的神经保护作用的潜在机制。雄性小鼠接受小ber碱(25,50 mg / kg / d,胃内; ig),甘草甜素(50 mg / kg / d,腹膜内)或小ber碱(50 mg / kg / d,ig)加上甘草酸(50 mg / d tMCAO之前连续14天。在tMCAO后24小时评估神经功能缺损评分,然后杀死小鼠以获得脑样本。我们显示,黄连素预处理可剂量依赖性地减少梗死面积,神经功能缺损,血清和缺血性皮层组织的病理变化,脑水肿和炎症介质。我们发现,小碱预处理可显着提高对黄连的吸收。脑卒中后24小时缺血半球的18 F-氟代脱氧葡萄糖与赋形剂组相比。此外,黄连素预处理可剂量依赖性地抑制高迁移率族box1(HMGB1)蛋白的核-胞质转运,核因子κB(NF-κB)的胞质-核转运和降低TLR4在缺血性组织中的表达。皮质组织。此外,与单独施用的小ber碱或甘草甜素相比,联合使用甘草甜素和小ber碱对HMGB1 / TLR4 /NF-κB途径的抑制作用更强。这些结果表明,小ber碱可保护大脑免受缺血-再灌注损伤,其机制可能依赖于其通过抑制HMGB1 / TLR4 /NF-κB信号传导介导的抗炎作用。
更新日期:2019-01-26
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