Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB 1 release and NF-κB nuclear translocation  

作　　者：Jun-rong Zhu Hal-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 

机构地区：[1]School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China [2]Department of Pharmacy, Nanjing First Hospital, Nanjing Medical Univers,ty, Nanjing 210006, China [3]Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China [4]Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China [5]Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China [6]Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

出　　处：《Acta Pharmacologica Sinica》2018年第11期1706-1715,共10页中国药理学报（英文版）

摘　　要：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, Lg.） plus glycyrrhizin （50 mglkgld, 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-KB signaling.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, Lg.） plus glycyrrhizin （50 mglkgld, 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-KB signaling.

关 键 词：BERBERINE GLYCYRRHIZIN ischemic stroke inflammation HMGB1 TLR4 NF-ΚB 

分 类 号：Q78[生物学—分子生物学] O562.1[理学—原子与分子物理]