The Effects of Berberine on Concanavalin A-Induced Autoimmune Hepatitis (AIH) in Mice and the Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase (AMPK) Pathway.
The Effects of Berberine on Concanavalin A-Induced Autoimmune Hepatitis (AIH) in Mice and the Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase (AMPK) Pathway.
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小檗碱对刀豆球蛋白a诱导的小鼠自身免疫性肝炎(AIH)及5α-单磷酸腺苷(AMP)激活蛋白激酶(AMPK)通路的影响
DOI：
10.12659/msm.907377
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发表时间：
2017-12-28
期刊：
影响因子：
--
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Wang Y;Zhou L;Li Y;Guo L;Zhou Z;Xie H;Hou Y;Wang B
小檗碱是一种草药提取物，据报道可以预防炎症性疾病。腺苷5′-单磷酸（AMP）激活的蛋白激酶（AMPK）信号通路可被小檗碱激活，并被合成的可逆AMP竞争性抑制剂化合物C抑制。本研究旨在探讨小檗碱对伴刀豆球蛋白A（ConA）诱导的小鼠自身免疫性肝炎（AIH）的影响。BALB/c小鼠用小檗碱处理，有或没有化合物C，然后用Con A处理。测定血清谷草转氨酶（AST）和谷丙转氨酶（ALT）。肝组织学检查评价肝损伤和AIH。通过酶联免疫测定法（ELISA）和定量聚合酶链反应（qPCR）测定血清和肝组织中的细胞因子水平。磷酸化乙酰辅酶-A羧化酶（ACC），代表AMPK激活的水平，通过蛋白质印迹法检测。小檗碱（100和200 mg/kg/d）可显著降低Con A诱导的肝炎小鼠的血清ALT和AST水平。黄连素也减少Con A诱导的肝细胞肿胀，细胞死亡和白细胞浸润。小檗碱预处理降低了肿瘤坏死因子（TNF）-α、干扰素（IF）-γ、白细胞介素（IL）-2和IL-1 β的血清水平;升高了血清IL-10（一种抗炎细胞因子）水平。小檗碱对Con-A诱导的AIH的这些保护作用可被化合物C逆转。在Con A诱导的AIH小鼠模型中，黄连素治疗通过激活AMPK途径减少肝损伤。建议进一步研究以确定黄连素在AIH中的潜在治疗作用。
Berberine, a herbal extract, has been reported to protect against inflammatory disorders. The adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway can be activated by berberine and inhibited by the synthetic, reversible AMP-competitive inhibitor, Compound C. The aim of this study was to investigate the effects of berberine on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) in mice via the AMPK pathway. BALB/c mice were treated with berberine, with or without Compound C, followed by treatment with Con A. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue histology was performed to evaluate hepatic injury and AIH. Cytokine levels in serum and hepatic tissue were measured by enzyme-linked immunoassay (ELISA) and used quantitative polymerase chain reaction (qPCR). Levels of phosphorylated acetyl coenzyme-A carboxylase (ACC), representing AMPK activation, were detected by Western blotting. Serum ALT and AST levels were significantly reduced by berberine (100 and 200 mg/kg/day) in mice with Con A-induced hepatitis. Berberine also reduced Con A-induced hepatocyte swelling, cell death, and infiltration of leukocytes. Serum levels of tumor necrosis factor (TNF)-alpha, interferon (IF)-gamma, interleukin (IL)-2, and IL-1beta were reduced by berberine pre-treatment; levels of serum IL-10, an anti-inflammatory cytokine, was elevated. These protective effects of berberine on Con-A-induced AIH were reversed by treatment with Compound C. In a murine model of Con A-induced AIH, berberine treatment reduced hepatic injury via activation of the AMPK pathway. Further studies are recommended to determine the potential therapeutic role for berberine in AIH.
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影响因子：
5.6
作者：
Marín-Aguilar F;Pavillard LE;Giampieri F;Bullón P;Cordero MD
通讯作者：
Cordero MD
影响因子：
5
作者：
Jin, Yingli;Liu, Shuping;Chen, Li
通讯作者：
Chen, Li
影响因子：
7.5
作者：
Liu, Xuefei;Zhang, Xinghua;Yuan, Haitao
通讯作者：
Yuan, Haitao
影响因子：
3.6
作者：
Lavon, I;Sheinin, T;Avraham, A
通讯作者：
Avraham, A
DOI：
10.1073/pnas.91.2.614
发表时间：
1994-01-18
影响因子：
11.1
作者：
TOYONAGA, T;HINO, O;YAMAMURA, K
通讯作者：
YAMAMURA, K