JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways

Author(s): Xiao ZHANG, Zhicheng DONG, Hui FAN, Qiankun YANG, Guili YU, Enzhuang PAN, Nana HE, Xueqing LI, Panpan ZHAO, Mian FU, Jingquan DONG
Affiliation(s): Jiangsu Key Laboratory of Marine Bioresources and Environment / Co-Innovation Center of Jiangsu Marine Bio-Industry Technology / Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University,Lianyungang222005,China; more
Corresponding email(s): fumian@mail.nankai.edu.cn, 2018000029@jou.edu.cn
Key Words: Scutellarin; Oxidative stress; Alcoholic liver disease; Inflammation

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Xiao ZHANG, Zhicheng DONG, Hui FAN, Qiankun YANG, Guili YU, Enzhuang PAN, Nana HE, Xueqing LI, Panpan ZHAO, Mian FU, Jingquan DONG. Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200612

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author="Xiao ZHANG, Zhicheng DONG, Hui FAN, Qiankun YANG, Guili YU, Enzhuang PAN, Nana HE, Xueqing LI, Panpan ZHAO, Mian FU, Jingquan DONG",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2200612"
}

%0 Journal Article
%T Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways
%A Xiao ZHANG
%A Zhicheng DONG
%A Hui FAN
%A Qiankun YANG
%A Guili YU
%A Enzhuang PAN
%A Nana HE
%A Xueqing LI
%A Panpan ZHAO
%A Mian FU
%A Jingquan DONG
%J Journal of Zhejiang University SCIENCE B
%P 617-631
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2200612"

TY - JOUR
T1 - Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways
A1 - Xiao ZHANG
A1 - Zhicheng DONG
A1 - Hui FAN
A1 - Qiankun YANG
A1 - Guili YU
A1 - Enzhuang PAN
A1 - Nana HE
A1 - Xueqing LI
A1 - Panpan ZHAO
A1 - Mian FU
A1 - Jingquan DONG
J0 - Journal of Zhejiang University Science B
SP - 617
EP - 631
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2200612"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Alcoholic liver disease (ALD) is the most frequent liver disease worldwide, resulting in severe harm to personal health and posing a serious burden to public health. Based on the reported antioxidant and anti-inflammatory capacities of scutellarin (SCU), this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration (10, 25, and 50 mg/kg). The results indicated that SCU could lessen serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the histopathological changes in acute alcoholic liver; it reduced alcohol-induced malondialdehyde (MDA) content and increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activity. Furthermore, SCU decreased tumor necrosis factor-‍α (TNF-‍α), interleukin-6 (IL-6), andIL-‍1β messenger RNA (mRNA) expression levels, weakened inducible nitric oxide synthase (iNOS) activity, and inhibited nucleotide-binding oligomerization domain (NOD)‍-like receptor protein 3 (NLRP3) inflammasome activation. Mechanistically, SCU suppressed cytochrome P450 family 2 subfamily E member 1 (CYP2E1) upregulation triggered by alcohol, increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, and suppressed the inflammation-related degradation of inhibitor of nuclear factor-‍κB (NF-‍κB)‍-‍α (IκBα) as well as activation of NF‍-‍κB by mediating the protein kinase B (AKT) and p38 mitogen-activated protein kinase (MAPK) pathways. These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT, p38 MAPK/NF-κB pathways.

灯盏花乙素通过调节Nrf2/HO-1通路抑制氧化应激以及通过调节AKT、p38 MAPK/NF-κB通路抑制炎症反应预防急性酒精性肝损伤

张潇¹，董志成²，樊慧¹，杨乾坤¹，余桂丽¹，潘恩壮¹，何娜娜¹，李雪晴¹，赵盼盼¹，付免¹，董井泉¹
¹江苏海洋大学药学院江苏省海洋生物资源与环境重点实验室/江苏省海洋生物产业技术协同创新中心/江苏省海洋药物化合物筛选重点实验室，中国连云港，222005
²连云港市第二人民医院肿瘤科，中国连云港，222000
³连云港市第一人民医院神经科学研究所，中国连云港，222000
摘要：肝病（ALD）是世界上最常见的肝脏疾病，严重危害个人健康，对公共卫生造成严重负担。基于灯盏花乙素（SCU）抗氧化和抗炎能力的报道，本研究探究了SCU（10、25和50 mg/kg，口服给药）对急性酒精性肝损伤BALB/c小鼠的保护作用。结果表明：SCU可降低血清谷丙转氨酶（ALT）和天冬氨酸转氨酶（AST）水平，改善急性酒精性肝组织病理改变；降低酒精诱导的丙二醛（MDA）含量，提高谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性。此外，SCU会降低肿瘤坏死因子-α（TNF-α）、白细胞介素6（IL-6）和IL-1β的mRNA表达水平，削弱诱导型一氧化氮合酶（iNOS）活性和抑制NOD样受体蛋白3（NLRP3）炎症小体激活。从机制方面而言，SCU可抑制酒精诱导的CYP450代谢酶家族中的CYP2E1上调，增加氧化应激相关的核因子E2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）通路的表达，通过介导蛋白激酶B（AKT）和p38 MAPK通路抑制炎症相关核因子-κB抑制蛋白α因子（IκBα）的降解以及核因子-κB因子（NF-κB）的激活。这些结果表明，SCU通过调控Nrf2/HO-1通路抑制氧化应激，通过调控AKT、p38 MAPK/NF-κB通路抑制炎症反应，从而保护急性酒精性肝损伤。

关键词组：灯盏花乙素；氧化应激；酒精性肝病；炎症

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灯盏花乙素通过调节Nrf2/HO-1通路抑制氧化应激以及通过调节AKT、p38 MAPK/NF-κB通路抑制炎症反应预防急性酒精性肝损伤

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