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On-line Access: 2023-07-15

Received: 2022-11-29

Revision Accepted: 2023-01-03

Crosschecked: 2023-07-17

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jingquan DONG

https://orcid.org/0000-0001-9696-9681

Mian FU

https://orcid.org/0009-0006-6733-0970

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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.7 P.617-631

http://doi.org/10.1631/jzus.B2200612


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


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, 2023, 24(7): 617-631.

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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",
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pages="617-631",
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publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200612"
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%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
%V 24
%N 7
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%@ 1673-1581
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200612

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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
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2200612


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:灯盏花乙素;氧化应激;酒精性肝病;炎症

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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