当前位置: X-MOL 学术Inflammation › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Hepatoprotective Effect of Apigenin Against Liver Injury via the Non-canonical NF-κB Pathway In Vivo and In Vitro.
Inflammation ( IF 5.1 ) Pub Date : 2020-05-26 , DOI: 10.1007/s10753-020-01238-5
Shuwen Yue 1 , Ning Xue 2 , Honglei Li 3 , Baosheng Huang 4 , Zhen Chen 1 , Xing Wang 1
Affiliation  

Apigenin, a flavonoid found in many plants, has various biological properties. We aimed to investigate the anti-inflammatory and anti-oxidative activity of apigenin against carbon tetrachloride (CCl4)-induced acute liver injury in mice and hydrogen peroxide (H2O2)-induced oxidative stress in HepG2 cells and possible mechanism. In vivo, apigenin significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in serum of mice challenged by CCl4 and markedly alleviated the lipid peroxidation as indicated by the increased level of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidases (GSH-Px) and catalase (CAT), and the decreased malondialdehyde (MDA) in liver tissue. Apigenin also ameliorated inflammation by downregulating tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and upregulating IL-10. Consistently, the elevated ALT and AST level; the impaired balance between SOD, GSH activity, and excessive ROS; and the increased gene expression of TNF-α and IL-6 resulting from H2O2-induced oxidative stress were restored by apigenin. Moreover, the results from Western blot, real-time qPCR, and immunofluorescence assay indicated that apigenin enhanced the activity of TNF receptor-associated factor (TRAF) 2/3 and cellular inhibitor of apoptosis protein (c-IAP) 1, ameliorated NF-κB-inducing kinase (NIK), and mediated the nuclear translocation of NF-κB2, therefore had an inhibitory effect on the non-canonical NF-κB pathway which was activated in both models. siNIK canceled the protective effect of apigenin on H2O2-induced HepG2 cells. Altogether, our results demonstrated that apigenin mitigated liver injury by ameliorating inflammation and oxidative stress through suppression of the non-canonical NF-κB pathway, indicating the potential of apigenin for treatment of the liver injury.



中文翻译:

芹菜素通过非典型的NF-κB途径体内和体外对肝损伤的肝保护作用。

芹菜素是一种在许多植物中发现的类黄酮,具有多种生物学特性。我们旨在研究芹菜素对四氯化碳(CCl 4)诱导的小鼠急性肝损伤的抗炎和抗氧化活性以及过氧化氢(H 2 O 2)诱导的HepG2细胞的氧化应激及其可能的机制。在体内,芹菜素显着降低了受CCl 4攻击的小鼠血清中的丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性。肝组织中超氧化物歧化酶(SOD)水平升高,谷胱甘肽(GSH),谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)含量降低以及丙二醛(MDA)含量降低表明,脂质过氧化作用明显减轻。芹菜素还通过下调肿瘤坏死因子-α(TNF-α),白介素-6(IL-6)和上调IL-10来减轻炎症。一致地,ALT和AST水平升高;SOD,GSH活性和过多的ROS之间的平衡受损;H 2 O 2导致TNF-α和IL-6基因表达增加芹菜素恢复了诱导的氧化应激。此外,Western印迹,实时qPCR和免疫荧光分析的结果表明芹菜素增强了TNF受体相关因子(TRAF)2/3和细胞凋亡蛋白(c-IAP)1的活性,改善了NF- κB诱导激酶(NIK),并介导NF-κB2的核易位,因此对两种模型均激活的非经典NF-κB通路具有抑制作用。siNIK取消了芹菜素对H 2 O 2的保护作用诱导的HepG2细胞。总之,我们的结果表明芹菜素通过抑制非典型的NF-κB途径来减轻炎症和氧化应激,从而减轻了肝损伤,表明芹菜素具有治疗肝损伤的潜力。

更新日期:2020-05-26
down
wechat
bug