Hepatoprotective Effect of Apigenin Against Liver Injury via the Non-canonical NF-κB Pathway In Vivo and In Vitro

• Published in: Inflammation Vol. 43; no. 5; pp. 1634 - 1648
• Main Authors: Yue, Shuwen, Xue, Ning, Li, Honglei, Huang, Baosheng, Chen, Zhen, Wang, Xing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2020; Springer Nature B.V
• Subjects: Alanine; Alanine transaminase; Apoptosis; Aspartate aminotransferase; Biomedical and Life Sciences; Biomedicine; Carbon tetrachloride; Catalase; CCL4 protein; Flavonoids; Gene expression; Glutathione; Hydrogen peroxide; IAP protein; Immunofluorescence; Immunology; Inflammation; Interleukin 10; Interleukin 6; Internal Medicine; Kinases; Lipid peroxidation; Liver; Malondialdehyde; NF-κB protein; Nuclear transport; Original Article; Oxidative stress; Pathology; Pharmacology/Toxicology; Rheumatology; Superoxide dismutase; Tumor necrosis factor receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; apigenin; non-canonical NF-κB pathway; inflammation; oxidative stress
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-020-01238-5

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 (CCl 4 )-induced acute liver injury in mice and hydrogen peroxide (H 2 O 2 )-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 CCl 4 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 H 2 O 2 -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 H 2 O 2 -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.