Cyanidin Alleviated CCl4-Induced Acute Liver Injury by Regulating the Nrf2 and NF-κB Signaling Pathways

Abstract

Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl4). High-dose Cy showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl4 were significantly mitigated by Cy supplementation. The total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase were increased and the content of malondialdehyde, lipid peroxide, tumor necrosis factor α, interleukin-1β, and interleukin-6 were decreased. Additionally, the Nrf2 and NF-κB signaling pathways, which regulate antioxidative and inflammatory responses, were analyzed using quantitative real-time polymerase chain reaction and western blot assay. Cy treatment not only increased Nrf2 transcription and expression but also decreased NF-κB signaling. Moreover, molecular docking simulation indicated that Cy had high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. In summary, Cy treatment exerted antioxidative and anti-inflammatory effects and ameliorated liver injury by increasing Nrf2 and inhibiting the NF-κB pathway, demonstrating the potential of Cy as a therapeutic agent in liver injury.

The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2

“…In addition, there was a significant decline in Th2 and Th17 cytokine gene expression in A18-treated infected mice. Considering that A18 inhibited NF-kB signaling pathway and cytokine production in infected cells in vitro, and its known immunomodulatory activity in different in vivo models [15,16], we propose that A18 may show a protective effect against pulmonary RSV infection by reducing viral infection, and by affecting the NF-κB signaling and cytokine response as well.…”

“…Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice [14]. Importantly, A18 also inhibits the NF-κB signaling pathway and secretion of proinflammatory cytokines in different cell types and conditions in vitro and in vivo [15,16].…”

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

“…The results of molecular docking suggested that echinatin might occupy pivotal residues required for the binding of Keap1 to Nrf2, such as Gly-367, Ala-510, and Val-606. Previous studies have reported that several compounds exhibited potent anti-oxidant effects via interacting with Gly-367 and Val-606 of Keap1 [ 51 , 52 ]. Combining with the present results, we presumed that echinatin might occupy the critical binding pocket of Keap1, blocking the interaction between Keap1 and Nrf2, thereby increasing Nrf2 nuclear translocation and exerting anti-oxidative effects.…”

TRAF2 as a key candidate gene in clinical hepatitis B-associated liver fibrosis

“…NF-κB is a crucial transcriptional regulator of the inflammatory response, and mediators released from Kupffer cells after hepatocyte damage (such as IL-1β) activate signaling pathways, such as NF-κB in hepatic stellate cells (HSC). NF-κB activation causes HSC to activate and secrete chemokines that make HSC more sensitive to TGF, which promotes liver fibrosis ( Luedde and Schwabe, 2011 ; de Souza Basso et al, 2021 ; Ebrahim et al, 2022 ; Wang et al, 2022 ). Further evidence supports that TRAF2 is involved in collagen I transport via tyrosine kinase-interacting kinase (TNIK), and thus in the progression of liver fibrosis in mice ( Buchl et al, 2022 ).…”