Cordycepin Protects against Hepatic Ischemia/Reperfusion Injury via Inhibiting MAPK/NF-κB Pathway

Abstract

Hepatic ischemia/reperfusion injury (HIRI) is a common complication of liver surgery requiring hepatic disconnection, such as hepatectomy and liver transplantation. The aim of this study was to investigate the effects of cordycepin on HIRI and to elucidate the underlying mechanisms. Balb/c mice were randomly divided into six groups: a normal control group, sham group, H-cordycepin group, HIRI group, L-cordycepin (25 mg/kg) + HIRI group, and H-cordycepin (50 mg/kg) + HIRI group. Mice were subjected to I/R, and cordycepin was intragastrically administered for seven consecutive days before surgery. Orbital blood and liver specimens were collected at 6 and 24 h after HIRI. Serum levels of ALT and AST were decreased in the cordycepin pretreatment groups. Notably, cordycepin attenuated the inflammatory response and the production of proapoptosis proteins, while increasing expression of antiapoptosis proteins and decreasing expression of autophagy-linked proteins. Furthermore, cordycepin inhibited activation of the MAPK/NF-κB signaling pathway. Collectively, these results indicate that cordycepin pretreatment ameliorated hepatocyte injury caused by HIRI. As compared with the HIRI group, cordycepin pretreatment mitigated the inflammatory response and inhibited apoptosis and autophagy via regulation of the MAPK/NF-κB signaling pathway.

Integration of network pharmacology and molecular docking to explore the molecular mechanism of Cordycepin in the treatment of Alzheimer’s disease

“…In a Parkinson's disease model, Cordycepin was found to relieve motor disorders and exert a neuroprotective role (Cheng and Zhu, 2019) by reducing inflammation and oxidative stress. Overwhelming evidence substantiates that Cordycepin can weaken the inflammatory response and the production of pro-apoptotic proteins, increase the expression of antiapoptotic proteins, and inhibit the activation of the MAPK/ NF-κB signaling pathway (Ding et al, 2022), consistent with the findings of this study (Figure 11). It has been established that Cordycepin can bind to the cysteine endopeptidase of the caspase family in mitochondria to inhibit the formation of the death-induced signal complex of endopeptidases recruited in the death domain and then affect the activation of apoptosis and slow down the death of neurons.…”

Protective effects of cordycepin pretreatment against liver ischemia/reperfusion injury in mice

“…Several studies have demonstrated the key role of TLR4/NF-κB signaling pathway in the regulation of apoptosis and inflammatory response. 38,39 This study showed that cordycepin pretreatment inhibited TLR4/NF-κB signal (reduction of TNF-α, MCP-1, TLR4, p-p65, and p-IκB) in liver after IR, recently Ding et al reported the protective role of cordycepin in hepatic IR through MAPK/NF-κB signaling pathway, 40 the role of TLR4/NF-κB signal and other pathways in cordycepin mediated hepatic IR improvement need to be further verified by using KO mouse lines and inhibitors in the future studies.…”

Exosomes derived from Baicalin‐pretreated bone mesenchymal stem cells improve Th17/Treg imbalance after hepatic ischemia–reperfusion via FGF21 and the JAK2/STAT3 pathway

“…2 Statistics indicate that approximately 10% to 20% of post-liver transplant patients experience liver I/R injury. 3 Clinical trials have confirmed the significant reduction in the incidence of liver I/R injury and the improvement of patient outcomes by employing antioxidants, anti-inflammatory drugs, and cytoprotective agents. 4 Additionally, ongoing research endeavors focus on developing novel drugs and treatment strategies to mitigate cellular damage resulting from liver I/R injury.…”

“…Severe liver I/R injury can further progress to hepatic failure, multiple organ dysfunction syndrome, and even mortality 2 . Statistics indicate that approximately 10% to 20% of post‐liver transplant patients experience liver I/R injury 3 . Clinical trials have confirmed the significant reduction in the incidence of liver I/R injury and the improvement of patient outcomes by employing antioxidants, anti‐inflammatory drugs, and cytoprotective agents 4 .…”