Multimodal modulation of hepatic ischemia/reperfusion-induced injury by phytochemical agents: A mechanistic evaluation of hepatoprotective potential and safety profiles

Background: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. Aims of the review: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. Materials and methods: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. Results: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-kappa B, Nrf2, Bcl-2 family proteins, and others. Conclusion: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.