Indicaxanthin Mitigates Hepatic Ischemia Reperfusion Injury in Rats via Bax/Bcl-2 Modulation: Experimental Evidence...

Indicaxanthin, a prominent betalain pigment known for its bioactivity and safety, has long been valued in traditional medicine for its antioxidant and anti-inflammatory effects. The leading cause of liver failure and dysfunction is hepatic ischemia-reperfusion (I/R) injury, which frequently happens during hemorrhagic shock, hepatectomy, and liver transplantation. Given the increasing global incidence of hepatic disorders, especially those involving ischemic damage and inflammation-mediated apoptosis, there is a pressing need for therapeutic agents that can target key molecular pathways. Liver ischemia and injury often result in the upregulation of inflammatory cascades, notably involving NF-κB p65, and pro-apoptotic markers such as caspase-3, both of which play central roles in hepatocellular injury. We constructed a protein-protein interaction (PPI) network integrating predicted indicaxanthin targets with liver ischemia-related proteins. The network identified NF-κB p65 and caspase-3 as central hubs, functionally associated with pro-inflammatory and apoptotic pathways. Gene Ontology and KEGG enrichment analyses further implicated TNF, IL-17, and Toll-like receptor pathways, highlighting the broader regulatory role of indicaxanthin in hepatic stress signaling. Molecular docking against NF-κB p65 (RelA) revealed a strong binding affinity (-6.89 kcal/mol), with key hydrogen bond interactions involving Lys221, Arg246, Val244, and Gln241. Subsequent molecular dynamics (MD) simulations confirmed the structural stability of the complex, showing low RMSD drift, consistent hydrogen bonding, compact ligand behavior, and favorable energy profiles over 100 ns. Furthermore, hepatic IRI was induced in male Wistar rats, and then the hepatoprotective effect of indicaxanthin was studied at histopathological, molecular, and biochemical levels.