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

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology
• Hepatology

Background:

• Hepatic ischemia-reperfusion (I/R) injury is a major cause of liver dysfunction and failure, often occurring during surgery and transplantation.
• Inflammation and apoptosis, mediated by pathways like NF-κB p65 and caspase-3, are central to I/R-induced hepatocellular injury.
• There is a critical need for novel therapeutic agents to mitigate I/R injury and its associated inflammation.

Purpose of the Study:

• To investigate the potential hepatoprotective effects of indicaxanthin against liver I/R injury.
• To elucidate the molecular mechanisms underlying indicaxanthin's action, focusing on inflammatory and apoptotic pathways.
• To evaluate indicaxanthin's efficacy in a preclinical rat model of hepatic I/R injury.

Main Methods:

• Construction of a protein-protein interaction (PPI) network integrating indicaxanthin targets with liver I/R proteins.
• Bioinformatic analyses including Gene Ontology and KEGG pathway enrichment.
• Molecular docking and molecular dynamics (MD) simulations to assess binding affinity and stability with NF-κB p65 (RelA).
• Induction of hepatic I/R injury in male Wistar rats to assess indicaxanthin's therapeutic effects.

Main Results:

• The PPI network identified NF-κB p65 and caspase-3 as key targets of indicaxanthin, linking it to inflammation and apoptosis.
• Enrichment analyses implicated TNF, IL-17, and Toll-like receptor signaling pathways.
• Molecular docking showed strong binding affinity of indicaxanthin to NF-κB p65 (RelA) (-6.89 kcal/mol) with stable interactions confirmed by MD simulations.
• Indicaxanthin demonstrated significant hepatoprotective effects in the rat model at histopathological, molecular, and biochemical levels.

Conclusions:

• Indicaxanthin exhibits promising therapeutic potential for mitigating hepatic I/R injury.
• Its mechanism involves the modulation of critical inflammatory (NF-κB p65) and apoptotic (caspase-3) pathways.
• Further studies are warranted to explore indicaxanthin as a clinical intervention for liver protection.