Preliminary Exploration of the Hepatoprotective Effect of Nanocrystalline Curcumin Against Traumatic Hemorrhagic Shock-Induced Liver Injury in a Desert Dry-Heat Environment: A Network Pharmacology-Based Study

Traumatic hemorrhagic shock (THS) under desert dry-heat conditions can exacerbate secondary liver injury, highlighting the need for effective therapeutic interventions. This study investigated the protective effects of nanocrystalline curcumin (NC-Cur) against THS-induced liver injury in a desert dry-heat environment and explored its potential molecular mechanisms. Network pharmacology, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and protein-protein interaction network analysis were used to identify candidate targets. Molecular docking and molecular dynamics simulations examined curcumin-protein interactions. Forty male Sprague-Dawley rats were randomly assigned to control, model, solvent, or NC-Cur treatment groups (n = 10 each). The model, solvent, and treatment groups underwent traumatic hemorrhagic shock under desert dry-heat conditions. Hepatic injury was assessed by histopathology, serum aminotransferases, inflammatory cytokines, oxidative stress markers, and Western blotting. Network analysis identified 116 overlapping targets, with heat shock protein 90 alpha A1 (HSP90AA1), AKT serine/threonine kinase 1 (AKT1), and B-cell lymphoma 2 (BCL-2) prioritized as the core targets. Docking predicted favorable interactions with all three proteins, while molecular dynamics simulations supported stable binding between curcumin and HSP90AA1. Compared with untreated model rats, NC-Cur-treated rats showed attenuated hepatic histopathological injury, reduced alanine and aspartate aminotransferases, tumor necrosis factor-α, interleukin-1β, and malondialdehyde, and increased superoxide dismutase. Western blotting indicated reduced HSP90AA1 and increased phosphorylated AKT1 expression after NC-Cur treatment, with changes also observed in BCL-2 expression. These findings suggest that NC-Cur may alleviate liver injury associated with THS under desert dry-heat conditions in male rats, potentially involving HSP90AA1-AKT1-BCL-2-related signaling.