Artemisinin competitively antagonizes aquatic pollutant binding to hepatic stress proteins in catfish, Pangasianodon hypophthalmus: A molecular docking study

Expanding aquaculture has increased farmed fish exposure to pharmaceutical and pesticide residues, including diclofenac, clofibrate, dichlorodiphenyltrichloroethane, chlorpyrifos, and endosulfan, which can induce hepatic oxidative stress and fibrosis. Protective interventions for pollutant-exposed fish remain limited. This in silico study examined whether artemisinin, a natural sesquiterpene lactone with reported antioxidant and hepatoprotective activity, can competitively displace these pollutants from key hepatic stress- and fibrosis-regulating proteins of the catfish, Pangasianodon hypophthalmus. Homology models of seven target proteins, including heat shock protein 70, heat shock protein 90, transforming growth factor beta 1, transforming growth factor beta receptor 2, matrix metalloproteinase 2, matrix metalloproteinase 14b, and tissue inhibitor of metalloproteinase 2a, were generated and docked against the five pollutants and against artemisinin. Diclofenac showed the strongest affinity for heat shock protein 70, while dichlorodiphenyl-trichloroethane bound most strongly to transforming growth factor beta receptor 2 and matrix metalloproteinase 2. In direct competitive docking, artemisinin formed more stable complexes than every tested pollutant at all three of these targets, with matrix metalloproteinase 2 showing the largest margin. Pathway enrichment linked the three proteins to innate immune and fibrotic signaling, with matrix metalloproteinase 2 acting as the principal hub gene. These findings provide preliminary computational evidence that artemisinin can competitively antagonize pollutant binding to hepatic stress-response and fibrosis-related proteins in fish, supporting further experimental evaluation of its hepatoprotective potential in aquaculture.