Curcumin inhibits koi herpesvirus (KHV) replication via Nrf2-Keap1/ARE and NF-κB pathways in ornamental koi (Cyprinus carpio haematopterus)

Koi herpesvirus (KHV) is a pathogen causing high contagion rate and elevated mortality in carp in the world. Curcumin has demonstrated antioxidant, anti-inflammatory, and antiviral properties in fish species. In this study, its preventive effects against KHV and inhibitory mechanism were investigated in koi carp. On day 3 post intraperitoneal injection with curcumin at a concentration of 0 (control), 20, 40, or 80 μg/g of body weight, the fish was injected with 200 μL KHV at the concentration of TCID50 = 10^–6.75. Enzyme activities in the gill and hepatopancreas were assessed on days 1, 2, and 3 after curcumin injection, and on day 7 following KHV infection. The highest antioxidant and anti-inflammatory effects were observed on day 3 after injection with 40 μg/g curcumin (P < 0.05). On day 7 after KHV infection, although all curcumin concentrations showed effectiveness in suppressing KHV replications (P < 0.05), the 40 μg/g treatment resulted in the highest and significant changes in all the parameters measured; in comparison with the positive control (KHV injection only), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) in both tissue samples increased significantly (P < 0.05) whereas the activities of nitric oxide (NO) and malondialdehyde (MDA) reduced significantly (P < 0.05). Concurrently, the expressions of Nrf2, Marf, CAT, SOD and HO-1 genes were significantly upregulated in curcumin treatments following the KVH injection, especially in the 40 μg/g treatment. In this treatment, the expressions of genes involving in inflammatory responses (e.g. Keap 1, NF-κB, p65, IL-6 and TNF-α genes) were significantly lower than those in the KHV positive control (P < 0.05). These findings indicate that curcumin could effectively inhibit KHV replications, activate antioxidant functions and alleviate both oxidative and inflammatory stresses via the Nrf 2-Keap1/ARE and NF-κB pathways. As this intervention enhanced the survival of koi carp infected by KHV, curcumin treatment could be an effective strategy to manage this disease in aquaculture.