Synergistic effects of berberine and curcumin-loaded chitosan nanoparticles in Nile tilapia: mitigating high-carbohydrate diet-induced metabolic dysfunction, hepatic injury, and immune-inflammatory responses

This study is the first to explore the effects of dietary supplementation with chitosan nanoparticles (CHNPs) loaded with berberine (B) and curcumin (CR), either individually or in combination, within high-carbohydrate diets (HCD) on growth performance, health status, and immune-inflammatory gene expression in Nile tilapia. A total of 150 healthy Oreochromis niloticus fingerlings (8.21 ± 0.08 g) were randomly assigned to five groups: control (29% carbohydrate), HCD (42% carbohydrate), and three supplemented groups; B-CHNPs (100 mg berberine/kg HCD), CR-CHNPs (100 mg curcumin/kg HCD), and B-CR-CHNPs (100 mg berberine + curcumin (50:50)/kg HCD) for 100 days. The B-CR-CHNPs treatment significantly enhanced growth, feed utilisation, protein efficiency, digestive enzyme activities, blood protein levels, liver function, and lipid metabolism compared to the HCD group (p < 0.05). Dietary supplementation with Berberine and Curcumin effectively reversed the aberrant changes in liver tissues caused by HCD, restoring hepatic morphology to a state closely resembling normal conditions. Additionally, the dietary treatments significantly enhanced antioxidant status by reducing malonaldehyde levels and increasing total antioxidant capacity and superoxide dismutase activity. B-CR-CHNPs treatment effectively restored the suppressed expression of IgM and LZM genes in the liver of HCD-fed fish. In contrast, the elevated hepatic expression of pro-inflammatory genes TNF-α and IL-1β induced by the HCD was significantly reduced, with the greatest reduction observed in the B-CR-CHNPs group. Berberine and Curcumin showed strong binding to antioxidant, immune, and inflammatory targets. Supplementing Nile tilapia diets with 100 mg B-CR-CHNPs improved growth and mitigated HCD-induced liver damage by modulating metabolism, immunity, and redox balance.