Ginsenoside 20(S)-Rg3 alleviates cage stress induced liver injury in laying ducks.

While cage rearing systems enhance the productivity of laying ducks, the initial transition period can induce significant stress, leading to hepatic inflammation and oxidative damage. Ginsenoside 20(S)-Rg3 (Rg3), a bioactive saponin derived from ginseng, is known for its antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects of Rg3 on cage stress-induced liver injury in laying ducks. 14-week-old ducks were randomly assigned to four groups: a floor-reared control (CON); a cage-stressed group (ST); and two cage-stressed groups supplemented with low (25 mg/kg; ST/Rg3-L) or high (50 mg/kg; ST/Rg3-H) dose of Rg3. After the experiment, blood and liver samples were collected for analysis. Results indicated that Rg3 ameliorated liver injury in a dose-dependent manner, evidenced by reduced plasma AST levels and hepatocyte vacuolization. Hepatic transcriptome profiling revealed that differentially expressed genes were primarily enriched in pathways related to inflammation, oxidative stress, and autophagy. High-dose Rg3 significantly decreased Fe2+, MDA, IL-1β, IL-6, and TNF-α levels, while increasing the concentration of SOD, T-AOC, GSH-Px, and IL-10 in both liver and plasma. Electron microscopy revealed that high-dose Rg3 alleviated mitochondrial damage and promoted mitophagy. Mechanistically, high-dose Rg3 appeared to inhibit ferroptosis by upregulating the expression of GPX4 and SLC7A11 and downregulating ACSL4. Furthermore, high-dose Rg3 downregulated mTOR and SQSTM1/p62 expression and upregulated LC3B expression. In conclusion, Rg3 protects laying ducks against cage stress-induced hepatic injury by enhancing antioxidant capacity, suppressing inflammation, and activating protective autophagy.