Salvianolic Acid B Regulates Oxidative Stress, Autophagy and Apoptosis against Cyclophosphamide-Induced Hepatic Injury in Nile Tilapia (Oreochromis niloticus)

SIMPLE SUMMARY: Nile tilapia (Oreochromis niloticus) as one of the main commercially cultivated fishes in China, is plagued by liver diseases caused by some stressors. Salvianolic acid B (Sal B) has the strongest antioxidant effect and has a good protective effect on the liver. The objective of this study is to evaluate the protective effect of Sal B on oxidative hepatic injury in Nile tilapia, followed by assessing the potential protective mechanism. Our experimental data show that Sal B can not only directly reduce the level of reactive oxygen species (ROS), but can also resist CTX-induced oxidative injury by adjusting the autophagy and apoptosis levels of hepatocytes. Notably, the hepatoprotective effect of Sal B on Nile tilapia is related to the regulation of Nrf2, AMPK/mTOR and MAPK pathways. The research will lay the foundation for the application of Sal B in tilapia culture. ABSTRACT: Salvianolic acid B (Sal B), as one of the main water-soluble components of Salvia miltiorrhizae, has significant pharmacological activities, including antioxidant, free radical elimination and biofilm protection actions. However, the protective effect of Sal B on Nile tilapia and the underlying mechanism are rarely reported. Therefore, the aim of this study was to evaluate the effects of Sal B on antioxidant stress, apoptosis and autophagy in Nile tilapia liver. In this experiment, Nile tilapia were fed diets containing sal B (0.25, 0.50 and 0.75 g·kg(−1)) for 60 days, and then the oxidative hepatic injury of the tilapia was induced via intrapleural injection of 50 g·kg(−1) cyclophosphamide (CTX) three times. After the final exposure to CTX, the Nile tilapia were weighed and blood and liver samples were collected for the detection of growth and biochemical indicators, pathological observations and TUNEL detection, as well as the determination of mRNA expression levels. The results showed that after the CTX treatment, the liver was severely damaged, the antioxidant capacity of the Nile tilapia was significantly decreased and the hepatocyte autophagy and apoptosis levels were significantly increased. Meanwhile, dietary Sal B can not only significantly improve the growth performance of tilapia and effectively reduce CTX-induced liver morphological lesions, but can also alleviate CTX-induced hepatocyte autophagy and apoptosis. In addition, Sal B also significantly regulated the expression of genes related to antioxidative stress, autophagy and apoptosis pathways. This suggested that the hepatoprotective effect of Sal B may be achieved through various pathways, including scavenging free radicals and inhibiting hepatocyte apoptosis and autophagy.