Fatty liver hemorrhagic syndrome (
FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism.
FLHS is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality.
Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protecting mitochondrial function, attenuating cell apoptosis and
inflammation, and promoting
antioxidant defense system. We aimed to determine the
therapeutic effects of SDS on
FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed
oleic acid (OA)-induced
fatty liver model in vitro and high-fat diet-induced
FLHS of laying hens in vivo. The results indicated that SDS inhibited OA-induced
lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the
mRNA expression of proliferation related genes
PCNA, CDK2, and cyclinD1 and increased the
protein levels of
PCNA and CDK2 (P < 0.05), as well as decreased the cleavage levels of
Caspase-9,
Caspase-8, and
Caspase-3 and apoptosis in hepatocytes (P < 0.05). Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-β, while inhibited the PI3K inhibitor (P < 0.05). Additionally, we found that high-fat diet-induced
FLHS hens had heavier
body weight, liver weight, and abdominal fat weight, and severe steatosis in histology, compared with the control group (Con). However, hens fed with SDS maintained lighter
body weight, liver weight, and abdominal fat weight, as well as normal liver without hepatic steatosis. In addition, high-fat diet-induced
FLHS hens had high levels of serum total
cholesterol (TC),
triglyceride (TG),
alanine transaminase (ALT), and
aspartate aminotransferase (AST) compared to the Con group, however, in the Model+SDS group, the levels of TC, TG, ALT, and AST decreased significantly, whereas the level of
superoxide dismutase (SOD) increased significantly (P < 0.05). We also found that SDS significantly decreased the
mRNA expression abundance of PPARγ, SCD, and FAS in the liver, as well as increased levels of PPARα and
MTTP, and decreased the
mRNA expression of TNF-α, IL-1β,
IL-6, and
IL-8 in the Model+SDS group (P < 0.05). In summary, this study showed that 0.3 mg/mL SDS attenuated ROS generation, inhibited
lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the PI3K/AKT/Gsk3-β pathway in OA-induced
fatty liver model in vitro, and 20 mg/kg SDS alleviated high-fat-diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.