Abstract
It is known that excessive hepatocellular apoptosis is a typical characteristic of hepatic disease, and is regulated by the mammalian target of rapamycin (mTOR) signaling pathway. As the main active component of Kudzu (Pueraria lobata) roots, which is frequently used to treat hepatic diseases, Puerarin (Pue) has been reported to alleviate and protect against hepatic injury. However, it is unclear whether Pue can inhibit mTOR signaling to prevent excessive apoptosis in the treatment of hepatic diseases. In the present study, Pue effectively ameliorated pathological injury of the liver, decreased serum enzyme (ALT, AST, γ-GT, AKP, DBIL, and TBIL) levels, regulated the balance between pro-inflammatory (TNF-α, IL-1β, IL-4, IL-6, and TGF-β1) and anti-inflammatory cytokines (IL-10), restored the cell cycle and inhibited hepatocellular apoptosis and caspase-3 expression in rats with liver injury induced by 2-AAF/PH. Pue inhibited p-mTOR, p-AKT and Raptor activity, and increased Rictor expression in the liver tissues of rats with experimental liver injury. These results indicated that Pue effectively regulated the activation of mTOR signaling pathway in the therapeutic and prophylactic process of Pue on experimental liver injury.
Highlights
Hepatopathy is a common and frequently occurring disease, which has severe adverse consequences in patients and is a heavy financial burden in China
Rats with a body weight of 250–350 g were included in the study. These animals were randomly divided into 5 groups: normal (Normal), 2-AAF/partial hepatectomy (PH) model (Model), 2AAF/PH rats treated with prophylactic administration of Pue (PueP), which was performed at the same time with the gavage of 2-AAF, 2-AAF/PH rats treated with therapeutic administration of Pue (PueT), and 2-AAF/PH rats treated with rapamycin (RAPA), which was performed on the second day after PH
Serum levels of enzyme activity are important biochemical markers of liver failure, and can confirm the protective effect of Pue in liver injury induced by 2-AAF/PH
Summary
Hepatopathy is a common and frequently occurring disease, which has severe adverse consequences in patients and is a heavy financial burden in China. Puerarin (Pue) is a natural flavonoid compound extracted from the traditional Chinese herb Radix puerariae, which has been used to treat alcoholic disease in traditional Chinese medicine for more than a millennium (Chen et al, 2013; Li et al, 2013; Peng et al, 2013). Hepatopathies treated with Pue include liver injury due to non-alcoholic fatty liver disease, liver ischemia/reperfusion injury, chronic and acute alcohol-induced liver injury, concanavalin A-induced liver injury, liver fibrosis induced by CCl4 and LPS/D-Gal-induced acute liver injury (Guo et al, 2013; Mahdy et al, 2014; Jiang et al, 2016; Zhao W. et al, 2016; Li et al, 2018; Xiao et al, 2018)
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