Abstract
Sochehwan (SCH) is an herbal prescription from traditional oriental medicine and is currently used to treat digestive ailments. In a previous study, SCH was found to have the potential to attenuate metabolic syndrome (MetS) by activating AMPK and downstream signaling. From the view of drug repurposing, the efficacy of SCH on alcoholic liver injury is implied in classic medical texts but is yet to be proven. C57BL/6J mice were pre-treated with SCH orally for 5 days and challenged by providing a pair-fed Lieber DeCarli diet containing alcohol for 20 days. Hepatic enzyme and triglyceride levels and endoplasmic reticulum (ER) stress-related markers were analyzed. Moreover, mitogen-activated protein kinases (MAPKs) and cytochrome P450 2E1 (CYP2E1) levels were determined. CYP2E1-transfected HepG2 cells were used to test the cytoprotective efficacy of SCH against the adverse effects of alcohol in vitro. In mice, SCH administration notably reduced hepatic enzyme activity and neural lipid levels. Furthermore, ER-stress markers and MAPK phosphorylation were reduced due to ROS suppression, which was attributed to decreased CYP2E1 expression in liver tissue. In addition, SCH successfully protected CYP2E1-transfected HepG2 cells against ethanol. Our findings suggest SCH attenuated alcohol-induced liver injury by inhibiting CYP2E1 expression and indicate drug repurposing should be considered as a valuable option for drug development in traditional herbal medicines.
Highlights
Excessive alcohol consumption is considered a major etiology of liver-related diseases [1]
We showed that SCH has multifaceted effects on metabolic syndromes by activating the AMP-activated protein kinase (AMPK) and its downstream signaling in the hepatic steatosis model in vitro and in vivo [19]
No difference was observed between mean body weights in the three alcohol-administered groups (AF, alcohol-fed group (AF)+SCH, AF+PC) and PF group (Figure 1a)
Summary
Excessive alcohol consumption is considered a major etiology of liver-related diseases [1]. Alcoholic liver disease (ALD) ( referred to as alcohol-related liver disease, ARLD) is widely acknowledged by hepatologists to be a pandemic and presents serious economic burdens and health issues worldwide [2,3]. ALD includes a wide-ranging spectrum of alcohol-induced liver damage from simple steatosis, to alcoholic hepatitis, and hepatic cirrhosis and fibrosis [4]. As a member of the classical cytochrome P450 family (CYP 450), CYP2E1 is regarded as a major source of alcohol- or drug-induced reactive oxygen species (ROS) in the liver [5]. Ethanol breakdown by cytochrome P450 is referred to as the microsomal ethanol oxidizing system (MEOS), and this system generates ROS as a by-product, which causes a
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