Abstract
Objective To evaluate the hepatoprotective mechanism of Xwak granule (Xwak) in treatment of mice with alcoholic liver injury via activating ERK/NF-κB and Nrf/HO-1 signaling pathways. Methods The chemical composition of Xwak was tested by liquid chromatography coupled with mass spectrometry (LC-MS). Herein, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical tests were performed in vitro. The hepatoprotective effect of Xwak was assessed at different concentrations (1.5, 3, and 6 g/kg) in a mouse model of alcoholic liver injury. Results Totally, 48 compounds, including 16 flavonoids, 8 tannins, 9 chlorogenic acids, and 15 other compounds, were identified from Xwak. Xwak showed to have a satisfactory antioxidant activity in vitro. In a group of Xwak-treated mice, the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were decreased compared with a group of the mouse model of alcoholic liver injury. In addition, the levels of antioxidant enzymes, such as glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), and catalase (CAT), were noticeably increased and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) were markedly reduced in the liver of mice. The state of oxidative stress in the mouse model of alcoholic liver injury was improved after treatment with Xwak. The improvement of inflammation-mediated disruption may conducive to the Xwak activity in the control of liver injury. The signals of p-ERK1/2, p-NF-κB, COX-2, iNOS, CYP2E1, Nrf, and HO-1 were significantly induced in the liver of mice after treatment with Xwak. Conclusions The abovementioned findings indicated that the hepatoprotective mechanism of Xwak could be achieved by activating ERK/NF-κB and Nrf/HO-1 signaling pathways to alleviate oxidative stress and inflammatory.
Highlights
Alcoholic liver disease (ALD) is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis [1]. e initial stage of ALD is liver damage caused by excessive consumption of alcohol, and in case of late treatment, it may further develop from alcoholic hepatitis to alcoholic fibrosis and deteriorate to alcoholic cirrhosis, and even hepatocellular carcinoma
We evaluated the scavenging effects of Xwak on free radicals of ABTS and DPPH in vitro, and the results showed that Xwak has a satisfactory antioxidant activity and can be used as a potential free radical scavenger. erefore, we further studied the antioxidant and anti-inflammatory activities of Xwak in the mouse model of alcoholic liver injury, in order to clarify its hepatoprotective mechanism
Transaminases are rapidly released into blood stream when injuries or diseases affected the body tissues [34]. e results of the present study unveiled that the levels of AST, ALT, and alkaline phosphatase (ALP) in the mouse model of acute alcoholic liver injury were significantly increased in serum, which is consistent with findings of previous reports [35]. is indicated that the mouse model of acute alcoholic liver injury was successfully established
Summary
Alcoholic liver disease (ALD) is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis [1]. e initial stage of ALD is liver damage caused by excessive consumption of alcohol, and in case of late treatment, it may further develop from alcoholic hepatitis to alcoholic fibrosis and deteriorate to alcoholic cirrhosis, and even hepatocellular carcinoma. E initial stage of ALD is liver damage caused by excessive consumption of alcohol, and in case of late treatment, it may further develop from alcoholic hepatitis to alcoholic fibrosis and deteriorate to alcoholic cirrhosis, and even hepatocellular carcinoma. Xwak has been registered in National Intellectual Property Administration (Beijing, China). It is mainly used in the treatment of liver diseases in ethnic medicine. The mechanism of hepatoprotection of Xwak in alcoholic liver injury has still remained elusive. We analyzed the chemical components of Xwak and evaluated the hepatoprotective mechanism of Xwak in mice with alcoholic liver injury
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