Abstract
Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injury which could be caused by viral, autoimmune, drugs, and so on. Unfortunately, there was no effective therapy available for liver fibrosis in clinic. In this study, we identified the anti-fibrotic effects of 1,7-dihydroxy-3,4,8-trimethoxyxanthone (ZYC-1) on the dimethylnitrosamine (DMN)-induced rat model. ZYC-1 was isolated from Swertia punicea Hemsl and was administrated to DMN-induced rat model. ZYC decreased the hyaluronic acid (HA), type IV collagen (CIV) and hydroxyproline (Hyp) levels and inhibited the expression of α smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-1β). The anti-fibrotic effect of ZYC-1 was also confirmed by Sirius Red staining. Finally, we identified 42 differentially expressed proteins by using proteomics analysis after ZYC-1 treatment, of which 17 were up-regulated and 25 were down-regulated. These Most of the 42 proteins are involved in the oxidative stress pathway, the mitochondrial-mediated apoptotic pathway and the amino acid metabolism pathway. Our study presented the first elucidated mechanisms of xanthone on liver fibrosis in vivo. This study pointed out that ZYC-1 may be used as a lead compound for hepatofibrosis treatment.
Highlights
It is estimated that 350 million people or so worldwide and 120 million in China alone are suffering from chronic liver injury [1]
DMN treatment significantly increased the levels of the Hyaluronic acid (HA) (P < 0.001 vs. normal group), type IV collagen (CIV) (P < 0.05 vs. normal group), and Hyp (P < 0.001 vs. normal group) (Fig 1C)
Our results showed that these 42 proteins were mainly involved in several biological processes (BP) (Fig 2B1) and molecular functions (MF) (Fig 2B2)
Summary
It is estimated that 350 million people or so worldwide and 120 million in China alone are suffering from chronic liver injury [1]. Liver fibrosis represents the results of a sustained wound healing response to chronic liver injury from a variety of causes, including viral, autoimmune, drugs, cholestatic, alcoholic, and metabolic diseases [2]. Prior studies have indicated that liver fibrosis is potentially reversible, meaning the early diagnosis and intervention of this disease might have important clinical implications [3]. Dimethylnitrosamine (DMN) is a hepatotoxin that is well-known to cause acute liver injury in rats and reproduce the features of human liver. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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