Antioxidant, antiapoptotic and amino acid balance regulating activities of 1,7-dihydroxy-3,4,8-trimethoxyxanthone against dimethylnitrosamine-induced liver fibrosis

• Published in: PloS one 2017-12, Vol.12 (12), p.e0189344-e0189344
• Main Authors: Zheng, Xi-Yuan, Zhao, Xin, Yang, Ying-Fan, Jiang, Han-Jie, Li, Wan, Sun, Yi, Pu, Xiao-Ping
• Format: Article
• Language: English
• Subjects: Acids; Actin; Amino acids; Analysis; Antioxidants; Antioxidants (Nutrients); Apoptosis; Bile; Biology and Life Sciences; Care and treatment; Causes of; Chinese medicine; Collagen (type IV); Dimethylnitrosamine; Drug dosages; Drugs; Fibrosis; Health aspects; Hyaluronic acid; Hydroxyproline; In vivo methods and tests; Laboratory animals; Liver; Liver diseases; Medical research; Medicine and Health Sciences; Metabolism; Mitochondria; Muscles; N-Nitrosodimethylamine; Oxidative stress; Pharmaceutical sciences; Pharmacology; Physiological aspects; Proteins; Proteomics; Research and Analysis Methods; Rodents; Smooth muscle; Swertia; Transforming growth factor-b1; Transforming growth factors; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0189344

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.