Application of Proteomic and Bioinformatic Techniques for Studying the Hepatoprotective Effect of Dioscin against CCl₄-induced Liver Damage in Mice

Abstract

In this study, the significant hepatoprotective effect of dioscin against CCl₄-induced acute liver damage in mice was first discovered, and the effect produced by dioscin at the dose of 100 mg/kg was equal to the action produced by silymarin at the dose of 200 mg/kg. Then, 1-dimension gel electrophoresis was used to separate the liver proteins, and five differentially expressed bands were selected. After in-gel digestion, 71 proteins were identified by nano-RP-HPLC-ESI-MS/MS/MS. Further network analysis suggested that the identified proteins formed a connected protein interaction subnetwork. Ten functional categories were selected to demonstrate the distribution of the proteins by Gene Ontology (GO) enrichment analysis. Six of the proteins, heat shock protein 5 (HSPA5), annexin 6 (ANXA6), isovaleryl-CoA dehydrogenase (IVD), ribosomal protein S6 (RPS6), cytoglobin (Cygb), and nucleoside diphosphate kinase A (NDPK-A), were validated by Western blotting assay. They might be involved in the hepatoprotective effect of dioscin, and their investigation could be useful, together with the determination of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels, as well as the liver histopathologic study, for the elucidation of the action mechanisms of dioscin against CCl₄-induced liver injury. Our work shows that the validated proteins should be considered as biomarkers for the investigation of acute liver injury, and its results should contribute to the therapy of liver damage by dioscin in the future.

Potent effects of dioscin against thioacetamide-induced liver fibrosis through attenuating oxidative stress in turn inhibiting inflammation, TGF-β/Smad and MAPK signaling pathways

“…Pharmacological investigations have demonstrated that dioscin possesses antiinflammatory, lipid-lowering and anti-cancer activities (Kaskiw et al, 2009;Lu, Yin, Xu, & Peng, 2011;Sautour, Mitaine-Offer, Miyamoto, Dongmo, & Lacaille-Dubois, 2004). Our previous investigations have shown that dioscin is highly effective against chemical-induced liver injury, non-alcoholic fatty liver disease, alcohol-induced liver injury and carbon tetrachloride (CCl 4)-induced liver fibrosis Xu T. T. et al, 2014;Zhang et al, 2015).…”

Involvement of Organic Anion-Transporting Polypeptides in the Hepatic Uptake of Dioscin in Rats and Humans

“…Dioscin, a spirostane saponin with antihepatitis activity (Lu et al, 2011), accumulates in the liver after intravenous or oral administration at a concentration much higher than dioscin in plasma and other tissues (Li et al, 2005). The value of hepatic clearance (CL in situ, predicted = 0.83 6 0.10 ml/min/kg) is 21.5% of plasma clearance (3.86 6 0.51 ml/min/kg) (Li et al, 2005).…”

“…For instance, di-ao-xin-xue-kang capsules prepared from D. nipponica Makino have been used for more than 10 years in China to treat coronary heart disease (Liu et al, 2004b). The bioactivity of dioscin (diosgenyl 2,4-di-O-a-L-rhamnopyranosyl-p-D-glucopyranoside), a major component of di-ao-xin-xue-kang capsules, has been reported and includes antihepatitis (induced by carbon tetrachloride) (Lu et al, 2011), antitumor (Mi et al, 2002;Liu et al, 2004a;Hu et al, 2012), and antifungal (Sautour et al, 2004) activity. Dioscin ( Fig.…”

In-silico prediction of drug targets, biological activities, signal pathways and regulating networks of dioscin based on bioinformatics

“…Pharmarcological studies have showed that dioscin has anti-tumor, anti-hyperlipidemic, anti-fungal and anti-virus activities [15-18]. And our previous studies showed that dioscin has significant hepatoprotective effects on carbon tetrachloride (CCl 4 ) and acetaminophen induced liver damage in mice [19-21]. In the future, more and more researches of dioscin will be investigated because of its important medical value.…”