Functional Proteome Platform Reveals the Role of Active Components from Hedyotis diffusa in Reversal of Liver Fibrosis

Hepatic fibrosis is a wound-healing response to prolonged liver injury due to viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Untreated fibrosis may progress to liver cirrhosis ultimately leading to organ failure and death. However, the clinical treatment of fibrosis or cirrhosis has been hampered by the limitation of various models to confirm mechanisms and to test antifibrotic agents as well as the lack of sensitive methodologies to quantify the degree of liver fibrosis and the dynamics of fibrosis progression or reversal in patients. Thus, most of therapeutic agents for liver fibrosis appear to be effective only if given as a prophylactic or early treatment. In addition, early diagnosis of liver fibrosis improves outcome and survival. A pile of evidence from previous studies suggested that both the removal of the aetiological agents and effective therapies can result in significant regression of hepatic fibrosis. Nowadays, a great amount of Chinese medicines have been reported to exhibit therapeutic or protective functions against hepatic diseases. Of note, Hedyotis diffusa Wilid has been wildly used to relieve fever and detoxify. It is also effective to eliminate tumor. Particularly, Hedyotis diffusa Willd has long been used as an important component in several Chinese medicine formulae to clinically treat hepatic carcinoma and hepatitis. Therefore, we attempt to discover the potential markers and underlying mechanisms associated with Hedyotis diffusa Willd-caused reversal of liver fibrosis in proper cellular and rodent models with functional proteomic and bioinformatic tools. This proposal will address the specific aims as follows: 1. To systematically screen the active compounds or extracts derived from Hedyotis diffusa Willd for anti-liver fibrosis by a proper in vitro model. 2. To establish the reversible liver fibrosis rodent models induced by thioacetamide (TAA) and dimethylnitrosamine (DMN). Given the effective extracts of Hedyotis diffusa Willd and collect the plasma/liver samples at specific stages. 3. To characterize the differential protein profiles from plasma and liver tissues among the various stages during the progress of liver fibrosis with gel-based (MALDI-TOF/TOF) and gel-free (LC-MS/MS) analytic systems to discover the possible biomakers for fibrosis/antifibrosis. 4. To establish the In vitro models which are essential to further explore the molecular mechanisms related to reversal of liver fibrosis (cell phenotype switch) and reveal the efficacy of the potential anti-fibrotic targets. 5. Targeted therapy: molecular targets or pathways involved in antifibrosis. Bioinformatics will be applied to develop and improve in the targeted delivery to relevant liver cells. 6. Development of diagnostic and prognostic panel for translational medicine. 7. To confirm the potential markers with clinical samples. The availability of such noninvasive protein biomarkers for fibrogenesis and antifibrosis will contribute to the clinical applications in future.

Project ID:PC10401-0164
External Project ID:NSC102-2628-B182-003-MY3