ABSTRACT
Histone acetyltransferases are responsible for histone acetylation, while histone deacetylases (HDACs) counteract histone acetylation. An unbalanced dynamic between histone acetylation and deacetylation may lead to aberrant chromatin landscape and chromosomal function. HDAC2, a member of class I HDAC family, serves a crucial role in the modulation of cell signaling, immune response and gene expression. HDAC2 has emerged as a promising therapeutic target for liver disease by regulating gene transcription, chromatin remodeling, signal transduction and nuclear reprogramming, thus receiving attention from researchers and clinicians. The present review introduces biological information of HDAC2 and its physiological and biochemical functions. Secondly, the functional roles of HDAC2 in liver disease are discussed in terms of hepatocyte apoptosis and proliferation, liver regeneration, hepatocellular carcinoma, liver fibrosis and nonalcoholic steatohepatitis. Moreover, abnormal expression of HDAC2 may be involved in the pathogenesis of liver disease, and its expression levels and pharmacological activity may represent potential biomarkers of liver disease. Finally, research on selective HDAC2 inhibitors and noncoding RNAs relevant to HDAC2 expression in liver disease is also reviewed. The aim of the present review was to improve understanding of the multifunctional role and potential regulatory mechanism of HDAC2 in liver disease.
Subject(s)
Histone Deacetylase 2/metabolism , Histones/metabolism , Liver Diseases/enzymology , RNA, Untranslated/genetics , Acetylation , Apoptosis , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/therapy , Cell Proliferation , Hepatocytes/enzymology , Histone Deacetylase 2/genetics , Humans , Liver Cirrhosis/enzymology , Liver Cirrhosis/therapy , Liver Diseases/therapy , Liver Regeneration , Non-alcoholic Fatty Liver Disease/enzymology , Non-alcoholic Fatty Liver Disease/therapyABSTRACT
The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.
Subject(s)
Calcium/metabolism , Dementia, Vascular/drug therapy , Drugs, Chinese Herbal/therapeutic use , Hippocampus/drug effects , Learning Disabilities/drug therapy , Memory Disorders/drug therapy , Memory/drug effects , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Dementia, Vascular/complications , Dementia, Vascular/metabolism , Dementia, Vascular/psychology , Drugs, Chinese Herbal/pharmacology , Female , Hippocampus/metabolism , Learning Disabilities/etiology , Learning Disabilities/metabolism , Male , Maze Learning/drug effects , Memory Disorders/etiology , Memory Disorders/metabolism , Phytotherapy , Rats, Sprague-Dawley , Signal Transduction , Up-RegulationABSTRACT
Root of Panax notoginseng (Sanqi in Chinese) is a highly valued and commonly used Chinese medicine. It has been widely used for treatment of cardio- and cerebro-vascular diseases. In this study, a method involving human platelet extraction and HPLC-DAD-ESI-MS/MS was developed for screening potential anti-platelet aggregation agents in Sanqi. Five compounds which could interact with human platelets were found, and four were identified as adenosine, guanosine, ginsenoside Rh1, and ginsenoside F1, respectively. The effects on rabbit platelet aggregation induced by arachidonic acid, adenosine diphosphate, and thrombin were also investigated in vitro. The results showed that the nucleosides adenosine and guanosine mainly contributed to the anti-platelet aggregation of Sanqi. The data suggest that human platelet extraction combined with HPLC-DAD-ESI-MS/MS is a useful method for screening anti-platelet aggregation agents from Chinese medicines.
