Gehua Jiejiu Dizhi decoction ameliorates alcoholic fatty liver in mice by regulating lipid and bile acid metabolism and with exertion of antioxidant stress based on 4DLabel-free quantitative proteomic study.

OBJECTIVE: To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction (, GJDD) on alcoholic fatty live disease (AFLD) by using proteomic methods. METHODS: The male C57BL/6J mouse were randomly divided into four groups: control group, model group, GJDD group and resveratrol group. After the AFLD model was successfully prepared by intragastric administration of alcohol once on the basis of the Lieber-DeCarli classical method, the GJDD group and resveratrol group were intragastrically administered with GJDD (4900 mg/kg) and resveratrol (400 mg/kg) respectively, once a day for 9 d. The fat deposition of liver tissue was observed and evaluated by oil red O (ORO) staining. 4DLabel-free quantitative proteome method was used to determine and quantify the protein expression in liver tissue of each experimental group. The differentially expressed proteins were screened according to protein expression differential multiples, and then analyzed by Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Finally, expression validation of the differentially co-expressed proteins from control group, model group and GJDD group were verified by targeted proteomics quantification techniques. RESULTS: In semiquantitative analyses of ORO, all kinds of steatosis (ToS, MaS, and MiS) were evaluated higher in AFLD mice compared to those in GJDD or resveratrol-treated mice. 4DLabel-free proteomics analysis results showed that a total of 4513 proteins were identified, of which 3763 proteins were quantified and 946 differentially expressed proteins were screened. Compared with the control group, 145 proteins were up-regulated and 148 proteins were down-regulated in the liver tissue of model group. In addition, compared with the model group, 92 proteins were up-regulated and 135 proteins were down-regulated in the liver tissue of the GJDD group. 15 differentially co-expressed proteins were found between every two groups (model group vs control group, GJDD group vs model group and GJDD group vs control group), which were involved in many biological processes. Among them, 11 differentially co-expressed key proteins (Aox3, H1-5, Fabp5, Ces3a, Nudt7, Serpinb1a, Fkbp11, Rpl22l1, Keg1, Acss2 and Slco1a1) were further identified by targeted proteomic quantitative technology and their expression patterns were consistent with the results of 4D label-free proteomic analysis. CONCLUSIONS: Our study provided proteomics-based evidence that GJDD alleviated AFLD by modulating liver protein expression, likely through the modulation of lipid metabolism, bile acid metabolism and with exertion of antioxidant stress.

Transformation of Chronic Atrophic Gastritis into Gastric Cancer and Prevention and Treatment： Based on Spleen Deficiency and Pathogen Stagnation / 中国实验方剂学杂志

Gastric ''inflammation-cancer'' transformation stars from inflammation and ends as gastric cancer （GC）， and the pathogenesis is still unclear. In China， GC features high morbidity and mortality and poor prognosis， influencing the quality of life and physical and mental health of patients. Therefore， it is of great significance to construct the prevention and treatment system for GC. Chronic atrophic gastritis （CAG） plays a key role in the occurrence， development， and outcome of gastric ''inflammation-cancer'' transformation. Modern therapies for CAG generally aim at eliminating causes and alleviating clinical symptoms， which show satisfactory short-term efficacy， but the reverse and recurrence are common. Based on the holistic view， syndrome differentiation-based treatment， and the ''inflammation-cancer'' transformation in modern medicine， traditional Chinese medicine emphasizes both prevention and treatment， with individualized therapies for CAG and GC to control the transformation. According to the pathogenesis of CAG-asthenia in origin and sthenia in superficiality and deficiency-excess in complexity， this study proposed the theory of spleen deficiency and pathogen stagnation in CAG， and believed spleen deficiency， pathogen， and stagnation are respectively the root cause of， the main factor of， and the key to ''inflammation-cancer'' transformation， respectively. Spleen deficiency and pathogen stagnation are closely related to the process of the transformation. For the treatment， the spleen-invigorating and pathogen-eliminating method should be used for invigorating the spleen to consolidate original Qi， improve the blood supply in stomach， and regulate immunity， and eliminating the pathogen to relieve stagnation， reduce the occurrence of non-controllable inflammation， and improve inflammatory micro-environment. As a result， the gastric inflammation is controlled at the early stage and the gastric ''inflammation-cancer'' transformation is blocked. The gastric mucosal lesions are blocked， delayed， or even reversed. This study provides a new idea in clinical diagnosis and treatment of CAG and in the prevention of GC.

Effect of Gehua Jiejue Dizhi decoction on the liver fatty deposition and expression of PXR in themousealcoholic fatty liver / 中国比较医学杂志

Objective To explore the effect of a herbalcompound Gehua Jiejue Dizhi Decoction (GJDD) on the liver fat deposition and the expression of PXR, and the mRNA and protein expression of its target genes CYP3A11 and CYP3A25in the liver tissues of mouse models of alcoholic fatty liver.Methods Twenty-nine healthy male C57BL/6J mice were randomly divided into control group (n=5), model group (n=8), high dose GJDD group (n=8)and low dose GJDD group (n=8).The mouse model of alcoholic fatty liver was prepared according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) method.Then, the mice were treated with the high dose and low dose GJDD for 9 days.Serum glutamic-pyruvic transaminase (AST) and aspartate aminotransferase (AST) were detected by enzyme-linked immunosorbent assay (ELISA).Liver fat deposition was detected by oil red O staining.Real-time RT-PCR and immunohistochemistry were performed to examine the expressions of PXR, CYP3A11 and CYP3A25.Results Compared with the model group, the liver fat deposition in the intervention groups was significantly reduced in a dose-dependent manner, with a significant increase of the expression of PXR and CYP3A25 (P < 0.01).The serum ALT level was significantly reduced in the model group (P < 0.01), while the transcriptional levels of CYP3A11 mRNA in the groups were similar (P ≥ 0.05).Conclusions Gehua Jiejue Dizhi Decoction has obvious therapeutic effect on the AFLD in mice, which may be related to the activation of PXR and its target genes CYP3A25.