Hepatic transcriptome delineates the therapeutic effects of Sanren Tang on high-fat diet-induced non-alcoholic fatty liver disease.

OBJECTIVE: To evaluate the effects of Sanren Tang (SRT, ) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice and to investigate the hepatic transcriptome regulated by SRT. METHODS: The primary SRT components were identified using ultra-high-performance liquid chromatography-high-resolution accurate mass spectrometry. The SRT-induced pharmacological effects on HFD-induced NAFLD were evaluated in mice for 16 weeks. Obeticholic acid was used as a control drug. Body weight, food intake, and homeostatic model assessment for insulin resistance (HOMA-IR) index were analysed. Hepatic histological changes were observed in haematoxylin and eosin-stained sections and quantified using the NAFLD activity score (NAS). Serum alanine aminotransferase (ALT) and hepatic triglyceride (TG) levels were measured. Lipids in hepatocytes were visualised by Oil red staining. RNA-sequencing was performed to determine the transcriptome profile of the liver tissue. The differentially expressed genes were validated using real-time polymerase chain reaction and Western blotting. RESULTS: Four principal compounds were identified in the SRT: adenosine, amygdalin, luteoloside, and magnolol. SRT ameliorated hepatic histology and lipid deposition in the NAFLD mice, and decreased HOMA-IR, NAS and ALT, and hepatic TG levels. Hepatic transcriptome analysis revealed 232 HFD-regulated genes that were reversed by SRT simultaneously. Retinol metabolism, cytokine-cytokine receptor interaction, and peroxisome proliferator-activated receptor (PPAR) γ signalling were the top three SRT-regulated pathways in NAFLD. CONCLUSIONS: SRT significantly ameliorated HFD-induced NAFLD, which was correlated with the regulation of genes enriched in the retinol metabolism, cytokine-cytokine receptor interaction, and PPARγ signalling pathways.

Systems Biology---New Approach for Study on Non-alcoholic Fatty Liver Disease with Traditional Chinese Medicine / 世界科学技术-中医药现代化

Systems biology, which includes genomics, proteomics, transcriptomics and metabolomics, is an integration of system theory and biology. It studies the life phenomena with thinking method of systems theory. And it provides an important methodological basis and technical conditions for recognizing syndrome of traditional Chinese medicine (TCM) and mechanism of therapeutic effect from multiple disciplines and perspectives. Systems biology is similar to the core idea of TCM system and holism concept. Therefore, systems biology can be used as a platform and pivot of non-alcoholic fatty liver disease (NAFLD) in modern TCM study. Systems biology will accelerate the modernization research of TCM in the prevention and treatment of NAFLD. It will also provide new ideas and methods for TCM study on NAFLD.

Diagnostic value of clinical indices in syndrome differentiation of chronic hepatitis B: an exploration based on receiver operating characteristic curves and stepwise discriminant analysis / 中西医结合学报

To explore the diagnostic value of 75 commonly used clinical laboratory markers for differentiation of traditional Chinese medicine syndromes such as liver and gallbladder damp-heat and liver depression and spleen deficiency in patients with chronic hepatitis B.

Effect of gypenosides on DMN-induced liver fibrosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of gypenosides on DMN-induced liver fibrosis in rats.</p><p><b>METHOD</b>A rat liver fibrosis model was established by injecting DMN intraperitoneally. Four weeks later, model rats were randomly devided into three groups: the model group, the gypenosides treated group (200 mg x kg(-1)) and the colchicine treated group (0.1 mg x kg(-1)), with 10 specimens for each group. After a 2-week treatment, following parameters were observed: (1) last body weight, weight ratio between liver and spleen; (2) content of liver hydroxyproline (Hyp); (3) activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), content of albumin (Alb) and total bilirubin( TBiL) in serum; (4) liver pathology (Sirius red staining and HE staining); (5) activity of liver superoxide dismutase (SOD), glutathione reduced (GSH), glutathione peroxidase (GSH-Px) and content of liver maleic dialdehyde (MDA).</p><p><b>RESULT</b>There were classic liver cirrhosis pathological changes in model groups. Compared with the normal group, liver Hyp content, activity of serum ATL, AST, gamma-GT and content of serum TBiL, MDA of model groups significantly increased; content of serum Alb and liver GSH, activity of liver SOD and GSH-Px decreased significantly in model groups. In comparison with the model group, liver cirrhosis remarkable improved in the gypenosides group, content of liver Hyp reduced significantly (P < 0.01), which was equal to the colchicine group. Compared with the model group, liver function parameters improved markedly in the gypenosides group; liver SOD and GSH-Px activities significantly increased; MDA content reduced significantly (P < 0.05).</p><p><b>CONCLUSION</b>Gypenosides shows an effect in treating DMN-induced liver fibrosis in rats.</p>

Analysis of major herbs in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability based on uniform design / 中西医结合学报

To investigate the herbal medicines which play a main role in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability and protect alcohol-induced liver injury and intestine damage, and to explore the analysis method for the material base of pharmacological effects of the Chinese herbal compound.

Effects of Chinese herbal medicine Yiguanjian Decoction on collagen metabolism of hepatic tissues in rats with CCl4-induced liver fibrosis / 中西医结合学报

Objective: To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on collagen metabolism of hepatic tissues in rats with carbon tetrachloride (CCl(4))-induced liver fibrosis. Methods: Liver fibrosis was induced in rats by intraperitoneal injection of 50% CCl(4)-olive oil solution at a dose of 1 mL/kg body weight, twice per week for 9 consecutive weeks. Six rats were sacrificed for dynamic observation at the end of the 3rd and 6th week respectively, and the other rats were divided into 9-week untreated group and Yiguanjian Decoction group which was given Yiguanjian Decoction intragastrically in the subsequent 3-week modeling period. Another 6 rats were used as normal group. Rats in the normal group and 9-week untreated group were treated with distilled water. At the end of the 9th week, all rats were sacrificed, and their blood serum and liver tissue were collected for measuring hepatic histology and expressions of α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-13, MMP-14, collagen type I (Col I), and activities of MMP-2 and -9. Results: Compared with the normal group, collagen fiber deposition, expressions of α-SMA, Col I, TIMP-1, TIMP-2, MMP-13 and MMP-14 and activities of MMP-2 and -9 in the liver tissues gradually increased in the untreated group (P<0.05, P<0.01). These changes were significantly suppressed by Yiguanjian Decoction. Conclusion: Yiguanjian Decoction exerts inhibition on formation of CCl(4)-induced cirrhosis in rats. The therapeutic mechanism may be related to inhibiting hepatic stellate cell activation, collagen secretion, and promoting collagen fiber degradation.

Effects of Qushi Huayu Decoction on cathepsin B and tumor necrosis factor-alpha expression in rats with non-alcoholic steatohepatitis / 中西医结合学报

OBJECTIVE: To study the mechanism of Qushi Huayu Decoction (QHD), a compound of traditional Chinese herbal medicine, in prevention and treatment of non-alcoholic steatohepatitis (NASH). METHODS: Thirty-five Wistar male rats were randomly divided into normal group, untreated group, QHD group and Ganle (diisopropylamine dichloroacetate) group. The rats except those in normal group were subcutaneously injected with carbon tetrachloride (CCl(4)) for 4 weeks (twice per week) and simultaneously fed with high-fat and low-protein diet for 2 weeks to induce NASH. Then, the rats were administrated with QHD, Ganle, or distilled water for 2 weeks, respectively. After harvest, alanine aminotransferase (ALT) activity and tumor necrosis factor-alpha (TNF-alpha) content in serum as well as triglyceride (TG) and free fatty acid (FFA) in liver tissue were evaluated, and relativity analysis among these parameters was performed. Cathepsin B (Ctsb), phospho-inhibitor kappa B (P-IkappaB), TNF-alpha protein expressions in liver tissue were assayed with western-blot. The expression and distribution of ctsb in liver tissue were observed with immunohistochemical method. RESULTS: The contents of TG, FFA and activity of ALT were significantly decreased in QHD group. While in the Ganle group, only the activity of ALT in serum was decreased significantly. Expressions of Ctsb, P-IkappaB and TNF-alpha proteins in liver tissues and serum TNF-alpha level were all enhanced in untreated group which, however, were significantly inhibited in the QHD group. And as expected, there were significant relativities among contents of TG in liver tissues and the content of FFA in liver tissue and activity of ALT in serum, content of TNF-alpha in serum and content of FFA in liver tissue and activity of ALT in serum. CONCLUSION: The inhibiting effects of QHD on fat deposition and inflammation in liver are related with its inhibition on the "FFA-Ctsb-TNF-alpha" pathway of lipo-toxicity.

Effects of Jianpi Huoxue Decoction on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide / 中西医结合学报

OBJECTIVE: To observe the effects of Jianpi Huoxue Decoction, a compound Chinese herbal medicine, on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide (LPS). METHODS: SD rats were divided into normal, control liquid diet, ethanol liquid diet and ethanol liquid diet plus Jianpi Huoxue Decoction group. Rats were administrated with Jianpi Huoxue Decoction or distilled water via gastrogavage for 4 weeks after administration with ethanol or control liquid diet for 2 weeks respectively. After that, rats in each group were stimulated with LPS via gastrogavage for 3.5 h and harvested. Alanine aminotransferase (ALT) in serum and triglyceride (TG) in liver were analyzed. Pathological changes in liver tissues were observed in HE staining section. Tumor necrosis factor-alpha(TNF-alpha) in portal vein plasma was assayed by ELISA. The protein expressions of CD68, Toll-like receptor 4 (TLR4), phosphorylation-I kappa B (P-I kappa B) and TNF-alpha in liver were evaluated with Western-blotting. RESULTS: After the treatment with Jianpi Huoxue Decoction, the pathologic changes in liver tissue were lightened, levels of ALT in serum, TG in liver and TNF-alpha in portal vein plasma were decreased, and the protein expressions of CD68, TLR4, P-IkappaB and TNF-alpha in liver were reduced. CONCLUSION: Jianpi Huoxue Decoction can inhibit Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and LPS.