Tanshinone IIA promotes reverse cholesterol transport to improve atherosclerosis / 中国药理学通报

Aim To explore the effect of tanshinone II A (Tan II A) on reverse cholesterol transport in atherosclerosis model mice and RAW264. 7 cells and the underlying mechanism. Methods Thirty-two male LDLR -/- mice were randomly divided into four groups. These mice were fed with normal diet or high fat diet for 12 weeks. The control group and model group were given normal saline. Tan II A group and atorvastatin group were given Tan II A solution and atorvastatin solution for 12 weeks. RAW264. 7 cells were induced with oxidized low-density lipoprotein (ox-LDL) 100 mg • L-

Salvianolic acid B reduces liver inflammation in mice with atherosclerosis by inhibiting MAPKs/NF-kB signaling pathway / 中国药理学通报

Aim To explore the effeet of salvianolic aeirl B on liver inflammation in atheroselerosis model mice and its mechanism.Methods Thirty-two male LDLR mice were randomly divided into control group, model group, salvianolic acid B group, and ator- vastatin group.The control group was fed with ordinary feed, and the other groups were fed with high-fat feed for 12 weeks.The control group and the model group were injected intraperitoneally with normal saline, the salvianolic acid B group was injected intraperitoneally with the salvianolic acid B solution,and the atorvastatin group was given intragastrically with atorvastatin solution for 12 weeks.Biochemical detection methods were used to detect the serum TC, TG, AST and ALT values of mice.Oil red 0 staining was used to observe mouse aortic sinus plaque area, and HE staining was used to observe pathological changes of mouse liver.ELISA and RT-PCR methods were used to detect serum IL- 1 p, 1L-6,and TNF-ot levels,and 1L-1 (3, 1L-6,and TNF-a mRNA in liver.Western blot was used to determine the protein expression of VCAM, iNOS, JNK, p38, ERK1/2, IkB, and NF-kB in mouse liver tissues.Results Compared with model group, salvianolic acid B and atorvastatin reduced the levels of serum TC, TG, AST,and ALT in mice ( P <0.05 ) ,reduced the plaque area of aorta in mice, and improved the pathological changes of liver tissues,and down-regulated mouse serum IL-l (3, IL-6, TNF-cx content and mRNA levels (P < 0.05 ).Salvianolic acid B reduced the protein levels of VCAM and iNOS in liver tissues of mice,as well as the phosphorylation levels of JNK, p38 , ERK1/2 , IkB , and NF-kB proteins ( P <0.05 ).Conclusions Salvianolic acid B reduces liver inflammation in atherosclerotic model mice,which may be related to its inhibition of MAPKs/NF-kB signaling pathway.

Attenuation and mechanism of endoplasmic reticulum stress-mediated hepatocyte apoptosis in rats with alcohol-induced liver injury by qinggan huoxue recipe and its disassembled formulas / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore attenuation and mechanism of endoplasmic reticulum stress (ERS)-mediated hepatocyte apoptosis in rats with alcohol-induced liver injury by Qinggan Huoxue Recipe (QGHXR) and its disassembled formulas (Qinggan Recipe and Huoxue Recipe respectively).</p><p><b>METHODS</b>A rat model of chronic alcoholic liver injury was successfully established using a compound reagent of alcohol, corn oil, and pyrazol. The modeled rats were randomly divided into the model group, the QGHXR group, the Qinggan Recipe (QGR) group, and the Huoxue Recipe group (HXR). The CCl4 control group and the normal control group were also set up. There were ten rats in each group. All rats of modeled groups were gastrogavaged with alcohol compound reagent every morning. Rats in the QGHXR group (at the daily dose of 9. 5 g/kg, QGR group (at the daily dose of 3.0 g/kg), and HXR group (at the daily dose of 6.5 g/kg) were administered with corresponding medicines by gastrogavage every afternoon. Equal volume of normal saline was given to rats of the model group by gastrogavage. CCl4 was intraperitoneally injected at the dose of 0.3 mL/kg to rats in the CCl4 control group, once per week. Normal saline was given to rats in the normal control group by gastrogavage. The treatment was lasted for two weeks. Pathological changes of the liver were observed by histopathology. Serum total homocysteine (tHCY) level was detected by ELISA. The hepatocyte apoptosis rate was detected using flow cytometry. The gene and protein expressions of eukaryotic translation initiation factor 2 alpha (elF-2alpha), phosphorylation elF-2alpha (pelF-2alpha), glucose-regulated protein 78 (GRP78), and Caspase-3 in the liver were examined using Real-time PCR and Westen blot respectively.</p><p><b>RESULTS</b>Compared with the normal control group, typical pathological changes of chronic alcoholic liver injury such as steatosis, inflammation, and even fibrosis occurred in model rats. The hepatocyte apoptosis obviously increased, with the apoptosis rate reaching the five-fold of that in normal rats. Besides, early apoptosis dominated. The serum tHCY level significantly increased. The expressions of p-elF-2alpha, GRP78, and Caspase-3 protein obviously increased (P < 0.01). Expressions of GRP78 and Caspase-3 mRNA significantly increased (P < 0.05, P < 0.01). Compared with the model group, the degrees of the liver injury and the hepatocyte apoptosis in the QGHXR group, the QGR group, and the HXR group were significantly alleviated. The serum tHCY level was significantly lowered. The protein expressions of p-elF-2a, GRP78, and Caspase-3 obviously decreased (P < 0.01). mRNA expressions of GRP78 and Caspase-3 obviously decreased in the QGHXR group (P < 0.05, P < 0.01). Only GRP78 mRNA expression obviously decreased in the QGR group (P < 0.05).</p><p><b>CONCLUSION</b>QGHXR and its disassembled formulas could attenuate ERS-mediated hepatocyte apoptosis in alcohol-induced liver injury rats by lowering the serum tHCY level and expressions of ERS apoptosis correlated factors.</p>

Role of PERK/eIF2a signaling pathway in hepatocyte apoptosis of alcoholic liver injury rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the role of PERK/eIF2alpha signaling pathway in hepatocyte apoptosis of alcoholic liver injury rats.</p><p><b>METHODS</b>Rat models with ethanol-induced liver injury were successfully developed by gastric gavage with ethanol-corn oil mixtures for 12 weeks. At different time points (4, 6, 10, 12 week), liver pathology was dynamically observed. The hepatocyte apoptosis was quantitatively analyzed by Annexin V-FITC/PI double-labeled flow cytometry, the serum total homocysteine (tHCY) level was detected by ELISA and the expressions of eIF2a, p-eIF2a, GRP78/Bip, GRP94, caspase-3 and caspase-12 in liver were examined using Real-time PCR and Western blot.</p><p><b>RESULTS</b>Typical acute liver injury and chronic liver injury were observed at week 4 and week 12 respectively. The hepatocyte apoptosis rates in 6-week model rats significantly increased compared with normal rats (P value less than 0.05), and the degree of hepatocyte apoptosis continued to increase with the modeling time, and the percentages of early and total apoptosis reached 26% and 29% at week 12. From week 6 to week 12, the serum tHCY levels in model rats were obviously higher than in normal rats (P value less than 0.01). Since week 4, eIF2a protein phosphorylation in model rat livers remarkably elevated compared with that in normal rat livers (P value less than 0.01), and at week 12 the peIF2a protein expression in model rat livers increased by 2.81-fold. Since week 4 the expressions of GRP78/Bip, GRP94, caspase-12 and caspase-3 mRNA and protein in model rat livers showed a significant increase as compared to normal rat livers, and at week 12, these gene and protein levels increased 4.70, 12.95, 3.83, 4.05 fold and 3.93, 6.93, 9.88, 3.31 fold, respectively (P value less than 0.01).</p><p><b>CONCLUSION</b>Activation of PERK/eIF2a signaling pathway contributes to the occurrence and development of hepatocyte apoptosis in alcoholic liver injury rats and it might be as a potential target for therapeutic applications in alcoholic liver diseases.</p>