Aspirin suppresses TNF-α-induced MMP-9 expression via NF-κB and MAPK signaling pathways in RAW264.7 cells.

Numerous studies have indicated that the expression of matrix metalloproteinase-9 (MMP-9) contributes to the atherosclerotic plaque hemorrhage and rupture. Aspirin, a non-steroidal anti-inflammation drug, has been known for its anti-platelet effect in the prevention of the vascular complications of atherosclerosis. The present study aimed to investigate the pharmacological effects of aspirin on tumor necrosis factor-α (TNF-α)-induced MMP-9 expression and the underlying molecular mechanisms in murine macrophage RAW264.7 cells. Western blot analysis indicated that the protein level of MMP-9 was reduced by aspirin in a dose-dependent manner. In addition, downregulation of MMP-9 mRNA and activity were detected in aspirin-treated cells using quantitative polymerase chain reaction and a gelatin zymography assay separately. It was also observed that aspirin has a suppressive effect on the activation of nuclear factor (NF)-κB and inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases 1/2, p38 and c-Jun N-terminal kinase. Furthermore, subsequent to inhibition of the MAPK pathway by specific inhibitors (PD98059, SB203580 and SP600125), the expression of MMP-9 was reduced, indicating that the inhibitory effect of aspirin on MMP-9 in TNF-α-treated RAW264.7 cells may be, at least in part, through suppression of NF-κB activation and the MAPK pathway. These findings support the notion that aspirin has therapeutic potential application in the prevention and treatment of atherosclerosis disease.

[Treatment of Chronic Heart Failure with Qi-Yang Deficiency, Blockage of Static Blood Syndrome by Xinmailong Injection: an Open Multi-center Clinical Study].

Objective To assess the safety and effectiveness of Xinmailong Injection (XI) for treating chronic heart failure (CHF) patients with qi-yang deficiency, blockage of static blood syndrome (QYDBSBS). Methods Totally 2 104 patients with QYDBSBS at 25 centers were recruited. XI at 5 mg/kg was intravenously injected to all patients after skin test, twice per day for 5 successive days. The safety and effectiveness were observed within 8 days after injection (5 days of treatment and 3 days of follow- ups). Results were analyzed after full analysis set (FAS) and safety set (SS). Efficacy of heart function (HF) and efficacy of Chinese medicine (CM) syndrome were subgroup analyzed by age ( ≤65 years old or >65 years old) or types of HF (whole HF, right HF, or left HF). Results FAS analysis showed after treatment markedly effective of HF in 550 cases, effective in 873 cases, ineffective in 673 cases, deteriorated in 8 cases. The markedly effective rate was 26.14% and the total effective rate was 67.63%. After treatment markedly effective of CM syndrome was shown in 795 cases, effective in 1 009 cases, ineffective in 288 cases, deteriorated in 12 cases. The markedly effective rate was 37.79% and the total effec- tive rate was 85.74%. Results of CM symptom score: CM symptom score was (11.381 ±4.574) before treatment and (4.987 ±3.984) after treatment, with statistical difference (P <0.01). The decrease rate was 56.8% ±27.0%. Results of subgroup analysis showed that markedly effective rates of HF efficacy and CM syndrome efficacy were superior in patients ≤65 years old than in patients >65 years old (P<0.01 Efficacy of HF was superior in patients with left HF than in those with whole HF or with right HF (P<0.01). In aspect of efficacy of CM, the markedly effective rate and the total effective rate were superior in patients with left HF or with whole HF than in those with right HF (P<0.01 ). No death occurred during the tri- al. No severe adverse event occurred either. Conclusions XI could improve clinical symptoms of CHF patients with QYDBSBS, reduce CM symptom score. No severe adverse event was observed.

[Effects of added therapy with Chinese herbal medicine Kanli Granule on skeletal muscle dysfunction in patients with chronic heart failure].

BACKGROUND: The pathological changes of skeletal muscle dysfunction in chronic heart failure (CHF) have caused widespread concern, and evaluating the functional properties of medication to improve these pathological changes has become a common area of study for clinicians. OBJECTIVE: To investigate the characteristics of skeletal muscle dysfunction in patients with CHF and the effects of Kanli Granule, a compound traditional Chinese herbal medicine, on the skeletal muscle dysfunction based on Western medical treatment in patients with CHF. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: All patients with CHF enrolled in this study were outpatients or inpatients in Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from December 2005 to December 2007. The patients were divided into Western medicine group (treatment with Western medicine) and Chinese herbs group (treatment with Kanli Granule based on Western medicine) based on their preference. The treatment course lasted for 12 weeks. MAIN OUTCOME MEASURES: The grip strength, grasp times, rate of perceived exertion (RPE), estimated heart rate, peripheral blood lactate levels and lactate dehydrogenase (LDH) isoenzyme activity in patients were measured. RESULTS: A total of 92 patients were recruited and 12 patients withdrew from the Western medicine group, therefore a total of 80 patients were included in the follow-up study. There were 46 cases in the Chinese herbs group and 34 cases in the Western medicine group. After treatment, grip strength and grasp times increased significantly compared with before treatment. RPE score and estimated heart rate significantly decreased in the two groups, showing greater changes in the Chinese herbs group than the Western medicine group (P<0.01). Peripheral blood lactate levels of the CHF patients in a resting state decreased, and the Chinese herbs group displayed a greater decrease than the Western medicine group (P<0.05); lactate levels 3 min after exercise decreased after treatment in both treatment groups, but no significant difference was found compared with before treatment; LDH1 levels in the two treatment groups were decreased compared with before treatment but showed no statistically significant changes; LDH5 levels in the two treatment groups increased after treatment, and an obvious difference was found in the Chinese herbs group (P<0.01). CONCLUSION: Treatment with the addition of Kanli Granule can significantly improve the function of skeletal muscle in patients with CHF by improving skeletal muscle energy metabolism.