Search

Objective: To investigate the effect of Red Peony 801 (propyl gallate,PrG) on cyclooxygenase (COX) activity in murine peritoneal macrophages.Methods: A screening model for COX inhibitors in vitro based on murine peritoneal macrophages was used. COX-1 activity was reflected by the level of 6-ketoprostaglandin F1α(6-keto-PGF1α) in supernatants of cultured macrophages which were stimulated with calcium ionophore A23187 for a short-term, while COX-2 activity was reflected by the level of prostaglandin E2 (PGE2) in supernatants of cultured macrophages which were stimulated with lipopolysaccharide (LPS) for a long-term.Results: PrG did not affect A23187-induced, COX-1-derived 6-keto-PGF1α synthesis at the concentrations of 1 × 10-6, 5 × 10-6 mol/L (P>0.05), but enhanced 6-keto-PGF1α synthesis at the concentrations of 1 × 10-6, 5 × 10-7, 1 × 10-7 mol/L (P

Objective: To study the targeted point and mechanism of the function of the blood-activating and stasis-removing Chinese drugs, Paeoniae Radix 801(PR801) in its cardiovascular protective effects and its specific binding with endothelin 1(ET-1) as well as the dynamics of the two’s interactive function by means of using affinity biosensors: IAsys Plus and quartz crystal microbalance (IAQCM).Methods: ET-1 was immobilized on the surfaces of IAQCM by using the new surface modification methods. The PR801 in the solution was detected by modified substrates and the specific binding between PR801 and ET-1 was studied.Results: The curves went up or down after adding PR801. There is specific binding between PR801 and ET-1. The bound mass were 0.458 ng/mm2 and 133. 54 ng/cm2, respectively. There exists relatively good stability with these two methods.Conclusion: The affinity biosensors: IAQCM can be used to study the interaction mechanism between PR801 and ET-1, providing a new way to study the interaction mechanism of TCM. PR801 can bind ET-1 specifically in the experiments. Therefore, ET-1 is another target that PR801 can bind specifically besides thromboxane A2.

Purpose Previous studies have shown that Fc receptor III A of immunoglobulin G (FcγRIIIA, also named CD16) was involved in the development of coronary heart disease (CHD). However, the mechanism of CD16 in contribution to CHD development remains largely unclear. Here, we focused on the signaling pathway it stimulates in the initiation and progression of CHD. Methods We investigated FcγRIIIA mRNA expression in the leukocytes, serum protein level of soluble CD16 (sCD16) and membrane CD16 on monocytes in 100 diagnosed CHD patients and 40 healthy people at similar ages. We determined soluble CD14 (sCD14) to analyse whether monocytes are activated or not. Macrophage colony stimulating factor (M-CSF), TNFα and IL-1 in sera were determined as well. Furthermore, the role of FcγRIIIA in the initiation and progression of CHD was analysed by monocytes adherence to human umbilical vein endothelial cells (HUVECs) in vitro and aortic atherosclerotic formation in ApoE-/-mouse model in vivo. Results There was a significant increase of Fcγ RIIIA at the mRNA level in leukocytes (1.372±0.454), the protein level of both serum sCD16 (3.237±0.988) and membrane CD16 on monocytes (4.8±2.2%) in CHD patients when compared to the healthy control. High level of sCD14 in sera (3.744±0.896 μg/ml) was found in CHD patients. Similar to sCD14, the levels of M-CSF (120.144±32.123 pg/ml), TNFα (48.297±11.545 pg/ml) and IL-1 (75.842±20.682 pg/ml) in sera were also higher in CHD patients. Further experiments showed that the elevated level of FcγRIIIA on monocytes dramatically correlated with the adhesive efficiency of HUVECs (10.5±5.5%) in vitro, and also aortic atherosclerotic formation in ApoE-/- mouse model, along with increased levels of TNFα (41.758±9.776 pg/ml), IL-1 (71.752±13.201 pg/ml;) and soluble E-selectin (sE-selectin) (2.977±0.560 μg/ml) in sera and both the mRNA level (3.968±0.284) and the protein level (0.455±0.018) of MMP-9 in aorta. Additionally, similar to Simvastatin, IVIG pretreatment inhibited this response in ApoE -/- mice. Conclusion Taken together, these results demonstrate that FcγRIIIA plays a crucial role in the development of athersoclerotic formation by targeting inflammatory cytokines and MMPs, and inhibition of FcγRIIIA or its signaling may represent a promising approach for the prevention and treatment of CHD.

Objectives To investigate the effects of active ingredients of Chuanxiong rhizome and red peony root (Chuangxiongol and paeoniflorin) on the platelet activation level and platelet gelsolin in rat model of acute myocardial infarction in vivo . Methods The rat model of AMI is prepared by ligation of left anterior descending (LAD) artery. Taken Xiongshao Capsule (XSC) as the intervention drug, while aspirin and verapamil (calcium antagonist) as the positive control drugs. Got PRP and PPP by density gradient centrifugation, then gelsolin, F-actin, DBP, P-selection, CK-MB and cTnI were detected by ELISA, the [Ca 2+ ]i of Platelet was detected by FCM, gelsolin expression of infracted myocardium was detected by WB. Results Compare with sham group, the concentration of CK-MB and cTnI of model group increased significantly after ligation of LAD for 3 hours (P 2 level markedly (P in vivo . Compare with the sham group, the plasma gelsolin, DBP of Model group reduced significantly (P Compare with sham group,the fluorescence intensity of Ca 2+ of model group increased markedly (P 0.05). Compare with sham group, the gelsolin expression of infracted myocardium of model group increased markedly, and XSC can inhibit gelsolin expression of infracted myocardium, but verapamil has no such effect. Conclusions The active ingredients of Chuanxiong rhizome and red peony root (Chuangxiongol and paeoniflorin) can reduce the platelet gelsolin level, enhance the activity of EASS, inhibit platelet activation and has the effect of calcium antagonist while it also can inhibit COX-1 and TXB 2 which has the similar effect of aspirin in vivo.