Component--Salvianolic Acid B inhibits platelet adhesion under conditions of flow by a mechanism involving the collagen receptor a2ß1
Abstract
Salvianolic acid B (SAB) is a component of Salvia miltiorrhiza Bge., a herb widely used in Chinese medicine, and was previously shown to exert a number of biological activities including inhibition of platelet function, but the exact mechanisms involved are unclear. SAB dose-dependently inhibited platelet deposition from flowing, anticoagulated whole blood to immobilized collagen at both venous and arterial shear rate, whereas platelet deposition to immobilized fibrinogen was not affected. The inhibitory effect of SAB on platelet adhesion to collagen was independent of aIIbß3, since SAB still inhibited platelet deposition in the presence of a aIIbß3-blocking peptide. SAB inhibited static platelet adhesion to a synthetic peptide specific for the collagen receptor a2ß1, whereas platelet adhesion to a glycoprotein VI-specific peptide was not affected. SAB inhibited binding of an antibody against a2ß1 to platelets as studied by flow cytometry, and inhibited the interaction of soluble a2ß1 to immobilized collagen in a solid phase binding assay. These combined results indicate that SAB inhibits platelet adhesion to immobilized collagen by interfering with the collagen receptor a2ß1.
Keywords: Collagen; Platelet; Flow; Salvianolic acid B
Interaction of salvianolic acids and notoginsengnosides in inhibition of ADP-induced platelet aggregation.
Yao Y, Wu WY, Liu AH, Deng SS, Bi KS, Liu X, Guo DA.
Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Salvia miltiorrhiza and Panax notoginseng were both considered to be beneficial to cardiovascular diseases in traditional Chinese medicine and often used in combination. To examine the possible interaction between them, the effects of the active fractions of these two herbs, salvianolic acids (SA) and notoginsengnosides (NG), on platelet aggregation were checked respectively or in combination in vitro and in vivo. Both the platelet aggregation of platelet rich plasma (PRP) and washed platelet after ADP induction were checked. In vitro study showed that both SA and NG had an inhibitory effect on platelet aggregation. However, there is no synergistic effect of the combination of SA and NG in vitro. In vivo study showed that i.g. 550 mg/kg/day SA or NG for 5 days could significantly inhibit ADP-induced platelet aggregation of PRP. Moreover, combination of SA and NG at a ratio of 5:1 had a synergistic effect on platelet aggregation of PRP. The mechanism for the synergism of SA and NG in vivo was not clear. High performance liquid chromatography analysis of the plasma of rats received SA, NG or combination of SA and NG showed that co-administration of NG caused change in the plasma distribution profile of SA. The influence of combination on the absorption and/or metabolism of SA may be one of the reasons for the synergism of SA and NG in vivo.
Effect of salvianolic acids from Radix Salviae miltiorrhizae on regional cerebral blood flow and platelet aggregation in rats.
Tang MK, Ren DC, Zhang JT, Du GH.
Pharmacology Department 2, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China. tangmk@imm.ac.cn
This study was conducted to observe the effect of salvianolic acids (SA) on regional cerebral blood flow (rCBF) in rats and on platelet aggregation in vitro and in vivo. Cerebral ischemia was produced in rats by occluding of the right middle cerebral artery, together with the right common carotid artery. rCBF was monitored by H2 clearance method with a tissue blood-flow meter. Platelet aggregation induced by collagen, ADP, and AA was measured in vitro and in vivo by platelet aggregometer. Doses of SA at 6 and 10 mg/kg body wt. (i.v.) improved rCBF in rats after ischemia, but had no obvious effect on normal rCBF. In vitro, SA inhibited significantly the platelet aggregation induced by collagen, ADP, and AA with IC50 values of 0.197, 2.22 and 3.29 x 10(3) mg/l, respectively. In vivo, doses of SA at 6 and 10 mg/kg body wt. inhibited significantly the platelet aggregation induced by collagen, and SA at 10 mg/kg body wt. inhibited remarkably platelet aggregation induced by ADP. The results suggest that SA could improve rCBF in the ischemic hemisphere and inhibit platelet aggregation in rats.
Effects of salvianolic acid-A on NIH/3T3 fibroblast proliferation, collagen synthesis and gene expression.
Liu CH, Hu YY, Wang XL, Liu P, Xu LM.
No 530, Lingling Road, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. liuliver@online.sh.cn
AIM:To investigate the mechanisms of salvianolic acid A (SA-A) against liver fibrosis in vitro.METHODS:NIH/3T3 fibroblasts were cultured routinely, and incubated with 10(-4) mol/L-10(-7)mol/L SA-A for 22h. The cell viability was assayed by (3)H proline incorporation, cell proliferation by (3)H TdR incorporation, cell collagen synthetic rate was measured with (3)H proline impulse and collagenase digestion method.The total RNA was prepared from the control cells and the drug treated cells respectively, and alpha(1) I pro-collagen mRNA expression was semi-quantitatively analyzed with RT-PCR.RESULTS:10(-4)mol/L SA-A decreased cell viability and exerted some cytotoxiciy,while 10(-5)mol/L -10(-7)mol/L SA-A did not affect cell viability, but inhibited cell proliferation significantly, and 10(-6)mol/L SA-A had the best effect on cell viability among these concentrations of drugs. 10 (-5)mol/L -10(-6)mol/L SA-A inhibited intracellular collagen synthetic rate, but no significant influence on extracellular collagen secretion. Both 10(-5)mol/L and 10(-6)mol/L SA-A could decrease alpha(1)I pro-collagen mRNA expression remarkably.CONCLUSION:SA-A had potent action against liver fibrosis. It inhibited NIH/3T3 fibroblast proliferation, intracellular collagen synthetic rate and type I procollagen gene expression, which may be one of the main mechanisms of the drug.
[Effect of acetylsalvianolic acid A on platelet function]
[Article in Chinese]
Yu WG, Xu LN.
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
Acetylsalvianolic acid A (ASAA) is an semisynthetic analogue of salvianolic acid A, isolated from Salvia miltiorrhiza Bge. (Salvia miltiorrhiza Bunge). In in vitro experiments, ASAA showed marked inhibitory effect on rat and rabbit platelet aggregation induced by ADP, collagen, arachidonic acid (AA) and thrombin. In ex vivo experiments with ADP, collagen, and AA as inducers, ASAA was also shown to inhibit platelet aggregation remarkably. The effect lasted more than two hours. In addition, ASAA was found to have suppressive effect on collagen induced platelet 5-HT release while inhibiting aggregation. The above results seemed to suggest that ASAA may be a widely effective inhibitor of platelet function.