Specific Inhibiting Characteristics of Tetramethylpyrazine, One of the Active Ingredients of the Chinese Herbal Medicine ‘Chuanxiong,’ on Platelet Thrombus Formation Under High Shear Rates

2001 ◽  
Vol 104 (1) ◽  
pp. 15-28 ◽  
Author(s):  
Min Li ◽  
Shunnosuke Handa ◽  
Yasuo Ikeda ◽  
Shinya Goto
Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 677-682 ◽  
Author(s):  
WX Li ◽  
AV Kaplan ◽  
GW Grant ◽  
JJ Toole ◽  
LL Leung

A novel thrombin inhibitor based on single-stranded (ss) deoxynucleotides with the sequence GGTTGGTGTGGTTGG (thrombin aptamer) has been recently discovered. In this study, we tested its efficacy in inhibiting clot-bound thrombin activity and platelet thrombus formation in an ex vivo whole artery angioplasty model. The thrombin aptamer showed a specific dose-dependent inhibition of thrombin-induced platelet aggregation (0.5 U/mL) in human platelet-rich plasma, with an IC50 of approximately 70 to 80 nmol/L. In an in vitro clot-bound thrombin assay system, heparin, used at clinically relevant concentrations of 0.2 U/mL and 0.4 U/mL, was ineffective in inhibiting clot-bound thrombin (6.5% and 34.9% inhibition at 0.2 U/mL and 0.4 U/mL, respectively). In contrast, the thrombin aptamer at an equivalent anticoagulant concentration inhibited clot-bound thrombin (79.7% inhibition). In an ex vivo whole artery angioplasty model, the thrombin aptamer markedly suppressed the generation of fibrinopeptide A (FPA), whereas heparin at 2 U/mL was ineffective. Compared with a scrambled ssDNA control, the thrombin aptamer reduced platelet deposition by 34.5% +/- 5% (mean +/- SEM, n = 4, P = .09) at low shear rates (approximately 200 s-1) and 61.3% +/- 11% (mean +/- SEM, n = 4, P = .05) at high shear rates (approximately 850 s-1). Thrombin aptamers based on ssDNA molecules represent a new class of thrombin inhibitors with potent anticoagulant and antithrombotic properties.


Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4214-4222 ◽  
Author(s):  
HJ Weiss ◽  
B Lages ◽  
T Hoffmann ◽  
VT Turitto

Previous studies on patients with storage pool deficiency (SPD) who are specifically deficient in platelet dense granules (delta-SPD) have suggested a role for dense granule substances, in all likelihood adenosine diphosphate (ADP), in mediating thrombus formation on subendothelium at high shear rates. The role of dense granule substances in mediating platelet adhesion appears to be more complicated Previous studies in delta-SPD suggested an adhesion defect that was strongly influenced by the patient's hematocrit (Hct) value. To explore further the possibility that red blood cells (RBCs) may influence the role that platelet storage granules play in mediating adhesion at high shear rates, we have measured adhesion (and thrombus formation) throughout a preselected range of Hct values (30% to 60%) in normal subjects and in patients with delta-SPD. The present studies confirm the defect in platelet adhesion in patients with delta-SPD, most significantly at Hct values of 30% to 40%. This defect (but not that of thrombus formation) can be completely corrected by the addition of RBCs. The correction of the platelet adhesion defect by RBCs was specific for delta-SPD; it was not observed in either von Willebrand's disease or thrombasthenia. Studies performed on normal blood under conditions that could be expected to block any effect of ADP on adhesion and an analysis of the type of adhesion defect in delta-SPD suggest that ADP may be involved in the process required for platelet spreading on the subendothelium. The corrective effect of RBCs on platelet adhesion in delta-SPD appears to be chemical rather than physical in nature, possibly due to shear-induced release of RBC ADP or to other recently described properties of RBCs that enhance collagen- induced platelet interactions.


2021 ◽  
Author(s):  
Wu Han Toh ◽  
Jude C. Clapper ◽  
Cheng-Chang Hsu ◽  
Chun-Bing Chen ◽  
Hua-en Lee ◽  
...  

Among the many health benefits Chinese herbal medicine (CHM) presents, anti-aging is of special interest. Reported to possess anti-aging effects, the CHM Rhodiola rosea, known colloquially as the golden root, has been widely incorporated in various drinks, daily supplements, and even cosmetics. This study investigates the effects of commercial Rhodiola extracts on preventing UV-induced photoaging of the skin and correlates such effects with the composition of active ingredients in the extracts. To simulate the photoaging process, drug treated HaCaT cells were exposed to UVA and UVB radiation. The pharmacological anti-aging effects of Rhodiola extracts were evaluated qualitatively and quantitatively through confocal immunofluorescence images with γ-H2A.X marker and telomerase activity assay (Telo TAGGG Telomerase PCR-ELISA). Preparatory thin layer chromatography and high-performance liquid chromatography were performed to isolate and quantify active ingredients. Cultured HaCaT cells showed morphological change after exposure to both UVA (>15.0 J) and UVB (>2000 mJ). The photoaging of keratinocytes was rescued by pretreating cells with Rhodiola extracts as well as salidroside and rosavin active ingredients (P < 0.05). Rhodiola-treated cells were characterized by increased telomerase activity and fewer γ-H2A.X foci compared to that of the control. Extracts with better preventative effects contained higher salidroside and rosavin content. The findings in this study reaffirm Rhodiola's efficacy as an anti-aging remedy and provide a basis for CHM's integration into the mainstream of global healthcare.


The Lancet ◽  
1997 ◽  
Vol 349 (9051) ◽  
pp. 543-544 ◽  
Author(s):  
Shinya Goto ◽  
Hiroyuki Sakai ◽  
Yasuo Ikeda ◽  
Shunnosuke Handa

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 677-682 ◽  
Author(s):  
WX Li ◽  
AV Kaplan ◽  
GW Grant ◽  
JJ Toole ◽  
LL Leung

Abstract A novel thrombin inhibitor based on single-stranded (ss) deoxynucleotides with the sequence GGTTGGTGTGGTTGG (thrombin aptamer) has been recently discovered. In this study, we tested its efficacy in inhibiting clot-bound thrombin activity and platelet thrombus formation in an ex vivo whole artery angioplasty model. The thrombin aptamer showed a specific dose-dependent inhibition of thrombin-induced platelet aggregation (0.5 U/mL) in human platelet-rich plasma, with an IC50 of approximately 70 to 80 nmol/L. In an in vitro clot-bound thrombin assay system, heparin, used at clinically relevant concentrations of 0.2 U/mL and 0.4 U/mL, was ineffective in inhibiting clot-bound thrombin (6.5% and 34.9% inhibition at 0.2 U/mL and 0.4 U/mL, respectively). In contrast, the thrombin aptamer at an equivalent anticoagulant concentration inhibited clot-bound thrombin (79.7% inhibition). In an ex vivo whole artery angioplasty model, the thrombin aptamer markedly suppressed the generation of fibrinopeptide A (FPA), whereas heparin at 2 U/mL was ineffective. Compared with a scrambled ssDNA control, the thrombin aptamer reduced platelet deposition by 34.5% +/- 5% (mean +/- SEM, n = 4, P = .09) at low shear rates (approximately 200 s-1) and 61.3% +/- 11% (mean +/- SEM, n = 4, P = .05) at high shear rates (approximately 850 s-1). Thrombin aptamers based on ssDNA molecules represent a new class of thrombin inhibitors with potent anticoagulant and antithrombotic properties.


2019 ◽  
Vol 16 (159) ◽  
pp. 20190148 ◽  
Author(s):  
B. J. M. van Rooij ◽  
G. Závodszky ◽  
V. W. Azizi Tarksalooyeh ◽  
A. G. Hoekstra

Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based modelling in these microfluidic devices is demonstrated by comparing our results with macroscopic models, wherein blood is modelled as a continuous fluid. Hemocell, a cell-based blood flow simulation framework is used to investigate the transport physics in the microfluidic devices. The simulations show an enlarged cell-depleted layer at the site where a platelet aggregate forms in the experiments. In this enlarged cell-depleted layer, the probability to find a platelet is higher than in the rest of the microfluidic device. In addition, the shear rates are sufficiently high to allow for the von Willebrand factor to elongate in this region. We hypothesize that the enlarged cell-depleted layer combined with a sufficiently large platelet flux and sufficiently high shear rates result in an haemodynamic environment that is a preferred location for initial platelet aggregation.


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Chen Wang ◽  
Shuang Ling ◽  
Jin-Wen Xu

Stem cells (SCs) are special types of cells with the ability of self-renewal and multidirectional differentiation. As the organism ages, the ability to maintain homeostasis and regeneration deteriorates and the number and activity of stem cells decline. Theoretically, the restoration of stem cells might reverse aging. However, due to their own aging, donor-derived immune rejection, and difficulties in stem cell differentiation control, a series of problems need to be solved to realize the potential for clinical application of stem cells. Chinese herbal medicine is a nature drug library which is suitable for the long-term treatment of aging-related diseases. Modern pharmacological studies have revealed that many active ingredients of Chinese herbal medicines with the effect of promoting stem cells growth and differentiation mainly belong to “reinforcing herbs.” In recent years, exploration of natural active ingredients from Chinese herbal medicines for delaying aging, improving the stem cell microenvironment, and promoting the proliferation and differentiation of endogenous stem cells has attracted substantial attention. This article will focus on active ingredients from Chinese herbs-mediated differentiation of stem cells into particular cell type, like neural cells, endothelial cells, cardiomyocytes, and osteoblasts. We will also discuss the effects of these small molecules on Wnt, Sonic Hedgehog, Notch, eNOS-cGMP, and MAP kinase signal transduction pathways, as well as reveal the role of estrogen receptor α and PPAR γ on selectively promoting or inhibiting stem cells differentiation. This review will provide new insights into the health aging strategies of active ingredients in Chinese herbal medicine in regenerative medicine.


Sign in / Sign up

Export Citation Format

Share Document