scholarly journals Antiplatelet Activity of Acylphloroglucinol Derivatives Isolated from Dryopteris crassirhizoma

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2212 ◽  
Author(s):  
Nam-Hui Yim ◽  
Jung-Jin Lee ◽  
BoHyoung Lee ◽  
Wei Li ◽  
Jin Yeul Ma
Keyword(s):  
Platelet Aggregation ◽  
High Performance ◽  
Clinical Symptoms ◽  
Water Extract ◽  
Initial Response ◽  
Butyl Alcohol ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Antiplatelet Activity ◽  
Concentration Dependent Manner

Platelets are an important component of the initial response to vascular endothelial injury; however, platelet dysfunction induces the acute clinical symptoms of thrombotic disorders, which trigger severe cardiovascular diseases such as myocardial infarction, ischemia, and stroke. In this study, we investigated the Dryopteris crassirhizoma’s antiplatelet activity. A water extract of D. crassirhizoma (WDC) was partitioned into dichloromethane (DCM), ethyl acetate, n-butyl alcohol, and water. Among these four fractions, the DCM fraction potently inhibited the collagen-stimulated platelet aggregation in a concentration-dependent manner. From this fraction, five different acylphloroglucinol compounds and one flavonoid were isolated by activity-guided column chromatography. They were identified by comparing their mass, 1H-, and 13C-NMR spectral data with those reported in the literature. Quantifying the six compounds in WDC and its DCM fraction by high-performance liquid chromatography (HPLC) revealed that butyryl-3-methylphloroglucinol (compound 4) was the most abundant in these samples. Additionally, butyryl-3-methylphloroglucinol showed the strongest inhibitory activity in the collagen- and arachidonic acid (AA)-induced platelet aggregation, with inhibition ratios of 92.36% and 89.51% in the collagen and AA-induced platelet aggregation, respectively, without cytotoxicity. On the active concentrations, butyryl-3-methylphloroglucinol significantly suppressed the convulxin-induced platelet activation. Regarding the structure–activity relationships for the five acylphloroglucinol compounds, our results demonstrated that the functional butanonyl, methoxy, and hydroxy groups in butyryl-3-methylphloroglucinol play important roles in antiplatelet activity. The findings indicate that acylphloroglucinols, including butyryl-3-methylphloroglucinol from D. crassirhizom, possess an antiplatelet activity, supporting the use of this species for antiplatelet remedies.

Trimucytin: A Collagen-Like Aggregating Inducer Isolated from Trimeresurus mucrosquamatus Snake Venom

1993 ◽  
Vol 69 (03) ◽  
pp. 286-292 ◽  
Author(s):  
Che-Ming Teng ◽  
Feng-Nien Ko ◽  
Inn-Ho Tsai ◽  
Man-Ling Hung ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Snake Venom ◽  
Inositol Phosphate ◽  
Shape Change ◽  
Platelet Activating Factor ◽  
Atp Release ◽  
Platelet Membrane ◽  
Thromboxane B2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner

SummaryTrimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro-X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD-containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytinand collagen-induced platelet aggregation and ATP release. However, trimucytin did not replace the binding of 125I-labeled MAB1988 to platelets. Platelets pre-exposed to trimucytin were resistant to the second challenge with trimucytin itself or collagen. It is concluded that trimucytin may activate collagen receptors on platelet membrane, and cause aggregation and release mainly through phospholipase C-phosphoinositide pathway.

scholarly journals Citrus bergamiaRisso Elevates Intracellular Ca2+in Human Vascular Endothelial Cells due to Release of Ca2+from Primary Intracellular Stores

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Purum Kang ◽  
Seung Ho Han ◽  
Hea Kyung Moon ◽  
Jeong-Min Lee ◽  
Hyo-Keun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Channel Blocker ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Concentration Dependent Manner ◽  
Carbonyl Cyanide ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

The purpose of the present study is to examine the effects of essential oil ofCitrus bergamiaRisso (bergamot, BEO) on intracellular Ca2+in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+concentration[Ca2+]i. In the presence of extracellular Ca2+, BEO increased[Ca2+]i, which was partially inhibited by a nonselective Ca2+channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased[Ca2+]iin a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced[Ca2+]iincrease was partially inhibited by a Ca2+-induced Ca2+release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased[Ca2+]iin the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+uptake. In addition, store-operated Ca2+entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+release and affect promotion of Ca2+influx, likely via an SOC mechanism.

scholarly journals Antithrombotic Effect of the Ethanol Extract of Angelica gigas Nakai (AGE 232)

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 939
Author(s):  
Pia Loreto Werlinger Bravo ◽  
Hui Jin ◽  
Hyunwoo Park ◽  
Min Sang Kim ◽  
Hirofumi Matsui ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Thrombus Formation ◽  
Umbilical Vein ◽  
Ethanol Extract ◽  
Developed Countries ◽  
Severe Bleeding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Angelica Gigas ◽  
Angelica Gigas Nakai

Cardiovascular diseases, such as stroke, are the most common causes of death in developed countries. Ischemic stroke accounts for 85% of the total cases and is caused by abnormal thrombus formation in the vessels, causing deficient blood and oxygen supply to the brain. Prophylactic treatments include the prevention of thrombus formation, of which the most used is acetylsalicylic acid (ASA); however, it is associated with a high incidence of side effects. Angelica gigas Nakai (AG) is a natural herb used to improve blood circulation via anti-platelet aggregation, one of the key processes involved in thrombus formation. We examined the antithrombotic effects of AGE 232, the ethanol extract of A. gigas Nakai. AGE 232 showed a significant reduction in death or paralysis in mice caused by collagen/epinephrine-induced thromboembolism in a dose-dependent manner and inhibition of collagen-induced human platelet aggregation in a concentration-dependent manner. Additionally, AGE 232-treated mice did not show severe bleeding in the gut compared to ASA-treated mice. AGE 232 resulted in a decrease in the number of neutrophils attached to the human umbilical vein endothelial cells (HUVECs) and lower inhibition of COX-1 in response to bleeding and damage to blood vessels, a major side effect of ASA. Therefore, AGE 232 can prevent thrombus formation and stroke.

Small Molecule Constituents of Periplaneta americana and Their IL-6 Inhibitory Activities

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110331
Author(s):  
Hua-Sheng Zhang ◽  
Yong-Ming Yan ◽  
Dai-Wei Wang ◽  
Qing Lv ◽  
Yong-Xian Cheng ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Periplaneta Americana ◽  
Ethanol Extract ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Chemical Methods ◽  
Concentration Dependent Manner ◽  
Inhibitory Activities ◽  
First Time

Two new glycosides, periplanosides A (1) and B (2), 3 compounds reported from a natural source for the first time (3 − 5), and 6 known compounds 6 − 11 were isolated from the ethanol extract of Periplaneta americana (Linnaeus). Their structures, including absolute configurations, were unambiguously identified by comprehensive spectroscopic and chemical methods. Compound 3 is a racemate whose enantiomers were purified by chiral high-performance liquid chromatography . The biological evaluation results showed that compound 7 (0 − 20 μM) did not affect the viability of RAW264.7 cells and could effectively inhibit the production of interleukin-6 stimulated by lipopolysaccharide in a concentration-dependent manner, indicating the potential to develop novel agents against inflammation-related diseases.

Potential Synergism of Green Tea and Aspirin as a Possible Cause of Bleeding in a Diabetic

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4504-4504
Author(s):  
Roger C Munro ◽  
Lisa J Wakeman ◽  
Saad Al-Ismail
Keyword(s):  
Metabolic Syndrome ◽  
Platelet Aggregation ◽  
Green Tea ◽  
Causal Effect ◽  
Daily Intake ◽  
Water Extract ◽  
Serum Triglyceride ◽  
Hot Water ◽  
Diabetic Patients ◽  
Dependent Manner

Abstract A 58 year old lady with Metabolic Syndrome of 10 years duration presented with post-menopausal PV bleeding, haematuria, occasional epistaxis and ecchymoses. Prescribed medication which had remained unchanged for the preceding two years included daily doses (mgms) of Aspirin (150), Atenelol (50), Metformin (500 × 3), Bendroflumethiazide (2.5), Losartan (50) and Simvastatin (20). Intravenous urogram, cystoscopy, cytological examination of urine sediment, hysteroscopy, a cervical scan and endometrial biopsies showed neither evidence of overt pathology nor any physiological indication for the cause of haematuria or PV bleeding. Tests for urinary infection were negative. Apart from the raised blood glucose (9.1: NR 3.3 – 6.0 mmol/L), the biochemistry profile including liver enzymes, coagulation profile and blood count were normal (Platelets = 265 × 109/L). Bleeding episodes were observed after commencement of a daily intake of 7–8 cups of green tea for a period of six months. Green tea intake was self-instigated in response to reported amelioration of risk factors associated with Metabolic Syndrome (reduction in LDL cholesterol and serum triglyceride levels; elevation of protective HDL; potent antioxidant activity; ACE inhibition and promotion of glucose metabolism). Hot water extract of green tea specifically inhibits platelet adhesion and lowers sub-maximal platelet aggregation and prolongs the lag time in a dose-dependent manner. Previous fractionation studies of these hot water extracts, has revealed that the tea catechins (tannins) actively inhibit thromboxane A2 production and that ester-type catechins are more effective than free-type catechins. One of the ester-type catechins, epigallocatechin gallate (EGCG), suppresses thrombin and collagen-induced platelet aggregation completely at a concentration of 0.2 mg/ml. EGCG also inhibits aggregation by a mechanism which differs from that of aspirin by inhibiting platelet activating factor (PAF). The IC50 values of EGCG and aspirin indicate that their potencies are comparable. Bleeding symptoms ceased two weeks after the patient stopped drinking green tea. Our assumption of the causal effect of green tea on anomalous bleeding in this patient needs to be confirmed by structured platelet function tests in both aspirinised and non-aspirinised patients. Since inhibition of cyclo-oxygenase is an additional anti-thrombotic property of aspirin which differs from that of green tea, diabetic patients taking prophylactic low-dose aspirin should continue to do so and potentially beneficial ingestion of green tea should not be considered without consultation with an appropriate health professional in view of its synergistic potential on the effect of aspirin and the associated haemorrhagic risks.

scholarly journals Inhibitory Effects of Polaprezine on the Inflammatory Response toHelicobacter pylori

2002 ◽  
Vol 16 (11) ◽  
pp. 785-789 ◽  
Author(s):  
Osamu Handa ◽  
Norimasa Yoshida ◽  
Yukiko Tanaka ◽  
Miho Ueda ◽  
Takeshi Ishikawa ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Zinc Sulphate ◽  
Water Extract ◽  
Gastric Cancer Cell Line ◽  
Mucosal Inflammation ◽  
Chelate Compound ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Adhesive Interactions ◽  
H Pylori

Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, againstH pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation withH pyloriwater extract (HPE) in a dose-dependent manner from 10-7M to 10-5M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibitH pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.

scholarly journals Interaction of Rifampin and Darunavir-Ritonavir or Darunavir-Cobicistat In Vitro

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Owain Roberts ◽  
Saye Khoo ◽  
Andrew Owen ◽  
Marco Siccardi
Keyword(s):  
High Performance ◽  
Linear Regression Analysis ◽  
Intrinsic Clearance ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Content Type ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Dosing Regimens

ABSTRACT Treatment of HIV-infected patients coinfected with Mycobacterium tuberculosis is challenging due to drug-drug interactions (DDIs) between antiretrovirals (ARVs) and antituberculosis (anti-TB) drugs. The aim of this study was to quantify the effect of cobicistat (COBI) or ritonavir (RTV) in modulating DDIs between darunavir (DRV) and rifampin (RIF) in a human hepatocyte-based in vitro model. Human primary hepatocyte cultures were incubated with RIF alone or in combination with either COBI or RTV for 3 days, followed by coincubation with DRV for 1 h. The resultant DRV concentrations were quantified by high-performance liquid chromatography with UV detection, and the apparent intrinsic clearance (CLint.app.) of DRV was calculated. Both RTV and COBI lowered the RIF-induced increases in CLint.app. in a concentration-dependent manner. Linear regression analysis showed that log10 RTV and log10 COBI concentrations were associated with the percent inhibition of RIF-induced elevations in DRV CLint.app., where β was equal to −234 (95% confidence interval [CI] = −275 to −193; P < 0.0001) and −73 (95% CI = −89 to −57; P < 0.0001), respectively. RTV was more effective in lowering 10 μM RIF-induced elevations in DRV CLint.app. (half-maximal [50%] inhibitory concentration [IC50] = 0.025 μM) than COBI (IC50 = 0.223 μM). Incubation of either RTV or COBI in combination with RIF was sufficient to overcome RIF-induced elevations in DRV CLint.app., with RTV being more potent than COBI. These data provide the first in vitro experimental insight into DDIs between RIF and COBI-boosted or RTV-boosted DRV and will be useful to inform physiologically based pharmacokinetic (PBPK) models to aid in optimizing dosing regimens for the treatment of patients coinfected with HIV and M. tuberculosis.

scholarly journals Hemolytic activity and platelet aggregation inhibitory effect of vipoxin’s basic sPLA2 subunit

2013 ◽  
Vol 6 (3) ◽  
pp. 136-140 ◽  
Author(s):  
Silviya Stoykova ◽  
Yana Goranova ◽  
Ivayla Pantcheva ◽  
Vasil Atanasov ◽  
Dobri Danchev ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Platelet Aggregation ◽  
Hemolytic Activity ◽  
Blood Cells ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Erythrocyte Morphology ◽  
Dose Dependent ◽  
Vipera Ammodytes

ABSTRACT In the present study we evaluated the effect of secreted phospholipase A2 (sPLA2) (the toxic subunit of the heterodimeric neurotoxin vipoxin, isolated from the Bulgarian long-nosed viper Vipera ammodytes meridionalis) on hemolysis, erythrocyte morphology and platelet aggregation. Hemolytic activity of sPLA2 was examined in the presence of saturated (palmitic) and unsaturated (oleic) fatty acids and it was found that oleic acid increased the hemolytic activity of sPLA2 in a concentration-dependent manner, compared to the effect of palmitic acid and controls. The addition of heparin to red blood cells (RBC) suspension containing sPLA2 or mixture of sPLA2 and the corresponding fatty acid led to an inhibition of hemolytic activity. The effect of sPLA2 on RBC morphology resulted in formation of echinocytes (spherocyte subtype), suggesting that RBC could be the possible targets attacked by sPLA2. Vipoxin sPLA2 inhibited (in a dose-dependent manner) platelet aggregation when arachidonic acid and collagen were used as inducers, while in the case of ADP its inhibitory effect was inappreciable.

scholarly journals Collagenase inhibition by water-pepper (Polygonum hydropiper L.) sprout extract

2019 ◽  
Vol 8 (2) ◽  
pp. 114-119 ◽  
Author(s):  
Tomoaki Kawaguchi ◽  
Kaori Nagata
Keyword(s):  
Column Chromatography ◽  
Inhibitory Activity ◽  
High Performance ◽  
Inhibitory Effect ◽  
Skin Aging ◽  
Dependent Manner ◽  
Dermal Matrix ◽  
Polygonum Hydropiper ◽  
Concentration Dependent Manner ◽  
Hplc Fraction

Introduction: Collagenase plays an important role in the degradation of dermal matrix proteins leading to wrinkle formation. The objectives of this study were to evaluate the inhibitory effect of water-pepper (Polygonum hydropiper L.) sprout extract on the activity of collagenase and to identify the inhibitory compounds.Methods: Collagenase inhibitory activity was measured by spectrophotometric assay. Activity-guided fractionation was performed using liquid-liquid extraction of water and n-butanol and Diaion HP-20 column chromatography, followed by high-performance liquid chromatography (HPLC) fraction collection.Results: A methanolic extract of water-pepper sprout inhibited collagenase activity in a concentration-dependent manner with an IC50 value of 156.7 μg/mL. Collagenase inhibitory activity (IC50 = 23.5 μg/mL) was found in 50% methanol eluate from the HP-20 column chromatography of the n-butanol soluble fraction. The active compound (IC50 = 1.9 μg/mL) in the eluate was isolated by HPLC and identified as quercetin-3-O-galactoside (hyperoside) from comparing retention time, UV-Vis absorption, and mass spectra with those of the standard. Lineweaver-Burk plots revealed that hyperoside was an uncompetitive inhibitor against collagenase. Hyperoside was also the most abundant flavonoid present in the methanolic extract.Conclusion: These results suggest that water-pepper sprouts could be beneficial as a natural source of collagenase inhibitor which might be used for the treatment of skin aging.

scholarly journals Uridine Triphosphate Thio-analogues Inhibit Platelet P2Y12 Receptors and Aggregation

2016 ◽  
Author(s):  
Dursun Guenduez ◽  
Christian Tanislav ◽  
Daniel Sedding ◽  
Mariana Parahuleva ◽  
Sentot Santoso ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Activity ◽  
Platelet Rich Plasma ◽  
P2y12 Receptor ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Uridine Triphosphate ◽  
Ic50 Value ◽  
Adp Receptor ◽  
First Time

Platelet P2Y12 is an important ADP receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio-analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma we demonstrate that UTP inhibits P2Y12 but not P2Y1 receptors and antagonises 10 &mu;M ADP-induced platelet aggregation in a concentration-dependent manner with an IC50 value of ~250 &mu;M. An 8-fold higher platelet inhibitory activity was observed with a 2-thio analogue of UTP (2S-UTP), with an IC50 of 30 &mu;M. The 4-thio analogue (4S-UTP) with an IC50 of 7.5 &mu;M was 33-fold more effective. A 3-fold decrease in inhibitory activity, however, was observed by introducing an isobutyl group at the 4S- position. A complete loss of inhibition was observed with thio-modification of the&nbsp;&gamma; phosphate of the sugar moiety, which yields an enzymatically stable analogue. The interaction of UTP analogues with P2Y12 receptors was verified by P2Y12 receptor binding and cAMP assays. These novel data demonstrate for the first time that 2- and 4-thio analogues of UTP are potent P2Y12 receptor antagonists that may be useful for therapeutic intervention.

Sign in / Sign up

Export Citation Format

Share Document