• Archives of Pharmacal Research
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• v.14 no.4
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• pp.352-356
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• 1991

The anti-platelet activity of ilexoside D isolated from the roots of Ilex pubescens Hook. et Arn. was investigated in in vitro and ex vivo models of platelet aggregation induced by ADP, thrombin or collagen in rats. In vitro ilexoside D inhibited more effectively platelet aggregation induced by ADP and thrombin than by collagen as compared with aspirin. Ex vivo ilexoside D also inhibited platelet aggregation induced by ADP and collagen, but not by thrombin, and the inhibitory action of ilexoside D was more effective than that of aspirin. However, in vitro ilexoside D inhibited very poorly the generation of malonyldialdehyde, which is known to be concomitantly released with thromboxane $A_2$ during platelet aggregation. These results suggest that the anti-platelet activity of ilexoside D may not be responsible for prostaglandin synthesis in platelets.

• Korean Journal of Pharmacognosy
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• v.26 no.2
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• pp.139-147
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• 1995

Crinum asiaticum var. japonicum is a wild plant growing only in Jeju-island, Korea, and in Japan. The whole part of this plant has been known to have the pharmacological actions such as analgesic, anti-inflammatory, platelet-aggregation inhibitory, antitussive, and expectorant. With these assumed actions, the leaves (Crinum folium) of this plant has been used in the folk remedies for arthritis and arthralgia. There is, however, no scientific evidences for the pharmacological actions of Crinum asiaticum var. japonicum. In the present study, the analgesic, anti-inflammatory, and platelet-aggregation inhibitory actions of Crinium folium were evaluated using writhing test, tail-flick test, carrageenin antiedema test, in vitro thromboxane $B_2$ quantitation assay and in vitro platelet aggregation test. In order to obtain the partially purified fraction whose pharmacological action is excellent, the methanol extract of Crinium folium was fractionated consecutively into four biological fractions such as ether, ethyl acetate, butanol, and water fractions and their pharmacological actions of the fractions were investigated. Putting our results together, Crinium folium, especially ethyl acetate fraction was proven to have significant analgesic, anti-inflammatory and platelet-aggregation inhibitory actions by inhibition of prostanoids biosynthesis as one of its mechanism of action.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.233-236
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• 1999

In order to clarify the anti-Ohyul activity of rhubarb, we investigated the effects of water extract from rhizomes of four different rhubarb on blood platelet aggregation induced by arachidonic acid, ADP, collagen and PAF in vitro. The cultivated Korean rhubarb rhizomes (Rheum undulatum) exhibited the most potent inhibitory action on the aggregation induced by arachidonic acid and also among the four fractions, stilbene components containing part showed strong inhibitory action. These inhibitory effect may partially contributed to anti-Ohyul activity of rhubarb.

• Journal of Sasang Constitutional Medicine
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• v.10 no.2
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• pp.589-613
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• 1998

The purpose of this research was to investigate effects of Bangpoongtongsungsan water extract(BTSE) on the immune reaction, anti-allergy action and anti-inflammatory action in BALB/c mice. The administration of BTSE (500mg/kg) enhanced the cell viability of thymocytes and the population of helper T cells in splenic T-lymphocytes. BTSE suppressed the production of nitric oxide, but enhanced the phagocytic activity in peritoneal macrophages. BTSE enhanced hemagglutination titer in mice. BTSE inhibited passive cutaneous anaphylaxis induced by egg albumin in rat, the lethal anaphylaxis induced by platelet activating factor and compound 48/80 in mice, and then inhibited the degranulation of peritoneal mast cells induced by compound 48/80. BTSE did not inhibit Arthus reaction, but inhibited the delayed type hypersensitivity induced by SRBC and contact dermatitis induced by DNFB. BTSE inhibited the acute hind paw edema induced by histamine after 30 minutes, the permeability of evans blue into peritoneal cavity induced by acetic acid and the writhing syndrome induced by acetic acid. These results suggest that BTSE has an immunopotentiative action, anti-allergy action and anti-inflammatory action via the inhibition of histamine release.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.490-497
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• 2021

Background and objective: Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3, Rg6, F4 and Ro have inhibitory actions on human platelets. However, the inhibitory mechanism of ginsenoside Rk1 (G-Rk1) is still unclear thus, we initiated investigation of the anti-platelet mechanism by G-Rk1 from Panax ginseng. Methodology: Our study focused to investigate the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane B2 secretion. Thrombin-induced clot retraction was also observed in human platelets. Key Results: Collagen, thrombin, and U46619-stimulated human platelet aggregation were dose-dependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagen-stimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca²⁺ release from endoplasmic reticulum, granule release, and α_IIbβ₃ activity without any cytotoxicity. Conclusions and implications: These results indicate that G-Rk1 possess strong anti-platelet effect, proposing a new drug candidate for treatment and prevention of platelet-mediated thrombosis in cardiovascular disease.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.239-245
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• 1997

Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1391-1398
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• 2005

The anti-thrombic properties of the oriental herbal medicine Daejowhan(DJW, 大造丸) which consists of 11 kinds of herbs (indicated as ratio) of Rehmanniae Radix 24%, Hominis Placenta 5%, Testudinis Carapax 9%, Eucommiae Cortex 9%, Asparagi Radix 9%, Phellodendri Cortex 9%, Achyranthis Radix 7%, Liriopis Tuber 7%, Angelicae Sinensis Radix 7%, Ginseng Radix 5% and Schizandrae Fructus 3% were investigated. The water extracts from DJW inhibited Platelet-activating factor(PAF) induced platelet aggregation. DJW was extracted with methanol and further fractionated by ethylacetate. A 70% methanol extract showed a strong inhibition against PAF-induced aggregation in vitro and in vivo assays. The ethylacetate soluble fraction was shown to have inhibitory effect on PAF-induced platelet aggregation in vitro assay. The ethylacetate soluble fraction specially protected against the lethality of PAF, while verapamil did not afford any protection. These results indicate that the water extracts and alcoholic-fractions inhibit the action of PAF in vivo by an antagonistic effect on PAF, so that it may be useful in treating disorders caused by PAF, such as acute allergy, inflammation, asthma, gastrointestinal ulceration, toxic shock and so forth. DJW was investigated regarding its assumed anti-thrombic action on human platelets which was deduced from its ability to suppress Arachidonic acid(AA)-induced aggregation, exocytosis of ATP, and inhibition of Cyclooxygenase(COX) and Thromboxane synthase(TXS) activity. The latter two effects were estimated from the generation of Prostaglandin $E_2(PGE_2)$ and Thromboxane $A_2(TXA_2)$ respectively. Exogenously applied AA ($100{\mu}mol/{\ell}$) provoked a $89\%$ aggregation of platelets, the release of 14 pmol ATP, and the formation of either 225 pg $TXA_2$ or 45 pg $PGE_2$, each parameter being related to 106 platelets. An application of DJW 5 min before AA dose-dependently diminished aggregation, ATP-release and the synthesis of $TXA_2$ and $PGE_2$ with $IC_{50}$ values of 74, 108, 65, $72{\mu}g/m{\ell}$, respectively. The similarity of the $IC_{50}$ values suggest an inhibition of COX by DJW as primary target, thus suppressing the generation of $TXA_2$ which induces aggregation of platelets and exocytosis of ATP by its binding on $TXA_2$-receptors.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.706-713
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• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.122-127
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• 2023

Cardiovascular disease (CVD) is increasingly increasing as the main cause of death worldwide, and activation of platelet in vascular damage is one of the important causes of CVD. In recent, there is a growing interest in anti-thrombotic materials through platelet suppression, and efforts are being made to reduce side effects by using natural bioactive compounds. Known as one of the Flavonoids, hydroxygenkwanin (HGK) is a purified substance in Daphne Genkwa, which is known to have antibacterial, anti-inflammatory and anti-cancer effects, and has been reported to serve as an inhibitor of tissue factor that prevents thrombosis, but its anti-platelet effects and the action mechanisms is not known. In this study, we confirmed that the effects of HGK on the collagen-induced human platelets activation. HGK suppressed phosphorylation of PI3K/AKT and mitogen-activated protein kinases during platelet signaling, and reduced granule secretion in platelets such as ATP and serotonin. In addition, HGK inhibited the phosphorylation of cPLA₂ and strongly undermined the production of TXA₂, which is a powerful aggregation amplifier. As a result, the platelet aggregation derived by Collagen, a cohesive induced substance, was strongly suppressed by HGK to an IC₅₀ of 86.36 µM. Therefore, HGK might be worth the antithrombotic substance that inhibits the activation and aggregation of human platelets that occur through blood vessel damage.

• Journal of Sasang Constitutional Medicine
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• v.13 no.3
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• pp.75-88
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• 2001

The purpose of this research was to investigate the effects of Kwakhyangjeonggisan (KJS) on the anti-allergic action. In the present study, we examined the effect of KJS on type I and type IV allergic reaction. KJS inhibited the systemic anaphylaxis induced by compound 48/80 and platelet activating factor (PAF), and inhibited the passive cutaneous anaphylaxis (PCA) induced by anti-dinitrophenyl (DNP)-IgE and DNP-human serum albumin (HSA) in vivo. In addition, KJS dose-dependently inhibited the release of histamine from peritoneal mast cells in rat. Also, KJS inhibited the delayed type hypersensitivity (DTH) induced by SRBC and the contact dermatitis induced by dinitrofluorobenzene (DNFB). KJS inhibited the proliferation of splenocytes, the subpopulation of B220+ cells and CD4+CD8-(Th) cells in splenocytes and the production of γ-interferon in serum and splenocytes. These findings suggest that KJS prevented the type I allergy by the inhibition of histamine release from mast cells and the type IV allergy by the inhibition of γ-interferon production and B lymphocytes subpopulation. These results indicate that KJS may be useful for the prevention and treatment of type I and type IV allergy related disease.