• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.218-223
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• 2005

According to the Chinese and Korean medicinal and herbal literature, SSG(Silsosangami) is effective for the treatment of inflammation, hyperlipemia and arteriosclerosis. The pharmacological action of SSG has been limitedly studied in regard to ischemic infarction. This herbal medicine has been shown to express diverse activities such as immunomodulating, anti-infarction, anti-allergic and anti-inflammatory effects. Antisclerotic effects of SSG in experimentally induced atherosclerosis in rabbits have also been reported. However, pharmacological mechanisms of SSG on lipid metabolism and atherosclerosis formation are poorly understood. The present paper reports the effect of extracts obtained from SSG on endotoxin-induced experimental DIC in rats. Also, these were tested for their effect on endotoxin-induced blood platelet aggregation, thrombin-induced conversion of fibrinogen and fibrinolysis in vitro experiments with aspirin as a positive agent. The anti-thrombic properties of SSG were also investigated by means of analytical parameters of bood composition. The extracts of SSG and its seven herbs, except Cnidii Rhizoma and Carthami Flos, inhibited the endotoxin-induced DIC and thrombosis in rats. Also the extract inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.132-140
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• 1997

The effects of ginsenosides purified from red ginseng on platelet aggregation were investigated. Preincubation of washed platelets from rats with either ginsenoside Rg3, ginsenosides non-polar fraction (G-NPF), ginsenoside Rg1(Rg1) or ginsenosides polar fraction(G-PF) reduced the plytelet aggrelation induced by collagen in a dose-dependent manner, whereas ginsenoside Rg2 failed to inhibit the aggregation. Their IC50 values of Rg3, G-NPF, Rgl, and G-PF were 8.7$\pm$1.0, 150.3$\pm$0.1, 369.9$\pm$ 1.0, 606.211.3 $\mu\textrm{g}$/ml, respectively. Aggrelation induced by thrombin was also inhibited by Rg3 and G-NPF with IC50 being 5.2$\pm$ 1.1 and 66.5$\pm$0.8 $\mu\textrm{g}$/ml, respectively. The alterations of Intracellular Ca2+ concentration in platelets were monitored using fura-2 as a fluorescent Ca2+ indicator. Both Ca2+ release from internal stores and Ca2+ influx into cytosol were suppressed by Rg3. Rg3 also inhibited granular release of ATP and TXA2 formation induced by thrombin in a dose-dependent manner in the washed platelets. Rg3 also inhibited Aggregation and ATP release from human platelets induced by collagen to a similar extent as were observed in rat platelets. In conclusion, Rg3 is a Potent anti-aggregating component in ginsenosides and may exert its anti-aggrega1ing activity by decreasing TXAa formation and granular secretion in platelets, most likely by inhibiting Ca2+ influx and Ca2+ mobilization from intracellular stores. Thus ginseng may contribute to the prevention and treatment of thrombosis.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.421-426
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• 2015

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through $G_0/G_1$ to S phase of the cell cycle, as measured by [$^3H$]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at $G_0/G_1$ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

• International Journal of Oral Biology
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• v.34 no.1
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• pp.43-48
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• 2009

Thrombin-induced platelet microbicidal protein (tPMP) is a small cationic peptide that exerts potent in vitro microbicidal activity against a broad spectrum of human pathogens, including Staphylococcus aureus and Streptococcus rattus BHT. Earlier evidence has suggested that tPMP targets and disrupts the bacterial membrane. However, it is not yet clear whether membrane disruption itself is sufficient to kill the bacteria or whether subsequent, presumably intracellular, events are also involved in this process. In this study, we investigated the microbicidal activity of rabbit tPMP toward S. rattus BHT cells in the presence or absence of a pretreatment with antibiotics that differ in their mechanisms of action. The streptocidal effects of tPMP on control cells (no antibiotic pretreatment) were rapid and concentration-dependent. Pretreatment of S. rattus BHT cells with either penicillin or amoxicillin (inhibitors of bacterial cell wall synthesis) significantly enhanced the anti-S. rattus BHT effects of tPMP compared with the effects against the respective control cells over most tPMP concentration ranges tested. On the other hand, pretreatment of S. rattus BHT cells with tetracycline or doxycycline (30S ribosomal subunit inhibitors) significantly decreased the streptocidal effects of tPMP over a wide peptide concentration range. Furthermore, pretreatment with rifampin (an inhibitor of DNA-dependent RNA polymerase) essentially blocked the killing of S. rattus BHT by tPMP at most concentrations compared with the respective control cells. These results suggest that tPMP exerts anti-S. rattus BHT activity through mechanisms involving both the cell membrane and intracellular targets.

• Journal of Haehwa Medicine
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• v.9 no.2
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• pp.241-250
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• 2001

A study on relation of angiogenesis and blood stagnation in cancer was done, and the results were as follows. 1. Angiogenesis is a sequence of vascular proliferation and accomplished by regulation of anti-angiogenesis factor and indicating factor. These factors are secreted in the course of blood coagulation, inflammation, and regeneration. 2. Angiogenesis in cancer is a important action in growth of tumor and metastasis because it supply oxygen and nutrition. 3. The complicated processes, for example, platelet coagulation, action of coagulator factor & dissolution factor and interaction of variety factors are related to blood stasis and promoting blood circulation to remove blood stasis in oriental medicine. 4. Promoting blood circulation to remove blood stasis is expected to suppress angiogenesis, and we expect advanced study will be accomplished in future.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.113-142
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• 1999

The purpose of this research was to investigate the effect of Kamidangkwieumja(KDEJ) water extract on the allergy reaction in mice. The results were obtained as follows: 1. The passive cutaneous anaphylaxis induced by egg albumin in fat was not affected. 2. The lethal anaphylaxis induced by platelet activating factor in mice. was inhibited. 3. The degranulation of peritoneal mast cells induced by compound 48/80 was not affected. 4. The acute hind paw edema was inhibited after 2hours later when it was induced by histamine. 5. The permeability of evans blue into peritoneal cavity induced by acetic acid was not affected. 6. Arthus reaction in mice was not affected. 7. The delayed type hypersensitivity induced by SRBC was inhibited. 8. The contact dermatitis induced by DNFB was not affected. 9. The hemagglutination titer induced by SRBC was inhibited. 10. The writhing syndrome induced by acetic acid was inhibited. 11. The population of heper T cells in mice thymus was enhanced. 12. The phagocytic activity of peritoneal macrophages was enhanced. 13. The production of nitric oxide from peritoneal macrophages was not affected. These results suggest that the anti-allergy effect of KDEJ is caused by steroidlike and enhanced immune action. The steroidlike action of KDEJ correspond with steroid-applying-method that frequently used in clinic, so it is used io treatment of psoriasis. The research on anti-allergy of KDEJ might has to be continued.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.139-157
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• 2006

In the present study, I have investigated the bee venom (BV) and melittin (a major component of BV) -mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 50 ng/ml platelet derived growth factor BB (PDGF-BB)-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. I examined the effects on $NF-{\kappa}B$ activation to investigate a possible mechanism for anti-proliferative effects of BV and melittin, the PDGF-BB-induced $I{\kappa}B{\alpha}$ phosphorylation and its degradation were potently inhibited by melittin, and DNA binding activity and nuclear translocation of $NF-{\kappa}B$ p50 subunit in response to the action of PDGF-BB were potently attenuated by melittin. In further investigations, melittin markedly inhibited the PDGF-BB-induced phosphorylation of Akt but not ERK1/2, upstream signals of $NF-{\kappa}B$. Treatment of melittin also potently induced pro-apoptotic protein p53, Bax, and caspase-3 expression, but decreased anti-apoptotic protein Bcl-2 expression. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs through induction of apoptosis via suppressions of $NF-{\kappa}B$ and Akt activation, and enhancement of apoptotic signal pathway. Based on these results, BV acupuncture can be a candidate as a therapeutic method for restenosis and atherosclerosis.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.375-383
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• 2006

The anti platelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen $(10{\mu}g/mL)$, thrombin (0.05 U/mL), arachidonic acid $(100{\mu}M)$, a thromboxane (TX) $A_2$ mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin $F_2,\;1{\mu}M$) and a $Ca^{2+}$ ATPase inhibitor thapsigargin $(0.5{\mu}M)$ ($IC_{50}$ values: $13.8{\pm}1.8,\;26.3{\pm}1.2,\;8.5{\pm}0.9,\;4.3{\pm}1.7\;and\;49.8{\pm}1.4{\mu}M$, respectively). KR-32570 inhibited the collagen-induced liberation of $[^3H]$arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at $50{\mu}M$. The $TXA_2$ synthase assay showed that KR-32570 also inhibited the conversion of the substrate $PGH_2$ to $TXB_2$ at all concentrations. Furthermore, KR-32570 significantly inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at $50{\mu}M$, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen $(10{\mu}g/mL)$induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, $TXA_2$ synthase, the mobilization of cytosolic $Ca^{2+}$ and NHE-1.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1494-1504
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• 2004

The present paper reports the effects of Hwaotang an atherosclerosis using a spontaneous experimental model, We have also investigated the pharmacological effect of Hwaotang on collagen- and ADP-induced blood platelet aggregation, thrombin-induced conversion of fibrinogen and fibrinolysis in in vitro experiments, and various effects on stimuli-induced superoxide generation in human neutrophils. Hwao-tang was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. Hwao-tang also significantly inhibited fMLP-induced superoxide generation in a concentration-dependent manner, but not that induced by arachidonic acid. Hwao-tang inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. In conclusion, the protection of extracts of Hwao-tang on the ischemic infarction induced artificially might be involved to their inhibition of thrombotic action. The results also indicate that Hwao-tang exerts the effects on superoxide generation related to the inhibition of neutrophil functions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.181-185
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• 2002

The thrombosis is the category of blood stasis. Blood stasis is a pathologicial state resulting from the reverse or impeded flow of blood in the body or the stagnation of blood flow in local parts as well as abnormal blood outside of the vessles which remains in the body and fails to disperse. Hwao-tang has been reported to have a hypolipidemic effect in patients with hypercholesterolemia, and in highcholesterol-induced experimental models. The present paper reports the effects of HOT on atherosclerosis using a spontaneous experimental model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. We have also investigated the pharmacological effect of extracts obtained from HOT on collagen-and ADP-induced blood platelet aggregation, thrombin-induced conversion of fibrinogen and fibrinolysis in in vitro experiments. In conclusion, the protection of extracts of Korean herbs' HOT on the ischemic infarction induced artificially might be involved to their inhibition of thrombotic action.