• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.463-468
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• 2013

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated $K^+$ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane $A_2$ ($TXA_2$) and hypoxia-activated nonselective cation channel ($I_{NSC}$) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and $TXA_2$-activated $I_{NSC}$ was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased $I_{NSC}$ might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.374-379
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• 2018

In this study, we investigated the effects of pelargonidin, an anthocyanidin found in many fruits and vegetables, on endothelium-independent vascular contractility to determine the underlying mechanism of relaxation. Isometric contractions of denuded aortic muscles from male rats were recorded, and the data were combined with those obtained in western blot analysis. Pelargonidin significantly inhibited fluoride-, thromboxane A2-, and phorbol ester-induced vascular contractions, regardless of the presence or absence of endothelium, suggesting a direct effect of the compound on vascular smooth muscles via a different pathway. Pelargonidin significantly inhibited the fluoride-dependent increase in the level of myosin phosphatase target subunit 1 (MYPT1) phosphorylation at Thr-855 and the phorbol 12,13-dibutyrate-dependent increase in the level of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at Thr202/Tyr204, suggesting the inhibition of Rho-kinase and mitogen-activated protein kinase kinase (MEK) activities and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxation effect of pelargonidin on agonist-dependent vascular contractions includes inhibition of Rho-kinase and MEK activities, independent of the endothelial function.

• Archives of Plastic Surgery
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• v.32 no.4
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• pp.408-415
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• 2005

Following a transverse rectus abdominis musculocutaneous(TRAM) flap breast reconstruction, denervated state of the flap causes the flap skin prone to thermal injury, calling for special attention. During the last 5 years, 69 breast reconstruction with 72 free TRAM flaps, were performed. Four out of thesse 69 patients sustained burn injury. Heat sources were a warm bag(n=2), heating pad(n=1) and warming light (n=1). The thermal injuries occured from 2 days to 3 months following the reconstruction. Three patients healed with conservative treatment, but one patient required debridement and skin graft. Initially 3 out of 4 patients with the burn had shown superficial 2nd degree burn with small blebs or bullae. However all 4 patients healed with scars. Mechanism of burn injuries of the denervated flap are known to be resulting from; 1) loss of behavioral protection due to denervation of flap with flap elevation and transfer, 2) loss of autonomic thermoregulatory control with heat dissipation on skin flap vasculature contributing to susceptibility of burn injury. 3) changes of immunologic and normal inflammatory response increasing thromboxane, and a fall in substance P & NGF (nerve growth factor). Including the abdominal flap donor site, sensory recovery of the reconstructed breast varies individually from 6 month even to 5 years postoperatively. During this period, wound healing is delayed, resulting in easier scarring compared to that observed in the sensate skin. Patients should be carefully informed and warned of possible burn injuries and taught to avoid exposure to heat source at least until 3 years postoperatively.

• Archives of Plastic Surgery
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• v.32 no.4
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• pp.403-407
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• 2005

Following a transverse rectus abdominis musculocutaneous(TRAM) flap breast reconstruction, denervated state of the flap causes the flap skin prone to thermal injury, calling for special attention. During the last 5 years, 69 breast reconstruction with 72 free TRAM flaps, were performed. Four out of thesse 69 patients sustained burn injury. Heat sources were a warm bag(n=2), heating pad(n=1) and warming light (n=1). The thermal injuries occured from 2 days to 3 months following the reconstruction. Three patients healed with conservative treatment, but one patient required debridement and skin graft. Initially 3 out of 4 patients with the burn had shown superficial 2nd degree burn with small blebs or bullae. However all 4 patients healed with scars. Mechanism of burn injuries of the denervated flap are known to be resulting from; 1) loss of behavioral protection due to denervation of flap with flap elevation and transfer, 2) loss of autonomic thermoregulatory control with heat dissipation on skin flap vasculature contributing to susceptibility of burn injury. 3) changes of immunologic and normal inflammatory response increasing thromboxane, and a fall in substance P & NGF (nerve growth factor). Including the abdominal flap donor site, sensory recovery of the reconstructed breast varies individually from 6 month even to 5 years postoperatively. During this period, wound healing is delayed, resulting in easier scarring compared to that observed in the sensate skin. Patients should be carefully informed and warned of possible burn injuries and taught to avoid exposure to heat source at least until 3 years postoperatively.

• Preventive Nutrition and Food Science
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• v.18 no.3
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• pp.181-187
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• 2013

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 ($TXA_2$) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and $TXA_2$, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.139-145
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• 2018

The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane $A_{2-}$, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle. Hypothermia significantly inhibited the fluoride-induced increase in pMYPT1 level and phorbol ester-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxing effect of moderate hypothermia on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activities.

• 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 Nutrition and Health
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• v.35 no.5
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• pp.505-511
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• 2002

The study was designed to compare the anti-carcinogenic effect of different level of conjugated linoleic acid (CLA) in 1,2-dimethylhydrazine (DMH)-treated rats by determining biomarkers (apoptosis, cell proliferation, eicosanoids, 1,2-diacylglycerol) and phospholipid fatty acid profile in colonic mucosa. Eighty male Sprague Dawley rats weighing 180-220g were randomly divided into 4 groups depending on the content of CLA, i.e. 0.0% CLA, 0.5% CLA, 1.0% CLA, 1.5% CLA. The experimental diet contained protein 21.6%, carbohydrate 54.6%, and fat 14.5% including CLA mixture at different level by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total amount of 180 mg/kg body weight. Regardless of the amount of CLA supplemented to diet, CLA significantly increased the apoptotic index but did not have significant effect on cell proliferation in colonic mucosa. CLA was undetected in colonic mucosal phospholipid of rats fed the 0% CLA diet and increased to 5.9mg/g phospholipid in rats fed the 0.5% diet. The apoptotic index was increased by 251% and the 1,2-DAG content was decreased by 57% in rats fed 0.5% CLA. No further changes in these variables were observed when CLA in the diet was raised to 1.0% or 1.5%. However, dietary CLA decreased mucosal levels of prostaglandin (PG)E$_2$, thromboxane (TX)B$_2$, and arachidonic acid in dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanism probably involving increased apoptosis.

• 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 the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.418-427
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• 2003

Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA, C18:2 $\omega$6), which is found abundantly in dairy products and meats. This study was peformed to investigate the anticarcinogenic effect of CLA in MCF-7 breast cancer cells. MCF-7 cell were treated with LA and CLA at the various concentrations of 15, 30, 60, 120 UM each. After incubation for 48 and 72 hours, cell proliferation, fatty acids incorporation into cell, peroxidation and activities of antioxidant enzymes were measured. Postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) were measured for the eicosanoids metabolism. There was no cell growth differences in both of LA and CLA treated MCF-7 cells at 48 hr incubation. Compared to LA, cell growth was decreased by CLA treatment according to increasing concentration at longer incubation times, respectively (p<0.05). Both of LA and CLA was incorporated into the cellular lipids 22~54% higher than in control but LA incorporation was not so linear as CLA according to concentration. Arachidonic acid (C20:4, $\omega$6) was synthesized after treatment of LA but did not in CLA, respectively. The lipid peroxide concentration in LA 120 $\mu$M group increased as 1.7 times as that in CLA 120 $\mu$M treated. The activities of antioxidant enzymes such as glutathione peroxidase and glutathione reductase were increased by the supplementation with CLA 120 $\mu$M at 72 hr incubation (p<0.001) compared to LA, otherwise activity of superoxide dismutase was not different in both. PGE$_2$ and TXA$_2$ levels were lower in condition of CLA treatments according to lower levels of arachidonic acids than those in LA treated group, respectively. Overall, the dietary CLA might change the MCF-7 cell growth by the changes of cell composition, production of lipid peroxide, activities of antioxidant enzymes and eicosanoid synthesis compared to dietary LA.