• Journal of Yeungnam Medical Science
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• 제40권4호
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• pp.328-334
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• 2023

An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.

• 한국수산과학회지
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• 제26권4호
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• pp.321-329
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• 1993

수산자원의 기능특성 해명을 위한 연구의 일환으로 전통수산발효식품으로 널리 이용되고 있는 멸치젓갈에 함유되어 있는 angiotensin-I 전환효소저해물질을 추출하여 gel 여과에 의하여 분리된 획분들의 작용 및 특성에 대해서 살펴보았다. 그 결과를 요약하면 다음과 같다. 1. ACE 저해물질의 추출 조건을 검토하기 위하여 가장 높은 ACE 저해효과를 나타내는 숙성 60일차의 멸치젓갈을 ethanol 및 acetone의 농도를 각각 10, 25, 50 및 $80\%$로 하여 추출하였을 때 ethanol 농도가 $50\%$인 획분이 가장 우수한 저해효과를 나타내었다. 2. 멸치젓갈 숙성중 시료액의 $50\%$ ethanol 가용성 peptide-nitrogen 함량 및 ACE 저해효과는 아미노 질소 함량이 최고치에 달하는 숙성 60일차에 최대값을 나타내다가 그 후 다소 감소하는 경향을 나타내었다. 3. Gel 여과에 의한 멸치젓갈의 획분별 ACE 저해효과를 검토한 결과, 획분 C 및 D가 가장 높은 ACE 저해작용을 나타내어 이들을 rechromatography하여 분리한 단일 획분인 C'와 D'획분의 $IC_{50}$은 각각 97, $65{\mu}g$로 나타났다. 4. 분리한 단일 획분인 C'와 D'획분의 아미노산 조성은 다소 차이가 있었으며, C'획분은 threonine, glutamic acid 및 lysine의 함량이 많은 것으로 나타났으며, D'획분은 serine과 proline의 함량이 많은 것으로 나타났다.

• 동국한의학연구소논문집
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• 제4권
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• pp.67-80
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• 1995

This study was done in order to investigate the treatment of occidental and oriental medicine on dementia(mainly senile dementia and cerobrovascular dementia). The results were as follows ; 1. Dementia must treat a direct causes, but uncountable dementia(senile dementia) and cerobrovascular dementia can't treat at present. 2. Sciopsychological treatment in very important in dementia patient ; maintance of appropriate stimulation, psychological rest, physical examination, dietary cure and safety device is needed. On secondary mental disorder, antipsychotics, anxiolytics and antidepressants have to prescribe properly. 3. Treatments of Senile dementia(uncountable cerebral degenerative disease) proscribed hydergine which is peripheral vasodilator and physostigmine which increase cholinergic activity of brain, but this have slight effect on some patients. On treatments of cerobrovascular dementia, the medication that improved the cell metabolism and circulation of brain, this improved only a subjective symptom, but isn't foundamental treatment. 4. A tonic medicine is used basically, the methods are as follows. 1) Kenwihwadam(健胃火痰)-Sesimtang(洗心湯) 2) Bosiniksu(補腎益髓)-Hwansodan(還少丹) 3) Bosimiksin(補心益腎)-Gyuibitang(歸脾湯), Singyuo(神交湯) 4) Boheoansin(補虛安神)-Cilbokem(七福飮), sanggitang(生氣湯) 5) geoeohwalhyel(祛瘀活血)-tonggyuhwalhyeltang(通竅活血湯), 5. Acupuncture therapy on dementia used follow acupuncture point ; Yamen(啞門 GVl5), Laokung(勞宮 HC8), Tsusanli(足三里 ST36), Shenshu(腎兪 BL23), Tachui(大椎 GVl4), Chiuwei(鳩尾 CVl5), Sanyinchiao(三陰交 SP6), Yungchuan(涌泉 KI1), Shipsun(十宣), Shousanli(手三里 LI10), Taichong(太衝 LV3) In moxibustion therapy, Dachui(大椎 GVl4) point is used.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.225-231
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• 2004

This study was designed to investigate the effect of Trolox, a hydrophilic analogue of vitamin E, on the alteration of vasoregulatory gene expression during hepatic ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia in vivo. The rats were treated intravenously with Trolox (2.5 mg/kg) or the vehicle as a control 5 min before reperfusion. Liver samples were obtained 5 h after reperfusion for a RT-PCR analysis on the mRNA for the genes of interest. These mRNA peptides are endothelin-1 (ET -1), potent vasoconstrictor peptide, its receptor $ET_A$ and $ET_B$, vasodilator endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and cyclooxygenase-2 (COX-2). It was seen that serum alanine aminotransferase and lipid peroxi-dation levels were markedly increased after I/R and Trolox significantly suppressed this increase. In contrast, the glutathione concentration decreased in the I/R group, and this decrease was inhibited by Trolox. ET-1 mRNA expression was increased by I/R, an increase which was prevented by Trolox. The mRNA levels for $ET_A$ receptor was significantly decreased, whereas ET$_{B}$ receptor transcript increased in the I/R group. The increase in $ET_A$ was prevented by Trolox. The mRNA levels for iNOS and HO-1 significantly increased in the I/R group and Trolox attenuated this increase. There were no significant differences in eNOS mRNA expression among any of the experimental groups. The mRNA levels for COX-2 and TNF-$\alpha$ significantly increased in I/R group and Trolox also attenuated this increase. Our findings suggest that I/R induces an imbalanced hepatic vasoregulatory gene expression and Trolox ameliorates this change through its free radical scavenging activity.y.

• Journal of Applied Biological Chemistry
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• 제62권1호
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• pp.93-100
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• 2019

The root of Panax ginseng is used in ethnomedicine throughout eastern Asia and various recent studies have proved that Panax ginseng has inhibitory effects on cardiovascular disease. Each factor causing cardiovascular disease is known to have a very complex process which is achieved by a diverse number of mechanisms. Among these factors, platelets are the most important because they directly participate in thrombogenesis. Therefore, inhibiting the activity of platelets is an essential element for prevention of cardiovascular diseases. Our previous study showed the antiplatelet effects of Korean red ginseng extract and two of its components, ginsenoside Rg3 and ginsenoside Ro. However, the inhibitory mechanism of other ginsenosides remains unclear. Therefore, we investigated the inhibitory mechanism of ginsenoside F4 (G-F4) from Korean red ginseng on the regulation of signaling molecules involved in human platelet aggregation. With the use of G-F4, collagen-induced human platelet aggregation was inhibited in a dose-dependent manner, and it suppressed collagen-induced elevation of $[Ca^{2+}]_i$ mobilization through elevated phosphorylation of inositol 1, 4, 5-triphosphate receptor I ($Ser^{1756}$). In addition, G-F4 inhibited fibrinogen binding to ${\alpha}IIb/{\beta}_3$ during collagen-induced human platelet aggregation. Thus, in the present study, G-F4 showed an inhibitory effect on human platelet activation, suggesting its potential use as a new natural medicine for preventing platelet-mediated cardiovascular diseases.

• Journal of Ginseng Research
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• 제47권6호
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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.

• The Korean Journal of Physiology
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• 제18권1호
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• pp.19-35
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• 1984

Since the first report of Drury and $Szent-Gy{\ddot{o}}rgyi$ in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 $M{\Omega}$. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of $3%\;CO_2-97%\;O_2$ at $35^{\circ}C$. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of $10^{-5}M$ and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of $Ca^{+2}$. Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM $Ca^{+2}$ decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra $Ca^{+2}$ was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at $35^{\circ}C$(mean{\pm}SEM, n=16) was $154{\pm}3.3\;beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), $-73{\pm}1.7\;mV: overshoot(OS), $9{\pm}1.4\;mV: slope of pacemaker potential(SPP), $94{\pm}3.0\;mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}M$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra $Ca^{2+}$ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate $Ca^{2+}$ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing $Ca^{2+}-permeability$ of nodal and atrial cell membranes.

• Journal of Yeungnam Medical Science
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• 제16권2호
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• pp.181-192
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• 1999

만성 문맥압 항진증에서 관찰되는 과혈류 순환과 말초혈관 이완에 대한 산화질소의 역할을 규명하기 위해 본 연구를 시행하였다. 실험동물은 수컷 흰쥐를 이용하여 문맥을 부분결찰하여 문맥 고혈압을 유발시킨 군과 겉보기 수술만을 시행한 대조군으로 구분하고 문맥 고혈압군은 문맥 부분 결찰후 부터 혈역학 측정 전까지 식수를 경구 투여한 식수 투여군과 산화질소 억제제인 $N^{\omega}$-Nitro-L-Arginine(1mg/kg/day)를 경구 투여한 NNA 투여군으로 나누었다. 혈역학적 측정은 수술 2주 후에 시행하였고 $^{51}Cr$과 $^{57}Co$-labeled microspheres를 이용하여 심박출량, 조직 혈류량, 문맥-전신 단락률, 문맥압, 말초혈관 저항 내장혈관 저항 등을 측정하였다. 평균 동맥압은 대조군 $129.3{\pm}9.6mmHg$, 식수 투여군은 $111.3{\pm}5.5mmHg$로 대조군에 비해 유의하게 감소되어 있었고, NNA 투여군은 $128.7{\pm}19.8mmHg$로 식수 투여군에 비해 증가되어 있었다. 심박출량은 대조군의 $105.2{\pm}6.5ml/min$에 비해 식수 투여군에서 $144.2{\pm}17.9ml/min$로 증가되었으며, NNA 투여군은 $89.9{\pm}14.4ml/min$로 식수 투여군에 비해 감소되어 있었다. 전말초 저항은 식수 투여군에서 $6.0{\pm}0.9dyne/sec/cm^5{\times}10^5$로 대조군의 $9.5{\pm}0.8dyne/sec/cm^5{\times}10^5$에 비해 감소되었고, NNA 투여군은 $11.2{\pm}2.1dyne/sec/cm^5{\times}10^5$로 식수 투여군에 비해 증가되어 있었다. 문맥으로 유입되는 혈류량은 대조군 $16.61{\pm}5.03ml/min$, 식수 투여군은 $29.66{\pm}4.27ml/min$로 식수 투여군에서 유의한 증가가 있었으며, NNA 투여군은 $11.43{\pm}2.24ml/min$로 식수 투여군에 비해 감소되어 있었다. 내장혈관 저항은 식수 투여군에서 $2.59{\pm}0.44dyne/sec/cm^5{\times}10^5$로 대조군의 $6.61{\pm}3.08$dyne/sec/$cm^5{\times}10^5$에 비해 감소되었으며, NNA 투여군은 $8.09{\pm}2.04$dyne/sec/$cm^5{\times}10^5$로 식수 투여군에 비해 증가되어 있었다. 문맥-전선 단락율은 대조군의 $1.35{\pm}0.42%$ 에 비해 식수 투여군은 $95.42{\pm}2.73%$로 증가되었으며, NNA 투여군은 $73.36{\pm}17.67%$로 식수 투여군보다 감소되어 있었다. 문맥압은 대조군 $7.94{\pm}1.29mmHg$, 식수 투여군 $17.16{\pm}3.17mmHg$, NNA 투여군은 $16.67{\pm}2.24mmHg$로 대조군에 비해 식수 투여군과 NNA 투여군에서 증가되었으나, 양군 사이에 유의한 차이는 없었다. 문맥 저항은 NNA 투여군에서 $12.23{\pm}3.93dyne/sec/cm^5{\times}10^5$로 식수 투여군의 $4.74{\pm}1.20yne/sec/cm^5{\times}10^5$에 비해 증가되었다. 결론적으로 문맥의 부분결찰로 유도된 만성 문맥압 항진 쥐에서 산화질소 합성 억제제인 NNA를 투여할 경우 문맥압의 변화 없이 동맥압의 증가, 심박출량의 감소, 내장 및 전신 혈관 저항의 증가 등이 유발되었다. 이상의 결과를 고려해 볼 때 만성 문맥압 항진증시 관찰되는 과혈류 순환의 형성에 산화질소가 중요한 역할을 하는 것으로 생각된다.

• 한국식품과학회지
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• 제26권3호
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• pp.213-220
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• 1994

본 연구는 고혈압을 비롯한 순환기 질환의 예방이나 치료의 목적을 위해 민간요법으로 전수되어 사용되고 있는 천마의 효능에 대한 사실성을 확인하고, 나아가서는 이러한 효능에 대한 천마의 작용기전을 유추하려고 하였다. 현재까지 천마 extracts에 대한 유효성분의 분석이 이루어져 있지 않기 때문에, 본 연구는 SD 실험쥐와 선천성 고혈압의 소질을 지닌 SHR 실험쥐를 이용하여 천마의 water-extracts나 ethanol-extracts의 심장 및 관상 순환기능에 대한 약리적인 효능을 과학적으로 구체적인 실험방법을 통해서 조사하였다. 천마 extracts는 추출과정에 사용된 용매, 추출기간 및 실험쥐 model에 따라 관상 순환기능에 대한 작용효과가 상반된 현상으로 나타났다. 물이나 50% ethanol에 16시간 추출된 extracts는 사용된 농도에서 SD 실험쥐의 관상 혈관저항을 저하시켜 혈관확장의 효과를 가져왔지만, SHR 실험쥐에서는 ethanol에 추출된 extracts는 사용된 농도에서 심장기능 그 자체에 유의적인 독성효과를 주지 않는다는 것을 말해준다. 본 연구결과는 천마의 water-extracts에 의해서 나타난 혈관확장작용이 일반적으로 국소적인 혈관확장에 관여한다는 lactate 생성의 증가에 기인하는 것보다는 오히려 extracts에 의한 대사적 acidosis 현상에 기인한다는 사실을 제시하고 있다. 본 연구에서 천마의 수용성 extracts가 혈관확장작용 또는 혈압강하작용을 나타낸다는 사실이 제시된 것은 심장이나 순환기 질환을 예방하고 치료하기 위한 천마의 임상적인 활용측면에서 매우 중요한 성과이다. 그러나, 천마의 순환기능에 대한 약리적 효능을 나타내는 성분추출은 조사되어야 할 과제로 아직 남아 있다. 또한, 천마를 한방에서 약재로써 이용되는 반면에 천마를 식이로 이용하기 위해서 식이성 천마에 대한 효능을 연구해야 할 필요가 있다. 이러한 연구결과로써, 천마는 혈관순환기질환의 예방이나 치료에 이용되는 생약으로써 활용될 뿐만 아니라 안전성을 가진 건강식품으로 개발되어 국민보건 향상에 이바지하리라 기대된다.