Ginsenoside와 심혈관에 관한 연구

현대pharmacological studies have confirmed that ginsenosides (GS) are the main active substances in ginseng. To date, more than 30 types of ginsenosides have been isolated from ginseng [1]. The total saponin is called ginsenoside R x, and each component is named R o, R a, R b1, R b2, R b3, R c, R d, R e, R f, Rg1, Rg2, Rg3, R h1, R h2, and R h3 in ascending order of the R f value from a thin-layer silica gel chromatogram. However, in recent years, most research on ginseng saponins has focused on R b1, R e, Rg1, R h2, etc. Ginseng saponins can be divided according to their chemical properties into: ginsenoside diol type (type A), including R b1, R b2, RC, R d, R h2, etc.; ginsenoside triol type (type B), including R e, R f, Rg1, Rg2, R hr, etc.; oleanolic acid type (type C) such as R o. Modern research has shown that ginsenosides have clinical significance for various diseases of the cardiovascular system, such as ischemic heart disease, arrhythmia, and heart failure [2]. The following is a summary of recent research on the pharmacological effects of ginsenosides on the cardiovascular system.

1. myocardial function에 미치는 영향

Tian Jianming 등 3)은 심근세포의 체외 배양법을 이용하여 저산소 및 글루코즈가 부족한 심근세포의 모델을 준비하였으며, ginsenoside Rg2가 저산소 및 글루코즈가 부족한 심근세포의 박동 진폭과 생존율을 유의하게 증가시킨다는 것을 발견하였다.또한 실험에서는 Rg2가 저산소 및 글루코스가 결핍된 심근세포에서 유리 Ca2+의 농도를 현저히 감소시키는 반면, KC l에 의해 유도된 심근세포로부터 Ca2+의 방출에는 큰 영향을 미치지 않는 것으로 관찰되었으며, 고농도에서는 CaC l2에 의한 세포 밖 Ca2+의 유입에 약한 억제 효과를 보인 반면, 저농도에서는 큰 영향을 미치지 않는 것으로 관찰되었다 [4].

Wang Tianxiao et al. [5] established a pressure overload ventricular remodeling model by ligating the abdominal aorta of rats to study the effect of ginsenoside Rb압력 과부하 심근비대가 있는 쥐에서 심실 리모델링 (ventricular remodeling in rats with pressure overload myocardial hypertrophy and its mechanism of action)ginsenoside Rb 가 쥐에서 심실 개조에 대한 보호 효과가 있다는 것이 밝혀졌는데, 이는 심실 개조가 있는 쥐에서 좌심실 수축기 및 확장기 기능을 개선하고, 항산화 효소 활성을 향상시키며, 활성산소와 혈관 수축 물질로 인한 심근 손상을 감소시키고, PGI2와 TXA2 사이의 불균형을 교정시키는 기작과 관련이 있을 것으로 보인다.

또한 수다원 등은 미국 인삼 잎에서 추출한 protopanaxadiol 군 사포닌 (PQDS)을 연구하여 PQDS 가 쥐에서 심근경색 후 심실 remodeling을 효과적으로 예방하고, 좌심실 내압의 최대 증가 및 감소 속도를 유의하게 증가시키며, 좌심실 용적, 좌심실 장축 길이, 좌심실 단축 길이,좌심실 절대체중과 좌심실 상대체중.또한 PQDS는 혈청 지질 과산화물과 심근 안지오텐신 II 및 아드레날린의 수치를 현저히 감소시키고 superoxide dismutase, catalase 및 glutathione peroxidase를 증가시킬 수 있습니다.이는 심장 내 안지오텐신 II의 국소적 생성을 억제하고 교감신경 말단으로부터 카테콜아민의 분비를 억제하는 것과 관련이 있을 것으로 추측되며, 심장 근육의 항산화 능력을 향상시킨다.

In addition, studies on ginseng fruit saponins (GFS) have shown that GFS can improve the systolic and diastolic functions of the heart muscle, relieve pump failure after myocardial infarction, and reduce myocardial oxygen consumption, which is beneficial to increasing myocardial blood supply.

심장성 쇼크에 대한 효과 2

pentobarbital sodium을 사용하여 심장성 쇼크와 심부전의 개 모델을 만들었습니다.진세노사이드가 혈압 (BP), 좌심실수축기압 (LVSP), 좌심실압상승률 (LVdp/dtmax), 심박수 (HR) 및 심박출량 (CO)에 미치는 영향을 관찰하였다.그 결과 인삼총사포닌 10 mg/kg과 20 mg/kg, 정맥주사 후 LVdp/dtmax, LVSP, BP, CO 모두 증가하였고, 좌심실 말단확장압 (LVEDP)은 감소하였으며, HR은 느려졌다.Lv Wenwei 등 8은 개 관상동맥의 전방 하강 지부를 결박하여 심장성 쇼크의 개 모델을 준비하였고, 각각 Rg20.5, 1, 2 mg/kg을 정맥 주사하였다.

They found that ginsenoside Rg2 can significantly increase the mean arterial pressure (MBP), left ventricular end-diastolic pressure and maximum change rate (±dp/dtmax), cardiac output; significantly reduced total peripheral resistance, elevated ST segment of the heart surface electrocardiogram; reduced the scope of myocardial infarction; reduced serum creatine kinase (CPK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activity; increased arterial and venous oxygen content, and reduce myocardial oxygen consumption index and myocardial oxygen uptake rate. It can reduce the damage to myocardial cells and their mitochondria, and has a significant protective effect on ischemic myocardium in dogs with cardiogenic shock. Later, by studying the effect of ginsenoside diol-saponin (PDS) on acute cardiogenic shock [9-10], it was found that PDS can significantly increase MBP and dp/dtmax in shocked dogs; significantly reduced the concentrations of serum inflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-a, and reduced myocardial ischemia and the extent of ischemia, shrinking the area of myocardial infarction, lowering whole blood viscosity and hematocrit, and protecting dogs with acute cardiogenic shock.

심근허혈-재관류에 미치는 효과 3

티안장밍 (Tian Jianming) 등 11명은 쥐의 관상동맥의 전방 하강 분지를 결박했고, 결박된 3시간 후에 결박된 곳을 느슨하게 해 20분 동안 혈류를 회복시킨 뒤 심장을 빠르게 제거했다.apoptosis 가 검출되었으며, Rg 21.0 및 2.0 mg/kg의 사전 투여시 허혈에 의한 apoptosis를 감소시킬 수 있고, 허혈에 의한 DNA 단편화 밴드를 현저히 감소시킬 수 있음을 시험결과 알 수 있었다.인삼 saponin R e는 pro-apoptotic 유전자인 Bax의 발현을 억제하고 Bcl-2/Bax 비율을 증가시킴으로써 심근사멸을 억제할 수 있다.

성체 잡종견은 대동맥 폐쇄 1시간 전과 재관류 직후 총 ginsenosides (12.5 mg/kg) 가 포함된 생리식염수를 2회 정맥 주입하였다.혈역학적 변수, 세포내 유칼슘 농도, 심근세포의 미토콘드리아 인지질 함량, 미토콘드리아 칼슘 펌프 활성도, 심근 조직화학을 normothermic 체외순환을 통해 측정하였다.재관류 30분, 60분에 ginsenosides 가 재관류 기간 동안 수축기 및 확장기 기능을 유의하게 향상시키고, 심근세포 내 유리 칼슘의 농도를 유의하게 감소시키며, 미토콘드리아 인지질의 함량과 미토콘드리아 칼슘 펌프의 활성을 증가시키고, 부정맥 발생을 유의하게 감소시키는 것으로 나타났다.

Myocardial histochemical examination showed that ginsenoside can maintain the myocardial tissue structure basically normal after ischemia-reperfusion. The mechanism of ginsenoside against myocardial ischemia-reperfusion injury is mainly to protect the activity of the mitochondrial calcium pump in cardiomyocytes, reduces the degradation of mitochondrial phospholipids, protects the integrity of the membrane system; and reduces the concentration of intracellular free calcium, prevents calcium overload in cardiomyocytes, and avoids myocardial reperfusion injury.

Qu Shaochun 등 [12]은 관상동맥의 전방 하강 분지를 쥐에서 30분 동안 결박한 후 24시간 동안 재관류하는 방법으로 심근 허혈-재관류 손상의 실험 모델을 준비하였다.Ginseng Rb group saponins (G-Rb) were given to rats at doses of 25, 50 and 100 mg/kg·d-1 by continuous gavage for 7 days. it was found that G-Rb has a significant protective effect on experimental myocardial ischemia-reperfusion injury in rats, which may be related to its mechanism of enhancing the activity of antioxidant enzymes, reducing oxidative damage to the heart muscle by free radicals, correcting the imbalance between PGI2 and TXA2, and inhibiting platelet aggregation activity.

Song Qing et al. [13] studied the protective effect of ginsenoside saponin (GSLS) preconditioning on myocardial ischemia-reperfusion injury (I-R) in spontaneously hypertensive rats (SHR) and its possible mechanisms. SHR was given GSLS 50 and 100 mg/kg once/d by gavage for 3 weeks before I-R modeling, and rat blood pressure, cardiac function and cardiac hemodynamic indicators were measured during ischemia for 40 min and reperfusion for 30 min. biochemical methods were used to determine myocardial ATPase, lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) and NO content, and cadmium hemoglobin saturation method was used to determine the content of metallothionein (MT) in the heart and liver, and immunohistochemical methods were used to determine the expression of heat shock protein 70 (HSP70). It was found that the GSLS 50 and 100 m g/kg pre-adaptation groups significantly improved the heart rate, peak left ventricular pressure, and ±dp/dtmax of the I-R injured SHR, significantly increased myocardial ATPase activity, reduced LDH leakage, increased myocardial SOD activity, increased NO content, decreased MDA content, increased myocardial and liver MT content, and increased the percentage of positive myocardial HSP70 cells. Its mechanism of action is related to improving the contractile function of the SHR heart, improving myocardial metabolism, enhancing antioxidant activity and inducing the release of endogenous myocardial protective substances.

심근경색에 미치는 효과 4

Lu Feng et al. [14] established an acute myocardial infarction model by ligating the left anterior descending branch of the coronary artery (LAD) in dogs. The study found that ginsenoside Rb1 has a significant protective effect on acute ischemic myocardium, and the mechanism of action may be related to its correction of metabolic disorders of free fatty acids (FFAs) during myocardial ischemia and its ability to scavenge free radicals to prevent lipid peroxidation, as well as enhancing the activity of antioxidant enzymes in the body. American ginseng leaf 20S-protopanaxadiol group saponin (PQDS) also has a protective effect on acute myocardial ischemia, and the mechanism may be related to its inhibition of sympathetic-adrenal medulla hyperactivity, reduction of catecholamine (CA) hypersecretion and inhibition of RAS activation, reduction of angiotensin (Ang) production, and breaking the vicious cycle caused by the mutual promotion of CA and RAS. Ginseng fruit saponin (GFS) also has a protective effect on acute myocardial ischemia induced by isoproterenol and pituitary adenylate cyclase-activating polypeptide. Ginseng saponin Rg2 has a protective effect on chemical myocardial ischemia in rats prepared with isoproterenol, sodium nitrite and pituitary adenylate cyclase-activating polypeptide.

류지 등 [15]은 개에서 청년을 결찰하여 급성 심근경색 모델을 확립했다.후 모델링,ginsenoside PDS was infused into the femoral vein at two doses of 12.5 and 25 mg/kg. It was found that both doses could significantly reduce the myocardial infarction rate. From the ultrastructural observation, the nuclear membrane of the cardiomyocytes in the low-dose group of PDS was intact, the nucleus was irregular, the surrounding sarcomere structure is clear, the mitochondria are arranged in a longitudinal direction between the myofilaments, and small vesicles can be seen in the cytoplasm; in the PDS high-dose group, the structure of the myocardial cell membrane is intact, the structure of the dark and light bands of the sarcomere is clear, the arrangement of the myofilaments is relatively neat, the mitochondria between the myofilaments are relatively large, arranged in a longitudinal direction, and the cristae are clearly visible. In both dose groups, the levels of NO and nitric oxide synthase (NOS) in the serum were significantly increased 4 hours after administration.

Jin Yan et al. [16,17] studied the effects of ginsenoside Rg1 on neovascularization after acute myocardial infarction and its mechanism of action. An acute myocardial infarction model was established in Wistar rats, and the rats were given ginsenoside Rg1 low-dose (1 mg/kg) and high-dose (5 mg/kg) treatment groups by intraperitoneal injection. RT-PCR was used to detect the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) mRNA in myocardial tissue in the infarct zone. The results showed that the treatment group had significantly lower myocardial enzymes and myocardial infarction areas, and the number of blood vessels in the infarct area increased steadily and continuously, which was significantly higher in the treatment group than in the control group. After myocardial infarction, the expression of VEGF and HIF-1α mRNA increased with the prolongation of ischemia (3, 7 and 10 d groups), and the treatment group showed a significant increase. At 14 d, the increase in VEGF stopped or decreased, while HIF-1α continued to rise; the VEGF expression in the sham operation group was significantly lower than that in each of the operation groups. Studies have shown that the acute phase of severe ischemia can stimulate myocardial tissue to produce large amounts of VEGF and HIF-1α, thereby protecting ischemic myocardium. Ginseng saponin Rg1 can stimulate angiogenesis in the myocardial infarction area and the establishment of collateral circulation by increasing the expression of the two.

요약하면,pharmacological research on ginsenosides in cardiovascular medicine has already begun and continues to deepen. While continuously extracting and modifying to obtain more ginsenoside-type active substances, research on the pharmacological activity of ginsenosides is expected to identify compounds with stronger activity and specificity, accelerating the industrial production and clinical application of ginsenoside ingredients. Theoretical and systematic summaries of current research results on ginsenosides are of profound research significance.

참조

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[3] Tian Jianming.ginsenoside Rg-2가 심근세포의 진폭과 생존율에 미치는 영향.중국신약학회지, 2003, 12 (11):912

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[5] 왕띠아오, 위샤오펑, 취샤오춘.ginsenoside Rb 가 압력부하 심근비대증을 가진 쥐에서 심실 개조에 미치는 영향 및 그 작용기전.Shi Zhen, Traditional Chinese Medicine, 한의학, 2008, 19 (7):1615

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[8] Lv 웬웨이, 류지.급성 심장성 쇼크를 동반한 개의 심근세포에 대한 ginsenoside Rg2의 보호효과.지린대학교 (의과대학), 2003, 29(4):392

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[10] Wang QJ, Liu J, Liu F.의 개에서 급성 심장성 쇼크에 대한 ginsenoside diol-saponin의 보호 효과.지린대학교 (의과학), 2005, 31(4):557

[11] Tian Jianming, Zheng Shuqiu.쥐의 심근허혈-재관류 손상에 의해 유발된 심근세포 사멸에 대한 ginsenoside Rg2의 보호효과.중국약리학회지, 2004, 20(4):480

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[16] 진 Y, 류 GN.ginsenoside Rg1이 급성 심근경색 쥐에서 신생세포화에 미치는 영향.중국의대논문집 2007, 36 (5):517

[17] 진옌, 류기난.효과의 ginsenoside Rg1 VEGF과 HIF-1에 α 급성 심근경색 후다.PLA Medical Journal, 2006, 31 (11):1079