ギンセノシドと心臓血管の研究

現代pharmacological 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. 心筋機能への影響

tian jianmingら[3]は、心筋細胞のin vitro培養を用いて低酸素およびグルコース欠乏心筋細胞のモデルを作成し、ginsenoside rg2が低酸素およびグルコース欠乏心筋細胞の拍動振幅および生存率を有意に増加させたことを明らかにした。実験で観測されるもRg2の濃度を大幅に減らして低酸素ではCa2 +无料glucose-deficient cardiomyocytes、目立った効果があるのに対し誘発型からCa2 + cardiomyocytes発散KC lを有する。濃度の高いお酒、爆薬著明た軽い抑制効果による細胞外Ca2 +流入腐防委l2した低浓度、[4]効果的はなかった。

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 Rbラットの心室リモデリングに圧力過負荷心筋肥大とその作用機序。発見されたあのginsenoside Rb護影響されたの、心臓の左右心室の間に改造ネズミのその機能にかかわるかもしれません、左心室に穴をあけ心臓収縮と拡張期機能を改善ネズミ心室改造と強化抗酸化酵素が働きやフリーラジカルによる心筋梗塞ダメージを减少するvasoconstrictor物质の説明に供するPGI2間の不均衡問題とTXA2。

蘇テウォンら[6]も検討protopanaxadiolグループsaponinsから抽出した(PQDS)米人参葉PQDS予防心室改造心筋梗塞ネズミ後、大幅に最大の引上げ率と左心室に穴をあけintra-pressure減少から、最近で、左心室に穴をあけ量を大幅に緩和するなど左心室に穴をあけ長軸方向長、左心室に穴をあけ短い軸長、左心室絶対体重と左心室相対体重。さらに、pqdsは血清の過酸化脂質、心筋のアンジオテンシンiiおよびアドレナリンのレベルを有意に低下させ、スーパーオキシドジムターゼ、カタラーゼおよびグルタチオンペルオキシダーゼを増加させる。これは、心臓でのアンジオテンシンiiの局所産生を阻害し、交感神経末端からのカテコールアミンの放出を阻害し、心筋の抗酸化能力を改善することに関連していると推測されている。

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.

2心原性ショックへの影響

ペントバルビタルナトリウムを使用して、心原性ショックと心不全の犬モデルを作成しました。ギンセノシドの血圧(bp)、左室収縮圧(lvsp)、左室圧上昇率(lvdp /dtmax)、心拍数(hr)、心拍出量(co)に対する影響が観察された。その結果、高麗人参の総サポニン10 mg/kgと20 mg/kgを静脈注射した後、lvdp /dtmax、lvsp、bp、coがすべて増加し、左室拡張末期圧(lvedp)が低下し、hrが低下した。lv wenweiら[8]は、冠動脈前方下降枝をライゲートすることにより、心原性ショックのイヌモデルを作成し、それぞれrg20.5、1、2 mg/kgを静脈注射した。

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.

3心筋虚血再灌流への影響

tian jianmingら[11]はラットの冠状動脈の前下がり枝を結紮し、3時間後に結紮をゆるめ、20分間血流を回復させ、速やかに心臓を摘出した。アポトーシスが検出され、rg 21.0および2.0 mg/kgの前投与は、虚血性アポトーシスを減少させ、有意に虚血性dna断片化バンドを減少させることができました。サポニンreは、プロアポトーシス遺伝子baxの発現を阻害し、bcl-2 / bax比を高めることで、心筋アポトーシスを抑制することができる。

雑種犬の成体には、大動脈閉塞1時間前と再灌流直後に、ギンセノシドを含む生理生理食塩水(12.5 mg/kg)を2回静脈注射した。正常体外循環を介して,血行動態パラメータ,細胞内遊離カルシウム濃度,心筋細胞のミトコンドリアリン脂質含量,ミトコンドリアカルシウムポンプ活性,心筋組織化学を測定した。発見しreperfusion 30および60分、ginsenosides規模で心臓収縮と拡張期機能さを大きく向上させreperfusion時代中自由カルシウム濃度cardiomyocytesの低下は、リン脂質がミトコンドリアの内容を拡大し、ミトコンドリアカルシウムポンプのイベントで、大幅に減らし不整脈风発作は起きません。

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らは、ラットを用いて冠動脈前下降枝を30分間結紮し、24時間再灌流することで心筋虚血再灌流損傷の実験モデルを作成した。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.

4心筋梗塞への影響

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.

liu jieら[15]は、イヌにおけるladのライゲーションによる急性心筋梗塞モデルを確立した。モデリング後、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.

これを大きくまとめれば、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.

参照

[1]朱連才、王伯初、丹俊。銀杏エキスとギンセノシスが血管活性物質に及ぼす影響。^『仙台市史』(仙台市史)、2007年、30頁

[2]王強、mo xuemei、ヤンxiaoying。現代の研究では、心血管疾患の治療におけるギンセノシドの進歩。心血管系疾患が进歩し、2006年27日的日(3):325

天安建銘[3]で上映された。心筋細胞の振幅と生存率に対するギンセノシドrg-2の影響。^ a b c d e f g h『日本の歴史』、2003年、12 - 12頁

[4]李チュング・テピョンロ)。高麗人参サポニンの薬理活性に関する研究。2003年(平成15年)4月1日- 1学科増設

【5】王天暁、余小豊、屈少春圧力負荷心筋肥大とその作用機序を有するラットにおける心室リモデリングに対するギンセノシドrbの効果。Shi Zhen汉方薬だけでなく、汉方薬だけでなく、2008年19(7):1615年

【6】隋大元、余小豊、屈少春米国人参の葉の効果20s-protopanaxadiol群サポニンがラットの実験的心室リモデリングに与える影響。中国医薬ジャーナル、2007年、42 (2):108

【7】何小夕、屈少春、虞小豊高麗人参の果実サポニンが急性心筋梗塞の犬の血行動態に及ぼす影響。『日本医学会誌』日本医学会、2008年、34(2):204

【8】呂文偉、劉傑。急性心原性ショックを有するイヌの心筋細胞に対するギンセノシドrg2の保護効果。日刊吉林大学(医科学)、2003年、29 (4):392

[9] liu j .急性心原性ショックを有するイヌの血清il-1レベルに対するギンセノシドrg2の影響。^ a b c d e f g h『漢書』、2005年、27頁

[10] wang qj、liu j、liu f .イヌの急性心原性ショックに対するギンセノシドジオール-サポニンの保護作用。吉林大学紀要(医学),2005,31(4):557

【11】田建明,鄭書秋。ラットにおける心筋虚血再灌流損傷による心筋細胞アポトーシスに対するギンセノシドrg2の保護効果。2004年中国薬理公報、20 (4):480

【12】屈少春、隋成、虞小豊ラットにおける実験的心筋虚血再灌流傷害に対するギンセノシドrbの保護効果。吉林大学紀要(医学),2007,33(5):849

【13】宋青、張小文、徐志偉。自発的高血圧ラットにおける心筋虚血再灌流傷害に対するギンセノシド前処理の保護効果。^「中国薬理学・毒物学ジャーナル」。中国薬理学・毒物学ジャーナル(2008年). 2008年8月22日閲覧

(1): 42

【14】陸峰、隋大元。急性心筋梗塞ラットにおける交感神経伝達物質およびレニン-アンジオテンシン系に対する米国人参の葉20 s-プロトパナキサジオールサポニンの効果。中国の漢方薬、2001年、32(7):619

[15] liu j, liu f, wang qj。心筋梗塞を有するイヌの血清中の一酸化窒素および一酸化窒素合成酵素濃度に対するギンセノシドの効果。中国人をもつ「実験TCMジャーナル」08年14 (4):46

[16] jin y, liu gn。急性心筋梗塞ラットにおける新卵巣形成に対するギンセノシドrg1の影響。中国医学大学ジャーナル2007,36 (5):517

【17】金燕、劉貴男。効果ginsenoside Rg1 VEGFとHIF-1α急性心筋梗塞を後という。^『官報』第1031号、大正11年(1922年)10月10日