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Pharmacology of Wenshan Sanqi
Sanqi has the effects of removing blood stasis, stopping bleeding, reducing swelling and relieving pain. Indications: hemoptysis, hematemesis, epistaxis, hematochezia, metrorrhagia, traumatic hemorrhage, chest and abdomen tingling, and swelling and pain caused by falling down. Compendium of Materia Medica says: "Sanqi can stop bleeding, disperse blood and relieve pain." "Yu JIU wants to solve" says: "Sanqiying stops bleeding, removes blood stasis, and removes blood stasis to collect new blood."

(1) Stop bleeding

Notoginseng is known as the "medicine for stopping bleeding", which can disperse blood stasis, stop bleeding without leaving blood stasis, and is more suitable for blood stasis bleeding. Panax notoginseng has a strong hemostatic effect, and it has obvious hemostatic effect on different animals, different routes of administration and different preparations. After notoginseng anesthesia, the coagulation time and prothrombin time of carotid blood in vitro were shortened. If the portal vein is ligated in advance, the hemostatic effect will disappear. It is speculated that after oral administration of Panax notoginseng, it must be metabolized by the liver to produce hemostasis. Intravenous injection of Notoginseng Radix in rabbits can shorten the clotting time, prothrombin time and thrombin time, increase the number of platelets and improve platelet adhesion. Intraperitoneal injection of Notoginseng Injection or intragastric infusion of Notoginseng Injection can shorten the bleeding time and coagulation time of mice. The hemostatic active component of Notoginseng Radix is Notoginsenoic acid. The bleeding time was measured by tail vein cutting method. intraperitoneal injection of notoginseng acid solution in mice could shorten the bleeding time and increase the number of platelets. Intravenous injection of dextran and thromboplastin in rabbits can cause different degrees of hemorrhage in interstitial lung and alveoli of rabbits, and at the same time, there are small thrombosis in small blood vessels and capillaries, resulting in a pathological model of bleeding and blood stasis. After the model animals were treated with Panax notoginseng injection, pulmonary hemorrhage and thrombosis were significantly reduced, which was very consistent with the theory of stopping bleeding without leaving blood stasis in traditional Chinese medicine. The hemostatic effect of Notoginseng Radix is mainly achieved by increasing the number of platelets and enhancing platelet function. Electron microscope observation showed that Notoginseng injection could make guinea pig platelets stretch pseudopodia, deform and aggregate in vitro, destroy and partially dissolve platelet membrane, and produce secretory reactions such as platelet degranulation, thus inducing platelets to release hemostatic active substances such as ADP, platelet coagulation factor III and Ca++, thus playing a hemostatic role. The hemostatic effect of panax notoginseng is also related to constricting local blood vessels and increasing thrombin content in blood. Panax notoginseng is easy to be destroyed by heating, so it is suitable for hemostasis.

(2) Anti-thrombosis

Panax notoginseng has the effects of promoting blood circulation and removing blood stasis, and can resist platelet aggregation and thrombosis. The effective component is panax notoginseng saponins, mainly ginsenoside Rg 1 Panax notoginseng saponins can significantly inhibit platelet aggregation induced by collagen and ADP in rats or rabbits. Intravenous administration in rats can inhibit experimental thrombosis. In the rat model of disseminated intravascular coagulation induced by thrombin, intravenous injection of Rg 1 can significantly inhibit thrombocytopenia and increase of fibrin degradation products (FDP), which indicates that RG 1 has the effects of anti-DIC and reducing the consumption of coagulation factors. Taking Radix Notoginseng in patients with hyperviscosity or (and) hyperlipidemia can significantly reduce the plasma fibrinogen content. Notoginseng Radix inhibits the conversion of fibrinogen to fibrin induced by thrombin, and can activate urokinase to promote the dissolution of fibrin.

The above results show that the antithrombotic effects of panax notoginseng include anti-platelet aggregation, antithrombin and promoting fibrinolysis.

Panax notoginseng can increase the content of cAMP in platelets, reduce the synthesis of thromboxane A2, and inhibit the release of active substances that promote platelet aggregation, such as Ca++ and 5-HT, thus playing an anti-platelet aggregation role. Some data show that it takes 20 days for rabbits to have obvious anti-platelet aggregation effect by intravenous injection or daily feeding of Panax Notoginseng saponins 200mg/kg, suggesting that the clinical effect of treating thrombotic diseases with Panax Notoginseng is slow.

(3) promoting hematopoiesis

Notoginseng "removes blood stasis and promotes regeneration", and modern research has confirmed that Notoginseng has the function of enriching blood. After irradiation with 60CO-γ rays, mice were injected with Panax Notoginseng saponins intraperitoneally for 6 days, which obviously promoted the proliferation of pluripotent hematopoietic stem cells. In spleen nodules, granulocytes and erythroid cells are active in mitosis, and the weight of spleen increases. PNS can also promote the recovery of leukopenia caused by cyclophosphamide in mice. In rats with acute hemorrhagic anemia, Sanqi injection can obviously promote the recovery of red blood cells, reticulocytes and hemoglobin.

④ Influence on cardiovascular system.

Sanqi can dissipate blood stasis, reduce swelling and relieve pain. Panax notoginseng saponins and other active components have extensive pharmacological activities on cardiovascular system. Influence on the heart When PNS is injected into anesthetized cats or great veins, the left ventricular internal pressure (LVP) and the maximum increase rate of left ventricular internal pressure (dp/dtmax) are significantly reduced, the time to peak (t-dp/dtmax) is significantly prolonged, the heart rate is slowed down, and the total peripheral vascular resistance and blood pressure are significantly reduced, but the cardiac output (CO), cardiac index and cardiac index are not reduced or increased.

The above results show that PNS can reduce myocardial contractility, slow down heart rate, dilate peripheral blood vessels and reduce peripheral resistance. Rg 1 and Rb 1 were removed from PNS, and the rest (RX) was injected intravenously into rats, which had similar effects on hemodynamics. PNS can antagonize the increase of contraction force and contraction frequency of isolated guinea pig myocardium caused by CaC 12, and shorten the plateau period of action potential, indicating that PNS has calcium channel blocking effect.

Effects on vascular blood pressure Panax Notoginseng and Panax Notoginseng saponins have antihypertensive effects on dogs, cats, rabbits, spontaneously hypertensive rats and other animals, especially on diastolic blood pressure. Panax notoginseng saponins can selectively dilate blood vessels in different parts, but its dilating effect on canine arteries such as thoracic aorta and pulmonary artery is weak, while its dilating effect on arterioles and veins such as renal artery, mesenteric artery, portal vein and inferior vena cava is strong, and it can significantly reduce coronary resistance (CR) and increase coronary blood flow (CBF). The effect of PNS is stronger than that of monomer, and the effect of Rbl is greater than that of Rg 1. The vasodilation and hypotensive effects of Panax notoginseng are mainly related to blocking Ca++ influx. PNS can specifically block the receptor-dependent calcium channel (ROC) in vascular smooth muscle, reduce the influx of Ca++, and also significantly reduce the influx of Ca++ caused by norepinephrine.

Anti-myocardial ischemia Panax Notoginseng, Panax Notoginseng total flavonoids and Panax Notoginseng hairy root extracts can resist the increase of T wave in rabbits with acute myocardial ischemia caused by pituitrin. For dogs with experimental acute myocardial infarction, Sanqi injection can obviously reduce ST segment deviation and pathological Q wave. In the experiment of acute myocardial ischemia caused by coronary artery ligation in rabbits, intravenous injection of panax notoginseng saponins 5 minutes before ligation can obviously improve ischemic electrocardiogram and reduce myocardial infarction area after reperfusion. Panax Notoginseng saponins can reduce the infarct area and inhibit the further increase of serum creatine phosphokinase (CPK) in a dose-dependent manner for myocardial ischemia caused by reperfusion after coronary artery ligation in rats.

The mechanisms of Panax Notoginseng saponins against myocardial ischemia are as follows: ① dilating coronary artery, promoting the formation of collateral circulation in experimental myocardial infarction area, increasing coronary blood flow and improving myocardial oxygen supply; ② Inhibit myocardial contractility, slow down heart rate, reduce peripheral vascular resistance and reduce myocardial oxygen consumption; ③ Anti-lipid peroxidation, increase the activity of superoxide dismutase (SOD) and reduce the production of malondialdehyde (MDA); ④ Improving hypoxia tolerance and obviously prolonging the survival time of mice under normal pressure hypoxia.

Intravenous injection of Panax Notoginseng Saponins can obviously dilate the pia mater microvessels, speed up the blood flow and increase the local blood flow in anesthetized mice. In the case of incomplete cerebral ischemia caused by rapid bleeding of bilateral common carotid arteries and femoral arteries in rabbits, intravenous injection of panax notoginseng saponins can significantly reduce the brain wave inhibition caused by ischemia, significantly reduce the contents of water, sodium and calcium in cerebral cortex and the activities of CPK and LDH in cerebral venous blood, and alleviate the structural damage of cerebral cortex. The anti-cerebral ischemia effect of Panax notoginseng is not only related to dilating cerebral vessels and increasing local blood flow, but also related to delaying ATP decomposition in ischemic tissue, improving energy metabolism, inhibiting lipid peroxidation, increasing SOD activity in brain tissue and scavenging oxygen free radicals.

Anti-arrhythmia Panax Notoginseng saponins can significantly improve the recovery rate of sinus rhythm in dogs with arrhythmia caused by ouabain and trichosanthin K, shorten the time required for sinus rhythm recovery, and prolong the duration of sinus rhythm. For rats with arrhythmia caused by aconitine, it can significantly prolong the latency of arrhythmia and shorten the duration of arrhythmia. Tachycardia induced by BaC 12 can restore sinus rhythm in rats. It can significantly reduce the incidence of ventricular fibrillation induced by chloroform in mice. Panax notoginseng diol glycoside (PDS) and Panax notoginseng triol glycoside (PTS) have obvious antagonistic effects on arrhythmia induced by aconitine and BaC 12 and arrhythmia induced by coronary artery ligation in rats. IqS can also shorten the duration of arrhythmia induced by adrenaline in rabbits and alleviate arrhythmia induced by myocardial ischemia-reperfusion in rats.

The antiarrhythmic mechanisms of Panax notoginseng saponins, Panax notoginseng saponins and Panax notoginseng saponins include:

Reduce self-discipline; Slow down conduction; Prolonging action potential duration and effective refractory period to eliminate reentry excitation; Blocking the slow calcium channel significantly reduces the peak value of slow inward current (Isi).

The electrophysiological characteristics of PTS and amiodarone are similar, mainly by prolonging APD and ERP, blocking the impulse conduction of premature beats and resisting arrhythmia.

Intra-abdominal injection of anti-atherosclerotic panax notoginseng saponins for 8 weeks can significantly inhibit the formation of intimal plaques in experimental atherosclerotic rabbits. The mechanism may be that PNS increased the content of prostaglandin I2 in arterial wall and decreased the content of thromboxane A2 in platelets, thus correcting the imbalance between prostaglandin I2 and thromboxane A2 and stabilizing the vascular environment. The methanol extract of panax notoginseng can inhibit the increase of β-lipoprotein, total lipid, phospholipid and free fatty acid in male rats fed with high cholesterol food in a dose-effect relationship.

(5) Anti-inflammatory

Panax notoginseng saponins can obviously inhibit the increase of capillary permeability caused by histamine, acetic acid, xylene, 5- hydroxytryptamine and bradykinin. It can significantly inhibit the swelling of rat feet caused by egg white, formaldehyde, dextran, 5- hydroxytryptamine and carrageenan, and the swelling of mouse ears caused by croton oil and xylene. It also has obvious inhibitory effect on the formation of cotton granuloma in rats.

The main effective component of anti-inflammation is saponin, mainly panaxadiol saponin.

The anti-inflammatory effect is related to the pituitary-adrenal system. Panax notoginseng saponins can reduce the content of vitamin C in adrenal gland of rats, and the concentration of corticosteroids in plasma increases after intraperitoneal injection of Panax notoginseng saponins in guinea pigs. However, it still has obvious anti-inflammatory effect on adrenalectomized rats, indicating that the anti-inflammatory effect of PNS does not depend entirely on pituitary-adrenal system.

(6) Protect the liver

Panax notoginseng has anti-liver injury effect. Panax notoginseng saponins can significantly reduce serum ALT activity in mice with carbon tetrachloride liver injury. The methanol extract of carbon tetrachloride significantly decreased the activities of AST and lactate dehydrogenase (LDH) in serum of rats, and alleviated the degeneration and necrosis of hepatocytes. Panax notoginseng also has anti-hepatic fibrosis effect. After 4 weeks of treatment with panax notoginseng, the degeneration and necrosis of collagen fibers between hepatocytes and hepatocytes were alleviated. In rats with hepatic fibrosis caused by carbon tetrachloride poisoning, oral administration of Notoginseng Radix for 9 weeks can alleviate hepatic steatosis, inflammatory cell infiltration and hepatocyte degeneration and necrosis. Reduce the proliferation of fibroblasts and collagen. Notoginseng Radix has certain cholagogic effect. Notoginseng Radix injection can significantly reduce serum bilirubin and promote bile secretion in rabbits with intrahepatic obstructive jaundice caused by α -naphthylisothiocyanate. Panax Notoginseng promoted the synthesis of protein in liver, increased the incorporation rate of 3H-TdR into damaged liver DNA, and increased the incorporation rate of 3H- leucine into liver protein.

(7) Anti-tumor

Ginsenoside Rh 1 has inhibitory effect on liver cancer cells in vitro. Ginsenoside Rh can inhibit the growth of mouse melanoma (B 16) in a concentration-dependent manner. When panax notoginseng saponins coexist with concanavalin (ConA) or phytohemagglutinin (PHA), spleen cells induced by panax notoginseng saponins have strong anti-tumor activity, which may be that panax notoginseng saponins enhance the killing ability of activated immune cells.

(8) Analgesia

Panax notoginseng is a commonly used drug for treating traumatic injury, which has definite analgesic effect. It has analgesic effect on various pain models such as writhing in mice, hot plate method and tail flick in rats by light radiation. The effective analgesic component is panaxadiol saponin.