Pharmacological efficacy of danshensu

1. Effects on myocardium: Danshensu has the effect of reducing the scope and duration of myocardial infarction, and at the same time, it has a protective effect on myocardial ischemia-reperfusion injury. Zhang Li et al. reported that danshenin is a superoxide anion scavenger, thus speculating that it can protect myocardial mitochondria from oxygen radical-induced damage by lipid peroxides. Su et al. showed that danshensu had a protective effect on ADP/O, RCR and cytochrome oxidase in rat myocardial mitochondria, suggesting that danshensu is a good OH scavenger and has a protective effect on rat myocardial mitochondrial membrane. Danshensu has a scavenging effect on exogenous O2, attenuates the effect of free radicals on mitochondrial membrane flow, and protects the mitochondrial function.

2. Inhibition of platelet aggregation and anticoagulant effect: Danshenshuin can significantly inhibit platelet aggregation and significantly increase the fluidity of platelet membrane, suggesting that it is effective in coronary heart disease. Shi Jutong and others reported that danshensu can improve the negative charge of red blood cells, so that each other are not easy to aggregate; reduce whole blood viscosity, inhibit platelet aggregation, and contribute to the activation of the fibrinolytic enzyme system; increase the mechanical strength of the red blood cell membrane, reduce the destruction of red blood cells. Large doses of danshensu can increase vascular fragility, which may be related to danshensu has anti-platelet aggregation and promote fiber degradation function. Danshensu can increase the fibrinolytic activity of the organism, improve blood rheology, improve the deformation ability of red blood cells and mediate the viscosity of blood, improve the microcirculation disorders of the organs of the whole body (especially the heart, liver, lungs and pancreas where the drug firstly reaches), and contribute to the recovery of the organism's tissues and the correction of the serious complications such as the adult respiratory distress syndrome.

3, antibacterial and anti-inflammatory and enhancement of the body's immune system: Danshensu prevented calcium ion inward flow, significantly inhibited the production of prostaglandin E2 (DGE2) and thrombomodulin B2 (TXB2) by macrophages in the rat peritoneal cavity. The regulatory effect of danshensu on cytokine production by mononuclear macrophages was observed by in vitro experiments, and it was found that danshensu activated the secretion of tumor necrosis factor (TNFα), IL-1, IL-6, and IL-8 factors by mononuclear macrophages, but the secretion was less than that of endotoxin-stimulated mononuclear macrophages. In addition, Wang Wenjun et al. reported that danshensu significantly inhibited the large secretion of the above factors induced by endotoxin (P<0.05), and possessed anti-inflammatory and body immune-enhancing effects. Application of danshensu to patients with infectious shock in clinical practice is expected to improve the survival rate.

4, anti-atherosclerosis and lipid-lowering effect: Danshensu inhibits the synthesis of endogenous cholesterol in cells, and also has the effect of anti-lipoprotein oxidation, lowering blood cholesterol, so it has the effect of protecting the vascular barrier, preventing lipid deposition and atherosclerosis AS). Wang Nan et al. showed that tanshin has an inhibitory effect on oxidative modification of low-density lipoprotein (LDL) in bovine aortic smooth muscle cells. Recent studies have found that peroxynitrite is an important mediator of diseases such as atherosclerosis. Liao Lifu et al. experimentally demonstrated that when tanshin is present, it can effectively protect the body from perinitrite damage and prevent the formation of atherosclerosis. Danshensu has the ability to inhibit cellular oxidative modification of LDL, and its antioxidant capacity is positively correlated with the amount of danshensu, suggesting that danshensu can be used in the prevention and treatment of atherosclerosis.

5. Antithrombotic effect: Yan Changkai et al. studied the effect of danshenin on activating blood circulation and removing blood stasis, and found that danshenin could significantly inhibit platelet aggregation activity induced by ADP in vitro, prolong the time of thrombosis after electrical stimulation of common carotid artery of rats, and significantly reduce the whole blood viscosity, blood viscosity, erythrocyte pressure volume, kathon yield stress, erythrocyte electrophoresis time, and erythrocyte aggregation index of rats with blood stasis in the low, medium, and high cut-off rates. and erythrocyte aggregation index. Jiang Kaiyu et al. measured the expression of cell adhesion molecules on the cell surface induced by TNFα, fMLP and thrombin by flow cytometry, and the results showed that danshensu dose-dependently inhibited fMLP-induced granulocyte expression of CD11b, and significantly inhibited the TNFα-induced expression of VCAM-1 and E-selectin on the surface of human umbilical vein endothelial cells, which indicated that danshensu had a significant inhibition on the cytokine activation of endothelial cells. Cytokine activation of endothelial cells has an inhibitory effect, which is conducive to the protection of vascular endothelial cells and reduce leukocyte adhesion, suggesting that this may be one of the mechanisms of its anti-thrombotic effect. Jin Xilu et al. observed the effects of eight danshenin derivatives on ADP-induced platelet aggregation in rabbits in vitro, and the results showed that the eight derivatives could significantly inhibit ADP-induced platelet aggregation in rabbits, and significantly increase the effective rate of 30-min depolymerization.

Prevention of cerebral thrombosis by Salvia divinorum Salvia divinorum can inhibit the aggregation of platelet releases and plasminogen through the effect on platelet releases and plasminogen, and reduce the coagulability of blood and play the role of activating blood and removing blood stasis. Fei Liping and other experiments have proved that danshenin has calcium antagonism, by inhibiting the voltage-dependent channel on the erythrocyte membrane, inhibiting the calcium inward flow of erythrocytes, reducing the intracellular calcium level, and making the erythrocyte deformability enhanced. It also increases the negative charge of erythrocytes, making them less likely to aggregate with each other; reduces whole blood viscosity and activates the fibrinolytic enzyme system. Due to the high distribution concentration of danshensu in the heart, kidney and brain, together with these effects on the blood, it is suggested that danshensu can prevent the occurrence of cerebral thrombosis.

6, to prevent excessive healing of wounds, the therapeutic effect on hyperplastic scars: recently by the Xi'an City Central Hospital Burns Plastic Surgery Department and the Fourth Military Medical University Xijing Hospital Plastic Surgery Department, jointly completed a Xi'an City, Science and Technology Social Development Program Fund-funded project proved that the single danshenin in the muscle shengshan has inhibition of the fibroblasts in the granulation tissues, and it can prevent the excessive healing of the wounds. From the study, it can be seen that the promotion of wound healing by danshensu is not a function of directly promoting the proliferation of fibroblasts, but most likely through the improvement of microcirculation, changing the local microenvironment of the wound, providing energy metabolism substances, and promoting the removal of metabolic products. Of course, because of the function of inhibiting the proliferation of fibroblasts in the granulation tissue, the dosage needs to be controlled in the early stage of wound healing, while the dosage can be increased in order to inhibit the excessive proliferation of fibroblasts after wound healing to prevent scar formation. Jiang Hui-Qing and others experimentally confirmed that danshenin has the effect of inducing apoptosis in fibroblasts. Its mechanism may be: 1, affecting the expression of genes controlling cell proliferation and apoptosis; 2, activating nucleic acid endonuclease, causing DNA strand breaks and inducing apoptosis. In addition, tanshin has the ability to regulate the binding activity of nuclear transcription factor NF-1 and play a role in reducing collagen synthesis and secretion in fibroblasts.

7, dilation of coronary artery effect: Danshenin can significantly dilate coronary artery, so that the coronary blood flow increased significantly, and can fight against morphine, cardiac glycosides and other shrinkage of coronary artery effect.

8, the role of treatment of liver injury: Danshenin can be in a certain range of dose-dependent direct stimulation of in vitro cultured mouse hepatocyte proliferation, suggesting that Danshenin also promotes hepatocyte repair and regeneration. Danshensu regulates NO content by decreasing ET content, up-regulating eNOS expression, down-regulating iNOS expression, reducing hepatic vasoconstriction, inhibiting platelet aggregation, and improving microcirculation disorders of the damaged liver, thus reducing acute severe liver injury. Li Yuehua et al. test proved that: with danshensu, on the other hand, it can significantly improve the function of mitochondria of hepatocytes and reduce the damage and necrosis of hepatocytes. Therefore, the mechanism of the protective effect of danshensu on hepatocytes in D-galactosamine-induced hepatocyte injury may be related to the stabilization of the biofilm and the maintenance of calcium homeostasis, which needs to be further studied. Li Jing et al. experimentally studied that potassium cyanide was toxic to hepatocytes, and danshensu could make LDO content in 2.5 mmol/L potassium cyanide hepatocyte culture solution, suggesting that the hepatocyte injury caused by potassium cyanide was closely related to the toxic effect of free radicals, and that danshensu had the effect of stabilizing the cell membrane to scavenge free radicals. Zhang Zhenyu et al. used carbon tetrachloride injury hepatocyte modeling experiments show that the medium and high dose groups can reduce Hyp and collagen content, and its inhibition of cell proliferation activity is consistent. It is suggested that danshensu can inhibit liver fibrosis. The mechanism of action may be that danshenin can induce apoptosis of fibroblasts.

9, anti-ischemic injury Danshenin can significantly reduce the area of cerebral infarction, improve the neurological deficits, and reduce the cerebral water content. Danshen saffron injection (7.2, 14.4mg/kg) can significantly reduce the pathological changes of cerebral index and cerebral water content induced by acute cerebral ischemia in rats, and at the same time, reduce the capillary permeability in the brain and maintain the normal morphology and structure of nerve cells in brain tissue. Ultrashort wave therapy, Salvia miltiorrhiza treatment and the combination of the two can reduce the cerebral water content on the ischemic side of the rat, increase the content of the antioxidant enzyme superoxide dismutase (SOD), and reduce the content of the free radical product malondialdehyde (MDA), and the difference between the three treatment groups was not significant. This indicates that ultrashort wave treatment with Salvia divinorum has a neuroprotective effect on focal cerebral ischemia-reperfusion injury in rats, and this effect may be related to the reduction of cerebral edema, the elevation of SOD and the reduction of MDA. Using the vascular endothelial cell model of ischemia and hypoxia, chemiluminescence was applied to observe the content of hypoxanthine in the culture medium, and it was found that the increase of hypoxanthine could be reduced in the danshen group, and the morphology of endothelial cells in the danshen group was found to be intact by phase contrast microscopy. Danshenin can inhibit the decrease of mitochondrial membrane potential caused by hypoxia and glucose deficiency injury, thus it has the effect of stabilizing the mitochondrial membrane potential and inhibiting the occurrence of apoptosis, and this effect may be related to its ability to inhibit intracellular calcium overload in nerve cells.

10, Danshenin on the treatment of pulmonary heart disease Danshenin has the role of dilation of the arteries, and can inhibit the platelet release of contractile substances. Danshensu can inhibit HPV at a concentration of 1.25-5g/L, and the higher the dose, the stronger the inhibitory effect, and finally achieve complete inhibition. Comparing the effects of the same dose of danshensu, compound danshen injection and danshen injection on HPV, the result was that danshensu had the strongest effect. It is suggested that danshensu may provide help in the treatment of critical diseases such as pulmonary heart disease and adult respiratory distress syndrome (ARDS).

11. Antitumor effect of danshensu The anticancer effect of danshensu may be one of the reasons for its anticancer effect. The experimental results of Sui Jian et al. showed that danshenin had obvious cancer inhibition effect in serum-free culture fluid (P value <0.05 compared with negative control group and danshenin group), and when the concentration of danshenin reached 80mg/ml, its cancer inhibition effect was the same as that of Aclacinomycin A (P>0.05). The mechanism of inhibition of gastric adenocarcinoma cell lines by danshenin is related to the blockage of cholesterol synthesis pathway in tumor cells.

12. Prevention and treatment of plateau disease by danshenin Plateau disease is a clinical syndrome that occurs when the physiological compensation of hypoxia at plateau (loss of compensation) leads to the aggravation of the load of tissues and organs (pathological changes), and the main reason is caused by hypoxia at plateau. Zhang Guangming et al. proved that danshenin can effectively remove the abnormally increased oxygen free radicals caused by hypoxia, improve the oxygen-carrying capacity of tissues, inhibit hypoxic pulmonary artery constriction caused by plateau hypoxia, and ensure the oxygen supply of heart, brain and other important organs. In conclusion, danshensu can improve the oxygen-carrying capacity of blood, prolong the body's ability to tolerate hypoxia, effectively reduce hypoxia-induced damage to the heart, brain, kidney, lungs and other vital organs, and provide a basis for the prevention and treatment of plateau disease.

13. The therapeutic effect of danshensu on psoriasis Adhesion molecules have a relatively close relationship with the development of psoriasis, and danshensu can affect the expression of adhesion molecules. The preliminary results of Wu Jinghai and other experiments showed that the expression of ICAM-1 on the surface of PBMC of patients with psoriasis vulgaris was obviously elevated, and after treatment with danshensu, there was a significant decrease in the expression, which indicated that danshensu had the effect of inhibiting the expression of ICAM-1. Incubation of danshensu with psoriatic PBMCs resulted in the weakening of their adhesion to HUVEC, which also suggested that danshensu might be able to achieve the therapeutic effect of psoriasis by inhibiting the adhesion of PBMCs to vascular endothelial cells. In addition, in normal subjects, tanshin did not significantly affect the adhesion of PBMC to endothelial cells and the expression of adhesion molecules. This experiment suggests that tanshin can treat psoriasis by reducing the expression of adhesion molecules.