Sophora flavescens is a plant in the legume family. It is distributed in Russia, Japan, India, North Korea and the northern and southern provinces of Chinese mainland, growing at an altitude of 1,500 meters, mostly growing on hillsides, sandy areas, grassy slopes, shrubs and near fields, and has not been cultivated by artificial introduction. Indications: clear heat and dampness, insecticide, diuretic. For hot diarrhea, blood in the stool, jaundice and urine, under the red and white belt, swelling and itching, eczema, eczema, skin itching, scabies leprosy; External treatment of trichomoniasis vaginitis.
Chemical composition
The roots contain alkaloids: matrine, oxymatrine, N-oxysophocarpine, sophoridine, d-allomatrine, I-somatrine, sophoranol, (+) sophoranol N-oxide), sophocarpine, sophoramine, n-methylcytisine, anagyrine, baptifoline. The root also contains a variety of flavonoids: kushenol A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, KURARIDINOL, KURARIDINOL, KURARINOL, NEOKURARINOL, NORKURARINOL, ISOKURARINONE , for-mononetin, kurarinone, norkurarinone, methylkushenol C, lmaackiain, trifolirhizin and rtifolirhizin-6"-O-malonate, Kushenin, isoanhy-droicaritin, noranhydroicaritin, xan-thohumol, isoxanthohumol, luteolin-7-glucoside. In addition, the root also contains triterpene saponins: sophoraflavoside I., II., III, IV., soyasaponin I and quinone compounds: sophoraflavoside I., II., III., IV., soyasaponin I and quinone compounds: soshequinone A.The aerial part contains alkaloids: matrine, matrine oxide, dextro-matrine, isomatrine, sophora alcohol, sophora N-oxide, stinky beanine, pseudoindigophylline, L-N-methyl valechine, L-sophoranine, L-sophoramine, L-locustin base, dex-N-oxacia root base, left-△7-dehydrosophoramine, isosophocarpine, L-13, 14 dehydrosophoidine (13, 14-dehy-drosophoridine), dex-9a-hydroxymatrine, 9a-hydroxysophocarpine, 9a-hydroxysophocarpine N-oxide, L-7,8-dehydrolocustamine base (7,8- Dehydrosophoramine), L-9a-hydroxysophoramine, dimer of N-methyleyti-sine, sophoramine, lehmannine. It also contains 2-alkylchromone derivatives, in which 2-n-docosyl-5,7-dihydroxy-6,8-dimethylchromone(2-n-heneicosyl-5,7-dihydroxy-6,8-dimethyl chromone) and 2-n-tridecyl-5,7-dihydroxy-6,8-dimethylchromone (2-n-tricosyl-5,7- dihydroxy-6,8-dimethylchromone), but also 2-n-tridecyl-, 2-n-pentadecyl-, 2-n-heptadecyl-, 2-n-heptadecyl-, 2-n-nonadecyl, 2-n-nonadecyl, and 2-n-pentacosyl-5,7- Dihydroxy-6,8-dimethylchromone (5,7-dihydroxy-6,8-dimethyl chromone).
Alkaloids in flowers: dex-matrine, dextro-oxymatrine, L-7,11-dehydromatrine (7,11-dehydromatrine), dextro-5a, 9a-dihydroxymatrine (5a,9a-dihydroxymatrine), L-sophora, N-oxacia oxide, L-locustamine base, L-9a-hydroxylocustamine base, dextro-locust alcohol, sophora alcohol-N-oxide, lupanine, L-stinky beanine, L-pseudoindigoline, L-N-methyl lorininine, L-rhombifoline, dextro-mamanine, d-kuraranine, isokuraramine.
Pharmacological action
1. Anti-tumor effect
Matrine has anticancer activity, and the survival rate of 2mo in the group of mice injected intraperitoneally with 500 μg.d is 40%, while the control group all died within 23 days. Matrine oxidized has no effect. Matrine has the effect of reducing the inhibition of P815 tumor cell proliferation by mouse peritoneal macrophages in vitro. Sophocarpine also has anticancer activity, and is resistant to S-180 and U-14 in experimental mice. ECA, L and other tumor strains showed obvious inhibitory effects. Matrine, Matrine oxide, Sophora matrine and their different proportions of mixed A, B and C bases have different degrees of inhibitory effects on S-180 solid tumors, the tumor suppression rate of each monomer alkaloid is above 35%, and when the C base dose is mixed with different proportions is 113mg/(kg.d), the tumor suppression rate of continuous intraperitoneal injection for 10 days is 61.38%, which is 23.5% higher than that of total alkali, and there is a significant difference compared with matrine alone (P<0.01). Matrine has a significant inhibitory effect on the colony rate of peripheral multidirectional hematopoietic progenitor cells in chronic myeloid leukemia, with an inhibition rate of 0.76 and an optimal inhibitory concentration of 100mg/L. Sophora sophora decoction acts on human promyelocytic leukemia cells cultured in vitro, and at a dose of 8mg/ml, it can significantly induce leukemia cells to differentiate in the direction of mononuclear macrophages.
2. Rise leukocyte effect
Oxidized matrine can prevent mouse leukopenia caused by MMC and cyclophosphamide, intravenous or intramuscular injection of 30mg/kg matrine and 100mg/kg oxymatrine have a significant increase effect on the number of peripheral blood leukocytes in normal rabbits, and the apparent time, maintenance time and peak white blood cell count of oxymatrine on normal rabbit whitening effect are basically the same within 18 days after administration, and the whitening effect is better than that of shark liver alcohol. In the treatment of leukopenia caused by rabbit X-ray 600 len irradiation, matrine oxymatrine and matrine in the sophora group, the white blood cell count was basically maintained above 6000/mm3 from 5 days after administration to the l9 day in the sophora group, while the control group did not recover the above level until 22 days. The whitening potency of oxymatrine was not higher than that of total alkali, while matrine had no therapeutic effect. Oxidized matrine has a dose rate of 31 Lun/min for leukopenia caused by body irradiation of 60 cobalt R-ray 500 Lun, showing a certain prevention and treatment effect, but no prevention and treatment effect at a dose rate of 120 Lun/min.
3. Effects on the cardiovascular system
1/4LD50 of matrine and oxymatrine intravenously significantly opposed aconitine and chloroform-epinephrine-induced arrhythmias in rats; Intraperitoneal injection significantly opposed chloroform-induced ventricular fibrillation in mice, and also increased the dosage required for aconitine-induced arrhythmias in rats, against barium chloride-induced arrhythmias in rats and ligation of anterior descending coronary artery induced arrhythmias in rats. Intravenous injection of 30mg/kg oxymatrine in rabbits shortened the recovery time of epinephrine-induced arrhythmias, shortening the average therapeutic administration by 43% and the preventive administration by 22%. Intravenous injection of 42mg/kg locustin can combat calcium chloride-induced ventricular arrhythmias in mice and aconitine-induced arrhythmias in rats; Intravenous injection of L6mg/kg can increase the dosage of wabaine to cause premature beats and cardiac arrest in rabbits, and can also fight coronary artery obstruction-reperfusion-induced canine arrhythmias, but not against calcium chloride-acetylcholine-induced atrial fibrillation (flapple) and chloroform-adrenaline-induced arrhythmia in rabbits. Intravenous l/5 LD50 locustinine (11mg/kg) can prevent or treat aconitine-induced rat rhythm, and can also improve guinea pigs' tolerance to various arrhythmias caused by wabain, and prevent barium chloride and calcium chloride induced arrhythmias in rats. The 1/10 LD50 dose (5 mg/kg) significantly shortened the time of epinephrine-induced arrhythmia in rabbits, and the duration of action was much longer than that of quinidine.It can also increase the left ventricular electrofibrillation threshold in rabbits, and increase with the increase of intravenous dose, and can also dose-related reduce the rate of chloroform or carbon tetrachloride-induced ventricular fibrillation in mice, and fight against carbon tetrachloride-adrenaline induced arrhythmias in rabbits. Sophora alkaloids have a vasodilating effect and a protective effect against acute myocardial ischemia. It can cause obvious antihypertensive effect on anesthetized rabbits, generally lowering blood pressure by about 20mmHg, lasting 2-3 minutes to return to normal; The ear blood vessels of ex vivo rabbits can immediately cause dilatation and last for about 10 minutes; For acute hemorrhagic heart, it can prolong its beating time, and the extension time is about 7 minutes; It has a significant protective effect on acute myocardial ischemia caused by posterior pituitary gland hormone. Matrine oxidation can increase atrial contractility in rabbits, and has a good dose-activity relationship, 9μm does not affect myocardial excitability, but shortens the functional refractory period; Reduces the threshold concentration of epinephrine-induced left atrial automaticity; Slows down the right atrial autorhythm and reduces the positive frequency effect of CaCl2 on the right atrium. The amount of poisoning (360 μm) reduces myocardial contractility and excitability. Matrine oxidized matrine 50 μmol/L antagonizes the positive frequency effect of isoproterenol. The lower (high) concentration of oxymatrine (100 μmol/L) in cultured cardiomyocytes can mediate the negative (positive) frequency effect with α (β) receptors. Matrine can slow down the right atrial autopilot frequency of guinea pigs, increase right atrial contractility and reduce left atrial MDF (maximum driving frequency), and is dose-dependent; Its negative frequency, positive inotropic and negative MDF effects are all linear correlated.Matrine can inhibit the left atrial autonomic effect of aconitine-induced rats or prolong the latency of aconitine-induced autorhythm and slow down its initial frequency; It can also increase the threshold concentration of right atrial arrhythmia induced by wabaine in guinea pigs and the left atrial automaticity induced by epinephrine injection, and have an enhancing effect on the positive inotropic effect of wabaine. Matrine can be significantly inhibited by the Ca2+ channel blocker verapamil (1μmol/l), and the inhibition of smooth muscle is greater than that of myocardium, suggesting that the positive inotropic effect of matrine may be related to the activation of Ca2+ channels. Matrine can increase the content of cAMP and decrease the level of cMP in rat plasma, without significant effect on the content of cAMP and cGMP in myocardial tissue. Sophoridine can increase cAMP levels in rat plasma and cAMP content in myocardial tissue. Matrine oxide 50μmol/L and 250μmol/L have a significant inhibitory effect on the increase of lactate dehydrogenase content in vitro cultured cardiomyocyte damage caused by mitomycin C, and can reduce cardiomyocyte damage caused by hypoglycemia and hypoxia, but have no protective effect on cardiomyocyte damage caused by chlorpromazine.Intramuscular injection of oxymatrine has the effect of significantly prolonging the survival of myocardium of allogeneic free transplantation in mice, and its effect is enhanced with the increase of dose. When the total flavonoids of Sophora sophora are 125-250μg/ml, it can slow down the frequency of spontaneous beating of cardiomyocyte clusters in cultured mice, and can fight against spontaneous cardiomyocytes and wabaine-induced beating rhythmias. Sophora flavonoids had a significant antagonistic effect on ventricular fibrillation caused by inhalation of chloroform in mice, with an LD50 of 23.9±1.1g/kg and a therapeutic index of 3.56. Intravenous injection of 8g and 30g/kg of sophorae flavonoids into rabbits, after 30-60 minutes, can significantly combat the arrhythmia caused by chloroform-epinephrine. The rates of complete confrontation are 40% and 70%, respectively. Intravenous injection of 20-40g/kg of total flavonoids of Sophora sophora has a significant therapeutic effect on arrhythmias in rats caused by intravenous injection of aconitine. The response rate of the first treatment was 63%, and the response rate of the second treatment was 84%. Intravenous injection of matrine in rats can significantly counter arrhythmias caused by aconitine, barium chloride and coronary ligation to anesthetized rats intravenously inject 30g/kg and 60g/kg of Sophora matrine, showing obvious negative autonomic effects, negative frequency effects and negative conduction effects. These effects are enhanced with increasing dose.
4. Calm wheezing expectorant effect
Matrine mainly produces asthmatic effect by excitating β receptors, especially β receptors in the excitatory center, relieving bronchospasm and inhibiting the release of antibodies and slow-reactive substances. Matrine in calcium-free or calcium-free Kirschner nutrient solution can counter the effect of acetylcholine barium chloride excitation in vitro guinea pigs, rat trachea and intestinal tube. The asthma effect of matrine and oxymatrine on histamine-induced asthma guinea pigs is basically similar to that of aminophylline, and the asthma rate in 1 hour is more than 90%, while the control group is about 15%; In terms of asthma time, aminophylline has a asthma rate of 55% in 6 hours, and the total sophora base is more than 80%. Sophora inline Ach has a stronger wheezing effect than aminophylline, and its asthmatic effect may be effected by excitating β-receptors in the midbrain. The phenol red excretion method proved that the total base of matrhophyllum and flavonoids in mice had obvious dispelling effect.
5. Stabilizing effect
Sophora sophora 50-100mg/kg can significantly inhibit the free activity of mice; 400mg/kg significantly inhibited the passive activity of mice. 100-200mg/kg can inhibit the European fighting aggression of lone mice; The combination of Sophora sophora base 25-40mg/kg and hibernation (5mg/kg) can cause the loss of the correct reflex in mice, and 100-200mg/kg Sophora total alkaline can significantly enhance the inhibitory effect of 0.5mg/kg reserpine on spontaneous activity in mice; the combination of Sophora sophora base 50-200mg/kg and intraperitoneal injection of subthreshold dose of pentobarbital sodium 20-25mg/kg can cause mice to sleep; respectively, it is combined with thiopental sodium (intraperitoneal injection, 40mg/kg) and chloral hydrate (intraperitoneal injection). , 200mg/kg) in combination, can significantly strengthen the central inhibitory effect. It can also significantly counter psychomotor excitement caused by central stimulants amphetamine (intraperitoneal injection, 4-6mg/kg) and caffeine (50mg/kg); Sophora sophora not only has no antagonistic effect on convulsions caused by strychnine and pentatetrazine, but also enhances its convulsions and increases the number of animal deaths. Sophora sophora alone has a mild analgesic effect, and in combination with threshold dose morphine, it can significantly increase its analgesic percentage.
6. Anti-allergic effect
Matrine can reduce the release of allergic mediators, as an immunosuppressant, which inhibits the proliferation of 50% T cells at a concentration of 0.55-0.56 mg/ml, and inhibits IL-2 production at a concentration of 0.1 mg/kg.
7. Immunosuppressive effect
Matrine and oxymatrine inhibited the immune function of mice at a dose of 1/5 LD50. Intramuscular injection of oxymatrine 150mg/kg or 100mg/kg in rabbits and rats had obvious inhibitory effects on passive or active skin allergic reactions, and had obvious inhibitory effects on the formation of serum IgE antibodies in rabbits. Intraperitoneal injection of oxymatrine 200mg/kg.d for 21 days had a protective effect on death caused by immediate allergic reactions in mice.
8. Other functions
Intramuscular injection of matrine oxide significantly combats exudative inflammation induced by croton oil, carrageenan, and glacial acetic acid (mice). Rabbit gavage, subcutaneous injection, intravenous injection, intraperitoneal injection and intramuscular injection of Sophora Sophora decoction, Sophora sophora injection and matrine have diuretic effects, and the amount of sodium chloride in urine has increased significantly. Sophora sophora 50% methanol extract has anti-ulcer effect caused by ethanol hydrochloride, and its active ingredient is Kurarinone. In addition, matrine has antibacterial effects in vitro and abroad, the intensity of action in vivo is comparable to chloramphenicol, and alcohol extract has anti-trichomoniasis effect in vitro, and its strength is similar to that of snake hemp.
