Ku Shen

Radix Sophorae, Sophora Root

Dosage

For oral use, it is decocted with 3-10g.

Toxicity

LD50 (mice): 1.18 ± 0.1g/kg (Ku Shen total alkaloids/oral feeding); 14.5g/kg (Ku Shen extract/oral feeding), 14.4g/kg (Ku Shen extract/intramuscular injection). (1) , (2)

Chemical Composition

Matrine; Oxymatrine; N-oxysophocarpine; Sophoridine; Allomatrine; Isomatrine; Sophoranol N-oxide; Sophocarpine; Sophoramine; N-methylcytisine; Anagyrine; Baptifoline; Kushenol A, B, C, D, E, F, G, H, I, J, K, L, M, N, O ; Kuraridin; Kuraridinol; Kurarinol; Neokurarinol; Norkurarinol; Isokurarinone; Formononetin; Kurarinone; Norkurarinone; Methylkushenol C; l-maackiain; Trifolirhizin; Trifolirhizin-6"-O-malonatel; Kushenin; Isoanhydroicaritin; Noranhydroicaritin; Xanthohumol; Isoxanthohumol; Luteolin-7-glucoside; Triterpene saponins; Sophoraflavoside I, II, III, IV; Soyasaponin I; Kushequinone A. (3)

Precautions

Contraindication: Spleen-yang deficiency.

Pharmacology

Effects on the heart

Matrine (Ma) at low concentration levels has a positive, dose-dependent, myodynamic effect, and it is toxic at high concentration levels. Oxymatrine can, without increasing heart rate, enhance myocardial contraction and increase cardiac output in both healthy isolated toad heart and heart failure models. Intramuscular injection of oxymatrine can prolong the survival time of grafted mouse cardiac muscles. (4) , (5)

Anti-arrhythmic effect

Matrine, oxymatrine and sophoridine can antagonize various causal factors of arrhythmia, such as barium chloride, aconitine, chloroform, adrenalin, electrical stimulation and myocardial ischemia. (6) , (7)

Counteracting myocardial ischemia

Ku Shen can dilate blood vessels. Ku Shen total alkaloids can inhibit pituitrin-induced coronary artery vessel contraction in isolated dog, rat, and rabbit hearts, increasing the volume of blood flow and protecting them from ischemia. Matrine can inhibit fibrin and fibrinogen degradation products (FFDP). (8) , (9)

Effects on the central nervous system

Matrine, oxymatrine and sophocarpine can significantly inhibit mice’s spontaneous activity, antagonize Benzedrine and caffeine-induced central excitation, and enhance the central inhibitory effects of pentobarbital sodium and chloral hydrate. Body-twist and heat irritation experiments show that matrine has a significant analgesia effect, and that it can decrease normal rats’ body temperature. Oxymatrine and serpentine tend to intensify cardiazol and strychnine-induced convulsion and increase the number of deaths. Matrine and oxymatrine can increase the quantity of transmitter in mice’s brain (b-aminobutyric acid and glycine) and have a transquilizing effect. (10)

Anti-asthmatic effects

With or without the presence of Ca+, matrine can antagonize histamine, acetylcholine and barium chloride’s stimulatory effects on the trachea and ileum smooth muscles of rats and guinea pigs. Oxymatrine can significantly ameliorate asthmatic tracheal inflammation in guinea pigs. (11) , (12)

Antibacterial, antiviral and anti-inflammatory effects

Matrine can inhibit Kupffer’s cells from releasing TNF and IL-6 in rats. Ku Shen total alkaloids can inhibit in vitro proliferation of Coxsackie B virus type 3 (CVB3). Ku Shen is sensitive to staphylococcus and Gardner’s bacterium. (13) , (14) , (15)

Anti-neoplastic effects

Matrine can significantly weaken the electrophoresis migration of Hela cells. Treating MA737 adenocarcinoma-carring mice with matrine can significantly increase the TH/TS ratio. Matrine can enhance the immunological functions of LAK cells, and increase the sensitivity of tumor cells to LAK cells. It can significantly inhibit the expression of CD44 and CD49 adherent factors, decreasing the permeability of endothelial cells, helping keep endothelial cells intact, and blocking tumor cells’ adherence to the matrix. Ku Shen decoction and Ku Shen-treated serum have significant antineoplastic effects. At the concentration level of 8mg/ml, Ku Shen decoction can significantly promote the differentiation of human promyelocytic leukemia cells into mononuclear phagocytes. (16) , (17) , (18)

Effects on the immune system

Matrine can significantly inhibit ConA and LPS-induced splenocyte proliferation and LPS-induced release of IL-1 and IL-6 by the peritoneal macrophages in mice. It can significantly inhibit DNFB-induced delayed hypersensitivity in mice, lower the carbon removal rate, decrease the weight of the spleen and thymus glands, and inhibit the formation of serum hemolysin. Oxymatrine can regulate the proliferation of human tonsil lymphocytes. Ku Shen can, in a dose-dependent manner, induce splenocytes to produce interferon in mice, and antagonize hydrocortisone’s inhibitory effect to promote the production of interferon with positive dose-effect correlation. (19) , (20) , (21)

Counteracting liver fibrosis, hepatic injury and hepatitis B

Experiments show that matrine can significantly lessen the degeneration of, and the formation of necrosis and fibrous tissue in liver cells. It can decrease the ALT, HA and HyP levels in liver tissues, lower the jaundice occurrence rate, and lessen hepatic injuries in mice. It can treat and prevent lethal hepatitis that is caused by lipopolysaccharides, LPS/D-GALN and inhibit LPS-induced release of TNF. Oxymatrine can lessen hepatic fibrosis in CCl4-induced hepatic injuries. (22) , (23)

Anti-allergic effects

Neither feeding Ku Shen solution to mice nor administering oxymatrine directly to splenocytes affects the forming of IgE antibodies. Oxymatrine does not block the combining of antigen and antibody, nor change the level of cAMP in cells. However, it does decrease the fluidity of cytomembrane, and stabilize cytomembrane, which may be the pharmacological basis of Ku Shen’s inhibition of mastocytes’ release of histamine in the treatment of type I allergy. Intraperitoneal administration of oxymatrine can significantly inhibit passive cutaneous allergic reaction in rats. Oxymatrine also significantly inhibits reverse cutaneous allergic reaction, Arthus reaction, and SRBC- and PC-induced DTH. (24)

Effects on the digestive system

Administered by either oral feeding or endogastric perfusion, methanol-based extract of Ku Shen can enhance the small intestine’s peristaltic function in mice, and prevent hydrochloric acid or alcohol-induced acute gastric mucosa injury in rats. Oral administration of matrine can prolong the duration of first-time black stool excretion during the first time; the same treatment can also significantly postpone the occurrence of castor oil-induced moist stool excretion. It had also significant effect in prolonging the duration of moist stool excretion by castor oil. Administered to mice, 13a-hydroxymatrine (HM) can significantly reduce the number of times of acetic acid-induced body twisting and inhibit capillary hyperpermeability, and inhibit senna leaf-induced mouse diarrhea. (25) , (26) , (27)

Other effects

Oxymatrine (OM) can inhibit phenobarbital sodium withdrawal-induced liver apoptosis in mice. (28) Ku Shen can, in a dose-dependent manner, increase the sister chromatid exchange rate of chick-embryo cells and the micronucleus rate of mouse bone marrow polychromatic erythrocytes. (29) Anagyrine has a significant inhibitory effect on the proliferation of colo-16 cells. Matrine can inhibit fibroblast proliferation and collagen synthesis in rats. (30) , (31) , (32)

References

  1. Wang Yu Sheng, et al. Pharmacology and Clinical Application of TCM. Beijing: People's Health Press; 1983.
  2. Li Xian Rong, et al. The pharmacology and clinical application of Ku Shen alkaloids. Shanxi Journal of TCM. 1985;1(3):49.
  3. Editorial Committee of Chinese Materia Medica. State Drug Administration of China. Chinese Materia Medica. Shanghai: Science and Technology Press; 1998.
  4. Jin Chao Jun, et al. Matrine’s effects on guinea pigs’ myocardial contraction. Journal of Medical Research. 1997;26(10):20-23.
  5. Qin Ze Lian, et al. Oxymatrine’s effects of enhancing immunity and prolonging the survival time of grafted mouse cardiac muscles. Journal of Integrated Medicine. 1990;10(2):99-100.
  6. Zeng Jian Xin, et al. The anti-arrhythmic effects of matrine and oxymatrine. Shaanxi Journal of New Medicine. 1981;10(4):58.
  7. Li Hong, et al. Sophoridine’s anti-arrhythmic effect. Journal of Medicine Analysis. 1986;6(2):96.
  8. Zha Li, et al. Ku Shen total alkaloids’ effects on coronary blood flow. Pharmacy Bulletin. 1984;19(12):58.
  9. Zhou Bin, et al. Ku Shen total alkaloids’ effects on fibrin and fibrinogen degradation product-induced blood vessel cell damage and proliferation, and peritoneal macrophages’ release of IL-1. Journal of Pharmacy. 1999;34(5):342-344.
  10. Geng Qun Mei, et al. The effects of matrine and oxymatrine on mice’s cerebral b-aminobutyric acid and glycine levels. Inner Mongolia Journal of Medicine. 1993;13(1):3-4.
  11. Bao Shu Juan, et al. Matrine’s anti-asthma mechanism. Journal of Pharmacology and Clinical Application of TCM. 1995;11(5):33-34.
  12. Jiang Lu Ning, et al. Matrine’s effect on asthmatic tracheal inflammation in guinea pigs. Journal of Jining Medical College. 1999;22(2):33-34.
  13. Lin Wen, et al. Matrine’s effect on bacterial polysaccharides-induced release of TNF and IL-6 by Kupffer’s cells in rats. Journal of Pharmacy. 1997;32(2):93-96.
  14. Chen Fu Xiang, et al. Ku Shen total alkaloids’ in vitro inhibitory effect on Type 3 Coxsackie B virus. China Journal of Experimental and Clinically Applied Virology. 1995;9(2):115-118.
  15. Chan Mei Ying, et al. Huang Qin and 15 other Chinese herbs’ anti-bacterial effect on vaginal Gardner’s bacteria. Journal of Bengbu Medical College. 1995;20(4):222-223.
  16. Mao Hui Sheng, et al. Matrine’s regulatory effect on immunity and on the malign expression of tumor cells. China Journal of Clinical Research on Tumor. 1996;23(11):799-803.
  17. Xu Jian Guo, et al. Ku Shen decoction’s effect on the differentiation of human promyelocytic leukemia cell. China Journal of Chinese Medicine. 1990;15(10):625-626.
  18. Lin Hong Sheng, et al. The effects of ligustrazine and matrine on the adherence of tumor cells and endothelial cells, and on the expression of adherent factors. China Journal of New Herbal Medicine. 1999;8(6):394-386.
  19. Hu Zhen Lin, et al. Matrine’s effects on in vitro mouse splenocytes’ proliferation and peritoneal macrophages’ release of IL-1 and IL-6. China Journal of Pharmacology. 1996;17(3):259-261.
  20. Wang Hui Xian, et al. Oxymatrine’s effect on the proliferation of lymphocytes. Journal of Chinese Materia Medica. 1994;25(7):362-363, 389.
  21. Zhu Li, et al. Ku Shen total alkaloids’ effect on mouse splenocytes’ production of interferon. Journal of Shanghai Second Medical University. 1998;18(3):104-106.
  22. Chen Wei Zhong, et al. Matrine’s effect on experimental rat liver fibrosis. Journal of Second Military Medical College. 1996;17(5):424-426.
  23. Hu Zhen Lin, et al. Matrine’s effects on lipopolysaccharides (LPS)/D-GALN-induced mouse hepatitis and LPS-induced release of TNF. China Journal of Pharmacology. 1996;17(4):351-353.
  24. Yin Jin Zhu, et al. Ku Shen’s mechanism in treating type I allergic reaction. Journal of Beijing Medical University. 1993;25(2):84-86.
  25. Li Yu Hao, et al. Ku Shen’s effect of reinforcing the middle warmer and strengthening the stomach. Journal of Guangzhou College of TCM. 1992;9(2):83-85, 92.
  26. Xin Shun Mei, et al. Matrine’s anti-diarrheic effects. Journal of Chinese Patented Medicine. 1998;20(5):30-32.
  27. Shen Ya Qin, et al. The anti-diarrheic and anti-inflammatory effects of 13a-hydroxymatrine. China Journal of Pharmacology and Toxicology. 1994;8(3):206-208.
  28. Wang Jun Xue, et al. The effects of oxymatrin and glycyrrhizin on the apoptosis of mouse liver cells. Journal of Second Military Medical College. 1999;20(4):222-224.
  29. Cui Shan Tian, et al. Ku Shen’s effects on the sister chromatid exchange rate of chick-embryo cells and the micronucleus rate of mouse bone marrow polychromatic erythrocytes. Journal of Yanbian College of Medicine. 1990;13(4):261-262.
  30. Tian Di, et al. The effects of 4 Ku Shen alkaloids on the proliferation of human keratin cells. Journal of Applied Integrated Medicine. 1997;10(11):1110-1111.
  31. Niu Yun Tong, et al. The clinical significance of oxymatrine’s effect on mice’s Langerhans cells. Journal of Traditional Chinese Medicine and Herbs. 1997;25(5):50-51.
  32. Pei Ren Jiu, et al. Matrine’s effects on fibroblast proliferation and collagen synthesis in rats. Strait Journal of Pharmacy. 1998;10(1):1-2.