General

Scientific Names: Sophora flavescens Ait, Sophora japonica, Sophora alopecuroides L, Radix Sophorae. 

Common Names: Ku Shen, Ku Gan Cao, Ku Shen Cao, Ku Dou Gen, Xi Dou Gen, Ku Ping Zi, Ye Huai Gen, Shan Huai Gen, Gan Ren Shen, Ku Gu.

BOTANICAL:  

Sophora japonica (kushen) is a kind of perennial leguminous plants,Sophorae sp, top plant grow out spring, bloom, seed, dry in Winter, year after year. Sophora japonica (kushen) is a kind of plant could live in salt soil, soil as following could be ok for this herb: Salt ＜ 0.02%, CI- ＜ 0.06%, SO4- ＜ 0.1%, HCO3- ＜ 0.02%. Seeds left for broadcasting and branches dried and died out, new root grow out from old root the next spring,year after year, Sophora japonica (kushen) grow and make large area full, and it's self-renew ability is very strong. Sophora japonica (kushen) in nature mainly live on soil with sands, root cross with good tenacity, stem woodened, and good sand soil character, content in Sophora japonica (kushen) mainlyphyto protein, sugar, organic acid, pigment and alkaloid.

Sophora japonica (kushen) is a kind of Sub-Shrub, grow up to 50~120 cm, root column, skin outside appear yellow, stem and branches herbage like, color green, yellow hair on young stem. Singular feather shape leaves, cross grow, line shape stipule; leaves reach to 20-25cm length, with small leaves 5 to 21 pieces, oval shape, complete edge. flower 10-20cm, short hair, flower yellow to white,10 stamen, 1 pistil, bloom from May to July, fruit from july to September. Seed 3 to 7, color lack, similar ball shape.

Sophora japonica (kushen) grow widely on grass land, sand soil, road side, and red soil sunny side. Nearly 12 species from inland China, disperse in north west China, especially aggregate in NingXia Province, GanSu Province, QingHai Province, Xin Jiang Province, and NeiMengGu Province of China, especially large quantity in middle area of NingXia Province, such as Salt City, LingWu, TaoLe and other sand soil are a of NingXia Province which famous for thousands of herb medicine in west China. Sophora japonica (kushen) grow widely and disperse widely, also have good character of liveing in salt-soil and strong wind environment, so good for soil protection, and local farmers would like protect this plant Sophora japonica (kushen).

Herb Medicine: Dry root shape column, 10-30cm length, 1-2.4cm diameter, clear vertical crinkle on surface, lenticel pop out and turn over a little, extend crossly. Root skin thin, light yellow brown to gray browm, break out and turn over, easy to flake off and appear yellow skin part.root rigid and not easy to break, section shape crude fibre, cross section yellow to yellow white, clear cambium. Smells stimulate, taste bitter, Sophora japonica root pieces all think pieces, length 2-5cm, rigid, taste bitter and color yellow to white.

Root long-terete, with branching roots at the lower part; 10-30 cm long, 1-2 cm in diameter; with transverse and long lenticels on the cork, the peel usually dehiscing and curved outwards or separated. Prepared as crosscut pieces, with bundles radially arranged and cracks on the section, and annual rings visible in the old ones. Bitter in taste, cold in nature, and attributive to heart, liver; stomach, large intestine and urinary bladder channels.

落叶亚灌木。单数羽状复叶，小叶披针形至线状披针形，顶端渐尖，基部圆形，背面有平贴柔毛。总状花序顶生；花冠淡黄色，旗瓣匙形，翼瓣无耳；雄蕊 10 ，花丝仅基部愈合；子房柄被细毛。荚果线形。种子 3 ～ 7 粒，黑色，近球形。花期 5 ～ 7 月，果期 7 ～ 9 月。 生于向阳山坡灌丛、草地中。根圆柱形，下部常分叉，长 10 ～ 20cm ，直径 1 ～ 2.5cm 。表面棕黄色至灰棕色，有纵皱纹及横长线形皮孔。栓皮薄，常破裂外卷，脱落处显黄色。

1. 干燥根呈圆柱形，长 10-30cm，直径 1-2.4cm 。表面有明显纵皱，皮孔明显突出而稍反卷，横向延长。栓皮很薄，棕黄色或灰棕色，多数破裂向外卷曲，易剥落而显现黄色的光滑皮部。质坚硬，不易折断，折断面粗纤维状。横断面黄白色，形成层明显。气刺鼻，味极苦。苦参片为斜切的薄片，形状大小不一，斜圆形或长椭圆形，长 2-5cm ，宽 1-1.5cm ，厚约 2-5mm 。质坚硬，切面淡黄白色，有环状年轮，木质部作放射纹。以整齐、色黄白、味苦者为佳。全国各地均产，以山西、湖北、河南、河北产量较大。 2. 显微鉴定：根横切面：木栓层为多列木栓细胞。皮层狭窄。韧皮部散有纤维束，纤维束周围细胞含草酸钙方晶，形成晶纤维，含晶细胞的壁不均匀木化增厚；射线较宽而明显，几达至木栓层形成不成环。木质部导管放射状排列；木纤维束也为晶纤维。粉末：淡黄色。 2.1. 淀粉粒类圆形或长圆形，直径 4-22 μ m ，脐点裂缝状，大粒层纹隐约可见；复粒由 2-12 分粒组成。 2.2. 纤维细长，平直或稍弯曲，直径 11-27 μ m ，壁甚厚，非木化，孔沟不明显，胞腔线形。纤维束周围的细胞含草酸钙方晶，形成晶纤维，含晶细胞的壁不增均匀木化增厚；草酸钙方晶类双锥形、菱形或多面形。 2.3. 具缘纹孔导管直径 27-126 μ m ，具缘纹孔排列紧密，有的数个纹孔口连接成线状。也有网纹导管。 2.4. 薄壁细胞类圆形或类长方形，壁稍厚，有的呈不均匀连珠状，非木化，纹孔大小不一，有的集成纹孔域，有的胞腔含细小针晶。 2.5. 木栓细胞表面观类多角形，垂周壁有纹孔呈断续状，表面有不规则细裂纹。另偶见石细胞 。

Pharmacology

Three bioactive alkaloids in Sophora flavescens Ait. Wang Y, et al demonstrated that the proliferation of Human hepatoma cell lines SMMC-7721 was inhibited markedly, and the malignant cell form tended to normal differentiation. It was also found that matrine could inhibit cell invasion and metastasis related factors, including adhesive ability to FN, migrative ability through the polycarbonate filter, and invasive ability through matrigel. In conclusion, Matrine is a good differentiation inducer, it can not only inhibit the cell proliferation and induce the cell form differentiation, but also significantly inhibit the invasion and metastasis ability of SMMC-7721 through several steps, involved cell adhesion, migration and invasion (See Ref). Also, Tan MQ et al found the effects of Sophora flavescens (SF) on CFU-GM proliferative ratio in human normal bone marrow/umbilical cord blood and on proliferation, differentiation and apoptosis in human acute myelogenous leukemia HL-60 cells by using CFU-GM/CFU-L colony assay, NBT/MTT reductant test and DNA fragmentation analysis. The results showed that 5, 10, 15, 20 micrograms.microliter-1 of SF significantly inhibited proliferation and induced apoptosis in the HL-60 cells in a dose-dependent fashion (See Ref).

In addttion, among 11 isoflavones tested, genistein [YS13] produced higher cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) than against normal cells (human gingival fibroblast, HGF), suggesting its tumor-specific action. Electron spin resonance (ESR) spectroscopy showed that YS13 did not produce radical, nor scavenged O2*- generated by hypoxanthine-xanthine oxidase reaction system, suggesting that radical-mediated oxidation mechanism is not be involved in the YS13-induced cytotoxicity. Addition of one prenyl group produced YS18 and YS19 with higher anti-Helicobacter pylori activity. Addition of two prenyl groups produced YS21 with the highest cytotoxic activity but lower tumor-specificity. Since YS21 produced the highest amount of radical and most efficiently scavenged O2*-, this compound may induce cytotoxicity by radical-mediated oxidation mechanism. All isoflavones failed to induce anti-human immunodeficiency virus (HIV) activity. These data suggest the medicinal efficacy of isoflavones.

Researchers begin to do research on Sophora japonica from 30th of last century by Russia Sceintist,Chinese Sceintists begin research on Sophora japonica pieces from early 70th of last century, all research pay much attention on phyto alkaloids,scientists and professionals from china now developed out successfully alkaloids from Sophora japonica root as following:

Oxymatrine (C15H24N2O2), Matrine (C15H24N2O), Iosmatrine (C15H24N2O), sophor-anol, Sophocarpine (C15H22N2O), N-oxysophocarpine (C15H22N2O2), Sophoridine (C15H24N2O), Aloperine, Sparteine, N－methylcytisine, Anagyrine, bap-iifoline, Sophocarpine, d-Matrine, d－isomatrine, d-Oxymatrine, l-Anagyrine, l-Methyleytisine, Baptifoline, kurarid-in, Sophoranol, C15H24N2O2, SophoranholN-oxide (C15H24N2O3), N-ethylcytisine (C12H16N2O), all these are bio alkaloids from root of Sophora japonica. They belong to tetracyclo-quinolizindine alkaloids.

Bio flavones from Sophora japonica root：Sophora japonica root flavones normally as following: Norkurarinone (C25H28O6), Kuraridinol; Kurarinol, Neo－kurarinol, Norkurarinol, isokurarinon (C26H30O6), Maackiain (C16H12O5), 4-methoxy-maackiain (C17H14O6), Trifolirhizin (C22H22O10), Nor-anhydroicaritin (C20H18O6), Sophoraflavanone B (C20H20O5), Formoronetin (C16H12O4), and other bio-flavones, such as Xanthohumol, Isoxanthohunol; 3, 4, 5-Tri-7-Meth-8-prenylkeamferol; Stem and Leaves contain Luteolin-7-glucoside.

1. Matrine and oxymatrine counter the arrhythmia induced by chloroform-adrenaline or aconitine, and its injection slows heart rate and weakens myocardial contractility in experimental animals.
2. Inhibitory on the contraction of sensitized guinea-pig intestine and release of allergic medium in vitro.
3. Antiasthmatic and expectorant.
4. Bacteriostatic, antiamebic and trichomonacidal.
5. Matrine 30 mg/kg and oxymatrine 100 mg/kg on X-ray induced leukopenia in rabbits.
6. Inhibitory on sarcoma180 in mice.

1. Shirataki Y, Tani S, et al Relationship between cytotoxic activity and radical intensity of isoflavones from Sophora species. Anticancer Res. 2001 Jul-Aug.
2. Ko WG, Kang TH, et al Lavandulyl flavonoids: a new class of in vitro apoptogenic agents from Sophora flavescens. Toxicol In Vitro. 2000 Oct.
3. Kojima R, Fukushima S, et al Antitumor activity of Leguminosae plants constituents. I. Antitumor activity of constituents of Sophora subprostrata. Chem Pharm Bull (Tokyo). 1970 Dec.

含苦参碱 (matrine) 、氧化苦参碱 (oxymatrine) 、苦参醇碱 (sophoranole) 、 N- 甲基金雀花碱 (N-methylcytisine) 、安那吉碱 (anagyrine) 、膺靛叶碱 (baptifoline) 、脱氢苦参碱 (sophocarpine) 、 d- 异苦参碱 (d-isomatrine) 、苦参啶 (kuraridin) 、去甲苦参酮 (norkurarinone) 、苦参碇醇 (kuraridinol) 、苦参醇 (kurarinol) 、新苦参醇 (neo-kurarinol) 、去甲苦参醇 (norkurarinol) 、异苦参酮，另含芒丙花黄素 (formononetin) 。

根含多种生物碱 (1%-2.5%) ，以 d- 苦参碱 (d-matrine) 及 d- 氧化苦参碱 (d-oxyma-trine) 为主，两者含量之比，因产地不同差别很大，我国东北产苦参中氧化苦参碱含量较多。另含微量 d- 苦参醇碱 (d-sophoranole) 、 l- 臭豆碱 (l-anagyrine) 、 l- 甲基金雀花碱（ l-methylcytisine ）、 l- 野靛叶碱 (l-baptifoline) 、 l- 槐果碱 (l-sophocarpine) 、 N- 氧化槐果碱 (N-oxysophocarpine) 、 l- 乙基槐明碱 (l-ethylsophoramine) 、槐定碱 (sophoridine) 、粉防己碱等。黄酮类化合物有苦参 (kurarinone) 、异苦参素 (isokurarinone) 、去甲苦参素 (norkurarinoe) 、次苦参素 (kuraridin) 、苦参醇素 (kutstinol) 、次苦参醇素 (kuraridinol) 、新苦参醇素 (neokurarinol) 、去甲苦参醇素 (norkurarinol) 、去甲脱水淫羊霍素 (noranhydroicaritin) 、异脱水淫羊霍素 (isoanhydroicaritin) 、蛇麻素 (xanthohumol) 、异蛇麻素 (isoxanthohumol) 及三叶豆高丽槐甙 (trifolirhizin ， l-maackiain- β -D-glucoside) 等。

Efficacy

The root of Sophora flavescens has been reported to possess antitumor activity in Sarcoma 180, lymphoid leukemia 1210 and melanotic melanoma.

IN VITRO:

1. Xu J, Ma J, Yang G. Differentiation of human leukemia cell (HL-60) induced by Sophora flavescens ait. Decoction. Zhongguo Zhong Yao Za Zhi, 1990 Oct.
2. Kajimoto S, Takanashi n, et al Sophoranone, extracted from a traditional Chinese medicine Shan Dou Gen, induces apoptosis in human leukemia U937 cells via formation of reactive oxygen species and opening of mitochondrial permeability transition pores. Int J Cancer. 2002 Jun 20.
3. Ko WG, Kang TH, et al Lavandulylflavonoids: a new class of in vitro apoptogenic agents from Sophora flavescens. Toxicol In Vitro. 2000 Oct.
4. Shirataki Yi, et al Cytotoxicty and radical modulating activity of isoflavones and isoflavanones from Sophora species. Anticancer Res. 2004 May-Jun.
5. Xiang Q, et al [Anti-leukemia effect of sophora flavescens combined with the low molecular weight natural tumor suppressor of the human fetal liver and its mechanism]. Hunan Yi Ke Da Xue Xue Bao. 2002 Apr28.
6. Tashiro M, et al Effects of prenylflavanones from Sophora species on growth and activation of mouse macrophage-like cell line. Anticancer Res. 2002 Jan-Feb.
7. Shirataki Y, et al Relationship between cytotoxic activity and radical intensity of isoflavones from Sophora species. Anticancer Res. 2001 Jul-Aug.
8. Kang TH, et al Cytotoxic lavandulyl flavanones from Sophora flavescens. J Nat Prod. 2000 May.
9. Wang Y, et al [Study on invasion and metastasis related factors in differentiation of SMMC-7721 cells induced by matrine]. Zhong Yao Cai. 2003 Aug.

IN VIVO:

1. Li XR. The effect of Sophora flavescens ait alkaloid on transplante neoplasm in mice . Zhong Xi Yi Jie He Za Zhi, 1982 Jan.

CLINICAL:

1. 抗肿瘤作用：苦参碱具有抗癌活性，小鼠腹腔注射 500 μ g.d 组 2mo 存活率为 40% ，而对照组在 23 天内全部死亡。氧化苦参碱则对此无作用。苦参碱在体外具有降低小鼠腹腔巨噬细胞抑制 P815 肿瘤细胞增殖的效应。槐果碱（ Sophocarpine ）亦有抗癌活性，在实验小鼠体内对 S-180 、 U-14.ECA 、 L 等瘤株均表现明显的抑制作用。苦参碱、氧化苦参碱、槐果碱及其不同比例混合的 A 、 B 、 C 碱对 S-180 实体瘤均有不同程度的抑制作用，各单体生物碱的抑瘤率均在 35% 以上，经不同比例混合的 C 碱剂量在 113mg／kg · d ）时，连续腹腔注射给药 10 天抑瘤率达 61.38% ，比总碱提高 23.5% ，与单纯苦参碱相比，有显著差异（P ＜ 0.01 ＝。苦参碱对慢性粒细胞白血病外周多向造血祖细胞集落产生率有显著的抑制作用，抑制率达 0.76 ，最佳抑制浓度为 100mg／L 。苦参水煎液作用于体外培养的人早幼粒白血病细胞，在剂量为 8mg／ml 时，可显著地诱导白血病细胞向单核巨噬细胞方向分化。

Safety

In TCM, this is considered very cold and bitter. Those with liver and kidney deficient but without heat do not use. Not compatible with bei mu ( Fritillaria), tu si zi (Cuscuta chinensis Lam), lou lu (Stemmacantha uniflora L. Dittrich).

苦参碱注射于家兔，发现中枢神经麻痹现象，同时发生痉挛，终则呼吸停止而死。注射于青蛙，初呈兴奋，继则麻痹，呼吸变为缓慢而不规则，最后发生痉挛，以致呼吸停止而死；其痉挛的发作，恐系起因于脊髓反射的亢进。对家兔的最小致死量为 0.4g／kg 。苦参生物碱对冷血和温血动物均有引起痉挛和麻痹呼吸中枢的作用。接受较大剂量药物的小鼠出现燥跳、痉挛性抽搐等兴奋现象；静脉注射家兔开始出现畏惧不安，最后呼吸困难而死亡。槐果碱当大剂量（150mg/kg）注入家兔体内时，引起静脉充血、血压下降、呼吸次数明显减少，呼吸麻痹而中毒死亡。苦参生物碱 LD50 测定结果报道不一致。苦参总黄酮给小鼠静脉注射的 LD50 为 103.1 ± 7.66g／kg。小鼠肌肉注射和静脉注射氧化苦参碱的 LD50 分别为 256.74 ± 573.6mg／kg 和 144.2 ± 22.8mg／kg 。灌胃和肌肉注射苦参浸膏小鼠的 LD50 分别为14.5g／kg 和 14.4g／kg。小鼠皮下注射苦参结晶碱的 LD50 为 571.2 ± 48.8mg／kg 犬肌肉注射苦参碱结昌（200mg／kg）或苦参浸膏（0.1g／kg），鸽肌肉注射苦参生物碱（100mg／kg）均未见中毒症状。苦参避孕栓对小白鼠阴道、宫颈无刺激性。