General

Scientific Names: Stephania tetrandra

Common Names: Han Fang Ji, Fen Fang Ji, Bai Mu Xiang.

BOTANICAL:

来 源： 为防己科植物石蟾蜍Stephania tetrandra S. Moore的根。

植物特征：多年生落叶缠绕藤本。茎纤细，有纵条纹。叶互生，宽三角状卵形，先端钝，具小突尖，基部截形或略心形，两面均被短柔毛，全缘，掌状脉5条；叶柄盾状着生。花小，单性，雌雄异株；雄花序为头状聚伞花序，排成总状，萼片4，花瓣4，雄蕊4，花丝连成柱状体，上部盘状，花药着生其上；雌花萼片、花瓣与雄花同，心皮1。核果球形，熟时红色。花期5～6月，果期7～9月。

资源分布: 生于山坡、丘陵地带的草丛及灌木林缘。主产浙江、安徽、湖北、湖南。

生药材鉴定： 根不规则圆柱形，或剖切成半圆柱形或块状，常弯曲，弯曲处有深陷横沟而呈结节状，长5～15cm，直径1～5cm。表面灰黄色，有细皱纹及横向突起的皮孔。质坚重，断面平坦，灰白色，粉性。气微，味苦。

Pharmacology

化学成分: 含多种异喹啉生物碱，主要有粉防己碱（tetrandrine ）、防己诺林碱（fangchinoline）、轮环藤酚碱（cyclanoline）、二甲基粉防己碱（dimethyltetrandrine）以及小檗胺（berbamine）等。

Efficacy

Tetrandrine is an antitumor alkaloid isolated from the root of Stephania tetrandra. We find that micromolar concentrations of tetrandrine irreversibly inhibit the proliferation of human colon carcinoma cells in MTT and clonogenic assays by arresting cells in G(1). Tetrandrine induces G(1) arrest before the restriction point in nocodazole- and serum-starved synchronized HT29 cells, without affecting the G(1)-S transition in aphidicolin-synchronized cells. Tetrandrine-induced G(1) arrest is followed by apoptosis as shown by fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated nick end labeling, and annexin V staining assays. Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively, these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1). (source)

Tetrandrine, a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, induces apoptosis in human T-cell lines, lung carcinoma and hepatoblastoma cells. However, the mechanisms by which tetrandrine inhibits tumor cell growth are poorly understood. The purpose of the present study was to investigate the intracellular signaling mechanism of tetrandrine-induced apoptosis in HepG2 cells. The induction of apoptosis was determined by morphological analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Treatment of cells with tetrandrine caused the upregulation of p53, downregulation of Bcl-X(L), cleavage of Bid and Bax, and release of cytochrome c, which were accompanied by activation of caspases 9, 3 and 8. The activation of caspases 9 and 3 preceded that of caspase 8. A broad-spectrum caspase inhibitor and a caspase 8-specific inhibitor completely blocked tetrandrine-induced Bid processing, cytochrome c release, activation of caspase 3, and cell death. These findings and data showing the early release of cytochrome c, cleavage of Bid and downregulation of Bcl-X(L) suggest that the mitochondrial pathway is primarily involved in tetrandrine-induced apoptosis. The activation of caspase 8 after early caspases 9 and 3 activation might act as an amplification loop for activation of upstream signals such as Bid cleavage or cytochrome c release. These data suggest that tetrandrine may constitute a plausible therapeutic for hepatocellular carcinoma. (source)

Tetrandrine, isolated from the root of Stephania tetrandra, has been used in Chinese medicine for the treatment of silicosis and arthritis, and it also has anti-tumor/growth activities. However, the signaling pathways of tetrandrine-induced growth arrest and apoptosis in cancer cells remain unclear. We investigated the molecular mechanisms of tetrandrine-induced apoptosis and growth arrest in human lung carcinoma cells. Upon treatment with tetrandrine, a time-dependent inhibition of cell growth was observed and cells developed many of the hallmark features of apoptosis. Flow cytometry analysis confirmed that tetrandrine increased populations of both apoptotic sub-G1 and G1 phase. Tetrandrine-induced growth inhibition was associated with induction of Cdk inhibitor p21, inhibition of cyclin D1 and activation of caspase-3. Tetrandrine also affected the expression patterns of cytoskeletons including distribution of F-actin and expression level of microtubule. These results suggest that tetrandrine merits further investigation as a cell cycle blocker as well as a cancer chemopreventive agent. (source)

IN VITRO:

1. Meng LH, et al., Tetrandrine induces early G1 arrest in human colon carcinoma cells by down-regulating the activity and inducing the degradation of G1-S-specific cyclin-dependent kinases and by inducing p53 and p21Cip1. Cancer Res. 2004 Dec 15; 64(24):9086-92.
2. Oh SH, et al., Induction of apoptosis in human hepatoblastoma cells by tetrandrine via caspase-dependent Bid cleavage and cytochrome c release. Biochem Pharmacol. 2003 Sep 1; 66(5):725-31.
3. Nortier JL, et al., Renal interstitial fibrosis and urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). Toxicology. 2002 Dec 27; 181-182:577-80. Review.
4. Lee JH, et al., Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells. Int J Oncol. 2002 Dec; 21(6):1239-44.
5. Ye Z, et al., [Synergistic interaction between Ys-96, a bisbenzylisoquinoline compound derived from Stephania tetrandra, and adriamycin or vincristine against human cancer cell lines in vitro]. Zhongguo Zhong Yao Za Zhi. 1999 Sep; 24(9):556-9, 576. Chinese.
6. Nortier JL, et al., Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med. 2000 Jun 8;342(23):1686-92.
   
   

Safety

用药忌宜: 阴虚而无湿热者慎服。①《本草经集注》：“殷孽为之使。恶细辛。畏萆薢。杀雄黄毒。” ②《药性论》：“木防己，畏女菀、卤咸。”③李杲：“上焦湿热者，不可用。”④《本草经疏》： “凡胃虚阴虚，自汗盗汗，口苦舌干，肾虚小水不利，及胎前产后血虚，虽有下焦湿热，均忌。”⑤《得配本草》：“气分风热，小便不通，禁用。”