General

Scientific Names: Taxus brevifolia.

Common Names: Duan Ye Zi Shan , Duan Ye Hong Dou Shan, Tai Ping Yang Zi Shan, Tai Ping Yang Hong Dou Shan.

 

BOTANICAL:

来 源： 红豆杉科短叶红豆杉（Taxus brevifolia.） 植物的树皮。

植物特征： 小灌丛或矮树，15(－25)m，雌雄异体，主干高6(－12)dm，直立或弯曲，具有凹槽，树冠呈倒圆锥形。树皮附有鳞片。鳞片外部呈淡紫色至紫褐色， 内部呈淡红色至紫红色。枝条水平排列或下垂。叶片长1-2.9cm，宽1－3mm，淡绿色，螺旋状排列，表皮气孔带有乳突，亮黄绿色，叶子表皮细胞从横截 面看大多比宽高。种子具2－4棱角，5－6.5mm。

 

 

 

Pharmacology

 

 

 

Efficacy

Produced by and purified from Taxus brevifolia, Taxol (paclitaxel) has become a widely used cancer drug in clinic. Due to the rapid growing market, current industrial production of taxol by semi-synthesis that consumes large amount of Taxus trees cannot meet the requirement of the market. The discovery of taxol-producing fungus Taxomyces andeanae, an endophyte of T. brevifolia, by Stierle et al (1993), paves a new way to the production of the drug, i.e. employing large-scale fungal fermentation to make Taxol at lower cost and yet higher yield. This review discusses the present problems in taxol production in pharmaceutical industry, the finding and research progress on taxol-producing fungi, and the potential application of fungal fermentation to manufacture this important drug. (source)

Herbs have been considered natural and valuable sources for anticancer drug discovery. Herbal medicine has been prescribed in many countries over centuries for treating various diseases including infectious and malignant diseases. Nowadays, many of the drugs that have been used for treatment of malignant diseases are derived from natural products such as Taxol, a natural product isolated initially from Pacific Yew (Taxus brevifolia). This review article describes research on molecular mechanisms, especially cytotoxic effect of natural products from plant sources, primarily preclinical studies, involving human lung cancer cells in vitro for providing more knowledge and issues for potential drug development from medicinal herbs in the future. (source)

Baccatin III, an intermediate of Taxol biosynthesis and a useful precursor for semisynthesis of the anti-cancer drug, is produced in yew (Taxus) species by a sequence of 15 enzymatic steps from primary metabolism. Ten genes encoding enzymes of this extended pathway have been described, thereby permitting a preliminary attempt to reconstruct early steps of taxane diterpenoid (taxoid) metabolism in Saccharomyces cerevisiae as a microbial production host. Eight of these taxoid biosynthetic genes were functionally expressed in yeast from episomal vectors containing one or more gene cassettes incorporating various epitope tags to permit protein surveillance and differentiation of those pathway enzymes of similar size. All eight recombinant proteins were readily detected by immunoblotting using specific monoclonal antibodies and each expressed protein was determined to be functional by in vitro enzyme assay, although activity levels differed considerably between enzyme types. Using three plasmids carrying different promoters and selection markers, genes encoding five sequential pathway steps leading from primary isoprenoid metabolism to the intermediate taxadien-5alpha- acetoxy-10beta-ol were installed in a single yeast host. Metabolite analysis showed that yeast isoprenoid precursors could be utilized in the reconstituted pathway because products accumulated from the first two engineered pathway steps (leading to the committed intermediate taxadiene); however, a pathway restriction was encountered at the first cytochrome P450 hydroxylation step. The means of overcoming this limitation are described in the context of further development of this novel approach for production of Taxol precursors and related taxoids in yeast. (c) 2005 Wiley Periodicals, Inc. (source)

Taxol (paclitaxel), a complex diterpene obtained from Taxus brevifolia and its semisynthetic analogue Taxotere are two of the most important new drugs for cancer chemotherapy. Their mechanism of cytotoxic action involves stabilization of microtubules leading to mitotic arrest. A similar mechanism has been proposed for an expanding set of other natural products, for instance, the epothilones, eleutherobin, the sarcodictyins, discodermolide, laulimalide, Rhazinilam, WS9885B, certain steroids and a group of polyisoprenyl benzophenones. In this review, we focus on the conformations of small molecule microtubule (MT) stabilizing compounds which have been isolated or synthesized and subjected to structural analysis. NMR and fluorescense spectroscopies, X-ray crystallography, high resolution microscopy (electron crystallography) and theoretical calculations comprise the most common methods used in this context. In particular, we describe how the structures were determined and with what accuracy. We also discuss the conformational diversity apparent from the three dimensional structures and compare the various proposals for bioactive conformations at the target MT binding sites. Of critical importance are the recently disclosed models for Taxol and its biomimetics binding to beta-tubulin. Several different conformational schemes derived from both pharmacophore construction and modeled protein ligand complexes are compared and critically evaluated. Although full consensus has yet to be reached, emphasis is placed on pharmacophore models for the various anti-MT agents that are internally consistent and encompass more than one structural class. (source)

1960年代後期，在美國國家癌症署所進行的大型抗癌物質篩選計劃中，發現一個由太平洋紫杉（Taxus brevifolia）樹皮所提煉而得到的粗萃取物，它具有對抗P388鼠白血病細胞株的活性。科學家分離出該萃取物中的活性分子，此即為 paclitaxel。 Paclitaxel於數種不同的惡性腫瘤已證實其抗癌作用，特別是卵巢癌與轉移性乳癌。在1995年美國食品藥物管理局核准使用的抗癌藥物50種之中， 最引人注目且於近期內通過國內衛生主管機關審核上市的化療新藥，便是太平洋紫杉醇(Paclitaxel)。

Paclitaxel具有獨特的作用機轉，它可影響細胞內的微管系統。細胞分裂時會形成大量管狀構造，也就是有絲分裂時的 線狀構造，在染色體分佈至兩子細胞後這微管系統便進行分解，而完成細胞分裂，Paclitaxel可抑制微管系統的分解過程，使細胞被"固定"在分裂的過 程中而死亡。因此Paclitaxel作用係一有絲分裂的抑制劑，可阻斷細胞於細胞周期之G2與M期。

早期研究發現Paclitaxel對於某些惡性黑色素瘤、白血病及惡性肉瘤細胞株具有抗癌之作用。美國國家癌症署在1983開始展開人體臨床試驗來測試其毒性及抗癌活性。有報告在其它化學治療失敗的卵巢癌患者Paclitaxel可達到30 %的緩解率，雖然平均緩解期只有四個月，但傳統上這類患者已無其它有效治療。在晚期乳癌的患者學者也發現Paclitaxel 也具有相當之療效。在未接受過化學治療的晚期卵巢癌患者，合併使用Paclitaxel與Cisplatin比傳統的標準化療Cisplatin加Cyclophosphamide有更高的緩解率(77% 比62%)，同時又有較長的平均存活(36個月比23個月)，因此Paclitaxel與Cisplatin的合併使用成為第一線治療晚期卵巢癌的標準。

Paclitaxel用於其它惡性腫瘤的治療目前也正積極研究中。在非小細胞及小細胞肺癌，頭頸部鱗狀上皮癌，膀胱癌，生殖細胞瘤等均報告有相當療效，但 在腸胃道癌症如大腸直腸癌，胰臟癌及肝癌方面則無效果。文獻顯示，單獨使用Paclitaxel 250mg/m2於先前沒有治療過的小細胞肺癌其療效可達34% ，對先前沒有治療過的非小細胞肺癌也有21%至24%的療效。此外對先前未曾接受過化療或曾使用過化療但間隔已達一年或以上的頭頸部鱗狀上皮細胞癌的病 人，使用Paclitaxel 250mg/m2單一藥物治療亦有47%之療效。 (source)

紫杉醇对动物移植性肿瘤B16、Lewis肿瘤、P388和C38等癌细胞有较强抑制生长作用；对KB细胞集落形成的抑制强度超过长春新碱和秋水仙碱；还能使肝癌、乳腺癌、子宫癌、白血病、淋巴癌等癌细胞自然死亡，且癌细胞株自然死亡率随紫杉醇浓度升高而增加。


临床应用：紫杉醇对卵巢癌、乳腺癌、头颈部癌、非小细胞性肺癌，前列腺癌等均有较好的良效。

短叶红豆杉（Taxus drevifolia）主要分布在美国西北部和加拿大西南部，是一种矮小且生长缓慢的植物。从它的树皮中提取分离出来的一种二萜类生物碱成份———紫杉 醇，是一种有效的植物抗癌药。近年来的试验结果表明，它对KB细胞有显著的细胞毒作用，对P388、P1534白血病有很高的活性，能抑制W256肉瘤、 S180和 肺癌 的生长。在美国、法国进行的临床试验证明，紫杉醇对乳腺癌、肺癌、胃癌、卵巢癌有较好的作用，被认为是近10年来发现的一种最有希望的抗癌药物。 (source)

IN VITRO:

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  6. Rosangkima G. et al., Antitumour activity of some plants from Meghalaya and Mizoram against murine ascites Dalton's lymphoma. Indian J Exp Biol. 2004 Oct; 42(10):981-8.
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  9. Chattopadhyay SK, et al., Absolute configuration and anticancer activity of taxiresinol and related lignans of Taxus wallichiana. Bioorg Med Chem. 2003 Nov 17; 11(23):4945-8.
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  14. Mltchell AK, et al., Acclimation of Pacific yew (Taxus brevifolia) foliage to sun and shade. Tree Physiol. 1998 Nov; 18(11):749-757.
  15. Walsh V, et al., From taxol to Taxol: the changing identities and ownership of an anti-cancer drug. Med Anthropol. 2002 Jul-Dec; 21(3-4):307-36.
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  18. Eldridge GR, et al., High-throughput method for the production and analysis of large natural product libraries for drug discovery. Anal Chem. 2002 Aug 15; 74(16):3963-71.
  19. Price KS, et al., Taxol reactions. Allergy Asthma Proc. 2002 May-Jun; 23(3):205-8.
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