Taxus brevifolia - Western Yew

Family: Taxaceae (Yew family) [E-flora]

[E-flora]

Origin Status: Native [E-flora]

Identification

Taxus brevifolia is an evergreen Tree growing to 15 m (49ft 3in) at a slow rate. [PFAF]

It is hardy to zone (UK) 6 and is not frost tender. It is in leaf 12-Jan It is in flower from Mar to May, and the seeds ripen from Sep to November. The flowers are dioecious (individual flowers are either male or female, but only one sex is to be found on any one plant so both male and female plants must be grown if seed is required) and are pollinated by Wind.The plant is not self-fertile. [PFAF]
Suitable for: light (sandy), medium (loamy) and heavy (clay) soils and prefers well-drained soil. Suitable pH: acid, neutral and basic (alkaline) soils and can grow in very acid and very alkaline soils.
It can grow in full shade (deep woodland) semi-shade (light woodland) or no shade. It prefers dry or moist soil. The plant can tolerates strong winds but not maritime exposure.
It can tolerate atmospheric pollution.[PFAF]

The Pacific or western yew is a small (to 15 m) evergreen coniferous trees species that is native to the Pacific Northwest of North America where is is found in Alberta, British Columbia, Alaska, Washington, Oregon, Idaho, Montana and California (Hils 2011). In British Columbia, this species is common in coastal areas and in the south-central and south-eastern regions of the province in the lowland and montane zones (Douglas et al.2000). Habitat range from "open to dense forests, along streams, moist flats, slopes, deep ravines, and coves" (Hils 2011). [E-flora]
The Pacific yew is on the IUCN red list of threatened species: "Native populations have been under considerable pressure from the scale of exploitation of the bark by pharmaceutical companies." (Conifer Specialist Group 1998). This species is a source of the cancer drug taxol (Hils 2011). [E-flora]

Similar Species: "Two introduced species, Japanese yew (Taxus japonicus), a popular ornamental landscaping shrub, and English yew (Taxus baccata), are poisonous and can be found wild throughout the Northwest." [Krumm PNBB]

Ecological Indicator Information
A shade-tolerant, submontane to subalpine, Western North American conifer distributed equally in the Pacific and Cordilleran regions. Occurs in cool temperate and cool mesothermal climates; its occurrence increases with increasing precipitation and decreases with increasing latitude and elevation. Scattered in coniferous forests; common on water-receiving sites, frequent on water-collecting sites, and occasional on water-shedding sites. Characteristic of temperate and mesothermal coniferous forests.(Information applies to coastal locations only)[IPBC][E-flora]


Food Uses

Other Uses

Medicinal Uses


Toxicology

"Until more research is available, yew should not be used during pregnancy and breastfeeding. It should not be given to children. Yew should not be used by persons who have hepatic disease or who are immunocompromised. Persons with hypersensitivity to yew should not use it. Yew is highly toxic and should be used only under the supervision of a skilled herbalist." [Skidmore-Roth MHH]

"The Chehali say that uva-ursi smoke causes a “drunken feeling” when inhaled. A S’Klallam man even warned against mixing yew needles (Taxus brevifolia Nutt.) and uva-ursi because the blend would have “too strong of an effect” (Gunther 1988, 44*)." [Ratsch EPP]

Taxus Sp
Exposure: Aqueous extracts of yew are an Indian folk medicine (i.e., Zarnab) used for their cardiotonic, expectorant, antispasmodic, diuretic, and antiseptic properties. 12 Extracts of Taxus celebica (Warb.) H. L. Li contain a flavonoid (sciadopitysin) used in traditional Chinese medicine for the treatment of diabetes mellitus. Paclitaxel (Taxol ® , Bristol -Myers Squibb Company, Princeton, NJ) and docetaxel (Taxotere ® , Sanofi - Aventis, Bridgewater, NJ) are semisynthetic derivatives of the bark of T. brevifolia (Pacific yew) and T. baccata (European yew), respectively. These compounds are spindle poisons that possess antitumor activities. Paclitaxel is also used as a starting skeleton for other chemotherapeutic agents and in paclitaxel - eluting stents in cardiovascular therapies. 13 Japanese and English yew plants are ornamental shrubs with red berries[TNS]
PRINCIPAL TOXINS Physiochemical Properties
Taxus species contain more than 350 naturally occurring taxoids (taxane diterpenoids).
Taxanes are novel compounds that share a complex taxane ring (baccatin III). This class of compounds includes the chemotherapeutic agent, paclitaxel fromT. brevifolia and docetaxel fromT. baccata . The concentration of taxanes in the low trailing shrub, Canadian yew (Taxus canadensis ) differs for other yews. This plant contains a variety of uncommon taxanes.
Poisonous Parts
Taxine alkaloids are present in all parts of the yew plant except the edible scarlet aril (berry). [4] The taxine content of yew plants varies with season and species. Maximal taxine concentrations occur in winter, and taxines are relatively abundant in English yew (T. baccata ) and Japanese yew (T. cuspidata ) compared with Pacific yews (T. brevifolia ).[2]
Mechanism of Toxicity
Taxine B is the principal cardiotoxin inTaxus species. In isolated papillary muscle preparations, taxine B significantly reduces the maximum rate of depolarization of the action potential similar to class I antiarrhythmic drugs (fl ecainide, quinidine, procainamide). 19 The mechanism of toxicity is an alteration of calcium and sodium channel conductance that increases cytosolic calcium concentrations. The clinical consequence of these alterations is hypotension, bradycardia, and depressed myocardial contractility and conduction delay, similar to digitalis poisoning. 20 Taxanes (paclitaxel, docetaxel) are spindle poisons that possess antitumor activity as a result of the binding of these compounds toβ - subunit of tubulin causing microtubule polymers, mitotic arrest, and cell death. Postmortem examination of patients dying of yew poisoning is usually nonspecific with generalized congestion of internal organs, dilation of the ventricles, and unremarkable microscopic findings. Histological evidence of taxine poisoning on postmortem examinations included alveolar hemorrhagic edema, focal pulmonary hemorrhages, and pronounced interstitial myocardial edema with early signs of ischemia (swollen nuclei, homogenization and eosinophilia of the sarcoplasm, perinuclear vacuolization). 21 Immunohistochemical staining for troponin C was positive with depletion of troponin C in many areas of the left ventricles.
DOSE RESPONSE
Most casual ingestions of berries result either in no symptoms or in mild gastrointestinal distress. After the ingestion of at least 5 whole leaves and 10 seeds, a 19 - month - old toddler remained asymptomatic following the administration of syrup of ipecac. 22 The fatal dose of yew leaves is unknown, but the estimated lethal dose of chopped yew leaves is about 50 – 100 g. The ingestion of 150 yew leaves (Taxus baccata ) by a 40 - year - old woman 23 and four to five handfuls of yew leaves by a psychiatric patient produced ventricular tachycardia, refractory cardiogenic shock, and death. [20]
CLINICAL RESPONSE
Most cases of yew berry ingestion result in no symptoms. Symptomatic patients typically develop gastrointestinal distress about 1 – 3 hours after ingestion. Serious cardiac toxicity may occur after large ingestions including ventricular dysrhythmias, intraventricular conduction delay, cardiogenic shock, and death. 27 Lightheadedness, nausea, and abdominal pain developed within 1 hour after the ingestion of four to five handfuls of yew leaves ingestion, followed by coma, wide complex ventricular tachycardia, QRS prolongation, and cardiopulmonary arrest. 20 Several case reports associate the administration of the flavonoid, sciadopitysin, from traditional Chinese extracts of Taxus celebica (Warburg) H. L. Li with acute interstitial nephritis, hemolysis, and acute tubular necrosis. 28 Allergic responses may develop following exposure to yew. Case reports associate chewing yew needles with the immediate onset of anaphylactic shock, 29 and cutting yew wood with a severe contact dermatitis. 30 [TNS]

Scientific Name Taxus species
Mechanism of Toxic Action All parts of the plant are toxic except the red fleshy aril; the toxin appears to inhibit sodium and calcium current in cardiac cells causing a block of the distal portion of the conduction tissue of the heart; the hard seed coat is resistant to digestive enzymes and is nontoxic unless chewed or broken
Adverse Reactions Cardiovascular: Sinus bradycardia, sinus tachycardia, arrhythmias (ventricular)
Signs and Symptoms of Overdose Abdominal pain, asthenia, AV block, cardiac arrhythmias (sinus bradycardia, ventricular tachycardia, ventricular fibrillation, heart block), coma, contact dermatitis, cyanotic lips, dizziness, headache, hypokalemia, hypotension, mydriasis, nausea, pale complexion, respiratory distress/arrest, seizures, tachycardia, vomiting. Death is usually secondary to arrhythmias, circulatory collapse, or respiratory failure.
Admission Criteria/Prognosis Asymptomatic patients with normal electrocardiogram and electrolytes can be discharged after a 12-hour observation; any symptomatic patient should be admitted to a cardiac monitor bed; patients who are symptomatic 3 hours postexposure should be admitted
Toxicodynamics/Kinetics Onset of symptoms: Generally within 1-3 hours; in large ingestions, cardiovascular collapse can occur within 30 minutes
Reference Range Postmortem 3,5-dimethoxyphenol blood and bile levels of 21 ng/mL and 104 ng/mL, respectively, were noted in a male who died of yew toxicity.
Overdosage/Treatment
Decontamination: Ipecac is contraindicated secondary to rapid onset of symptoms; lavage is of questionable benefit, due to the large size of the seeds, unless the seeds are chewed well; activated charcoal with sorbitol is recommended; do not consider gastric decontamination if fewer than 6 berries are ingested; whole bowel irrigation is beneficial for ingestions of large amounts of plant material
Supportive therapy: Hypotension can be resistant to dopamine and dobutamine, and may require norepinephrine; bradycardia and complete heart block has on occasion been resistant to atropine; external pacing and/or digoxin immune Fab may be of benefit; monitor electrolytes; anaphylactoid reactions should be treated with epinephrine, antihistamines and fluids. Dysrhythmias with widened QRS complex should be treated with I.V. sodium bicarbonate.
Antidote(s)
-Digoxin Immune Fab [ANTIDOTE]
-Norepinephrine [ANTIDOTE]
Additional Information
Literature suggests that B 6 berries produce minimal symptoms, and ingestion of 150 leaves can produce death within 5 hours; LD50 in mice and rats is  20 mg/kg. Red aril is not toxic; ingestion of 150 yew leaves has been fatal; ingestion of intact berries may cause only mild GI symptoms.
Family: Taxaceae. Range: The Yew genus occurs in many areas of the world, however in the U.S., it is located deep in the woods of Western North Carolina to the North Central and Northeastern U.S. Toxin: Taxine.[PTH]


Phytochemicals

Taxane alkaloids have a very limited distribution within the plant kingdom, and occur only in two genera of the yew family (Taxus and Austrotaxus). Alkaloids were present in Taxus baccata and Taxus brevifolia.[Taxine]
The red aril surrounding the seeds does not contain taxoids, and the alkaloids, at least in the European yew, seem to be concentrated mainly in the needles, where their concentration can be higher than 1% on dry weight basis [29]. The alkaloid contents varies greatly during the course of the year, and is higher in winter [29]. It was recognized eariy that taxine from different yews is different [5][Taxine]

"Paclitaxel is an effective antineoplastic agent originally extracted in low yield from the bark of Taxus brevifolia." [EMNMPV.1]

"Theoretically, in order to produce 2.5 kg of taxol, 27,000 t of Taxus brevifolia bark is required and altogether 12,000 trees must be cut down (Rates, 2001). [Arora MPB]

"In 1971 Wall and Wani reported the isolation of paclitaxel from the stem bark of the pacific yew Taxus brevifolia. Paclitaxel (a complex diterpenoid that is the active ingredient of Taxol®) has received considerable attention because of its activity against various kinds of cancer, inter alia breast cancer, ovarian cancer, AIDS-related Kaposi’s sarcoma, and non-small cell lung cancer. The annual sales of paclitaxel and related taxanes in 2004 exceeded 2 billion US dollars (Tabata, 2004). Obtaining commercial supplies of paclitaxel from natural sources is not economically feasible because the source Taxus plants grow very slowly, and their paclitaxel contents are very low (~0.01% of the dry weight of the bark, where levels are highest). Tabata (2004) calculated that a 100-year-old yew tree would yield just 300 mg of the compound. The total synthesis of paclitaxel has been achieved, but this too is not economically viable. Therefore, paclitaxel is now produced commercially in large-scale plant cell suspension cultures (by Phyton and Samyang Genex Corporation), in one of the most remarkable examples of the potential value of plant in vitro culture. Hairy root cultures of Taxus x media var. Hicksii have also been found to produce paclitaxel at amounts of 69 g/g dry weight. Further, Furmanowa and Syklowska-Baranek (2000) found that the content of paclitaxel in transformed roots can be enhanced through elicitation with MeJA; a week after addition of 100 M MeJA the paclitaxel content increased to 210 g/g dry weight. Another compound that is produced by transformed root cultures (of Ophiorrhiza mungos) is camptothecin, an alkaloid with anticancer activities, in amounts (~0.3% per unit dry weight) significantly exceeding those obtained from cell suspension cultures (~0.01% per unit dry weight) of the same species (Wink et al., 2005)." [Arora MPB]

"In 1992, Hauser Chemical Research reported that their current production capacity had reached 130 kg of 3 which was extracted from 730,000 kg of Pacific yew bark collected in 1991 (Suffness and Wall, 1995). These data indicate that the extraction of 3 from naturally growing Taxus trees is quite limited compared to the large number of trees which are needed to obtain a sufficient amount...." [BCNS] "Paclitaxel and its analogue docetaxel work through promotion of tubulin polymerization and microtubule stabilization and are used to treat breast, ovarian, and non-small cell lung cancers. It is naturally derived from Taxus brevifolia (bark of Pacific Yew) that has traditionally been used by Native Americans for treating non-cancerous conditions. In addition, leaves of this plant have been used in Ayurveda for a variety of ailments including cancer." [Cho EBAMM]

Taxol
The bark of western yew contains the complex chemical taxol, which is used to treat breast and ovarian cancer. The bark of ten trees was required to make enough taxol for one patient, so overharvesting threatened the tree with extinction. Now, pharmaceutical companies manufacture a semisynthetic form of the drug. [Berries]

"Taxol, a taxane-type diterpene, is a tetracyclic lactam found in the genus Taxus [18]. All Taxus species are reported to contain taxanes. Taxol is an anticancer drug that acts as a microtubule inhibitor. Taxol was first reported to be produced by Taxomyces andreanae, an endophytic fungus associated with Taxus brevifolia [19]. Since then, more than 20 genera that produce taxol have been isolated, representing several species of unrelated endophytic fungi [20]. In several cases, more than one endophytic isolate from the same host has been reported to produce taxol.... Taxol-producing endophytes have been isolated from various hosts including Taxus species, cypress [22], Wollemia pine [23], and a variety of other non-Taxus species [24, 25]. These hosts include some that are reported to contain taxol and some that are not.... In cases where taxol-producing endophytic isolates were isolated from hosts that are reported not to produce taxol, the authors suggest that the endophytic isolate may have been associated with a Taxus species, but through time came to be associated with a different host [23]." [Jetter PBFA]

"Various taxanes are also found in the alkaloid mixtures obtained from Taxaceae, exemplified by ()-10-deacetylbaccatin from the needles and the bark of European Taxus baccata and ()-taxol 19 from the bark of Pacific Taxus brevifolia and T. cuspidata. The latter is applied for the chemotherapy of leukemia and various types of cancer." [Breitmaier Terpenes]


Taxine
Taxine is a collective name, referring to mixtures of diterpene alkaloids obtainable from yew biomass or extracts through an acid/Base partition scheme. Taxine is actually a mixture of several compounds: taxine A (1%), taxine B (30%) and taxine C (traces) [20]. Taxine I and II were recently isolated from the seeds of the European yew [22].[Taxine]
Taxine is responsible for the poisonous properties of the yew and its long and legendary history. The toxicity of this tree is well documented in historical and fictional literature, and has fascinated poets and writers [8]. Scientific investigations on the poisonous constituents of the yew date from the early 19th century. The needles were mentioned in several pharmacopoeias as a foxglove substitute, but the yew was better known as a livestock poison.[Taxine]
Taxine can be extracted from yew tissues using a conventional acid/base partition scheme. Taxine is a mixture of diterpenoid alkaloids present in all parts of the yew tree except the red aril surrounding the seed. The composition of taxine depends on the botanical source (yew species and variety) and the plant part. Taxine is unstable in the plant material.[Taxine]
Taxine is a powerful heart poison, and has traditionally been considered responsible for the toxic properties of the yew [65], although recent work suggests a non-negligible contribution also from certain degradation products of the alkaloid mixture (see infra). Most investigations were carried out using the crude alkaloid mixture from the European yew [65]. The infusion of taxine in different animal species causes multiple rhythm disturbances, including severe bradycardia, atrio-ventricular blocks, enlargement of the QRS complex, ventricular tachycardia and/or fibrillation, complicated by respiratory and neuromuscular disorders [65]. These cardiac alterations are similar to those reported for yew poisoning [65]. [Taxine]

"The phomopsolides have also been isolated from a Penicillium species that was found growing as an endosymbiont in the inner bark of the Pacific yew, Taxus brevifolia. It is possible that these compounds may confer a wider protective role against bark-boring beetles." [ChemofFungi]

History of Scientific Discovery

"The most enthusiastic reports concern the diterpenoids paclitaxel, Taxol® (from Taxus brevifolia) and docetaxel, Taxotere® (from Taxus baccata) having unique tri- or tetracyclic 20 carbon skeletons extracted from the bark of yew. This tree was known as a toxic plant for animals and humans for centuries.167 Monroe E. Wall and Mansukh C. Wani, at the Research Triangle Park (Chapel Hill, USA), identified the active principle of the yew tree in 1971.168 In 1979, Susan Horwitz of the Department of Molecular Pharmacology, Albert Einstein College of Medicine (New York) suggested that paclitaxel’s mechanism of action was different from that of any previously known cytotoxic agent. She observed an increase in the mitotic index of P388 cells and an inhibition of human HeLa and mouse fibroblast cells in the G2 and M phases of the cell cycle.169 It has been suggested that Taxol exerted its activity by preventing depolymerization of the microtubule skeleton. Clinical use of paclitaxel includes a lot of solid tumors with best results in ovarian and breast cancers. Extraction of paclitaxel from the yew bark was quite difficult: three trees for 1g of drug (one cure of chemotherapy). This difficulty encouraged the pursuit of semi-synthetic production." [Wermuth MedChem]

"The strategy included immediately increasing the amount of paclitaxel derived from yew bark and establishing a broad research program to evaluate alternative sourcing options and their commercial feasibility.170 The prospects for finding a solution to the paclitaxel supply problem through semi-synthesis using a naturally occurring taxan as a starting material, were considerable. This approach was pioneered by Pierre Potier (Figure 1.26 in the Institut de Chimie des Substances Naturelles (Gif-sur-Yvette, France).171 He found in the early 1980s that a naturally occurring taxan containing the paclitaxel core, 10-deacetylbaccatin III, was 20 times more abundant than paclitaxel and was primarily contained in the needles of the abundant English Yew (Taxus baccata). Potier succeeded in the difficult conversion of 10-DAB into paclitaxel, in 1988, with only four steps with an overall yield being 35%, still significantly less than needed for an efficient commercial process.172 The discovery and development of the taxans class of antitumor compounds, involved the discovery of a paclitaxel semi-synthetic analog, docetaxel (Taxotere®), by Pierre Potier et al., represent significant advances in the treatment of patients with a variety of malignancies. Although paclitaxel and docetaxel have a similar chemical root, extensive research and clinical experience indicate that important biological and clinical differences exist between the two compounds. Although the mechanism by which they disrupt mitosis and cell replication is unique, there are small but important differences in the formation of the stable, non-functional microtubule bundles and in the affinity of the two compounds for binding sites.173 These differences may explain the lack of complete cross-resistance observed between docetaxel and paclitaxel in clinical studies.174 Besides natural products, synthetic anticancer drugs flourished in various directions." [Wermuth MedChem]


Activities

PACIFIC YEW (Taxus brevifolia Nutt.) X [HMH Duke]
PHR treats the European yew, Taxus baccata; APA treats the Western Yew, Taxus brevifolia; DEM treats both; all apparently contain the antitumor compound, Monroe Wall, named taxol (Paclitaxel).
Activities (Pacific Yew) — Anticancer (1; APA); Antimelanomic (1; APA); Antimitotic (1; APA);

Antitumor (1; APA); Depurative (f; DEM); Diaphoretic (f; DEM); Poison (1; DEM).

Indications (Pacific Yew) — Cancer (1; APA; DEM); Cancer, breast (1; APA); Cancer, cervix (1;

APA); Cancer, ovary (1; APA); Cancer, skin (1; APA); Debility (f; DEM); Dysuria (f; APA); Enterosis (f; DEM); Fever (f; DEM); Gastrosis (f; DEM); Hematuria (f; DEM); Hepatosis (f; APA); Melanoma (1; APA); Metastasis (1; APA); Pain (f; DEM); Pulmonosis (f; DEM); Rheumatism (f; APA); Stomachache (f; DEM); Sunburn (f; DEM); Tumor (1; APA); Wound (f; DEM).

Dosages (Pacific Yew) — Not appropriate for home use (APA).
Contraindications, Interactions, and Side Effects (Pacific Yew) — Not covered (AHP; KOM).

Very poisonous plant, causing colic, dry mouth, dyspnea, hypotension, mydriasis, paleness, queasiness, rash, reddening or blueness of the lips, unconsciousness, vertigo, and vomiting. Death may result from asphyxiation and diastolic cardiac arrest. 50–100 g fresh needles can kill an adult (APA; PHR). Fatalities reported from drinking yew tea (APA). Still, Indians ate the berries as food.

Bark/Branch Tips "Yew is known for its antineoplastic properties. The main chemical component responsible for these effects is taxol, from which the drug paclitaxel (Taxol) is derived. This drug currently is used to inhibit metastatic breast cancer. It does so by inhibiting reorganization of the microtubule network needed for interphase in the cell division cycle and for mitotic cellular functions; it also causes abnormalities in bundles of microtubules during the cell cycle and multiple esters of microtubules during mitosis. Research has documented the effi cacy of using Taxol in combination with radiation to treat head and neck cancers, cervical carcinomas, and breast adenocarcinomas (Pradier et al, 1999). Another study evaluated the needles of different yew species for the presence of paclitaxel and related taxoids (Van Rozendaal et al, 2000). There appears to be a wide variation in taxane content in the different species found in different countries."
Dosages: "Adult PO extract: 10-60 drops bid-qid; Adult PO tea: 8 oz daily; Adult topical salve: apply to affected area prn" [Skidmore-Roth MHH]

Cultivation

Thrives in almost any soil, acid or alkaline, as long as it is well-drained[1, 200]. Succeeds in dry soils. Plants are very shade tolerant[81]. Dormant plants are very cold-hardy, though the young growth in spring can be damaged by late frosts. A slow-growing but apparently long-lived tree[229]. Plants produce very little fibrous root and should be planted in their final positions when still small[200]. Because of its useful wood, large trees are unscrupulously poached from the wild and, in some areas, the species has been nearly extirpated. Exploitation of the species for medicinal purposes is further threatening it in the wild[270].. Plants in this genus are notably resistant to honey fungus[200]. Dioecious. Male and female plants must be grown if seed is required.[PFAF]

"The Karuk considered that the best yew (Taxus brevifolia) wood for making pipes and games was gathered in the wet, shaded areas along creek beds because it grows straight in the shade." [Anderson TTW]

"However, Pacific yew (Taxus brevifolia) and the lichen Lobaria spp., which have strong preferences for old-growth forests, are strongly affected by decreases in the spatial extent of old-growth forests (Spies 1991)." [EIPNWFM 2000]

Propagation
Seed - can be very slow to germinate, often taking 2 or more years[78, 80]. It is best sown as soon as it is ripe in the autumn when it should germinate 18 months later. Stored seed may take 2 years or more to germinate. 4 months warm followed by 4 months cold stratification may help reduce the germination time[113]. Harvesting the seed 'green' (when fully developed but before it has dried on the plant) and then sowing it immediately has not been found to reduce the germination time because the inhibiting factors develop too early[80]. Prick out the seedlings into individual pots once they are large enough to handle and grow them on in pots in a cold frame. The seedlings are very slow-growing and will probably require at least 2 years of pot cultivation before being large enough to plant out. Any planting out is best done in late spring or early summer, after the last expected frosts[K]. Cuttings of half-ripe terminal shoots, 5 - 8cm long, July/August in a shaded frame. Should root by late September but leave them in the frame over winter and plant out in late spring[78]. High percentage[11]. Cuttings of ripe terminal shoots, taken in winter after a hard frost, in a shaded frame[113].[PFAF]


Synonyms


References

  1. [E-flora]http://linnet.geog.ubc.ca/Atlas/Atlas.aspx?sciname=Taxus%20brevifolia, Accessed Jan 15, 2018
  2. [PFAF]http://www.pfaf.org/user/Plant.aspx?LatinName=Taxus+brevifolia, Accessed Jan 12, 2015
  3. [Taxine] Giovanni Appendino Dipartimento di Scienza e Tecnologia del Farmaco Via Giuria 9, 1-10125 Tonno, Italy (Alkaloids: Chemical & Biological Perspecives, Volume 11, S. William Pelletier, 1996 Pergamon, Elsevier Science Ltd. )