Substances & Homeopatic Remedies

Taxus baccata

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The foliage and seeds contain several alkaloids, in particular taxine, very poisonous, which alters to hydrotaxine by hydrolysis. Also one glucoside, taxicatine. The wood, bark, foliage and seeds are toxic. The foliage is the principal source of taxine. Old and desiccated foliage are more poisonous than young and fresh foliage. Poisoning is frequent in animals. Horses, asses and mules are extremely sensitive and can be killed in less than one hour. Rabbits, guinea-pigs and cats are insensitive to taxine. In humans, the yew generates digestive, nervous, respiratory and cardiovascular disorders which can result in death. Symptoms include excitation, hyperventilation, and tachycardia, followed by deceleration of the heart, hypotension, nausea, stomach pains, cramps, giddinesses, colic, violent diarrhoea, dizzy spells, convulsions, coma and death (L'Herbier Virtuel).

The red aril surrounding the seed can be eaten just as it is like delicacy with the proviso of not chewing the seed. It is sweetened and very mucilagineux. The arilles, removed from their seeds, have diuretic and laxative effects

Adverse Drug React Toxicol Rev. 2000 Aug;19(3):223-40.  Related Articles, Links  
Therapeutic applications of medicinal plants in the treatment of breast cancer: a review of their pharmacology, efficacy and tolerability.
Mantle D, Lennard TW, Pickering AT.
Neurochemistry Department, Newcastle General Hospital, Newcastle upon Tyne.

Various active compounds (or their semi-synthetic derivatives) derived from medicinal plants have been assessed for their efficacy and tolerability in the treatment of breast cancer. Some of these plant species, including Taxus baccata (paclitaxel, docetaxel), Podophyllum peltatum (etoposide), Camptotheca acuminata (camptothecin) and Vinca rosea (vinblastine, vinorelbine) have well recognized antitumour activity in breast cancer, and have been evaluated in clinical trials. For example, results from recent Phase II/III trials have established docetaxel as the most active single agent in the treatment (first or second-line) of advanced metastatic breast cancer. For other plant species such as Panax ginseng and Allium sativum, antitumour activity has been evaluated in experimental studies using cultured cells and animal models, but the therapeutic potential in patients remains to be determined. Antitumour activity derived from medicinal plants may produce results via a number of mechanisms, including effects on cytoskeletal proteins which play a key role in mitosis (paclitaxel), inhibition of activity of topoisomerase enzymes I (camptothecin) or II (etoposide), stimulation of the immune system (Viscum album), or antiprotease-antioxidant activity. Medicinal plant-derived antineoplastic agents may be used in single agent or in combinational therapies, and have been used in first-line or second-line (including anthracycline-refractory patients) treatment of localized or metastatic breast cancer. Adverse effects resulting from the use of these agents include neutropenia and peripheral neuropathies.

Docetaxel (Taxotere) in the Treatment of Non-Small Cell Lung Cancer
Vassilis Georgoulias*
Medical Oncology, School of Medicine, University of Crete, Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, 711.10 Heraklion, Crete, Greece

Abstract: Docetaxel is a new semi-synthetic anticancer agent derived from bacatin III of the needles of the European yew Taxus baccata. Docetaxel has a novel mechanism of action since it binds to tubulin inducing its polymerization and promoting stable microtubule formation. Several differences exist between docetaxel and paclitaxel: (i) broader activity of docetaxel against freshly explanted human tumors than paclitaxel; (ii) a 2- fold higher affinity than paclitaxel; (iii) 2.5-fold more potent than paclitaxel as an inhibitor of cell replication and (iv) docetaxel acts at the S-phase whereas paclitaxel at the G2/M phases of the cell cycle.

Preclinical and phase II studies revealed that docetaxel is active against NSCLC. In chemotherapy-naïve patients with NSCLC response rates ranged from 19% to 54% with a median duration of survival ranging from 6.3 months to 11 months, and 1-year survival ranging from 21% to 71%. Docetaxel as single agent provided a survival as well as a clinical benefit over BSC in untreated patients with NSCLC. Docetaxel has been efficiently combined with cisplatin (ORR 33%-46%), carboplatin (ORR 30%-48%), vinorelbine (ORR 20%-51%), gemcitabine (ORR 37%-47%), with a median survival ranging from 5-14 months. A preliminary analysis of a multicenter randomized trial comparing docetaxel/CDDP with docetaxel/gemcitabine revealed that the two regimens had comparable activity in terms, of response rates, duration of response, TTP and overall survival; however, the docetaxel/gemcitabine combination has a most favourable toxicity profile compared to docetaxel/CDDP.

Docetaxel has also demonstrated radiosensitizing properties and encouraging results have been achieved in combination with irradiation. Finally, docetaxel has shown an important activity in previously-treated patients with NSCLC with ORR ranging from 16% to 25% with a median survival ranging from 7.2 months to 10.5 months. Randomized trials revealed that second-line docetaxel confers a survival benefit over either BSC or ifosfamide/vinorelbine in pretreated patients with NSCLC.

Introduction

Lung cancer remains the most frequent cancer worldwide and its mortality exceeds that of breast cancer, with only 13% of patients surviving 5 years [1]. Although non-small cell lung cancer (NSCLC) is a relatively chemotherapy-resistant disease, randomized studies comparing cisplatinum-based chemotherapy with best supportive care demonstrated survival benefits for patients receiving chemotherapy [2]. Based on this evidence, active new drugs are needed for the treatment of patients with NSCLC.
Docetaxel is one of the new anticancer agents developed during the last decade. It is a semisynthetic taxoid closely related to paclitaxel and is derived from baccatin III which is obtained from the needles of the European yew (Taxus baccata) [3]. Docetaxel has shown considerable activity against several types of solid tumors including breast, lung, head and neck and ovarian [3]. Docetaxel promotes stable microtubule formation by binding to and inducing polymerization of tubulin subunits and, thus inhibits their depolymerisation [4,5]. In the presence of docetaxel the normal dynamic equilibrium between tubulin and microtubules in cells is altered, and the stability of the microtubules leads to disruption of the normal mitotic process and, probably to cell death. In addition, docetaxel phosphorylates the antiapoptotic oncoprotein bcl-2, which inactivates the oncoprotein and promotes apoptosis [6]. Although in vitro studies have shown that docetaxel induces both apoptotic and necrotic cell death in mouse fibroblasts [7], in vivo studies of mice implanted with carcinomas or sarcomas failed to demonstrate a clear relationship between the docetaxel-induced apoptosis and the drug’s antitumor effect [8].
In vivo evidence from murine tumor models indicated that the antitumor activity of docetaxel is independent of the tumor suppressor gene p53 [8]; however, there is some evidence that in human lung cancer cell lines docetaxel is more active in cells with p53 and bax expression [9].
Docetaxel displays a number of differences from paclitaxel in antineoplastic and cytotoxic activity. Indeed, docetaxel has shown greater activity against freshly explanted human tumors than paclitaxel [10]. Docetaxel has a 2-fold higher binding affinity than paclitaxel [11], induces a slightly faster rate of tubulin polymerization than paclitaxel and is 2.5-fold more potent than paclitaxel as an inhibitor of cell replication in P388 and J774.2 cell lines [12]. Finally, paclitaxel blocks cell division at transition point between G2 and M phases, whereas docetaxel preferentially halts the cell cycle at the S phase [13]
A number of in vitro studies have evaluated the efficacy of docetaxel in combination with other antineoplastic drugs. Thus, docetaxel plus cisplatin has been shown to exert an additive cytotoxic effect on NSCLC cell lines, and docetaxel plus vinorelbine has shown a synergistic effect on a squamous carcinoma cell line [14]. On the other hand, docetaxel plus etoposide did not show additive or synergistic activity when tested on cell lines obtained from patients with adenocarcinoma or squamous cell carcinomas [15]. In addition, the simultaneous administration of docetaxel and gemcitabine resulted in an antagonistic effect in NSCLC cell lines, whilst the sequential administration of docetaxel followed by gemcitabine 48 hours later resulted in a synergistic effect [16].


(Expert Rev Anticancer Ther. 2003 Jun;3(3):261-8)  
Docetaxel (taxotere) in the treatment of prostate cancer.
Beer TM, El-Geneidi M, Eilers KM.
Department of Medicine, Division of Hematology and Oncology, Oregon Health and Science University, Portland 97329, USA. beert@ohsu.edu

Docetaxel (Taxotere) is a taxoid derived from the needles of the European yew tree, Taxus baccata. With an overall prostate-specific antigen response rate of 42% in four Phase II studies, docetaxel has important single-agent activity in androgen-independent prostate cancer. Phase II studies suggest that the addition of estramustine (Emcyt) to docetaxel results in higher response rates but also increased toxicity. Docetaxel with and without estramustine is being evaluated in Phase III studies that will provide definitive information about its role in androgen-independent prostate cancer. Novel combinations of docetaxel with biologic response modifiers are in early stages of development. Similarly, a number of investigators are conducting exploratory trials that incorporate docetaxel into multimodality approaches to high-risk localized prostate cancer treatment.

Onkologie. 2003 Dec;26 Suppl 7:37-40.  Related Articles, Links  
[Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer]
Wolff JM.
Caritas-Krankenhaus, Bad Mergentheim.

Docetaxel (Taxotere) is a taxoid derived from the European yew tree, taxus baccata. In 4 phase-II studies docetaxel has important single agent activity with an overall prostate-specific antigen response rate of 42% in hormone refractory prostate cancer. Other phase-II studies suggest that the addition of estramustine to docetaxel results in a higher response rate but also in an increased toxicity. At present Docetaxel with and without estramustine is being evaluated in phase-III studies that will provide definitive information about its role in hormone refractory prostate cancer

Z Naturforsch [C]. 2003 Jan-Feb;58(1-2):65-9.  Related Articles, Links  
Antifungal activity of biflavones from Taxus baccata and Ginkgo biloba.
Krauze-Baranowska M, Wiwart M.
Department of Pharmacognosy, Medical University of Gdansk, Gen. J. Hallera 107 str., 80-416 Gdansk, Poland. krauze@farmacja.amg.gda.pl

Bilobetin and 4'''-O-methylamentoflavone were isolated and identified in the needles of Taxus baccata, for the first time in this species. The antifungal activity of biflavones from T. baccata and Ginkgo biloba, namely amentoflavone, 7-O-methylamentoflavone, bilobetin, ginkgetin, sciadopitysin and 2,3-dihydrosciadopitysin towards the fungi Alternaria alternata, Fusarium culmorum, Cladosporium oxysporum was determined employing computer-aided image analysis couplet to a microscope. Bilobetin exhibited a significant antifungal activity with values of ED50 14, 11 and 17 microM respectively. This compound completely inhibited the growth of germinating tubes of Cladosporium oxysporum and Fusarium culmorum at a concentration 100 microM. Activity of ginkgetin and 7-O-methylamentoflavone towards Alternaria alternata was stronger than that of bilobetin. Moreover, slight structural changes in the cell wall of Alternaria alternata exposed to ginkgetin at concentration of 200 microM were observed.

 J Ethnopharmacol. 2003 Dec;89(2-3):265-70.  Related Articles, Links  
Anti-inflammatory and antinociceptive activity of taxoids and lignans from the heartwood of Taxus baccata L.
Kupeli E, Erdemoglu N, Yesilada E, Sener B.
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler 6330, Ankara, Turkey.

Four taxoids (taxusin, baccatin VI, baccatin III and 1beta-hydroxybaccatin I) and five lignans (lariciresinol, taxiresinol, 3'-demethylisolariciresinol-9'-hydroxyisopropylether, isolariciresinol and 3-demethylisolariciresinol) were isolated from the heartwood of Taxus baccata L. (Taxaceae) growing in Turkey through chromatographic techniques. In vivo anti-inflammatory and antinociceptive activity of these compounds were investigated. All the compounds were shown to possess significant antinociceptive activity against p-benzoquinone-induced abdominal contractions, while only lignan derivatives significantly inhibited carrageenan-induced hind paw edema in mice.

Pacing Clin Electrophysiol. 2002 Apr;25(4 Pt 1):511-2.  Related Articles, Links  
Intoxication with taxus baccata: cardiac arrhythmias following yew leaves ingestion.
Willaert W, Claessens P, Vankelecom B, Vanderheyden M.
Department of Cardiology, Imelda Ziekenhuis, Bonheiden, Belgium.

The use of yew leaves (Taxus Baccata) as a means of deliberate self-harm is infrequent. The potent effect of the toxin is primarily cardiac and results in rhythm alterations and ultimately ventricular fibrillation. As there is no known antidote, and classic antiarrhythmic therapy proves to be ineffective, a prompt diagnosis is of great importance as immediate supportive action is the only valuable alternative. This case describes a 43-year-old women who attempted suicide by ingesting the leaves of Taxus Baccata. We discuss the effects and the difficulty of treatment associated with yew leaf poisoning.