Taxus wallichiana Zucc . ( Himalayan Yew ) : insights on its anti-microbial and pharmacological activities

Introduction Taxus wallichiana Zucc. (Himalayan Yew) has a remarkable history of medicinal uses in contrast to the other yews. In this critical review, we focused our discussion on the analgesic, anti-inflammatory, anti-fungal, anti-bacterial, anti-convulsant, antipyretic and anti-cancer activity of


Introduction
Taxus wallichiana Zucc.(Himalayan Yew) is a small to medium sized evergreen tree, growing 10-20 m tall.In exceptional cases, it can grow up to 28 m tall.Its leaves are flat, dark green, arranged spirally on the stem 1 .Depending on taxonomic treatment, T. wallichiana are found to have a wide growth range in Asia, stretching from Afghanistan through the Hima-layas to Philippines.It is found growing in Afghanistan, Bhutan, China, India, Indonesia, Malaysia, Myanmar, Nepal, Pakistan, Philippines and Vietnam.
This plant is used traditionally for the treatment of high fever and painful inflammatory conditions.The leaves of this plant are used to make herbal tea for indigestion and epilepsy.Previously published literatures on T. wallichiana have reported immunomodulatory, anti-bacterial, anti-fungal, analgesic, anti-pyretic and anti-convulsant activities 2,3 .In India, extracts from its bark and leaves are used in Unani medicine as a source of the drug Zarnab, prescribed as a sedative, aphrodisiac and as a treatment for bronchitis, asthma, epilepsy, snake bites and scorpion stings 4 .In Ayurvedic medicine, young shoots are used to prepare a medicinal tincture for the treatment of headache, diarrhoea and biliousness.The leaves are also used for the treatment of hysteria, epilepsy and nervousness.Its bark and leaves are considered to possess anti-fertility properties.It has also been used in steam baths to treat rheumatism 5 .A paste made from the bark is used to treat fractures and headaches.The inhabitants of the buffer zone villages of the Nanda Devi Biosphere Reserve in India collect the Taxus bark and leaves, mainly for traditional teas and for curing colds and coughs, a practice also commonly seen in other rural areas 6 .Extracts from this tree are also used in medicinal hair oils.In Pakistan, a decoction of the stem is used as a treatment against tuberculosis 7 .In this present critical review, we have discussed some important medicinal properties of T. wallichiana.

Discussion
Analgesic and anti-infl ammatory activities Tasumatrol B, 1,13-diacetyl-10-deacetylbaccatin III and 4-deacetylbaccatin III were isolated from the bark extract of T. wallichiana.All the compounds were assessed for analgesic and anti-inflammatory activities.All the compounds, especially tasumatrol B revealed significant analgesic activity 2 .In this case, the acetic acid induced abdominal writhing model, which is well-known as a visceral pain model, was used.The acetic acid is responsible for releasing arachidonic acid, involving the prostaglandin and cyclooxygenase biosynthetic pathway.Thus, acetic acid plays a critical role in nociception 8 .High doses of T. wallichiana were shown to produce significant analgesia, and this may be correlated to their inhibitory effect on the biosynthesis of arachidonic acid metabolites 2 .
Similarly, all of the test compounds, particularly tasumatrol B, showed significant anti-inflammatory activity in carrageenan induced models 2 .Carrageenan induced paw oedema, being an in vivo investigational model for acute inflammation, has been extensively used to determine the anti-inflammatory effect of new investigational agents 9,11  compound Baicalein showed an IC 50 value of 22.1 ± 0.03 μM.Taxusabietane A also showed significant antiinflammatory activity (at doses of 5 mg/kg and 10 mg/kg) when induced by carrageenan 1 .
These findings highlighted the potential of T. wallichiana to be further explored as a new lead for the management of pain and inflammation.

Anti-fungal and anti-bacterial activities
Literature survey has revealed that no significant work has been done on the anti-bacterial and antifungal activities of the T. wallichiana.However, Nisar et al. tested methanol extracts of the leaf, bark and heartwood of T. wallichiana against six bacterial and six fungal strains using the hole diffusion and macro-dilution methods.All extracts and fractions displayed significant anti-microbial effects 12 .Taxol and related bioactive taxoids from T. wallichiana 13 may be responsible for the observed antimicrobial activities.These activities may also be attributed to the presence of alkaloids, phenols, polyphenols, saponins, tannins, anthraquinones, steroids, and especially diterpenes, found in the extract.These families of natural products and phytochemical groups are known to display antimicrobial activities 14 .

Anti-convulsant and anti-pyretic activities
Nisar et al. carried out a study to establish the scientific basis of T. wallichiana used as an anticonvulsant and anti-pyretic drug 15 .They found that the plant extract controlled pentylenetetrazol-induced convulsions in mice 15 .They showed that 100 mg/kg and 200 mg/kg intraperitoneal doses of the extract significantly (p < 0.05) inhibited mioclonus and clonus while inhibition of tonus and hind limb tonic extension was found to be much more significant (p < 0.01) 12 .Furthermore, the anti-convulsant effects of T. wallichiana were compared with that produced by the GABA A agonist diazepam, a potent anti-epileptic drug, highly effective to prevent convulsions induced by pentylenetetrazole 16 .The benzodiazepine site in the GABA A receptor and T-type Ca 2+ currents could be targets for future studies to learn more about the mechanisms of action of the T. wallichiana extract and/or its constituents.
In the case of the yeast-induced pyrexia model, a 200-mg/kg dose showed very significant (p < 0.01) inhibition, while 50-and 100-mg/ kg doses caused a less significant (p < 0.05) inhibition 12 .
Overall, the anti-nociceptive and anti-pyretic activities may be attributed to the presence of alkaloids, phenols, polyphenols, saponins, tannins, anthraquinones, steroids, and especially diterpenes (i.e.taxoids), found in the crude extract 12 .

Anti-cancer activities
Chattopadhyay et al. carried out systematic studies on the chemical constituents acquired from different parts of T. wallichiana 17 .They isolated and identified several taxoids of different structural types with five of them being new molecules 17 .They isolated three lignans from the heartwood of the plant which were shown to have anti-cancer activity 17 .These three lignans have been characterised as taxiresinol 1, isotaxiresinol 2 and (−)-secoisolariciresinol 3 on the basis of their spectral characteristics 18 .Amongst these compounds, the absolute configuration of taxiresinol 1 showed notable in vitro anti-cancer activity against colon, liver, ovarian and breast cancer cell lines 17 .

Conclusion
Various biological activities of the isolated lignans from T. wallichiana have been summarised in this critical review.These lignans exerted diverse biological activities against tested methods.They were found to show high activity especially as analgesic, anti-inflammatory, anti-fungal, anti-bacterial, anti-convulsant, antipyretic and anti-cancer agents.These lignans should be further evaluated to develop safe agents which can be introduced in modern therapy.Further studies should be conducted to reveal the mode of action of these lignans which might be helpful in understanding their possible role in human physiology.