Phytochemistry Reviews (v.9, #2)

Phytochemistry reviews: special issue on high altitude plants by Franz Bucar; Simon Gibbons (195-196).

Plants in alpine habitats are exposed to severe environmental stresses including temperature and radiation extremes. The observation that flowering heads from high altitude populations of Scorzoneroides helvetica (Mérat) J.Holub (synonym: Leontodon helveticus Mérat) contained higher amounts of luteolin derivatives than conspecific populations in lower altitudes prompted further investigations. An elevational increase of phenolics was confirmed in flowering heads of neophytic populations of three additional taxa of the Cichorieae tribe in New Zealand. A solely genetic basis of the altitudinal trends of flavonoids and phenolic acids was eliminated by field experiments with cultivars of the medicinal herbs Arnica montana L. and Matricaria chamomilla L. planted at nine different altitudes ranging from 600 to 2,200 m in the Tyrolean Alps. Parallel experiments on potted plants excluded soil characteristics as the factor causing the observed variation. The initial hypotheses that enhanced UV-B radiation in higher altitudes was triggering an increase in the ratio of B-ring-ortho-diphenolic versus B-ring-monophenolic flavonols in flowering heads of Arnica was disproved by climate chamber experiments resulting in no significant difference between plants grown in ambient and threefold ambient UV-B radiation regimes. In contrast, an increase of this ratio similar to the changes observed in higher altitudes resulted from a decrease in temperature by 5°C in a second climate chamber experiment. Conclusively, enhanced UV-B radiation is probably not the key factor inducing shifts in the phenolic composition in Asteraceae growing at higher altitudes but it is rather the temperature which decreases with altitude.
Keywords: Antioxidants; Chemical ecology; Free radicals; Temperature; UV-B radiation

Phytochemistry of heather (Calluna vulgaris (L.) Hull) and its altitudinal alteration by M. Monschein; J. Iglesias Neira; O. Kunert; F. Bucar (205-215).
Calluna vulgaris (L.) Hull (heather) is the only species within the genus Calluna (Ericaceae). It is a dominant species of heather communities and can be found in most parts of Europe and Northern America from lowland up to alpine regions. Common heather is traditionally used to treat urinary tract disturbances and inflammatory related disorders. This review covers the current knowledge on phytochemical investigations of C. vulgaris which revealed a complex pattern of flavonoid glycosides including acetylated compounds as well as other classes of phenolics (chromones, procyanidins and simple phenols). Recently, an acetophenone (rodiolinozide) was identified. C. vulgaris occurs in habitats comprising several altitudinal zones which makes it an attractive species to study the variation of its metabolic profiles in wild populations growing under different climatic conditions. Within phenolic compounds, flavonols showed significant differences in samples collected at different altitudes with increased levels of quercetin glycosides at higher altitudes whereas no significant correlation could be found for caffeoyl quinic acids and the dihydroflavonol glycoside callunin. Expanding such investigations to different species and different geographical areas should give a more accurate picture of suitable marker compounds within the group of phenolics in order to detect adaptive processes in high altitude plants. Furthermore, investigations on the specific patterns of phenolics at cellular and subcellular level and their variation due to factors like enhanced solar radiation and low temperature should be expanded.
Keywords: Flavonoids; Calluna vulgaris ; Phenolic compounds; Altitude; Radical scavengers

Mallotus species from Vietnamese mountainous areas: phytochemistry and pharmacological activities by C. Rivière; V. Nguyen Thi Hong; Q. Tran Hong; G. Chataigné; N. Nguyen Hoai; B. Dejaegher; C. Tistaert; T. Nguyen Thi Kim; Y. Vander Heyden; M. Chau Van; J. Quetin-Leclercq (217-253).
The genus Mallotus belongs to Malphighiales order and Euphorbiaceae family. Mallotus, commonly known as “Ba bet” in Vietnam, is one of the most diverse and richest genera of the Euphorbiaceae family in Vietnam, where about 40 Mallotus species may be found. Some Mallotus species are used in traditional medicine in Vietnam for different indications. They are concentrated in mountainous areas with an altitude below 1,000 m, but some species can grow at an altitude of 2,000 m, such as Mallotus oreophilus Müll. Arg. Some Mallotus species are known to contain different natural compounds, mainly diterpenoids, triterpenoids, steroids, flavonoids, coumarinolignoids, phloroglucinol derivatives or benzopyrans, and to exhibit interesting biological activities such as antimicrobial, antioxidant, antiviral, or cytototoxic ones. Some of these properties may be explained by their chemical composition as, for example, benzopyrans accounting for the cytotoxicity of Mallotus apelta extracts. However, although these species seem to have a great medicinal potential, the existing knowledge about most Mallotus species is still in most cases very limited. This review underlines the interest to continue the study of this genus of the Euphorbiaceae.
Keywords: Mallotus; Euphorbiaceae; Vietnam; Natural compounds; Biological activities

Hypericum species in the Páramos of Central and South America: a special focus upon H. irazuense Kuntze ex N. Robson by Sara Crockett; Marianne Eberhardt; Olaf Kunert; Wolfgang Schühly (255-269).
Knowledge about members of the flowering plant family Clusiaceae occurring in the tropical mountain regions of the world is limited, in part due to endemism and restricted distributions. High altitude vegetation habitats (Páramos) in Central and South America are home to numerous native Hypericum species. Information related to the phytochemistry of páramo Hypericum, as well as ecological factors with the potential to influence chemical defenses in these plants, is briefly reviewed. Results of the phytochemical analysis of Hypericum irazuense, a species collected in the páramo of the Cordillera de Talamanca in Costa Rica, are presented. Lastly, guidelines for the viable and sustainable collections of plant material, to facilitate future investigations of these interesting plants, are given.
Keywords: Clusiaceae; Hypericum ; Montane; Páramo; Phytochemistry; Xanthone

Bioactive metabolites from the Andean flora. Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids by Gloria María Molina-Salinas; Jorge Bórquez; Alejandro Ardiles; Salvador Said-Fernández; Luis Alberto Loyola; Alejandro Yam-Puc; Pola Becerril-Montes; Fabiola Escalante-Erosa; Aurelio San-Martin; Isidro González-Collado; Luis Manuel Peña-Rodríguez (271-278).
Natural products are recognized as an important source of new and better pharmaceuticals for the treatment of diseases such as tuberculosis. The azorellane and mulinane diterpenoids represent an interesting group of bioactive metabolites produced by Andean plants belonging to the Azorella, Mulinum, Laretia and Bolax genus. Testing of natural and semisynthetic azorellanes and mulinanes against two Mycobacterium tuberculosis strains showed that while most changes in the structure of the natural metabolites result in the loss of antituberculosis activity, methylation of the C-20 carboxyl group improves the biological activity of the corresponding derivatives.
Keywords: Apiaceae; Azorella spp.; Azorellane; Diterpenoids; Mulinum spp.; Mulinane; Mycobacterium tuberculosis

Natural products in modern life science by Lars Bohlin; Ulf Göransson; Cecilia Alsmark; Christina Wedén; Anders Backlund (279-301).
With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure–activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science.
Keywords: Pharmacognosy; Geodia; COX-2; ChemGPS-NP; Chemical space; Phylogeny; Cyclotide; Viola; Truffle; Tuber; Lateral gene transfer; Trypanosoma

Lichens as a potential natural source of bioactive compounds: a review by Vertika Shukla; Geeta Pant Joshi; M. S. M. Rawat (303-314).
Biological activity of material whether known in folk medicine or observed in planned screening program has been the starting point in the drug research. The general pattern is the isolation of active principles, elucidation their structures, followed by attempts for modulation of its activity potential by chemical modification. Lichens are valuable plant resources and are used as medicine, food, fodder, perfume, spice, dyes and for miscellaneous purposes throughout the world. Lichens are well known for the diversity of secondary metabolites that they produce. Compounds isolated from various lichen species have been reported to display diverse biological activities. Here we review the medicinal efficacy of lichen substances, which intends to explore the pharmaceutical potential of lichen substances.
Keywords: Lichen; Lichen substances; Natural product; Bioactivity

Azaphilones: a class of fungal metabolites with diverse biological activities by Natalia Osmanova; Wulf Schultze; Nahla Ayoub (315-342).
This review presents an overview of azaphilones isolated from different species of fungi, detailing their chemical structures and biological activities as covered in the recent literature. Over 170 different azaphilone compounds occur in fungi belonging to 23 genera from 13 families: these azaphilones can be classified into ten different structural groups. Numerous azaphilone structures have been described, particularly from members of the Trichocomaceae and Xylariaceae families. Azaphilones exhibit a wide range of interesting biological activities, such as antimicrobial, antifungal, antiviral, antioxidant, cytotoxic, nematicidal and anti-inflammatory activities. Many of these effects may be explained by the reactions of azaphilones with amino groups, such as those found in amino acids, proteins and nucleic acids, resulting in the formation of vinylogous γ-pyridones.
Keywords: Azaphilones; Bioactivity; Lactones; Trichocomaceae ; Xylariaceae

In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production by A. B. Sabater-Jara; L. R. Tudela; A. J. López-Pérez (343-356).
Interest in Taxus species has increased since paclitaxel, an anticancer drug, was isolated from the bark of Taxus brevifolia (Pacific yew) in the 1960’s. Great effort has been carried out to establish an efficient callus cultures of Taxus species. Culture media must be optimized for each Taxus species, and in general, there is no one method that guarantees success for Taxus cultures. The source of explant, culture medium composition and the growth regulators used appear to affect callus initiation and maintenance. Research effort has focused on obtaining a cell culture that exhibits good growth and a high rate of taxoid accumulation. In this sense, many strategies have been employed to stimulate taxoid production without affecting cell growth. In an attempt to scale-up cell culture, problems such us shear stress, oxygen supply and gas composition have been studied. A more detailed knowledge of the pathway and the fluxes of intermediates towards taxane accumulation will be key factors to obtain cell lines with increased taxane accumulation through metabolic engineering.
Keywords: Biotechnology; Paclitaxel accumulation; Plant cell culture; Secondary metabolite production