Phytochemistry Reviews (v.10, #3)

Bioactive lichen metabolites: alpine habitats as an untapped source by Joel Boustie; Sophie Tomasi; Martin Grube (287-307).
Lichens are fungal and algal/cyanobacterial symbioses resulting in the production of specific metabolites. Some of these are forming an available biomass for phytochemical investigations, including the assessment of biological activities of the isolated compounds. The alpine or polar region are characterised by highly stressful environmental conditions for many organisms, but lichens are among the dominating organisms in these habitats. In the performant mutual protective system, lichen fungi often accumulate high amounts of metabolites with specific physicochemical properties (UV absorbents, hydrophobicity) which help the lichens to survive. Unique secondary metabolites and polysaccharides have been isolated and tested from these organisms. Even though this has been tested until now only with a low number of compounds so far, interesting activities have been recorded. We review here some of the antimicrobial, anti-inflammatory, antiproliferative and antioxidant activities properties described. Solutions with axenic biotechnological cultivation of each symbiotic partner and particularly the mycobiont to obtain the lichen secondary metabolites are challenging to overcome the limitations for the supply of these rare compounds. Additionally, these lichens appear to harbour a diversity of culturable microorganisms from which active compounds have also been isolated recently.
Keywords: Bioactivity; Cold habitat; Natural compounds; Pharmacy; Symbiosis

Anticancer potential of Himalayan plants by Anjana Bhatia; Saroj Arora; Bikram Singh; Gurveen Kaur; Avinash Nagpal (309-323).
Plants used in traditional medicine have stood up to the test of time and contributed many novel compounds for preventive and curative medicine to modern science. India is sitting on a gold mine of well recorded and traditionally well practiced knowledge of herbal medicine. Specially, plants growing at high altitude in Himalayan pastures are time-honored sources of health and general well being of local inhabitants. As of today, Himalayan plants are a major contributor to the herbal pharmaceutical industry both of India and other countries. Plants growing at higher altitudes are subjected to an assault of diverse testing situations including higher doses of mutagenic UV-radiation, physiological drought, desiccation and strong winds. Plants interact with stressful environments by physiological adaptation and altering the biochemical profile of plant tissues and producing a spectrum of secondary metabolites. Secondary metabolites are of special interest to scientists because of their unique pharmacophores and medicinal properties. Secondary metabolites like polyphenols, terpenes and alkaloids have been reported to possess antimutagenic and anticancer properties in many studies. The fundamental aspiration of the current review is to divulge the antimutagenic/anticancer potential of five alpine plants used as food or medicine by the populations living at high altitudes.
Keywords: Arnebia euchroma ; Hippophae rhamnoides ; Hypericum perforatum ; Podophyllum hexandrum ; Rheum emodi

An overview on genus garcinia: phytochemical and therapeutical aspects by M. Hemshekhar; K. Sunitha; M. Sebastin Santhosh; S. Devaraja; K. Kemparaju; B. S. Vishwanath; S. R. Niranjana; K. S. Girish (325-351).
The genus Garcinia belongs to the family Clusiaceae and has been involved in ayurvedic preparations to medicate various pathophysiological disorders. The bioactive molecules like hydroxycitric acid (HCA), flavonoids, terpenes, polysaccharides, procyanidines and polyisoprenylated benzophenone derivatives like garcinol, xanthochymol and guttiferone isoforms have been isolated from the genus Garcinia. The genus has received the attention of pharmaceutical industries due to their immense remedial qualities. The HCA has been known for its hypolipidemic property. The polyisoprenylated benzophenone and xanthone derivatives are known for their antioxidant, apoptotic, anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, anti-fungal, anti-ulcer, anti-protozoal, and HAT inhibiting properties. Future studies on the synthesis of therapeutically important products and their analogs and evaluation of their safety and efficacy would be of great interest. Though the genus includes more than 300 species, we have made an effort to conceive the curative qualities of bioactive compounds of selected plants to the best of our knowledge.
Keywords: Garcinia; Garcinol; Gambogic acid: caged xanthones; Hydroxy citric acid; Nutritive value; Anti-tumour; Anti-inflammatory; Anti-microbial

The chemical and biological activities of quinones: overview and implications in analytical detection by Nahed El-Najjar; Hala Gali-Muhtasib; Raimo A. Ketola; Pia Vuorela; Arto Urtti; Heikki Vuorela (353-370).
Quinones are a class of natural and synthetic compounds that have several beneficial effects. Quinones are electron carriers playing a role in photosynthesis. As vitamins, they represent a class of molecules preventing and treating several illnesses such as osteoporosis and cardiovascular diseases. Quinones, by their antioxidant activity, improve general health conditions. Many of the drugs clinically approved or still in clinical trials against cancer are quinone related compounds. Quinones have also toxicological effects through their presence as photoproducts from air pollutants. Quinones are fast redox cycling molecules and have the potential to bind to thiol, amine and hydroxyl groups. The aforementioned properties make the analytical detection of quinones problematic. However, recent advances of the available analytical techniques along with the possibility of using labeled compound facilitate their detection hence allowing a better understanding of their action. This review summarizes the current knowledge with respect to the oxido-reductive and electrophilic properties of quinones as well as to the analytical tools used for their analysis. It includes a general introduction about the physiological, and therapeutical functions of quinones. A number of studies are reported to cover the chemical reactivity in an attempt to understand quinones as biologically active compounds. Data ranging from normal analytical methods to study quinones derived from plant or biological matrices to the use of labeled compounds are presented. The examples illustrate how chemical, biological and analytical knowledge can be integrated to have a better understanding of the mode of action of the quinones.
Keywords: Quinone; Chemotherapeutic agents; One electron reduction; Two electron reduction; Labeled compounds analysis

Engineering secondary metabolite production in hairy roots by Sheela Chandra; Ramesh Chandra (371-395).
Plants are a rich source of valuable secondary metabolites. Plant cell culture technologies developed in the past as possible tools for secondary metabolites production. In most cases, for the large scale production of these compounds, production is too low for commercialization. The cultured cell suspensions being undifferentiated have not gained momentum because of their instability and non-uniformity of the product formation. Secondary metabolite production is under strict metabolic regulation and tissue specific localization. Hence the differentiated cultures such as hairy root cultures are widely studied. Agrobacterium rhizogenes causes hairy root disease in plants. Transformed roots produced by A. rhizogenes infection are characterized by high growth rate, genetic stability and growth in hormone free media. These genetically transformed root cultures can produce amounts of secondary metabolites comparable to that of intact plants. Elicitation of hairy roots leads to increased production of secondary metabolites and also helps in designing of metabolic traps to allow adsorption of product, preventing feedback inhibition and protection of metabolites from degradation in the culture media. Permeabilization and in situ product adsorption result in many fold increase in product yield. T- DNA activation tagging allows overexpressing the respective gene and increasing the product formation in transformed hairy roots. Recent progress in transgenic research has opened up the possibility of the metabolic engineering of biosynthetic pathways to produce high-value secondary metabolites. Metabolic engineering offers promising perspectives to improve yields; however it requires the understanding of the regulation of the secondary metabolite pathways involved in the regulation of levels of product, enzymes and genes, including aspects as transport and compartmentation. This article reviews the recent advances in secondary metabolites production in transformed hairy roots.
Keywords: Elicitation; Hairy roots; Metabolic engineering; Secondary metabolites; Transcriptional factors

Chalcone synthase and its functions in plant resistance by T. T. H. Dao; H. J. M. Linthorst; R. Verpoorte (397-412).
Chalcone synthase (CHS, EC is a key enzyme of the flavonoid/isoflavonoid biosynthesis pathway. Besides being part of the plant developmental program the CHS gene expression is induced in plants under stress conditions such as UV light, bacterial or fungal infection. CHS expression causes accumulation of flavonoid and isoflavonoid phytoalexins and is involved in the salicylic acid defense pathway. This review will discuss CHS and its function in plant resistance.
Keywords: Chalcone synthase; Flavonoids; Plant resistance

Vochysiaceae: secondary metabolites, ethnopharmacology and pharmacological potential by Fausto Carnevale Neto; Alan Cesar Pilon; Dulce Helena Siqueira Silva; Vanderlan da Silva Bolzani; Ian Castro-Gamboa (413-429).
Many Vochysiaceae species, in special Qualea and Vochysia genera, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activity and the secondary metabolites reported so far for Vochysiaceae. The chemical constituents of this family include triterpenoids, steroids and polyphenols like flavonoids and ellagic acid derivatives.
Keywords: Ellagic acid derivatives; Ethnopharmacology; Flavonoids; Triterpenoids; Vochysiaceae

Seaweeds are the primary producers of all aquatic ecosystems. Chemical constituents isolated from diverse classes of seaweeds exert a wide range of nutritional, functional and biological activities. Unique metabolites of seaweeds possess specific biological properties that make them potential ingredients of many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Cosmeceuticals of natural origin are becoming more popular than synthetic cosmetics. Hence, the investigation of new seaweeds derived functional components, a different source of natural products, has proven to be a promising area of cosmeceutical studies. Brown seaweeds also produce a range of active components including unique secondary metabolites such as phlorotannins and many of which have specific biological activities that give possibilities for their economic utilization. Brown seaweeds derived active compounds have been shown various functional properties including, antioxidant, antiwrinkling, whitening, antiinflammatory and antiallergy. It is well-known that these kind of biological effects are closely associated with cosmeceutical preparations. This communication reviews the current knowledge on brown seaweeds derived metabolites with various biological activities and the potential use as cosmeceutical ingredients. It is hoped that the reviewed literature on multifunctional properties of brown seaweeds will improve access to the seaweed based natural products specially the ability to incorporate these functional properties in cosmeceutical applications.
Keywords: Biological properties; Natural products; Phaeophyceae; Phytochemicals; Secondary metabolites

Advanced methods for the study of the chemistry and the metabolism of lichens by Wolfgang Eisenreich; Nihat Knispel; Andreas Beck (445-456).
Lichens are compound entities of a fungal partner (“mycobiont”) and one or more photosynthetically active algae or cyanobacteria (“photobionts”). The organisms live in an intimate, symbiotic association which has been classified as a mutualistic or controlled parasitic relationship. Several metabolites from lichens display unique structures with unknown functions, and only a few model species have been analysed comprehensively. The complex metabolic interplay between the organisms in lichens is also incompletely understood. Earlier experiments with 14C-labelled precursors indicated that the photobionts produce from CO2 glucose or sugar alcohols (e.g. ribitol and arabitol) which are then transferred to the mycobionts. In the fungi, these compounds are believed to be converted into mannitol serving as the carbon and energy source in the downstream metabolic processes. Recent methodological developments in spectroscopy and “systems biology” now enable a concise analysis of the metabolite profiles, networks and fluxes by non-targeted quantitative approaches. In this review, we summarize the current knowledge about lichen metabolism and report on the potential of the advanced methods to reinvestigate lichen chemistry and metabolism on a quantitative basis.
Keywords: Metabolite flux; Metabolomics; Peltigera ; Stable isotopes; Xanthoria