Phytochemistry Reviews (v.16, #1)

Biological activities associated to the chemodiversity of the brown algae belonging to genus Lobophora (Dictyotales, Phaeophyceae) by Christophe Vieira; Julie Gaubert; Olivier De Clerck; Claude Payri; Gérald Culioli; Olivier P. Thomas (1-17).
Although Lobophora belongs to a marine algal family (Dictyotaceae) that produces a large array of secondary metabolites, it has received little attention compared to other genera, such as Dictyota, in terms of natural compounds isolation and characterization. However, metabolites produced by Lobophora species have been found to exhibit a wide array of bioactivities including pharmacological (e.g. antibacterial, antiviral, antioxidant, antitumoral), pesticidal, and ecological. This review aims to report the state-of-the-art of the natural products isolated from Lobophora species (Dictyotales, Phaeophyceae) and their associated bioactivities. All bioactivities documented in the literature are reported, therefore including studies for which pure active substances were described, as well as studies limited to extracts or fractions. From the early 1980s until today, 49 scientific works have been published on Lobophora chemistry and bioactivity, among which 40 have reported bioactivities. Only six studies, however, have identified, characterized and tested no less than 23 bioactive pure compounds (three C21 polyunsaturated alcohols, three fatty-acids, a macrolactone, 11 polyketides, a few sulfated polysaccharides, three sulfolipids, a tocopherol derivative). The present review intends to raise awareness of chemists and biologists given the recent significant taxonomic progress of this brown algal genus, which holds a promising plethora of natural products yet to be discovered with ecological and pharmacological properties.
Keywords: Bioactivity; Brown algae; Lobophora ; Natural products

Transgenic studies for modulating terpenoid indole alkaloids pathway in Catharanthus roseus: present status and future options by Priyanka Verma; Ajay Kumar Mathur; Shamshad Ahmad Khan; Neha Verma; Abhishek Sharma (19-54).
The anti-neoplastic herb Catharanthus roseus (Madagascar periwinkle; Family Apocynaceae), known to harbor >130 bioactive terpenoid indole alkaloids (TIAs), is in global attention of transgenic research for pathway engineering. This medicinal herb has a long folklore history of its usage in the treatment of several health disorders owing to the presence of a variety of secondary metabolites, particularly the alkaloids, phenolics and anthocyanins. Among its various bioactive molecules, C. roseus is most valued for being the exclusive bio-resource of two of the most effective anti-cancerous drugs—vincristine and vinblastine that are indispensible components of several modern day chemotherapeutic regimens. The in-planta yields of these bioactive TIAs are extremely low (<0.0002 %) owing to very rigid developmental, genetical and environmental regulation controls as a part of plant’s own auto-protection strategies against these cytotoxic molecules. Consequently the high cost of production coupled with increasing market demand for these alkaloidal drugs have made TIAs pathway as one of the preferred target for plant metabolic engineering efforts to boost their commercial production. The transgenic approaches so far applied in C. roseus can be grouped into three major lines of investigations. The first line of efforts have been dominated by the genetic transformation studies carried out with wild type Ti or Ri plasmids to measure the influence of their random insertion on TIAs biogenesis. These studies, besides helping the optimization of basic transformation protocols at different levels of cellular differentiation, have largely contributed towards the better resolution and expression of TIAs pathway architecture at the level of associated genes and enzymes. Second line of metabolic engineering works is being centered around the efforts on preparation of genomic libraries and genome mapping to hunt for TIAs pathway genes and associated transcription regulators/factors, followed by their cloning, insertion and hyper-expression to modulate the carbon flux towards desired end products. Modern day transgenic attempts in C. roseus are largely focused on superimposing the concurrent influences of biotic and abiotic elicitation, T-DNA activation and RNAi or virus induced gene silencing approaches for higher TIAs biogenesis. The pace of transgenic research in C. roseus in last two decade has been rapid and demands periodic compilation and reviewing of published literature to provide a handy status up-date of the subject. The present compilation is an effort in this direction and intends to provide a state-of-art account of various transgenic approaches currently being pursued in this high value herb. More than 130 research papers have appeared on various aspects of transgenic cells, tissues and plant production in C. roseus in 30 years. The bulk of these efforts (64.96 %) were made at the level of Agrobacterium rhizogenes-mediated hairy root cultures, followed by 26.80 % in A. tumefaciens-mediated transformed tissues and 8.24 % in cells/tissue cultures subjected to particle bombardment approach. In the present compilation, these studies are further grouped into specific categories wherein over-expression of TIAs pathway specific genes, transcriptional factor regulation, elicitation/stress superimposition, transgenic plant regeneration, metabolites profiling and gene silencing etc. were investigated in different transformed tissue.
Keywords: Catharanthus roseus ; Transgenics; Agrobacterium tumefaciens ; Agrobacterium rhizogenes ; Particle bombardment; Transcription factors; Terpenoid indole alkaloids; Post translational gene silencing

The development of new drugs will certainly benefit from an ever improving knowledge of the living beings chemistry. However, identification of drugable molecules within the immense biodiversity of forests, soils or oceans still requires considerable investments in technical equipments, time and human resources. An important part of this process is the quick identification of known substances in order to concentrate the efforts on the discovery of new ones. A range of “dereplication” procedures are currently emerging to meet this challenge as key strategies to improve the performance of natural product screening programs. Initially defined in 1990 as “a process of quickly identifying known chemotypes”, dereplication is today a not so univocal concept and has evolved over the last years in different ways. The present review covers all dereplication-related sudies in natural product research from 1990 to 2014. Its writing brought to light five distinct dereplication workflows that can be characterized by the nature of starting materials, by the selected analytical technique, and above all by the final objective. Dereplication can be used as an untargeted workflow for the rapid identification of the major compounds whatever their chemical class in a single sample or for the acceleration of bioactivity-guided fractionation procedures. In other cases dereplication is fully integrated in metabolomic studies for the untargeted chemical profiling of natural extract collections or for the targeted identification of a predetermined class of metabolites. Finally a quite distinct dereplication approach mainly based on gene-sequence analyses is frequently used for the taxonomic identification of microbial strains.
Keywords: Dereplication; Natural products; Metabolomics; Drug discovery; Taxonomic classification

A review of the ethnomedicinal uses, phytochemistry and pharmacology of the Pleiocarpa genus by Olubunmi A. Omoyeni; Ahmed A. Hussein; Emmanuel Iwuoha; Ivan R. Green (97-115).
Pleiocarpa genus is a flowering plant from the Apocynaceae family which are rich sources of phytochemicals and have been reported to be useful in the treatment of gastrointestinal ailments, fever, malaria, pain, diabetes and cancer. The aim of this review is to present the past and current ethnomedicinal uses, phytochemistry and the pharmacology of Pleiocarpa genus which are underexploited as revealed through this review in order to enhance its potential source of phytochemical leads in medicine. Some pharmacological activities of these plants based on their acclaimed ethnomedicinal uses have been investigated by various researchers. The chemical profile of the genus is limited to alkaloids and triterpenoids, where indole alkaloids may be considered as important taxonomical markers.
Keywords: Pleiocarpa mutica ; Pleiocarpa pycnantha ; Ethnomedicine; Phytochemistry; Pharmacology; Apocynaceae

White cabbage (Brassica oleraceae var. capitata f. alba) is a cruciferous vegetable used worldwide as a food and in traditional medicine. Due to its common availability in local markets, affordability, and consumer preference, it represents a significant source of phytonutrients in the human diet. This review provides an overview of white cabbage origin, taxonomy, geographical distribution, botanical characteristics, and contemporary and traditional uses, as well as its phytochemicals and pharmacology. Special emphasis is placed on a health-promoting phytochemicals such as glucosinolates, polyphenols, and vitamins, as well as anticancerogenic, antioxidant, anti-inflamantory and cardioprotective effects. The majority of so far published research on white cabbage was focused on qualitative determination of phytochemicals (targeted analysis), while only few recent papers published data based on untargeted metabolomic profiling. Hence, this review discusses and emphasizes a further need of studying the white cabbage phytochemicals using modern metabolomics platforms which will enable scientists to pinpoint the exact bioactive metabolites which are responsible for certain bioactivity.
Keywords: Anticancer-, anti-inflammatory-, antiobesity-, and antioxidant activities; Carotenoids; Contemporary and traditional use; Gastrointestinal activity; Glucosinolates; Geographical distribution; Hypolipidemic and hypoglycemic activities; Polyphenols; Taxonomy; Vitamins

Seven-carbon (7-C) sugars and sugar alcohols are common in higher plants, algae, fungi and bacteria. The biochemical origin and physiological function of these monosaccharides in plants and algae however is not well understood and has not been fully investigated. Here the occurrence, metabolism, and transport of heptuloses, heptitols, and heptoses are integrated in accordance with function to emphasise the importance of these apparently neglected sugars. This therefore is the first comprehensive synthesis of knowledge about 7-C sugar biochemistry, a relatively underexplored area of carbohydrate biology that needs to be integrated into mainstream sugar research. Available information on the metabolism of heptuloses, heptitols, and heptoses in Medicago sativa (alfalfa), Persea americana (avocado), Primula sp., Kalanchoë pinnata, and the red alga Porphyridium sp. was thoroughly investigated and evaluated. Results indicate that 7-C sugars share a common precursor and are products of a TKT-dependent heptulose shunt in which Suc-derived Fru 6-P is converted either to Sed 7-P or mannoheptulose 7-P or both in competent tissues and species. In plants, free heptuloses probably arise as a consequence of phosphatase activity, whereas heptoses appear to be formed by isomerisation of the corresponding phloem translocated heptuloses following import into non-photosynthetic tissue. It is proposed that the major physiological function of 7-C sugars and heptitols, in addition to serving as a carbon sink, involves metal ion chelation, translocation and remobilisation to fulfil nutrient requirements essential for growth and development.
Keywords: Heptitols; Heptuloses; Mannoheptulose; Metabolism; Sedoheptulose

The discovery of the ellagitannin geraniin was made exactly 40 years ago. It is a secondary metabolite found in plants and is categorised as a hydrolysable tannin under the huge family of polyphenolic compounds. At present, the occurrence of geraniin has been verified in at least 71 plant species, many of which are used in traditional medicine. Hence, like other polyphenols, geraniin has also received widespread interest as a research focus to unearth its beneficial biological effects and therapeutic values apart from understanding its chemical properties, biosynthesis and interaction with the body system. Indeed, it has been demonstrated that geraniin possesses antioxidant, antimicrobial, anticancer, cytoprotective, immune-modulatory, analgesic properties besides exerting promising therapeutic effects on hypertension, cardiovascular disease and metabolic dysregulation. The objective of this review is to summarise the current knowledge about the basic chemistry, natural sources, isolation techniques, biosynthesis, pharmacokinetics and pharmacodynamics of geraniin. With reference to this information, the clinical significance, obstacles and future perspectives in geraniin research will also be scrutinised.
Keywords: Antioxidants; Ellagic acid; Hydrolysable tannins; Polyphenols; Urolithins