Phytochemistry Reviews (v.14, #2)

Schisandraceae triterpenoids: a review by Yong-Gang Xia; Bing-You Yang; Hai-Xue Kuang (155-187).
This article describes 221 new triterpenoids especially schinortriterpenoids, published from February 2008 through July 2013 as constituents of the family Schisandraceae. The article discusses their source, biological activity, synthetical studies, stereochemistry aspects and chemotaxonomy significance. Applications of hyphenated techniques to the qualitative and quantitative analysis of schinortriterpenoids are also reviewed, together with advances in microbial transformation and synthetic studies.
Keywords: Schisandraceae; Schisandra ; Kadsura ; Triterpenoids

Biotechnological advances on in vitro capsaicinoids biosynthesis in capsicum: a review by Mechuselie Kehie; Suman Kumaria; Pramod Tandon; Nirala Ramchiary (189-201).
One of the main characteristics of chili pepper fruit is its pungent taste due to the presence of a group of compounds known as capsaicinoids. Capsaicinoids biosynthesis in chili plant is defined by two pathways: phenylpropanoid, which determines phenolic structure; and fatty acid metabolism, which determines the molecule’s fatty acids. The potency of chili pepper cells, tissue and organ to biosynthesize capsaicinoids in in vitro cultures have been a subject of intensive research. Recent findings demonstrated that manipulation of culture strategies viz., immobilization of cells, precursors feeding, cell selection, elicitors treatments, osmotic stress, influence of calcium channel modulators, nutrient stress, pH stress etc. to enhance the accumulation of capsaicinoids in in vitro cultures of chili pepper have resulted in significant increase. However, the levels of capsaicinoids accumulation in cell cultures have never reached the levels in the fruits and require more efficient strategies to enhance the capsaicinoids biosynthetic activity. The present review highlights a comprehensive overview of capsaicinoids biosynthesis, its clinical applications and consolidated results of studies on biotechnological advances in chili pepper research leading to the biosynthesis of capsaicinoids in in vitro cultures.
Keywords: Chili; Capsaicinoids; Biosynthesis; Cell cultures; In vitro cultures

Recent advances in synthesis and biological activity of triterpenic acylated oximes by Barbara Bednarczyk-Cwynar; Lucjusz Zaprutko (203-231).
During the last few decades more and more attention has been paid to triterpenes—a group of compounds with five- or four-ring skeleton and carboxyl, hydroxyl or oxo groups. Triterpenes with unsubstituted C-3 hydroxyl group can be easily transformed into appropriate ketones and then into oximes. The carbonyl group can be created not only from the hydroxyl group at C-3 position, but also at C-2, C-12 or C-28 positions. Several methods of creation of two = NOH groups within one molecule of triterpene are known. There are also known triterpenes with two carbonyl groups, e.g. at C-3 and C-11 positions, which differ in reactivity: among them only C-3 group can be transformed into oxime. A reactive hydroxyimine group can undergo the action of acylating agents, such as carboxylic acids or their derivatives, also the ones with significant pharmacological activity. Acyl derivatives of triterpenic oximes exhibit important pharmacological activity. The biological tests performed with the use of cell cultures inoculated with viruses showed inhibitory activity of some triterpenic acyloximes against type 1 HSV (H7N1), ECHO-6 and HIV-1 viruses. Another acylated oximes derived from triterpenes shown cytotoxic or antiproliferative activity against many lines of cancer cells. In many cases the pharmacological effects of the tested acyloxyiminotriterpenes were comparable to those of appropriate standard drugs. One of the newest application of acyl derivatives of triterpenic oximes is their ability to form organogels.
Keywords: Acyl derivatives of triterpenic oximes; Derivatives of triterpenes; Triterpenes; Triterpenic oximes

Flavonoid compounds as reversal agents of the P-glycoprotein-mediated multidrug resistance: biology, chemistry and pharmacology by Ana Ferreira; Sarah Pousinho; Ana Fortuna; Amílcar Falcão; Gilberto Alves (233-272).
Multidrug resistance (MDR) represents one of the major problems in pharmacotherapy of important diseases (e.g., cancer, epilepsy). Although many factors may contribute to the development of MDR phenotype, the increased expression and/or functional activity of P-glycoprotein (P-gp; active drug efflux transporter) across the cell membrane has been recognized as the main one. Therefore, a great attention has been given to the search of P-gp inhibitors as therapeutic agents to reverse the MDR mediated by P-gp. Since the chemical entities identified over the last three decades as potential P-gp inhibitors did not show suitable pharmacological properties, more recently herbal components, such as flavonoid compounds, have gained a great interest as safe P-gp inhibitors. The interest in flavonoids as P-gp inhibitors is increasing due to their potential favourable characteristics, including selectivity and non-cytotoxic effects. Flavonoids integrate the third-generation non-pharmaceutical category of P-gp inhibitors, and some of them exhibited effects comparable to those of the classic P-gp inhibitors. In fact, some flavonoids found in foods and beverages of herbal origin appear to be quite promising to inhibit the P-gp–mediated drug efflux, indicating their potential value to enhance the systemic/cellular bioavailability of P-gp drug substrates when administrated in co-therapy. This review paper summarizes the current evidence of P-gp inhibitory effects produced by flavonoids, taking into account studies performed in cell-based in vitro models, in vivo animal models and clinical trials.
Keywords: Flavonoids; P-glycoprotein inhibition; Drug efflux; Multidrug resistance

Assessing the response of plant flavonoids to UV radiation: an overview of appropriate techniques by Riitta Julkunen-Tiitto; Nikolaos Nenadis; Susanne Neugart; Matthew Robson; Giovanni Agati; Jouko Vepsäläinen; Gaetano Zipoli; Line Nybakken; Barbro Winkler; Marcel A. K. Jansen (273-297).
Flavonoids are a large group of plant secondary metabolites that are present in most plants, and are vital for plant growth, development and protection. Among the many functions of these compounds is their contribution to stress amelioration. The accurate identification and quantification of total or individual flavonoids in plants exposed to stressful conditions (e.g. ultraviolet radiation) is challenging due to their structural diversity. The present review provides the up to date knowledge and highlights trends in plant flavonoid analysis. The review covers all steps from the field to the laboratory, focussing on UV-B effects on flavonoids, and identifying critical issues concerning sample collection, pre-treatment, extraction techniques and quantitative or qualitative analysis. A well-planned sampling and sample prehandling strategy is vital when capturing organ, tissue and developmental-stage dependent changes in flavonoids, as well as the dynamic changes due to time of UV-exposure and diurnal or seasonal parameters. A range of advanced extraction and purification techniques can facilitate the quantitative transfer of flavonoids to solvents. The advantages and disadvantages of analytical methods, including chromogenic assays, liquid and thin-layer chromatography, mass spectrometry, nuclear magnetic resonance detection, and non-destructive in situ fluorescent analysis need to be consciously evaluated in the context of the specific biological question posed. Thus, no one method can be applied to every single study of flavonoid. The message of this review is that researchers will need to carefully consider the biological process that they intend to study, and select an analytical method that optimally matches their specific objectives.
Keywords: Plant flavonoids; Flavonoid extraction; Qualitative and quantitative analyses; Sampling and sample prehandling; UV-B

The pharmaceutical industry and natural products: historical status and new trends by Bruno David; Jean-Luc Wolfender; Daniel A. Dias (299-315).
Owing to the high diversity of terrestrial and marine organisms, natural products (secondary metabolites) are some of the most successful source of drug leads for the treatment of many diseases and illnesses. In the 1990s, advancements in automation [high-throughput screening (HTS)] and isolation technologies resulted in the surge in research towards natural products both in the fields of human health and agriculture. These strategies and techniques generated a substantial shift towards this ‘green Eldorado’, a real ‘Green Rush’ between 1990 and 2000. However, in the early 2000s most of the big Pharmas terminated their HTS and bioprospecting endeavours but to date, the low productivity of combichem and rational drug design is silently positioning pharmacognosy back on the rails and natural product discovery is remerging as a reputable source of current drugs on the market. Meanwhile, the World Health Organization has come to the realisation of the importance of biodiversity which would be able to offer affordable, therapeutic solutions to the majority of the world population. The preservation of the world’s biodiversity and its access is a critical issue which could hamper a serene utilisation of natural products in the developing world with herbal-based phytopharmaceuticals representing a significant share of the total world pharmaceutical market. This review presents an industrial perspective discussing natural product drug discovery, lead research, botanicals, pro-drugs, synergy effects, drugs interactions with botanicals, traditional medicines, reverse pharmacognosy and presents the difficulties in accessing biodiversity.
Keywords: Drug discovery; High-throughput screening (HTS); Biodiversity; Pharmaceutical industry; Access and benefit sharing