Phytochemistry Reviews (v.17, #4)

Plant biodiversity: phytochemicals and health by Pinarosa Avato; Mariapia Argentieri (645-656).
Biodiversity may be defined as the variability occuring among living organisms and affecting all species of animals and plants, their genetics and their environment. Biological diversity of plants also relies on the chemical diversity deriving from their specialized metabolites which possess a wide range of different chemical structures as a result of plant evolution. They are responsible for the plant ecological properties and are required for the plant-environment interactions. In addition, many of them display important pharmacological properties. In the recent years, the growing interest in using plant metabolites to treat diseases in humans and animals and the high request of health products originating from natural sources rather than synthetic has revived the research on plant biodiversity to identify new bioactive molecules. Based on our studies on the chemical and biological characterization of rare or less studied plant species, the present paper aims to describe a selection of botanical species with phytopharmaceutical importance in order to highlight the chemical polymorphism deriving from their biodiversity along with its implications on bioactivity.
Keywords: Biodiversity; Brassicaceae; Passiflora L.; Lavandula L.; Thapsia L.

Valorization of a biomass: phytochemicals in oilseed by-products by Selin Şahin; Elaf Abdelillah Ali Elhussein (657-668).
A huge amount of residue is released every year in agricultural and food industries. If this waste is valorised properly, it would be very beneficial from both economic and environmental aspects. Recently, seeds of oil crops have been getting great interest due to their waste rich in a great variety of lipophilic and hydrophilic phytochemicals. On the other hand, oilseed processing by-products comprise approximately 35 millions of tons seed for oil in European Union. Therefore, this remarkable amount of residue should be considered as a resource from waste to health. The purpose of the present research is to introduce the types of oilseed by-product and their high added value phytochemicals by summarizing the recent studies on the valorization of different wastes of several oilseed crops. This research also supplies an overview of the oilseed sources with their botanical names, production regions and target phytochemical ingredients. Moreover, further remarks with some certain concerns are discussed.
Keywords: Oilseed by-products; Biomass; Phytochemicals; Bioactive substances; Natural additives

Diels–Alder adducts from Celastraceae species by Isabel L. Bazzocchi; Marvin J. Núñez; Carolina P. Reyes (669-690).
Celastraceae species are a rich source of adducts whose biosynthesis has been hypothesized as involving a Diels–Alder reaction. The co-occurrence of these natural terpenoids adducts with their corresponding precursors, and the reported regio- and stereoisomers support that their biosynthesis may occur via a Diels–Alderase. Triterpene dimers, composed of a quinonemethide and a phenolic nor-triterpene, are the most numerous group of adducts and are all restricted to the Celastraceae family. This review covers natural Diels–Alder adducts from Celastraceae species, providing an overview of the reported terpenoid adducts classified by their monomer nature. In addition, synthetic efforts on the chemical feasibility of the biosynthetic Diels–Alder reactions involved and the biological activities of these metabolites are discussed.
Keywords: Biological properties; Biosynthesis; Celastraceae species; Diels–Alder adducts; Triterpene dimers

The risk of exhaustion of natural resources and raw materials have given rise to emerging trends such as recycling of food waste. From the economical and ecological points of view, conversion of biowaste to high added value compounds has been getting great attention among the science and commercial entities. Due to their high-added value phytochemicals, agricultural and food residues have been a great significant to the researchers around the world. This study focuses on the valorisation of cake derived from sesame oil processing. If the very valuable non-nutrient phytochemicals in sesame cake are not evaluated properly, they would be consumed as just animal feed or fertilizers. They might be employed as antiaging (in pharmaceutical products), or free radical scavenger (in dietary supplements), or preservative additive against lipid oxidation (in fat containing food products). This review article aims to present pharmacological and therapeutic effects of sesame cake extract by pointing out its application in pharmaceutical, cosmetic and food industries.
Keywords: Sesame cake; Biowaste; Phytochemicals; High-added value chemicals; Natural additives; Natural preservatives

Genus Retama: a review on traditional uses, phytochemistry, and pharmacological activities by A. J. León-González; I. Navarro; N. Acero; D. Muñoz Mingarro; C. Martín-Cordero (701-731).
Plants of the genus Retama (Fabaceae) are used in traditional medicine of the Mediterranean Basin as an emetic, purgative, and vermifuge. Certain Retama species are also employed to treat a multitude of disorders, including diabetes, hepatitis, jaundice, sore throat, skin diseases, joint pain, rheumatism, fever, and inflammation. This review deals with updated information on the distribution, botanical characteristics, ethnopharmacology, phytochemistry, pharmacological activities, and toxicity of the Retama species in order to support their therapeutic potential and to provide an input for future research prospects. The Retama species are mainly employed as ethnomedicinal remedies in Mediterranean countries, including Algeria, Egypt, Italy, Lebanon, Libya, Morocco, and Spain. Previous phytochemical studies show a complex composition, rich in carbohydrates (galactomannans), polyols (pinitol), fatty acids, phenolic compounds (genistein, daidzein) and alkaloids (retamine, lupanine). The pharmacological activity of their various extracts has been widely studied, revealing, among others, the anti-microbial, anti-inflammatory, and anti-diabetic effects of these species. The potential toxicity of these medicinal plants has also been discussed. Although recent experimental evidence confirms the pharmacological interest of this genus, further studies are necessary.
Keywords: R. monosperma ; R. raetam ; R. sphaerocarpa ; Quinolizidine alkaloids; Isoflavones

Chemical composition and nutraceutical properties of hempseed: an ancient food with actual functional value by Giuseppina Crescente; Simona Piccolella; Assunta Esposito; Monica Scognamiglio; Antonio Fiorentino; Severina Pacifico (733-749).
The seeds of hemp (Cannabis sativa L.) have been an important source of nutrition for thousands of years in Chinese and European cultures but, nowadays, in spite of the multiple clinical evidence, which highlights their huge health-promoting properties, people are still unaware about their nutritional as well as nutraceutical benefits. Indeed, the extraordinary richness of essential polyunsaturated fatty acids is odds with oxidative stability of hemp seed by-products. This is the reason for which different and innovative extractive strategies are daily employed, as well as the preservation of antioxidant hemp seed phenols and polyphenols is claimed as a key issue to pursue. Recent insights into the phenol and cannabinoid baggage of hemp seed highlight it is an inestimable source of health promoting ingredients. This review aims to provide a detailed and updated background for research on seeds of this niche crop, pointing out the chemistry and bioactivity of their phytochemicals.
Keywords: Cannabis sativa L.; Polyunsaturated fatty acids; Phenols; Lignanamides; Functional food

Cedrela and Toona genera: a rich source of bioactive limonoids and triterpenoids by Marinella De Leo; Luigi Milella; Alessandra Braca; Nunziatina De Tommasi (751-783).
Cedrela P. Browne is a genus of trees, strictly related to Toona, in the Meliaceae, a family of flowering plants in the order Sapindales, which is among the most diverse sources of secondary metabolites in the Angiospermae. The most abundant metabolites in these genera are limonoids, tetranortriterpenes possessing diverse structural features, apotirucallanes, tirucallanes, and other triterpenes. The chemical constituents isolated from the genera Cedrela and Toona over the past decades, together with their biological activities, have been compiled in this article. The allelochemical and the phytotoxic activity of limonoids and triterpenoids seem to play a crucial role in the ecological function of these metabolites. While, the most promising use in human field seems related to their antimalarial and anti-inflammatory effects, even that further investigation are still needed.
Keywords: Cedrela ; Toona ; Meliaceae; Limonoids; Triterpenoids; Biological activity

Wild aromatic plants bioactivity: a function of their (poly)phenol seasonality? A case study from Mediterranean area by Simona Piccolella; Giuseppina Crescente; Francesca Pacifico; Severina Pacifico (785-799).
Wild medicinal and aromatic plants are in the market as herbal raw or processed and packaged materials, playing, even today, a strategic role in the production of plant-based products. Indeed, their content in active ingredients, mainly specialized secondary metabolites, is not constant; it undergoes significant seasonal variations, as abiotic stress heavily affects secondary metabolism network. The present review deals with the seasonality influence on the polyphenolic composition on antioxidant and anti-inflammatory properties of medicinal and aromatic plants. To this aim, firstly the factors influencing the content of active ingredients in a plant drug will be discussed, and, in particular, the increased occurrence of phenols as a response to abiotic stress. In the last part of the review a brief reference will be made to four meaningful case studies, which involve wild medicinal aromatic herbs, native to the Mediterranean area: Calamintha nepeta L. Savi, Foeniculum vulgare Mill., Ruta graveolens L. and Thymus longicaulis C. Presl. These species, grown in the same geographical area and collected at the same harvesting time, showed a great variability in phenol constituents throughout the year. The comparison among data acquired clearly evidences that the seasonal variation in polyphenols’ occurrence and amount leads to a more/less pronounced antioxidant and anti-inflammatory activity of the hydroalcoholic extract therefrom. It is worth of note that the presence of the same metabolite, but in different phytochemical complexes, could result in different biological activities.
Keywords: Anti-inflammatory activity; Antioxidant activity; MAPs; Phenophase influence; Polyphenols

Effects of PUFAs on animal reproduction: male and female performances and endocrine mechanisms by Margherita Maranesi; Cesare Castellini; Cecilia Dall’Aglio; Linda Petrucci; Simona Mattioli; Cristiano Boiti; Massimo Zerani (801-814).
Adequate fat diet supplementation shows variable positive effects in farm animal breeding. Omega-3 and n-6 PUFAs are able to modulate several reproductive effectors: the luteolytic PGF2α, the luteotropic PGE2, the nuclear receptor PPARG, and steroids such as E2 and P4. PUFA supplementation favours fertility, onset of estrus, embryo survival, and also parturition by reducing preterm labour risk. These effects are likely mediated by the balance modulation of PGF2α and PGE2 productions, the syntheses of E2 and P4, and the activation of PPARG. As regards to male fertility, the effects of n-3 or n-6 PUFA supplementation at high concentrations in the diet are relatively unknown. PUFAs confer to the spermatozoa plasma membrane the fluidity it needs to achieve fertilization and seem to stimulate the Leydig cell production of testosterone through the regulation of the steroidogenic acute regulatory protein, a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. As regards to female fertility, PUFA supplementation mediates a broad range of actions in reproductive processes involving pregnancy establishment, uterine endocrinology, and preterm birth. The perfectly composed follicular environment shapes oocyte quality and thus female fertility. Since both oocytes and embryos are vulnerable to microenvironment changes, nutritional alterations and FA unavailability can lead to their defects. The aim of the present review is to examine the effects of n-3 and n-6 PUFAs on male and female reproductive performances and the correlated endocrine mechanisms.
Keywords: Fatty acids; PPARs; Prostaglandins; Reproduction; Steroids

Linking plant phytochemistry to soil processes and functions: the usefulness of 13C NMR spectroscopy by Fabrizio Cartenì; Tushar C. Sarker; Giuliano Bonanomi; Gaspare Cesarano; Alfonso Esposito; Guido Incerti; Stefano Mazzoleni; Virginia Lanzotti; Francesco Giannino (815-832).
The organic matter cycle is one of the most fundamental processes in ecosystems affecting the soil and controlling its functions. The soil complex microbiome is made up of thousands of bacterial and hundreds of fungal strains that coexist on the many different available organic carbon sources. In natural plant communities, freshly fallen leaf-litter and dead roots are subject to decomposition by a complex food-web composed of both microbial saprotrophs and invertebrate detritivores. The litter chemical composition varies dramatically among species in relation to plant life forms (conifer, broadleaf, nitrogen-fixing, graminoid) and, within species, with plant organs (leaf, root, woody tissues). This paper reviews the usefulness of advanced chemical technologies to study the composition of both plant litter and organic amendments, supporting the description of their mechanism of action and attention to their potential applications. First, a critical review is presented on the limitations of C/N and lignin/N ratios, still widely used as basic indicators of litter chemistry. Second, the potential of the solid state 13C-CPMAS NMR is reported as a powerful tool to assess the chemical composition of both litter and organic amendments. Finally, six different study cases are reported to provide evidence of the usefulness of such metabolomic approach for the description of organic matter chemistry aimed to an effective prediction of its impact on soil ecosystem functions.
Keywords: Soil microbiome; Litter decomposition; Soil structural stability; Phytoxicity; Disease suppression; Soil water repellency; Soil fungistasis

Family Juncaceae: promising source of biologically active natural phenanthrenes by Csaba Bús; Barbara Tóth; Dóra Stefkó; Judit Hohmann; Andrea Vasas (833-851).
Phenanthrenes represent a relatively small group of aromatic secondary metabolites, which can be divided into three main subgroups (mono-, di-, and triphenanthrenes). Phenanthrenes are reported as an intensively researched field in phytochemistry according to their structural diversity and promising biological activities. Because of their limited occurrence phenanthrenes are considered to be as important taxonomic markers. Juncaceae is a relatively large plant family divided into seven genera of which Juncus and Luzula are the most important ones from phytochemical and pharmacological points of view. To date, almost one hundred natural phenanthrenes have been isolated but only from eight (Juncus acutus, J. effusus, J. inflexus, J. maritimus, J. roemerianus, J. setchuensis, J. subulatus, and Luzula luzuloides) Juncaceae species, including mono-, and diphenanthrenes, and phenanthrene glucosides. Great deal of the isolated compounds are substituted with a vinyl group. This substitution is characteristic exclusively to Juncaceae species. Juncusol (2) was isolated from every investigated species. The richest source of phenanthrenes, as well as the most extensively investigated species is J. effusus. Several isolated compounds possessed different biological activities, e.g. antiproliferative, antimicrobial, anti-inflammatory, antioxidant, spasmolytic, anxiolytic, and antialgal effects. Among them, dehydroeffusol (60) is the most promising one, as it showed antimicrobial, anxiolytic, sedative, spasmolytic, cellular protective and antiproliferative activities. The aim of this review is to summarize the occurrence of phenanthrenes in the family Juncaceae, and give a comprehensive overview of their isolation, structural characteristics and biological activities.
Keywords: Phenanthrenes; Juncaceae; Juncus ; Luzula ; Biological activities

Papaver somniferum L. taxonomy, uses and new insight in poppy alkaloid pathways by Fabiana Labanca; Jaroslava Ovesnà; Luigi Milella (853-871).
Since ancient times, opium poppy (Papaver somniferum L.) is known for its medicinal properties, related to its secondary metabolite content. Its most important secondary metabolites, called benzylisoquinoline alkaloids (BIAs), are still essential in pharmaceutical field. Few of them, like morphine, have specific clinical application but also effects on CNS. Not all poppy cultivars are able to biosynthesize morphine in high amount, making this plant useful for other purposes like food uses. For this reason it is crucial to deeply understand the origin of poppy, its possible use and have a deep knowledge of the BIA biosynthesis. These aspects are crucial for the final use of P. somniferum. This review aims to summarize the state-of-the-art on its taxonomy and origin beside its uses and BIA biosynthetic pathways, its most important metabolites. The review focuses on conflicting or unsolved questions about enzymatic localization, role of different plant organs in the biosynthesis, and storage and external conditions that influence the alkaloid production, highlighting the significant involvement of transcription factors. Behind this review, there is the firm belief that only a deep knowledge of alkaloid biosynthetic processes could lead to the characterization of undefined step and to the development of engineering cultivars optimizing the potential uses of P. somniferum. The goal is answer in more sustainable way to ever-increasing worldwide request of such products, in particular morphine and derivates, obtaining high morphine content cultivars useful for pharmaceutical market or no morphine producing cultivars appreciated as food. Devising cultivars with different BIA content could lead to decrease, or even avoid, illicit use and illegal extraction, confining only low alkaloid content cultivars to consumers market.
Keywords: Benzylisoquinoline alkaloid; BIAs; Biosynthesis; Poppy; Phylogenetic; Transcription factors

Origanum spp.: an update of their chemical and biological profiles by Mariangela Marrelli; Giancarlo A. Statti; Filomena Conforti (873-888).
The purpose of this review is to provide an overview of most recent studies about potential pharmaceutical applications of plants belonging to Origanum genus. Oregano is one of the most famous and economically important culinary herbs in the world. The genus Origanum includes more than 70 species mainly distributed around the Mediterranean region. The vernacular name “oregano” is attributed to a vast number of species. O. vulgare L. is the most variable species of the genus and the most commonly known as oregano in most countries. Today, it is generally accepted that oregano is a characteristic flavour produced by a number of plant species that yield carvacrol-rich essential oils. The genus Origanum is characterised by a large morphological and chemical diversity. Because of their several biological activities, such as antimicrobial, expectorant, antispasmodic and carminative, Origanum species have been used in traditional medicine to treat various diseases. The botany and chemotaxonomy of the species are thoroughly reported, along with chemical constituents. The in vitro and in vivo effects of Origanum extracts are presented and discussed.
Keywords: Biological activity; Essential oil; Origanum sp.; Phenols; Terpenes

Plants react towards changes in their environment, which can be a result of biotic or abiotic activities. Numerous studies have investigated the effects of abiotic stress on plants, and how it affects the primary as well as secondary metabolism. Generally it is accepted that plants react to environmental stress by increasing secondary metabolites. This is however a very broad and simplified explanation and often inaccurate. Various examples are provided where plants react positively, and often negatively towards seasonal variation and water availability, resulting in a lowering of certain secondary metabolites concentration, while others are increased. Furthermore species differences, cultivars and interaction of other environmental factors such as temperature complicates a simple conclusion from the effect of stress on plants. The differential expression of genes in different species and in different metabolic pathways ensures a complex and very specific reaction of a plant to environmental stress. Overall the paper provides support for a complex and intricate response system which differs for each plant species, and could be explained by understanding and studying the different metabolic pathways responsible for secondary metabolite production.
Keywords: Season; Water; Irrigation; Secondary metabolites; Metabolic pathways; Flavonoids

Carvacrol and its derivatives as antibacterial agents by Lisa Marinelli; Antonio Di Stefano; Ivana Cacciatore (903-921).
In recent years, essential oils constituents have attracted interest as alternative approach in the traditional medicine for their therapeutics properties. In this field, carvacrol, since it showed strong antimicrobial activity against a wide range of Gram-positive and -negative bacteria, has emerged as active molecule for therapeutic purpose. This review focuses on the antimicrobial properties of carvacrol and highlights the advantageous impact of the medicinal chemistry and technological-based approaches employed to improve its therapeutic profile.
Keywords: Antimicrobials; Carvacrol; Carvacrol derivatives; Essential oils

The present review gives an overview about the status of research on seasonal variation of natural products in European trees. Due to their different life forms, gymnosperms, deciduous angiosperms, and evergreen angiosperms are reviewed separately. Besides trying to give an overview about the existing newer literature, the review tries to define some repetitively found trends and discusses some possible explanations for these trends. Moreover, open research questions are highlighted and some suggestions for future studies are given. These suggestions encompass both subjects and desirable quality standards with regards to experimental designs. The reviewed publications are mainly focused on leaves, some on fruits, and some on barks and twigs. Phenolics, including phenolic acids and flavonoids of different types as well as tannins, are the most often studied compound class; additionally, some papers assess seasonal variation of alkaloids, diterpenes, essential oils, lignans, simple organic acid, secoiridoids, and stilbenoids.
Keywords: Chemical ecology; Trees; Holarctis; Seasonal variation; Plant natural products

Evaluation of the therapeutic effects of Artemisia absinthium L. on pseudopregnancy model in rats by Murşide Ayşe Demirel; Ipek Suntar; Songul Ceribaşı; Gökhan Zengin; Ali Osman Ceribaşı (937-946).
Researchers have been investigating new treatment strategies for the management of pseudopregnancy, due to some long term causes of this disease including mastitis and mammary tumor. Owing to the side effects of hormone therapy, much attention has been focused on more tolerable treatment options including natural remedies. In the present study, we aimed to investigate the therapeutic effects of Artemisia absinthium L. (wormwood) on pseudopregnancy model in rats. A. absinthium, which is a perennial shrubby plant from Asteraceae family, was reported to be used as an emmenagogue in folk medicine and was previously shown to modulate dopaminergic system. In the present study, pseudopregnancy model was induced in female Sprague–Dawley rats by injection of pregnant mare’s serum gonadotropin and human chorionic gonadotropin. The petroleum ether, dichloromethane and methanol extracts of A. absinthium, prepared by successive extraction method, were orally administered to the rats at 100 mg/kg dose, once daily for 10 days. Bromocriptine (3 mg/kg/per os) was administered to the reference group animals. At the end of the experiment, all of the animals were sacrificed, the blood samples, ovaries and uterine tissues were taken for histopathological and biochemical analysis. According to the results of the present study, the petroleum ether extract displayed beneficial effects in pseudopregnancy model in rats when compared with the control group. Therefore, Gas Chromatography analysis was conducted on this extract to reveal its phytochemical profile.
Keywords: Asteraceae; Artemisia absinthium ; Dopaminergic; Pseudopregnancy; Rat