Phytochemistry Reviews (v.16, #2)

Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been well known in Far Eastern medicine for a long time. However, schisandra seems to be a plant still underestimated in contemporary therapy still in the countries of East Asia. The article presents latest available information on the chemical composition of this plant species. Special attention is given to dibenzo cyclooctadiene lignans. In addition, recent studies of the biological activity of dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated. The paper gives a short resume of their beneficial effects in biological systems in vitro, in animals, and in humans, thus underlining their medicinal potential. The cosmetic properties are depicted, too. The analytical methods used for assaying schisandra lignans in the scientific studies and also in industry are also presented. Moreover, special attention is given to the information on the latest biotechnological studies of this plant species. The intention of this review is to contribute to a better understanding of the huge potential of the pharmacological relevance of S. chinensis.
Keywords: Schizandra; Dibenzocyclooctadiene lignans; Schisandrin; Gomisin A; Triterpenoids; In vitro cultures

Natural products and phytotherapy: an innovative perspective in leishmaniasis treatment by Luiz Filipe Gonçalves de Oliveira; Bernardo Acácio Santini Pereira; Benjamin Gilbert; Arthur Luiz Corrêa; Leandro Rocha; Carlos Roberto Alves (219-233).
The interest in phytopharmaceutical products and herbal medicines has been a trend in recent years and this approach may be useful as basis for developing new treatment against leishmaniasis. In this review, we discuss the perspectives of leishmaniasis treatment based on natural products and phytotherapy and compare it to the advantages and disadvantages of using the current drugs of first- and second-choice against leishmaniasis. The reports gathered herein reinforce the leishmanicidal effects of medicinal plants and its derivatives, such as Kalanchoe pinnata, Plumbago scandens, Physalis angulata, Piper aduncum, Peschiera (Tabernaemontana) australis, Phyllanthus amarus, and Artemisia annua, and indicates their use as possible alternative or complementary treatments against leishmaniasis. The data presented here support the use of medicinal plants as safe and inexpensive treatments for leishmaniasis.
Keywords: Natural products; Herbal medicines; Phytotherapy; Leishmaniasis treatment

Furanoditerpenoids are a special group of diterpenoids composing of one or more furan rings, which are rarely found in nature. This review aims to survey the various naturally occurring furanoditerpenoids and their pharmacological activities. A fairly large number of furanoditerpenoids have been reported from the families Euphorbiaceae, Fabaceae and Lamiaceae, and a few ones from the families Asteraceae, Codoniaceae, Dioscoreaceae, Fossombroniaceae, Jamesoniellaceae, Meliaceae, Menispermaceae, Olacaceae, Psathyrellaceae, Sapindaceae and Scapaniaceae. Their distribution correlates strongly with the taxonomic divisions. Most of these plants are widely used in traditional medicines, and furanoditerpenoids have therefore been disclosed with a wide range of bioactivities including anti-cancer, anti-inflammation and anti-microorganism. To structure this review, the furanoditerpenoids were classified into seven types, including clerodane-type (Type I), labdane-type (Type II), cassane-type (Type III), abietane-type (Type IV), spongian-type (Type V), prenylbisabolane-type (Type VI) and miscellaneous type (Type VII). On the basis of 170 references, this review covers the distribution, phytochemistry, synthesis and pharmacological activities of furanoditerpenoids, describing 444 compounds. The information provided in this review might shed light on further research and development of furanoditerpenoids as potential therapeutic agents.
Keywords: Furanoditerpenoids; Distribution; Phytochemistry; Biological properties

Endolichenic fungi are diverse groups of predominantly filamentous fungi that reside asymptomatically in the interior of lichen thalli. Natural products from endolichenic fungi, isolated from a variety of different lichen species, have been attracting increased attention for their potential to produce bioactive metabolites possessing new structures and representing different structural classes. This is evident from the steady increase of publications devoted to endolichenic fungal metabolites over the past decade, since the first report of endolichenic secondary metabolites. The bioactive metabolites produced by endolichenic fungi originate from multiple biosynthetic pathways and occupy different chemical structure classes, including steroids, quinones, terpenoids, peptides, xanthones, sulfur-containing chromenones, etc. Endolichenic fungal metabolites possess a diverse array of bioactivities, such as anticancer, antiviral, antibacterial, antifungal, and anti-Alzheimer’s disease. This review provides the first thorough assessment of endolichenic fungi, their biodiversity, secondary metabolites, and associated bioactivity. This review will highlight the bioactive metabolites reported in recent years from endolichenic fungi, as well as discussing the potential of these symbiotic fungi as sources of new, diverse natural products with varying bioactivities.
Keywords: Bioactivity; Biodiversity; Endolichenic fungi; Lichen; Natural products

The chemistry and pharmacology of Edelweiss: a review by Jan Tauchen; Ladislav Kokoska (295-308).
Leontopodium nivale ssp. alpinum (syn. Leontopodium alpinum) is a perennial herb commonly known as Edelweiss, which has a long tradition in Alpine countries and adjacent regions as a medicinal plant. This review discusses current knowledge on the traditional uses, chemistry, biological activities and toxicology of this species. Several different classes of compounds such as terpenoids (analogues of sesquiterpenes, bisabolenes), phenylpropanoids (phenolic acids, flavonoids, coumarins, lignans), fatty acids and polyacetylenes were previously isolated from various parts of Edelweiss. Different types of extracts and compounds derived from this plant have been found to possess a broad spectrum of pharmacological activities on the cardiovascular and nervous systems. Furthermore, the plant have known anti-inflammatory, antimicrobial, antioxidant and chemo-protective effects. The observed pharmacological activities as well as toxicological profile of preparations and isolated compounds of Edelweiss support the view that these might be used in the development of agents with therapeutic benefit in various human diseases. Some suggestions for further research on chemical characterization and pharmacological properties are also given in this review.
Keywords: Asteraceae; Leontopodium alpinum ; Leontopodium nivale ; Medicinal plant; Secondary metabolites

Prosopis juliflora (SW) D.C. “algaroba” is an abundant invasive tree species native to South America, Central America and the Caribbean, present in arid and semi-arid zones. In Brazil, this species is widespread in the Caatinga biome, a xeric region that is going through a process of desertification. Algaroba was introduced to this region in order to promote reforestation and provide animal feed. However, this specie has adapted too well and has affected a botanical alteration of the endemic and native Caatinga specie. This has become a problem since algaroba could inhibit the growth and development of some endangered species. Therefore, it is important know the potential of algaroba and promote new uses aiming for a conscious exploitation of the use of this specie in several fields. This review aims to provide an up-to-date overview of botanical information, chemical compounds, traditional uses, pharmacological activities, as well as technological, biotechnological and toxicological aspects which could be helpful for future research in the development of new bioactive natural products. This review could help provide insights for new research aimed at both the rational exploration of bioactive metabolites and their application in new products.
Keywords: Prosopis juliflora ; Natural products; Phytochemistry; Overview

Scopolamine: a journey from the field to clinics by Sophie Friederike Ullrich; Hansjörg Hagels; Oliver Kayser (333-353).
Tropane alkaloids are present in many different plants of the Solanaceae family and widely known for their anticholinergic properties. Among them, most valued and increasingly demanded is scopolamine, also known under the name of hyoscine, which is used as pharmaceutical active substance in the treatment of postoperative nausea and vomiting, motion sickness and gastrointestinal, renal and biliary spasms for instance. It naturally occurs in various plant genera, e.g. Anisodus, Anthocercis, Atropa, Brugmansia, Datura, Duboisia, Hyoscyamus, Mandragora and Scopolia and the purified substance has a long history of use dating back to the nineteenth century. Until today, the supply in scopolamine is mainly covered by large scale field plant cultivation of hybrids between Duboisia myoporoides and Duboisia leichhardtii. Biotechnological approaches optimising the alkaloid biosynthesis, for example the use of callus cultures or genetically transformed hairy root cultures, are not competitive by now. The aim of this review is to give a comprehensive overview regarding the current knowledge on botanical origin, pharmacology, biosynthesis as well as agricultural and biotechnological production of scopolamine.
Keywords: Anticholinergics; Hyoscine; Solanaceae; Tropane alkaloids

In vitro metabolism studies of natural products are crucial in the early development of medicines by Fernanda L. Moreira; Lucas M. M. Marques; Norberto P. Lopes; Anderson R. M. de Oliveira (355-373).
Finding new drugs is imperative especially in the case of diseases such as serious infections and cancer, for which a gap in drug development exists. Plant-derived compounds display large structural diversity and constitute a source of novel medicinal agents. However, some drug candidates have failed in advanced stages of clinical and commercial use. In vitro tools have been effectively used to anticipate and to explore undesirable drug properties during early drug development. In this review, we address the purpose and advantages of conducting metabolic studies on natural products, and we describe how in vitro metabolism methods have contributed to delineating plant-based drug candidates. We also deal with the applications of in vitro metabolism studies on natural product-based drug development, which include characterization of the metabolites, investigation into enzymatic kinetics, prediction of drug clearance, phenotyping studies, and evaluation of natural product–drug interactions.
Keywords: In vitro metabolism; Natural products; Enzymatic kinetics; Metabolites; Natural product–drug interaction; CYP