Phytochemistry Reviews (v.15, #4)

Rhodiola rosea L.: from golden root to green cell factories by Andrey S. Marchev; Albena T. Dinkova-Kostova; Zsuzsanna György; Iman Mirmazloum; Ina Y. Aneva; Milen I. Georgiev (515-536).
Rhodiola rosea L. is a worldwide popular plant with adaptogenic activities that have been and currently are exploited in the traditional medicine of many countries, as well as, examined in a number of clinical trials. More than 140 chemical structures have been identified which belong to several natural product classes, including phenylpropanoid glycosides, phenylethanoids, flavonoids and essential oils, and are mainly stored in the rhizomes and the roots of the plant. A number of mechanisms contribute to the adaptogenic activities of R. rosea preparations and its phytochemical constituents. Among them, the intrinsic inducible mammalian stress responses and their effector proteins, such as heat shock protein 70 (Hsp70), are the most prominent. Due to its popular medicinal use, which has led to depletion of its natural habitats, R. rosea is now considered as endangered in most parts of the world. Conservation, cultivation and micropropagation are all implemented as potential preservation strategies. A number of in vitro systems of R. rosea are being developed as sources of pharmaceutically valuable secondary metabolites. These are greatly facilitated by advances in elucidation of the biosynthetic pathways and the enzymes, which catalyse the production of these secondary metabolites in the plant. In addition, biotechnological approaches show promise towards achieving sustainable production of R. rosea secondary metabolites.
Keywords: Roseroot; Medicinal use; Clinical trials; In vitro systems; Secondary metabolites

Review on Saussurea laniceps, a potent medicinal plant known as “snow lotus”: botany, phytochemistry and bioactivities by Qi-Lei Chen; Xi-Yu Chen; Lin Zhu; Hu-Biao Chen; Hing-Man Ho; Wing-Ping Yeung; Zhong-Zhen Zhao; Tao Yi (537-565).
Saussurea laniceps (Compositae), commonly known as “cotton-headed snow lotus”, is the most effective “snow lotus” used in both Tibetan and Chinese folk medicine. It performs outstandingly in treating rheumatoid arthritis, which mainly is credited for its anti-inflammatory and anti-nociceptive efficacy, as explained by modern pharmacological studies. Extracts of the herb, including umbelliferone and scopoletin, exert such effects in various in vivo and in vitro studies. Besides the two chemicals above, more than 100 organic compounds have been found in S. laniceps, and 58 of them are presented here in molecular structure, including cynaropicrin, mokko lactone, apigenin, acacetin, and luteolin, all contributing to different bioactivities, such as analgesic, antioxidant, immunomodulatory, anti-microbial and anticancer effects. We provide a natural product library of S. laniceps, giving inspirations for structure modification and bioactivity-oriented screening, enabling sustainable use of this valuable plant. The ethnomedical applications and pharmacological discoveries are compared and crosslinked, revealing modern evidence for traditional usages. Despite that S. laniceps is a representative “snow lotus” herb, its material medica records and clinical applications are complicated; there is considerable confusion with the different snow lotuses in the academic community and on the market. This review also aims at clearing such confusion, and improving quality assessment and control of the herb. To better utilize the valuable plant, further comparison among the chemical constitutions, pharmacological activities and therapeutic mechanisms of different snow lotuses are needed.
Keywords: Anti-inflammatory; Chinese medicine; Saussurea laniceps ; Scopoletin; Umbelliferone

Advances in phytochemistry, pharmacology and biotechnology of Bulgarian Astragalus species by Ilina Krasteva; Aleksandar Shkondrov; Iliana Ionkova; Petranka Zdraveva (567-590).
The genus Astragalus L., Fabaceae (Leguminosae) is presented in Bulgarian flora by 31 species including local endemics, nine of them listed in the Red Data Book. The main biologically active compounds found in the Bulgarian Astragalus plants are saponins and flavonoids with a variety of effects: immunomodulatory, hepatoprotective, cytotoxic, antioxidant, antihypoxic and others. In the recent years volatiles with cytotoxic activity have also been determined. Saponins and flavonoids are still preferably produced by plants due to their complex structures. Variable quantities and qualities of the wild plant material, plants that need to grow several years before they are ready for harvesting and over-collecting of endangered Astragalus species are just a few of the problems connected with the production of these natural products. Therefore, cultured cells are possible alternative for production of high-value secondary metabolites. This review is focused on phytochemical, pharmacological and biotechnological studies of Bulgarian Astragalus plants and includes also results from our investigations.
Keywords: Saponins; Flavonoids; In vitro production

The antigenotoxic potential of dietary flavonoids by Vlad Simon Luca; Anca Miron; Ana Clara Aprotosoaie (591-625).
Human exposure to genotoxic agents has dramatically increased. Both endogenous (reactive species generated during physiological and pathological processes) and exogenous (UV light, ionizing radiation, alkylating agents, antimetabolites and topoisomerase inhibitors, air, water and food pollutants) factors can impair genomic stability. The cumulative DNA damage causes mutations involved in the development of cancer and other disorders (neuromuscular and neurodegenerative diseases, immune deficiencies, infertility, cardiovascular diseases, metabolic syndrome and aging). Dietary flavonoids have protective effects against DNA damage induced by different genotoxic agents such as mycotoxins, food processing-derived contaminants (polycyclic aromatic hydrocarbons, N-nitrosamines), cytostatic agents, other medications (estrogenic and androgenic hormones), nicotine, metal ions (Cd2+, Cr6+), radiopharmaceuticals and ionizing radiation. Dietary flavonoids exert their genoprotection by reducing oxidative stress and modulation of enzymes responsible for bioactivation of genotoxic agents and detoxification of their reactive metabolites. Data on structure–activity relationship is sometimes contradictory. Free hydroxyl groups on the B ring (catechol moiety) and C-3 position of the C ring are important structural features for the antigenotoxic activity. As dietary flavonoids are extensively metabolized, more in vivo studies are needed for a better characterization of their antigenotoxic potential.
Keywords: Genotoxic damage; Oxidative stress; Quercetin; Epigallocatechin gallate; Cyanidin

Imperatorin–pharmacological meaning and analytical clues: profound investigation by Ewelina Kozioł; Krystyna Skalicka-Woźniak (627-649).
Imperatorin, a furanocoumarin derivative, has many documented pharmacological properties which make it a candidate for possible drug development. In this review, the activity on the central nervous system, the anticancer and antiviral properties and the influence on the cardiovascular system are described. The aim of this review is also to present an overview of the techniques used for the analysis, isolation, and separation of imperatorin from plant material from the practical perspective.
Keywords: Imperatorin; Furanocoumarin; Psoralen derivatives

The alarming growth of the number of antibiotic resistant bacteria and in the same time limited possibilities to develop new antimicrobial compounds, lead to an urgent need to keep the sensitivity of bacteria against currently used antibiotics. Bacterial efflux pumps are an important mechanism of antibiotic resistance as the bacteria use efflux pumps for the extrusion of different types of antibiotics and chemicals. The knowledge about inhibitors of efflux pumps from natural sources suggests that this mechanism may be a good target for new drugs based on synergistic interactions of antibiotics with plant extracts, essential oils, or their constituents with efflux pump inhibitory activity. This review summarizes the current knowledge of staphylococcal efflux pumps and potential strategies to overcome them. Natural inhibitors of efflux pumps and their synergistic interactions with antibiotics are summarized.
Keywords: Efflux pump inhibitor; Antibiotic resistance; Plant extract; Essential oil

Natural products from marine invertebrates against Leishmania parasites: a comprehensive review by Marta Oliveira; Luísa Barreira; Katkam N. Gangadhar; Maria João Rodrigues; Tamára Santos; João Varela; Luísa Custódio (663-697).
Parasitic infections by Leishmania parasites remains a severe public health problem, especially in developing countries where it is highly endemic. Chemotherapy still remains a first option for the treatment of those diseases, despite the fact that available drugs exhibit a variety of shortcomings. Thus, innovative, less toxic more affordable and effective antileishmanial agents are urgently needed. The marine environment holds an immeasurable bio- and chemical diversity, being a valuable source of natural products with therapeutic potential. As invertebrates comprise about 60 % of all marine organisms, bioprospecting this class of organisms for antileishmanial properties may unravel unique and selective hit molecules. In this context, this review covers results on the literature of marine invertebrate extracts and pure compounds evaluated against Leishmania parasites mainly by in vitro methods. It comprises results obtained from the phyla Porifera, Cnidaria, Bryozoa (Ectoprota), Mollusca, Echinodermata, Annelida, Cetnophora, Platyhelminthes, sub phyla Crustacea (phylum Arthropoda) and Tunicata (phylum Chordata). Moreover, structure–activity relationships and possible mechanisms of action are mentioned, whenever available information is provided. About 70 species of marine invertebrates belonging to seven different phyla are included in this work. Besides a variety of crude extracts, a total of 140 pure compounds was tested against different Leishmania species. Although the research on the antileishmanial potential of marine invertebrates is in its early beginnings, promising results have been achieved that encourage further research. As more extracts and compounds are being screened, the possibility of finding active and selective antileishmanial molecules increases, rising new hope in the search for new treatments against leishmaniases.
Keywords: Antileishmanial activity; Marine invertebrates; Parasitic infections; Structure–activity relationship (SAR)