Barbara Tóth

Phenanthrenes: A Promising Group of Plant Secondary Metabolites

Although phenanthrenes are considered to constitute a relatively small group of natural products, discovering new phenanthrene derivatives and evaluating their prospective biological activities have become of great interest to many research groups worldwide. Based on 160 references, this review covers the phytochemistry and pharmacology of 213 naturally occurring phenanthrenes that have been isolated between 2008 and 2016. More than 40% of the 450 currently known naturally occurring phenanthrenes were identified during this period. The family Orchidaceae is the most abundant source of these compounds, although several new plant families and genera have been involved in the search for phenanthrenes. The presence of certain substituent patterns may be restricted to specific families; vinyl-substituted phenanthrenes were reported only from Juncaceae plants, and prenylated derivatives occur mainly in Euphorbiaceae species. Therefore, these compounds also can serve as chemotaxonomic markers. Almost all of the newly isolated compounds have been studied for their biological activities (e.g., potential cytotoxic, antimicrobial, anti-inflammatory, and antioxidant effects), and many of them showed multiple activities. According to the accumulated data, denbinobin, with a novel mechanism of action, has great potential as a lead compound for the development of a new anticancer agent.

Screening of Luzula species native to the Carpathian Basin for anti-inflammatory activity and bioactivity-guided isolation of compounds from Luzula luzuloides (Lam.) Dandy & Wilmott

The present study focused on the anti-inflammatory screening of Luzula species native to the Carpathian Basin and bioactivity-guided isolation of compounds of Luzula luzuloides (Lam.) Dandy & Wilmott. The anti-inflammatory properties of extracts with different polarity prepared from Luzula species were determined. Among them, the CH2Cl2-soluble fraction of L. luzuloides possessed strong inhibitory effects on superoxide anion generation (99.39±0.37%) and elastase release (114.22±3.13%) in fMLP/CB-induced human neutrophils at concentration of 10μg/mL. From this fraction, six compounds (1-6) were isolated by the combination of different chromatographic methods. The structures of the compounds were determined by means of MS, 1D and 2D NMR spectroscopy. The results allowed the identification of the new 1,6-dihydroxy-2-keto-1,7-dimethyl-8-vinyl-1,2-dihydrophenanthrene (1) from the plant, named luzulin A. Chiral HPLC and HPLC-ECD analysis revealed that 1 possesses low enantiomeric excess and TDDFT-ECD calculations afforded the configurational assignment of the separated enantiomers. Three known phenanthrenes [juncuenin B (2), dehydrojuncuenin B (3) and juncusol (4)] and two flavonoids [apigenin (5) and luteolin (6)] were also isolated. The anti-inflammatory activity of the isolated compounds was tested and IC50 values were determined. This was the first time that phenanthrenes were detected in a Luzula species. The oxidative transformation of juncuenin B (3) led to the isolation of its possible biometabolites, namely luzulin A (1), dehydrojuncuenin B (4), and juncuenin D (7). The isolated compounds (1-4) confirm that besides flavonoids, phenanthrenes could also serve as chemotaxonomic markers for Luzula species and prove the close relationship of Juncus and Luzula genus.

Antibacterial screening of Juncaceae species native to the Carpathian Basin against resistant strains and LC-MS investigation of phenanthrenes responsible for the effect.

The main objective of this project was to investigate the antibacterial activity of 19 species (Juncus acutus, J. alpinoarticulatus, J. articulatus, J. compressus, J. conglomeratus, J. effusus, J. filiformis, J. gerardii, J. inflexus, J. maritimus, J. monanthos, J. squarrosus, J. tenuis, J. trifidus, Luzula campestris, L. forsteri, L. luzuloides, L. sudetica and L. sylvatica) belonging to the family Juncaceae against methicillin-resistant S. aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing C. freundii, E. coli, E. cloacae, K. pneumoniae, and multiresistant A. baumannii and P. aeruginosa. Antibacterial susceptibilities were screened for inhibitory zones and MIC values determined by microdilution method. Among the tested extracts (n=96) 16 extracts prepared from Juncus species and 3 extracts from Luzula species showed mild to strong inhibitory activities against MRSA strains (inhibition zones=6.7mm-14.6mm; MIC values 9.75-156μg/mL). It can be concluded that Juncus and Luzula species demonstrated promising anti-MRSA effect, and J. maritimus, J. tenuis and J. gerardii considered worthy of activity-guided phytochemical investigations. The main bioactive constituents of Juncaceae species are phenanthrenes. Four phenanthrenes [juncuenin D (1), juncusol (2), dehydrojuncuenin B (3), and jinflexin B (4)] isolated previously from J. inflexus with anti-MRSA activity were investigated by LC-MS in extracts proved to be active in antimicrobial test.

Family Juncaceae: promising source of biologically active natural phenanthrenes

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.

Abietane diterpenoids from Sideritis montana L. and their antiproliferative activity

The present study aimed at the phytochemical and pharmacological investigation of Sideritis montana L. (Lamiaceae). Two new abietane diterpenes [sideritins A (1) and B (2)] were isolated from the methanol extract of the plant. Six known compounds [pomiferin E (3), 9α,13α-epi-dioxyabiet-8(14)-en-18-ol (4), paulownin (5), 6-methoxysakuranetin (6), 3-oxo-α-ionol (7) and 4-allyl-2,6-dimethoxyphenol glucoside (8)] were also obtained from the plant. The structures were determined by means of HREIMS and NMR experiments. The antiproliferative effect of the isolated compounds was investigated on human cancer cell lines (HeLa, SiHa and C33A) at 10 and 30μM concentrations, using the MTT assay. The results demonstrated that pomiferin E (3) and 6-methoxysakuranetin (6) displayed considerable activity [inhibition (%)±SEM: 46.93±2.35 on HeLa (pomiferin E), and 51.52±2.45 on C33A (6-methoxysakuranetin)] at 30μM concentration.

Ginger (Zingiber officinale): An alternative for the prevention of postoperative nausea and vomiting. A meta-analysis

BACKGROUND Postoperative nausea and vomiting (PONV) is a distressing outcome related to surgeries. Traditionally, ginger has been used in the treatment of nausea and vomiting for thousands of years. Recently, several randomized, placebo-controlled clinical trials (RCTs) have been conducted to evaluate the efficacy of ginger in PONV. PURPOSE To systematically evaluate the efficacy of ginger on postoperative nausea and vomiting (PONV) compared to placebo, based on RCTs. STUDY DESIGN The meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. METHODS PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched for relevant studies. Human, placebo-controlled clinical studies of patients undergoing any types of surgery, receiving pharmacological doses of ginger per os were included. Only clinical trials with explicit description of the ginger preparation used were analysed. No language or publication year restrictions was applied. RESULTS Ten randomized trials including a total of 918 patients were pooled for the statistical analysis. The present meta-analysis supports that ginger has a significant effect on the severity of PONV based on visual analogue scale (VAS) results: in a fixed effects model the pooled standardized mean difference (SMD) was -0.247 (favouring ginger; [LL]: -0.455, [UL]: -0.040, p-value: 0.019). Moreover, our results suggest that ginger reduces the incidence of postoperative nausea and vomiting, as well antiemetic drug demand; however, these effects are not statistically significant compared to placebo, which may be explained by underdosing. CONCLUSIONS According to our thorough meta-analysis ginger is safe and well tolerated, and decreases the severity of PONV, and may lower the incidence of postoperative nausea and vomiting, which in turn may reduce antiemetic drug demand, suggesting that ginger may be a useful alternative to antiemetic medications to alleviate PONV.