Chemical Composition and Phytotoxic and Antibiofilm Activity of the Essential Oils of Two Moroccan Retama Species.

This study reports chemical composition, phytotoxic and antibiofilm activities of essential oils (EOs) of R. dasycarpa and R. sphaerocarpa from Morocco. EOs were analyzed by GC/MS and their phytotoxicities were evaluated against germination and seedling growth of Lolium multiflorum, Sinapis alba and Raphanus sativus. The antimicrobial and anti-biofilm activities were studied against Gram-negative (Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes). Both EOs were abundant in oxygenated monoterpenes (40.01% and 23.57 %, respectively). Carvacrol is the predominant component in R. dasycarpa EO (17.80 %), and it also represents an appreciable amount in R. sphaerocarpa (8.96 %). R. sphaerocarpa showed total inhibition at high doses against all seeds. S. alba seeds were the most sensitive to all EOs. Minimum inhibitory concentration (MIC) values indicated significant inhibition for R. sphaerocarpa, between 24 and 30 µg/mL, with a remarkable antibacterial potential and biofilm formation inhibition. R. sphaerocarpa EO showed significant biofilm inhibition with variable efficacy depending on the strain and concentration, except for S. aureus. R. dasycarpa exhibited activity against all bacterial strains and effect on metabolism with activity also on mature biofilms. Results suggest that Retama EOs could have potential applications in the fields of food and health.

Correction to: Increasing the synthesis of bioactive abietane diterpenes in Salvia sclarea hairy roots by elicited transcriptional reprogramming.

Unfortunately, the second author name was wrongly published in the original publication. The correct author name should read as follows.

Increasing the synthesis of bioactive abietane diterpenes in Salvia sclarea hairy roots by elicited transcriptional reprogramming.

KEY MESSAGE: Transcriptional activation of genes belonging to the plastidial MEP-derived isoprenoid pathway by elicitation with methyl jasmonate and coronatine enhanced the content of bioactive abietane diterpenes in Salvia sclarea hairy roots. We have shown that aethiopinone, an abietane diterpene synthesized in Salvia sclarea roots is cytotoxic and induces apoptosis in human melanoma cells. To develop a production platform for this compound and other abietane diterpenes, hairy root technology was combined with the elicitation of methyl jasmonate (MeJA) or the phytotoxin coronatine (Cor). Both MeJA and Cor induced a significant accumulation of aethiopinone, but prolonged exposure to MeJA irremediably caused inhibition of hairy root growth, which was unaffected by Cor treatment. Considering together the fold increase in aethiopinone content and the final hairy root biomass, the best combination was a Cor treatment for 28 days, which allowed to obtain up to 105.34 ± 2.30 mg L-1 of this compound to be obtained, corresponding to a 24-fold increase above the basal content in untreated hairy roots. MeJA or Cor elicitation also enhanced the synthesis of other bioactive abietane-quinone diterpenes. The elicitor-dependent steering effect was due to a coordinated transcriptional activation of several biosynthetic genes belonging to the plastidial MEP-derived isoprenoid pathway. High correlations between aethiopinone content and MeJA or Cor-elicited level of gene transcripts were found for DXS2 (r 2 = 0.99), DXR (r 2 = 0.99), and GGPPS (r 2 = 0.98), encoding enzymes acting upstream of GGPP, the common precursor of diterpenes and other plastidial-derived terpenes, as well as CPPS (r 2 = 0.99), encoding the enzyme involved in the first cyclization steps leading to copalyl-diphosphate, the precursor of abietane-like diterpenes. These results point to these genes as possible targets of metabolic engineering approaches to establish a more efficient production platform for such promising anti-proliferative plant-derived compounds.

Does pregnancy have an influence on otosclerosis?

OBJECTIVE: Otosclerosis affects women twice as often as men, especially during fertile age. A role of female hormones has been claimed, but controversy still exists regarding the influence of pregnancy. The purpose of this research was to analyse the role of pregnancy on the course of otosclerosis. METHOD: PubMed was searched in May 2019 using the terms 'otosclerosis AND pregnancy', 'otosclerosis AND pregnant', 'otosclerosis AND parous', 'otosclerosis AND parity', and 'otosclerosis AND puerperium'. Age at diagnosis, number of pregnancies and the temporal relationship of the disease with childbearing were considered. RESULTS: From 65 articles, 11 were chosen for review. They described 2323 women affected by otosclerosis: 1805 had at least 1 pregnancy, while 518 did not. During childbearing, otosclerosis began in 1 per cent of pregnant women, worsened in 21 per cent and worsened during puerperium in 4 per cent. Often, the authors reported hearing change with pregnancy without details, so a further group has been considered composed of women belonging to any of the groups just mentioned or to another group of women not further characterised. Overall, hearing change occurred during pregnancy in 44 per cent. A statistically significant correlation emerged between hearing change and number of pregnancies (p = 0.003). CONCLUSION: Because of wide data heterogeneity and the difficulty in analysing a single factor, absolute statements could not be formulated. According to this review, pregnancy seems to have a worsening effect on the course of otosclerosis.

Degenerative cervical myelopathy: Neuroradiological, neurophysiological and clinical correlations in 27 consecutive cases.

•New insight into prognostic factors for recovery of clinical function following posterior decompression for degenerative cervical myelopathy.•An increase of IOM amplitude of at least 50% coupled with preoperative T2-only and diffuse T2 signal changes on MRI is a positive prognostic factors for clinical improvement 6 months after surgery.•Clinical improvement at 6 months follow-up can be expected in patients with T1 hypo intensity if a diffuse border of the lesion on T2 images is present.

The plant diterpene epoxysiderol targets Hsp70 in cancer cells, affecting its ATPase activity and reducing its translocation to plasma membrane.

The ATP-dependent molecular chaperone Hsp70 is over-expressed in cancer cells where it plays pivotal roles in stabilization of onco-proteins, promoting cell proliferation and protecting cells from apoptosis and necrosis. Moreover, a relationship between the ability of cancer cells to migrate and the abundance of membrane-associated Hsp70 was shown. However, although Hsp70 is a promising target for cancer therapy, there is a still unsatisfied requirement of inhibitors possibly blocking its cancer-associated activities. Moving from the evidence that the plant diterpene oridonin efficiently targets Hsp70 1A in cancer cells, we set up a small kaurane diterpenoids collection and subjected it to a Surface Plasmon Resonance-screening, to identify new putative inhibitors of this chaperone. The results obtained suggested epoxysiderol as an effective Hsp70 1A interactor; therefore, using a combination of bioanalytical, biochemical and bioinformatics approaches, this compound was shown to bind the nucleotide-binding-domain of the chaperone, thus affecting its ATPase activity. The interaction between epoxysiderol and Hsp70 1A was also demonstrated to actually occur inside cancer cells, significantly reduced the translocation of the chaperone to the cell membrane, thus suggesting a possible role of epoxysiderol as an anti-metastasis agent.

The effect of isoquinoline alkaloids on opiate withdrawal.

Our interest has been centered on isoquinoline alkaloids obtained from Argemone mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro. The activity of these alkaloids was compared to the control compound, papaverine. Furthermore, the effect of these isoquinoline alkaloids was also determined on naloxone-precipitated withdrawal in isolated guinea pig ileum exposed to DAMGO (highly selective mu opioid receptor agonist) and U50-488H (highly selective kappa opioid receptor agonist) to test whether the possible interaction of isoquinoline alkaloids on opioid withdrawal involves mu- and/or kappa-opioid receptors. Isoquinoline alkaloids from A. mexicana (from 5 x 10(-6) to 1 x 10(-4) M), from A. constricta (1 x 10(-5) x 10(-5)-1 x 10(-4) M) as well as papaverine treatment (1 x 10(-7)-5 x 10(-6)-1 x 10(-6) M) before or after the opioid agonists were able of both preventing and reversing the naloxone-induced contraction after exposure to mu (morphine and DAMGO) or kappa (U50-488H) opiate receptor agonists in a concentration-dependent manner. Both acetylcholine response and electrical stimulation were also reduced by isoquinoline alkaloids and papaverine treatment as well as the final opiate withdrawal was still reduced. The results of the present study indicate that isoquinoline alkaloids as well as papaverine were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at mu and kappa opioid agonists.

Antioxidant activities and quali-quantitative analysis of different Smallanthus sonchifolius [(Poepp. and Endl.) H. Robinson] landrace extracts.

Five landraces of Smallanthus sonchifolius [(Poepp. and Endl.) H. Robinson], known as yacon, were investigated in total phenolic content, antioxidant activity and chemical composition of ethanol extracts (EEs) and decoction extracts (DEs). The results demonstrated that DEs are rich in phenolic acids as caffeic acid, while the EEs show an higher amount of flavonoids, as luteolin 3',7-O-diglucoside and luteolin 7-O-glucoside. These flavonoid glycosides were identified for the first time in yacon extracts, together with apigenin and luteolin. The phytochemical profile explains the different antioxidant activities shown in our study. The landraces PER6-DE and PER4-DE showed the highest radical-scavenging activity and reducing power related to their polyphenolic contents. Results also show that yacon can be considered an important source of bioactive compounds with significant differences among the analysed landraces.

Inhibition of HIV infection by flavanoids.

Of a variety of flavanoids, the flavans were generally more effective than flavones and flavanones in selective inhibition of HIV-1, HIV-2 or SIV infection. Studies of their effects on the binding of sCD4 and antibody to gp120 indicated that the effective compounds interact irreversibly with gp120 to inactive virus infectivity and block infection.

Flavonoids from Aconitum napellus subsp. neomontanum.

Three flavonol glycosides quercetin 7-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (1), kaempferol 7-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (2), and kaempferol 7-O-(6-trans-p-coumaroyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (3), together with the known beta-3,4-dihydroxyphenethyl beta-glucopyranoside, were isolated from the flowers of Aconitum napellus subsp. neomontanum. Their structures were elucidated by spectroscopic methods, including 2D NMR spectral techniques.

Aryl and triterpenic glycosides from Margyricarpus setosus.

Investigation of aerial parts of Margyricarpus setosus afforded three new aryl glycosides, beta-hydroxyphenylethyl-O-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside, benzyl-O-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside, 4-methoxybenzyl-O-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside, and three new triterpene glycosides, tormentic acid 3 beta-O-beta-D-quinovopyranoside, tormentic acid 3 beta-O-beta-D-fucopyranoside and tormentic acid 3 beta-O-alpha-L-rhamnopyranoside. Twelve known compounds were also found, among them beta-hydroxy-3',4'-dimethoxyphenylethyl glucoside and beta-hydroxy-3',4'-dimethoxyphenylethyl rutinoside, which were obtained previously by partial synthesis, were isolated for the first time from a natural source. The structures of the new compounds were elucidated on the basis of chemical and spectral data.

Constituents of Werneria ciliolata and their in vitro anti-HIV activity.

The aerial part of Werneria ciliolata afforded a series of new diterpenes: two ent-kaurane derivatives, a norkaurane, an ent-manoyloxide derivative, a dimeric diterpene, as well as a rare diterpene. Their structures were elucidated by spectroscopic methods, including the concerted application of 1D NMR techniques (DEPT and NOEDS) and 2D NMR techniques (1H-1H COSY and HETCOR). In addition, four known kauranes, four coumarins and 6-hydroxytremetone were isolated. All isolated compounds from W. ciliolata and W. dactylophylla were tested in vitro for anti-viral activity against HIV-1, but only 6-hydroxytremetone showed a significant anti-HIV-1 activity.

The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line.

Uncaria tomentosa, also known as "Uña de gato", is a Rubiaceae species widely used in South-American folk medicine for the treatment of cancer, arthritis, gastritis and epidemic diseases. Extracts of the plant have been shown to possess cytostatic and anti-inflammatory activity as well as mutagenic and antimutagenic properties. However, to date no studies have been carried out to verify the direct antitumor activity of the extracts. The present study investigates the effects of some extracts and their chromatographic fractions from the bark of U. tomentosa on the growth of a human breast cancer cell line (MCF7). Our data indicated that, in addition to the antimutagenic activity, U. tomentosa extracts and fractions exert a direct antiproliferative activity on MCF7. The bioassay-directed fractionation from barks and leaves resulted in the isolation of two active fractions, which displayed an IC50 of 10 mg/ml and 20 mg/ml, respectively and an antiproliferative effect, with about 90% of inhibition at a concentration of 100 mg/ml.

New metabolites from onopordum illyricum

A phytochemical investigation of Onopordum illyricum afforded, in addition to several known compounds, two new eudesmane sesquiterpenes (1 and 2), two new elemane sesquiterpenes (3 and 4), and one new neolignan derivative (5). The structure elucidation of all compounds was based on their (1)H and (13)C NMR spectral data, including those derived from 1D TOCSY, 2D NMR, COSY-DQF, HSQC, and HMBC experiments, as well as extensive 1D ROESY studies.

New 12a-hydroxyrotenoids from gliricidia sepium bark

The investigation of a methanolic extract of Gliricidia sepium bark afforded, in addition to vestitol and 2'-O-methylvestitol, three new 12a-hydroxyrotenoids, gliricidol (1), 2-methoxygliricidol (2), and gliricidin (3). The structures of 1-3 were elucidated by analysis of their spectroscopic data. Compounds 1-3 exhibited activity against Artemia salina larvae.

Studies on the constituents of Cyclanthera pedata fruits: isolation and structure elucidation of new triterpenoid saponins.

The isolation of nine triterpenoid saponins (1-9), among them six new natural compounds (1-6), from the MeOH extract of the fruits of Cyclanthera pedata is reported. All of the structures were elucidated by spectroscopic methods, including the concerted application of one-dimensional (1)H-(1)H total correlation spectroscopy, (1)H-(1)H nuclear Overhauser effect spectroscopy), and (13)C-(13)C DEPT-NMR and two-dimensional NMR techniques (double-quantum filtered correlated spectroscopy, rotating-frame Overhauser enhancement spectroscopy, heteronuclear single quantum coherence, and heteronuclear multiple bond correlation). A comparative study of seeds and fruits has been also carried out.

Studies on the constituents of Cyclanthera pedata fruits: isolation and structure elucidation of new flavonoid glycosides and their antioxidant activity.

The isolation of six flavon glycosides (1-6), among them four new natural compounds (1-4), from the CHCl(3)/MeOH extract of the fruits of Cyclanthera pedata is reported. All of the structures were elucidated by spectroscopic methods, including the concerted application of one-dimensional ((1)H, (1)H TOCSY, (13)C, and (13)C DEPT-NMR) and two-dimensional NMR techniques (DQF-COSY, HSQC, and HMBC). For all of the isolated compounds the antioxidant activity was determined by measuring the free radical scavenging activity, using the Trolox equivalent antioxidant capacity (TEAC) method, and the coupled oxidation of beta-carotene and linoleic acid.

Triterpenoids from Salvia wagneriana.

From the exudate of Salvia wagneriana Polak, beside the known ursolic acid, two pentaoxygenated triterpenoids were isolated. Their structures were determined as 3-oxo-11alpha,19beta,20,22beta-tetrahydroxy-lupane (1) and 3beta,11alpha,19beta,20,22beta-pentahydroxy-lupane (2) using a combination of one- and two-dimensional NMR techniques.

Effect of sesquiterpene lactone coronopilin on leukaemia cell population growth, cell type-specific induction of apoptosis and mitotic catastrophe.

OBJECTIVES: The aim of this study was to investigate anti-leukaemic potential of coronopilin, a sesquiterpene lactone from Ambrosia arborescens, and to characterize mechanism(s) underlying its activity. MATERIALS AND METHODS: The study was conducted on Jurkat and U937, two leukaemia-derived cell lines. Apoptosis and impairment of cell cycle progression were evaluated by flow cytometry and by microscopic analysis. Changes in protein expression and activation were evaluated by western blot analysis. Coronopilin-tubulin covalent adducts were demonstrated by mass spectrometry. RESULTS: Coronopilin inhibited (IC(50) ≤ 20 µm) leukaemia cell population growth, but displayed poor cytotoxicity to normal white blood cells. On Jurkat cells, coronopilin exerted cell population growth inhibition activity, mainly by triggering caspase-dependent apoptosis. Conversely, in U937 cells, coronopilin's primary response was a robust arrest in G(2) /M. Marked increase in mitotic index and presence of activated cyclin B1/Cdk1 complex, phosphorylated histone H3 at Ser10, and hyperpolymerized tubulin indicated that cells accumulated in mitosis. Prolonged mitotic arrest ultimately resulted in U937 mitotic catastrophe, and dying cells exhibited the features of non-caspase-dependent death. CONCLUSIONS: This study demonstrated that coronopilin efficiently inhibited leukaemia cell population growth by triggering cell type-specific responses. Moreover, coronopilin-mediated cell population expansion inhibition was specific to neoplastic cells, as normal white blood cell viability was not significantly affected. Thus, coronopilin may represent an interesting new chemical scaffold upon which to develop new anti-leukaemic agents.