Marrubiin Inhibits Peritoneal Inflammatory Response Induced by Carrageenan Application in C57 Mice.

Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.

Scilla bifolia Wax as a Source of Diverse Long-Chain Resorcinols and Alkane-1,3-diols.

GC, GC/MS and NMR analyses of Scilla bifolia washings allowed for the identification of thirty-six long-chain compounds belonging to six homologous series (five of which are from the class of resorcinols, a group of biologically important phenols): 1-alkyl-3,5-dimethoxybenzenes, 5-alkyl-3-methoxy-2-methylphenols, 3-alkyl-5-methoxyphenols, 5-alkyl-2-methylresorcinols (five compounds from each of the series); 5-alkylresorcinols (six compounds) and 1,3-alkanediols (ten compounds). Many of these compounds rarely occur in Nature. Retention indices of these compounds, as well as indices of the corresponding trimethylsilyl derivatives, were reported, some of them for the first time. The exact regiochemistry was unambiguously determined by two-dimensional NMR experiments; in some cases, the complete NMR assignment was augmented by computer spin-simulation of 1 H-NMR spectra.

On the configuration and occurrence of 2,6-cyclocuparan-3-ols: Resolving a lasting discrepancy.

2,6-Cyclocuparan-3-ols are chemical markers and major volatiles of several liverwort species. Conflicting reports on the structures of these cyclocuparanols can be found in the literature-different research groups assigned the same spectral data to different structures, yet these inconsistencies were never addressed, let alone satisfactorily explained. Following the isolation of all four diastereoisomeric cyclocuparanols from Marchantia polymorpha, their relative and absolute configurations were extensively studied by chemical and spectroscopic methods and definite stereostructures were proposed.

Two goitrogenic 1,3-oxazolidine-2-thione derivatives from Brassicales taxa: Challenging identification, occurrence and immunomodulatory effects.

1,3-Oxazolidine-2-thione derivatives are glucosinolate-related food constituents known to impart (thyreo)toxic properties to some cruciferous vegetables. In this work, 5,5-dimethyl-1,3-oxazolidine-2-thione and (-)-(R)-5-phenyl-1,3-oxazolidine-2-thione, known goitrogens, were isolated from Draba lasiocarpa Rochel (Brassicaceae) and Reseda luteola L. (Resedaceae), respectively, and were fully spectrally characterized. Subsequently, the occurrence of the two 1,3-oxazolidine-2-thiones was verified in six additional taxa out of in total 78 screened Serbian Brassicales taxa. The stereochemistry of 5-phenyl-1,3-oxazolidine-2-thione was inferred from nuclear magnetic resonance experiments with a chiral lanthanide-shift reagent, employed in this work for the first time for this type of compounds. Unexpectedly, during gas chromatography, 5-phenyl-1,3-oxazolidine-2-thione underwent an unreported thermal core isomerization (1,3-oxazolidine-2-thione to 1,3-thiazolidine-2-one). These goitrogenic volatile glucosinolate products were tested for their effect on rat macrophage viability (three assays) and nitric oxide production. It was shown that the compounds displayed different levels of cytotoxicity. All tested compounds caused a significant lactate dehydrogenase leakage, but only (R)-5-phenyl-1,3-oxazolidine-2-thione statistically significantly reduced macrophage mitochondrial activity, whereas the racemic 5-phenyl-1,3-oxazolidine-2-thione and 5,5-dimethyl-1,3-oxazolidine-2-thione had little or no effect. Again only (R)-5-phenyl-1,3-oxazolidine-2-thione exerted nitric oxide production-inhibiting properties, suggesting the higher immunomodulatory potential of this enantiomer compared with its antipode and racemic mixture.

Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy.

ETHNOPHARMACOLOGICAL RELEVANCE: Reseda lutea L. (Resedaceae) or Wild Mignonette is a widely distributed plant species. Pliny the Elder (AD 23-AD 79), a Roman scholar and naturalist, reported the use of R. lutea for reducing tumors in his Historia naturalis. Accounts of the beneficial effects of R. lutea in tumor treatment could also be found in the works of later authors, such as Étienne François Geoffroy (1672-1731) and Samuel Frederick Gray (1766-1828). However, to date no in vivo or in vitro evidence exists in support of the alleged tumor healing properties of R. lutea. MATERIALS AND METHODS: The composition of autolysates obtained from different organs (root, flower and fruit) of R. lutea was investigated by GC and GC-MS analyses and IR, 1D and 2D NMR spectroscopy. These analyses led to the discovery of a new compound isolated in pure form from the flower autolysate. Autolysates and their major constituents were submitted to MTT-dye reduction cytotoxic assay on human A375 (melanoma) and MRC5 (fibroblast) cell lines. Mechanism of the cytotoxic effects was studied by cell cycle analysis and Annexin V assay. RESULTS: Benzyl isothiocyanate and 2-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate were identified as the major constituents of the root and flower autolysates, respectively (the later represents a new natural product). These compounds showed significant antiproliferative effects against both cell lines, which could also explain the observed high cytotoxic activity of the tested autolysates. Cell cycle analysis revealed apoptosis as the probable mechanism of cell death. CONCLUSIONS: Tumor healing properties attributed to R. lutea in the pre-modern texts were substantiated by the herein obtained results. Two isothiocyanates were found to be the major carriers of the observed activity. Although there was a relatively low differential effect of the plant metabolites on transformed and non-transformed cell lines, one can argue that the noted strong cytotoxicity provides first evidence that could explain the long forgotten use of this particular species.

Chemistry of spices: bornyl 4-methoxybenzoate from Ferula ovina (Boiss.) Boiss. (Apiaceae) induces hyperalgesia in mice.

UNLABELLED: Ferula ovina (Boiss.) Boiss. is a traditional Iranian flavoring agent used as an ingredient of spices and condiments. METHODS AND RESULTS: GC-MS analyses of F. ovina aerial parts' essential oil revealed the presence of a number of rare aromatic esters of monoterpenic alcohols. The structures of these esters were corroborated by synthesis, and one of them, bornyl 4-methoxybenzoate, turned out to be a new natural compound. The antinociceptive activities of the oil and the new ester were assessed in mice using several different laboratory models. The oil exerted strong peripheral and moderate central analgesic activities. Surprisingly, mice treated with bornyl 4-methoxybenzoate had an increased sensitivity to the noxious stimulus compared to that of the control group. A dynamic hot plate test was used to demonstrate that bornyl 4-methoxybenzoate induces hyperalgesia and not allodynia. CONCLUSION: Essential oil constituents impart this spice with both antinociceptive and hyperalgesic potentially flavor-related properties.