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.

Fabrication of a Simple and Efficient HPLC Reduction Column for Online Conversion of Aristolochic Acids to Aristolactams Prior to Sensitive Fluorescence Detection.

Aristolochic acids (AAs) are nephrotoxic and carcinogenic nitrophenanthrene carboxylic acids produced naturally by plants from the Aristolochia and Asarum genera, which have been used extensively as herbal medicines. In addition to consuming AA-containing herbal medicinal products, there is emerging evidence that humans are also exposed to AA through the environment. In 2022, the World Health Organization (WHO) called for global action to remove AA exposure sources and to implement preventative measures against the development of AA-associated cancers. Herein, we report the development of a simple and efficient iron powder-packed reduction column that allows online post-column conversion of the nonfluorescing AA to its corresponding strongly fluorescing aristolactam (AL), facilitating the sensitive and selective detection of AA in herbal medicinal products, food grain, arable soil, or groundwater samples by high-performance liquid chromatography with fluorescence detection. Moreover, AL, a group of naturally occurring derivatives of AA that have demonstrated toxicity to cultured bacteria, human cells, and rats, is monitored and quantified simultaneously with AA in one single run without sacrificing sensitivity. In comparison with existing analytical methods for AA measurement, the newly developed method is not only inexpensive and less laborious, but it also offers improved sensitivity. We believe this novel method will find wide application in identifying the presence of AA in food, herbal medicines, and environmental samples, thus assisting in the identification and removal of AA exposure sources.

New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features.

Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were developed. Twelve new ferrocene-CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ-resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b, 6c, and 6d) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure-activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for malaria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.

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.

Optimization of a plastic optical fiber based sensor for dye sensing coupled with an adapted neuro-fuzzy inference system.

In this study, estimation capacities and optimization of a dye concentration sensing model by an adapted neuro-fuzzy inference system (ANFIS) as well as central composite design coupled with response surface methodology using a plastic optical fiber (POF) based sensor were investigated. Various diameters d of POF were used for sensing different concentrations of Remazol Black B (RBB), which acts as a sensing medium of the process. The efficiency of sensing was studied as a function of three independent variables: diameter of POF, concentration of RBB dye, and initial temperature of the solution. First, the independent parameters were fed as inputs to an ANFIS, and the output of the system was the output intensity of dye ratio to output the intensity of distilled water. ANFIS showed that this established model is reliable for a dye concentration sensing process and is mainly influenced by its diameter.

Adaptive neuro fuzzy selection of important factors for prediction of plasmons in silver nanorods.

The major goal of this study was to find predictors of plasmon positions in silver nanorod (NR) optical absorption spectra. The goal of this study is to use an adaptive neural fuzzy inference system to identify the various input parameters for longitudinal surface plasmon resonance (LSPR) and transverse surface plasmon resonance (TSP). A seed strategy has been used for preparation of the silver NRs. During the preparation, the seed particles are synthesized in the presence of cetyltrimethylammonium bromide (CTAB). To produce the silver NRs, metal salt (AgNO3) has been added, as well as ascorbic acid (AA) and CTAB. Skillful prediction could play a pivotal role in the plasmon NR production management. The combination of CTAB and the seeds has the largest influence on the TSPR. The combination of CTAB and AA has the largest influence on the LSPR. The study considering different input parameters simultaneously, to the best of our knowledge, is the first on a small scale and should attract great general interest.

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.

A novel pathway for the thermolysis of N-nitrosoanthranilates using flash vacuum pyrolysis leading to 7-aminophthalides.

Flash vacuum pyrolysis of methyl N-methyl-N-nitrosoanthranilate leads to elimination of nitric oxide and disproportionation of the formed N-radical to 7-(methylamino)phthalide and methyl N-methylanthranilate. This transformation was found to be a convenient, solvent-free method for the preparation of 7-(methylamino)phthalides. An alternative route through pyrolysis of N-benzyl-N-methyl anthranilates was also investigated.

Human development index in a context of human development: Review on the western Balkans countries.

INTRODUCTION: The Human Development Index (HDI), as one of the more complex composite indicators of the level of human potential and quality of life, is a combination of three dimensions (indicators, factors): life expectancy at birth, the middle number of years of education and the expected number of years of schooling combined into a single education index and economic benefits expressed by production, or GDP (gross domestic product) according to purchasing power (PPP US $). METHODS: The same measures and average achievements in the field of health, education, and living standards are presented. The HDI was first developed in 1990 under the United Nations Development Program (UNDP) and is published as Human Development Reports (HDR). At present, it has become the most widely used complex indicator suitable for international comparisons and assessments of the achieved development level of a particular country or region. RESULTS: The paper deals specifically with the more perspective view of human development in the Western Balkans, with a series of socio-economic implications for the development policy of the countries under observation. CONCLUSION: The particular significance of the conducted research stems from the fact that in the countries of the Western Balkans are identified factors at the beginning of the transition period were often marginalized in the creation of macroeconomic policies, but in recent years there have been more positive developments in that regard.

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.

Further antibacterial Geranium macrorrhizum L. metabolites and synthesis of epoxygermacrones.

4,5- and 1,10-Epoxygermacrones were isolated from the essential oil of aerial parts of Geranium macrorrhizum L. (Geraniaceae). The structures of the epoxy derivatives were deduced from their 1D- and 2D-NMR spectra, molecular modeling, and confirmed by synthesis starting from germacrone. The epoxy compounds were screened for their antimicrobial activities by a microdilution assay, which revealed high activities of both compounds against Bacillus subtilis (minimum inhibitory concentrations (M/Cs) determined were 4.3 and 43 nmol/ml for 1,10- and 4,5-epoxygermacrone, resp.) and Pseudomonas aeruginosa (0.043 and 0.855 µmol/ml for 1,10- and 4,5-epoxygermacrone, resp.). The discovery and observed activity of the two epoxides fills the gap in our knowledge of the active principles in this highly renowned ethnomedicinal plant species.

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.