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 1H‐NMR spectra.
Structural elucidation of three new sesquiterpenoids, namely, (1Z,4E)-lepidoza-1(10),4-dien-14-ol (1), rel-(1(10)Z,4S,5E,7R)-germacra-1(10),6 diene-11,14-diol (2), and ...rel-(1(10)Z,4S,5E,7R)-humula-1(10),5-diene-7,14-diol (3), isolated from the liverwort Conocephalum conicum, was accomplished by a combination of extensive NMR experiments, 1H NMR simulation, and other means. Additionally, the change of the identity of bicyclogermacren-14-al, previously reported as a C. conicum constituent, to isolepidozen-14-al is proposed. Compounds 2 and 3 appear to be related to 1 via hydration involving a shared intermediate, a substituted cyclopropylmethyl cation, formed by a highly regio- and stereoselective protonation of 1, followed by a stereospecific fission of the three-membered ring. In other words, an isolepidozene derivative might be a branchpoint to humulanes and germacranes; this transformation could be of, up to now, unknown, biosynthetic and/or synthetic relevance. Multivariate statistical analysis of the compositional data of C. conicum extract constituents was used to probe the hypothesized biochemical relations. The immunomodulatory effect of 1–3 and conocephalenol (4) was evaluated in an in vitro model on both nonstimulated and mitogen-stimulated rat splenocytes. The compounds displayed varying degrees of cytotoxicity to nonstimulated splenocytes, whereas 2 and 3 were found to exert immunosuppressive effects on concanavalin A-stimulated splenocytes while not being cytotoxic at the same concentrations.
The present study aimed to evaluate the protective action of thymol towards l-arginine-induced acute pancreatitis (AP) by studying the function of rat peritoneal immune cells.
Rat peritoneal exudate ...cells (PECs), obtained 24 h after the injection of l-arginine (350 mg/100 g of b.w.), were evaluated for mitochondrial activity (MTT assay), adherence capacity (methylene-blue assay), and phagocyte enzyme activity (myeloperoxidase, MPO, assay). The activity of α-amylase and free MPO, as well as the concentration of reactive oxygen species (ROS, i.e. O2−), were determined in the peritoneal exudate fluid. Also, serum α-amylase activity determination and pancreatic tissue pathohistological analysis were performed.
The administered thymol (50 and 100 mg/kg, per os) caused a significant decrease in the PEC mitochondrial activity and adherence capacity when compared with these functions of PECs isolated from rats with AP. A decrease in cellular MPO activity, as well as in the levels of ROS, α-amylase, and free MPO in peritoneal exudates was found in animals treated with thymol compared to the control animals with AP. Additionally, thymol administration prevented an increase in serum α-amylase activity, accompanied by the decrease in pancreatic tissue damage that follows l-arginine application.
The present results showed that thymol exerts significant immunomodulatory properties and a potential to silence PEC functions in inflammatory conditions such as the AP induced by l-arginine.
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•Artemisia annua L., important in the treatment of malaria, is a rich source of both artemisinin and essential oil.•Chemical and pharmacological profiles of A. annua oil are complex ...and can differ for different plant populations.•Artemisia ketone/α-pinene/1,8-cineole-type A. annua essential oil has low acute toxicity.•It also has modest antinociceptive, nephroprotective, antimicrobial, but low antioxidant properties.•Benefits of A. annua botanical drugs usage is not limited only to their antimalarial properties.
Botanical drugs based on Artemisia annua L. (Asteraceae) are important in the treatment of malaria. Alongside with artemisinin, this aromatic species produces high and variable amounts of other chemicals that have mostly unknown biological/pharmacological activities. Herein, we have studied the toxicological/pharmacological profile of volatile constituents of a Serbian population of A. annua. Fifty-eight components were identified, among them, artemisia ketone (35.7%), α-pinene (16.5%) and 1,8-cineole (5.5%) were the most abundant ones. Significant variability of A. annua volatile profile was confirmed by means of agglomerative hierarchical cluster analysis indicating the existence of several different A. annua chemotypes. In an attempt to connect the chemical profile of A. annua oil with its biological/toxicological effects, we have evaluated in vivo and/or in vitro toxicity (including hepato- and nephrotoxicity/protection), antinociceptive, antioxidant (DPPH, ABTS and superoxide radical scavenging activity assays), enzyme inhibiting (protein kinase A and α-amylase) and antimicrobial potential of A. annua oil and of its constituents. Our results revealed that the beneficial properties of A. annua botanical drugs are not limited only to their antimalarial properties. Taking into account its relatively low toxicity, the usage of A. annua volatiles (at least of the herein studied population) does not represent a health risk.
Organotin(IV) compounds show great potential as antitumor metallodrugs with lower toxicity and higher antiproliferative activity. Histone deacetylases (HDAC) inhibitors are characterised by high ...bioavailability and low toxicity. In this research, the two novel octahedral organotin(IV) complexes of physiologically active hydroxamate-based ligands, N-hydroxy-4-phenylbutanamide (HL1) and N-hydroxy-2-propylpentanamide (HL2), have been prepared and characterized using FTIR, 1H-, 13C- and 119Sn-NMR spectroscopy. Particular emphasis was put on the binding characteristics of ligands. The structures were additionally analysed by the density functional theory at B3LYP-D3BJ/6- -311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level. The theoretical IR and NMR spectra were compared to the spectroscopic data, and it was concluded that the predicted structures described well the experimental ones. The stability of different isomers of HL1 and HL2 was assessed by the natural bond orbital analysis, and the importance of intramolecular hydrogen bond was outlined. The interactions between donor atoms and Sn were investigated and correlated with the changes in chemical shift and the wavenumbers of characteristic vibrations.
Two novel β-diketones, 2,6,9-trimethyl-8-decene-3,5-dione (A) and 3,7,10-trimethyl-9-undecene-4,6-dione (B), were identified from the renowned medicinal plant Hypericum perforatum L. The structures ...of β-diketones A and B were corroborated by syntheses (4 steps starting from methyl acetoacetate, overall yields 30% and 23%, respectively). In solution, these β-diketones predominantly exist as two rapidly interconverting β-keto-enol tautomers. The structures of A and B show some common fragments with the molecules of hyperforin and adhyperforin, respectively, the acknowledged multi-target secondary metabolites from St. John's wort. It is therefore not surprising that A displayed a noteworthy biological activity profile as well (including brine shrimp toxicity, antinociceptive, antidepressant and acetylcholinesterase inhibitory activity). β-Diketone A manifested the most outstanding potency as an acetylcholinesterase inhibitor with IC50 value of 1.51 μM pointing again to the β-keto-enol moiety as a promising lead structure for the development of drugs that could lessen symptoms of Alzheimer's disease (such as dementia, depression and pain).
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•Two new β-diketones were identified from the medicinal plant Hypericum perforatum L.•These β-diketones were synthetized in 4 steps starting from methyl acetoacetate.•Noteworthy antinociceptive and antidepressant activity of diketone A was observed.•Diketone A is toxic to A. salina and a highly potent AChE inhibitor (IC50 = 1.51 μM).•β-Keto-enol moiety is the likely key pharmacophore part of this multi-targeted agent.
In many countries, the leaves of Allium ursinum L. (Liliaceae) are a popular substitute for garlic and, for centuries, the herb has been taken internally to treat an array of medical conditions. ...Herein, we report the chemical composition of 12 different A. ursinum essential-oil samples (five populations; fresh/air-/oven-dried plant material; leaves/inflorescences). GC–MS/GC–FID analyses, quantitative structure–property relationship modeling (simple 0D/1D-descriptors) of retention indices and the synthesis of selected compounds, enabled the identification of >200 different constituents, mainly organo(poly)sulfides. Some of these were new compounds (allyl (methylthio)methyl, (methylthio)methyl (Z)/(E)-1-propenyl and allyl 1-(methylthio)propyl disulfides) or were previously not detected in samples of natural origin (heptyl methyl, methyl octyl, allyl hexyl (1), allyl octyl (2) and propyl (propylthio)methyl sulfides). A multivariate statistical analysis revealed the onset of significant changes in the plant material volatile profile during the drying process.
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•Allium ursinum L. (Liliaceae) is a popular substitute for garlic in many countries.•New organosulfur compounds were found during an analysis of 12 A. ursinum samples.•Their identification was based on GC–MS/NMR/IR and confirmed by synthesis and QSPR.•The volatile profile of A. ursinum changed during plant material drying.
Carvacrol (5-isopropyl-2-methylphenol) is a biologically active monoterpene phenol abundantly present in the essential oils of many Lamiaceae aromatic/ethnomedicinal plants. Herein, we aimed to ...evaluate the damaging effect of carvacrol to rat pancreatic tissue, but also to assess its possible ameliorative impact on pancreatic damage induced by L-arginine. The toxic and beneficial (in a dose of 10 mg/kg) properties of carvacrol were assessed by measuring serum α-amylase and lipase activities, tissue malondialdehyde (MDA) content, and pathohistological changes in pancreatic tissue. Application of 100/500 mg/kg of carvacrol produced a significant increase in α-amylase activity, followed by inflammatory-cell infiltration and patchy interlobular edema in the pancreas. In the L-arginine-induced pancreatitis model, a dose of 10 mg/kg of carvacrol prevented an increase in α-amylase and lipase activities, and MDA formation, when compared to the animals that received L-arginine only. Animals treated with carvacrol prior to L-arginine administration displayed mild edema and inflammatory infiltration with few necrotic areas. Contrary to that, animals that received only L-arginine showed a massive leukocyte infiltrate with edema and substantial necrotic areas. In our study carvacrol showed significant protective effects and a potential to modulate leukocyte recruitment in pancreatic tissue after L-arginine injection.
•Higher doses of carvacrol (100 and 500 mg/kg) induce elevation in α-amylase and lipase activities.•Higher doses of carvacrol cause an increase in MDA levels and inflammatory-cell infiltration.•Carvacrol, at 10 mg/kg, prevents a rise in serum enzyme activities and tissue MDA formation caused by L-arginine.•A low dose of carvacrol prior to that of L-arginine resulted in mild pancreatic edema and inflammatory infiltration.
The currently used immunohistochemical approach in determining the estrogen receptor (ER) positivity of breast cancers (BCs) is inherently subjective and additionally limited by its semi-quantitative ...nature. The application of software in the analysis of digitized slide images may overcome some of these limitations. However, the utilization of such an approach requires that the entire staining procedure is standardized.
We aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters that can possibly be used for a diagnostic purpose that is in line with the current semi-quantitative scoring system.
Semi-quantitative analysis of ER-stained tissue sections was performed following the Allred scoring system guidelines. The quantitative analysis was performed in ImageJ software after color deconvolution. The quantitative analysis of 66 cases of invasive lobular BC included: Percent of ER-positive cells, average nuclear coloration intensity, and the quantitative ER score. The percent of ER-positive tumor cells was counted using a standard grid overlay, while optical density (0.0-1.0) was measured within each nucleus at the grid points.
A statistical analysis revealed a significant positive correlation (
= 0.886,
< 0.001) between the subjective semi-quantitative and quantitative ER scores, with a large effect size (
= 3.8215). We observed strong statistically significant correlations between individual parameters of the total ER score, percentage of ER-positive nuclei, and color intensity, obtained by the two independent methods.
Additionally, besides excluding subjectivity, the up to now unreported cases of 3 + 0, 4 + 0, and 5 + 0 Allred scores were detected only by the application of the proposed quantitative approach.
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