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Interesting photobiological properties have been demonstrated for some Cachrys species, including C. libanotis L., C. sicula L., and C. pungens Jan. The present study was designed to assess the photocytotoxic activity of Prangos ferulacea Lindl. (synonym of C. ferulacea (L.) Calest.). This plant was previously considered a Cachrys species but, at present, it is part of the Prangos genus. P. ferulacea is an orophilous plant present in the eastern Mediterranean and in western Asia. Three different extraction techniques were utilized. Obtained extracts were compared both for their phytochemical content and for their photobiological properties on human melanoma cells irradiated with UVA light. The apoptotic responses, together with the antioxidant activity, were also assessed. P. ferulacea extracts were able to affect cell viability in a concentration-dependent manner, with the sample obtained through supercritical CO 2 extraction showing the highest activity (IC 50 = 4.91 μg/mL). This research points out the interesting content in the photoactive compounds of this species, namely furanocoumarins, and could provide a starting point for further studies aimed at finding new photosensitizing agents useful in cancer photochemotherapy.

Different phytochemical compounds have been demonstrated to modulate the JAK/STAT signaling pathway. Here, three Cachrys species from Southern Italy were investigated for both the phytochemical profile and the potential anti-inflammatory properties. The aerial parts were extracted with methanol through Naviglio Extractor ® , an innovative solid-liquid extraction technique that allows to obtain high quality extracts by working with gradient pressure. Extracts were analyzed with GC-MS and standardized in furanocoumarin content, resulting rich in xanthotoxin, bergapten and isopimpinellin. Given the known ability of bergapten to inhibit the JAK/STAT signaling pathway by decreasing the levels of pro-inflammatory cytokines (TNF-α, IL-6) and inflammatory mediators (NO) in RAW 264.7 cells activated by LPS, Cachrys extracts were investigated for their biological properties. The results obtained in this study showed that Cachrys pungens extract, presenting the highest content in furanocoumarins (7.48 ± 0.48 and 2.94 ± 0.16 mg/50 mg of extract for xanthotoxin and bergapten, respectively), significantly decreased STAT3 protein levels, pro-inflammatory cytokines (TNF-α, IL-6) and increased IL-10 anti-inflammatory cytokine. Cachrys ferulacea significantly decreased JAK2 phosphorylation, being even more effective than bergapten. In conclusion, investigated extracts could be potential candidates for the search of novel anti-inflammatory agents acting via inhibiting the JAK/STAT signaling pathway.

Lipids are essential compounds for all living organisms. Agents that inhibit fat digestion are of theoretical benefit in the treatment of obesity. A total of 18 species (21 hydroalcoholic extracts) of edible plants from Calabria region (Italy) were evaluated for their in vitro pancreatic lipase inhibitory activity. Lipase activity was measured by monitoring the hydrolysis of p-NPC, which releases the yellow chromogen, p-nitrophenol. The aqueous ethanol extracts of Portulaca oleracea (leaves) and Silene vulgaris (leaves) exhibited the strongest inhibitory effect on lipase. The amounts of total phenolics, measured by Folin-Ciocalteu method, varied widely in the different analysed extracts and ranged from 29 to 482 mg/g of extract. In this study, the findings do not show any relationship between lipase inhibitory activity and total phenolic content., (Copyright © 2011 John Wiley & Sons, Ltd.)

The two studied Calamintha species showed different polyphenolic content and sterol composition. Calamintha grandiflora possessed twice the polyphenolic content of Calamintha nepeta subsp. glandulosa, while the latter contained a higher number of sterols. Among them, stigmast-5-en-3β-ol was found to be the major constituent. The methanolic extract of C. grandiflora was more potent than the C. nepeta subsp. glandulosa methanolic extract in a DPPH assay, while the activity of the C. grandiflora EtOAc fraction was weaker than its C. nepeta subsp. glandulosa counterpart. Fractions of C. nepeta subsp. glandulosa showed higher activity using a β-carotene bleaching test. The petrol ether fraction of C. grandiflora showed significant inhibition of NO production.

Twenty samples of two caper species were collected from various natural habitats of Calabria (South Italy). A sample program was designed in order to cover all taxa and morphotypes present in the studied area, trying to correlate ecological conditions, phytochemical content, and biological activities. These species were characterized through the detection, isolation, and capillary GC-GC/MS quantitative evaluation of chemical markers (phytosterols and vitamin E). The antioxidant activity of MeOH caper extracts was assayed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and β-carotene bleaching tests. The chemical investigation showed a different composition according to the species and the populations. The best free radical (DPPH) scavenging activity was exerted by Capparis orientalis sample C4 (collected near Copanello village, granodiorite sea cliff) and Capparis sicula ssp. sicula sample C5 (collected near Tarsia village, clay soil). Sample C2 (Galatrella Valley, clay soil) showed the highest inhibition of linoleic acid oxidation with more efficacy than propyl gallate, the reference drug., (Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.)

In the present work the qualitative and quantitative analysis of Amaryllidaceae-type alkaloids in the aerial parts and bulbs of Galanthus reginae-olgae Orph. subsp. vernalis Kamari is presented for the first time using GC-MS analysis. The alkaloids galanthamine, lycorine, and tazettine were identified in both extracts while crinine and neronine were found only in the bulbs. The yield of alkaloid fraction from bulbs (36.8%) is very high compared to the yield from aerial parts (9.34%). Lycorine was the major component in both fractions. The antioxidant potential was determined by three complementary methods. The preparations to reduce the stable free radical DPPH to the yellow-colored 1,1-diphenyl-2-picrylhydrazyl with IC(50) values of 39 and 29 mug/mL for MeOH extracts from aerial parts and bulbs, respectively. The higher activity was given by EtOAc fraction of aerial parts with IC(50) of 10 mug/mL. This activity is probably due to the presence in EtOAc fraction of polar compounds such as polyphenols. The fraction exhibited a significant antioxidant capacity also in the beta-carotene-linoleic acid test system. A higher level of antioxidant activity was observed for EtOAc fraction from bulbs with IC(50) of 10 mug/mL after 30 min and 9 mug/mL after 60 min of incubation. In contrast, the fraction from bulbs performed poorly in the lipid peroxidation liposomes assay. Significant activity was obtained for dichloromethane fraction from aerial parts (IC(50) of 74 mug/mL). The major abundance of alkaloid in dichloromethane fraction may be responsible of the bulbs anti-cholinesterase highest activity (38.5%) at 0.5 mg/mL.

Five hydroalcoholic extracts of edible plants from Calabria region (Italy) used in local traditional medicine for the treatment of inflammatory diseases were evaluated for their in vivo topical anti-inflammatory activity (inhibition of croton oil-induced ear oedema in mice) and in vitro antioxidant and antiradical properties (inhibition of linoleic acid oxidation and bovine brain liposomes peroxidation, DPPH radical scavenging). All the extracts showed an anti-inflammatory effect: 300 microg/cm(2) provoked oedema reductions ranging from 21 to 27%. All the extracts exerted also radical scavenging and/or antioxidant properties, the most active plant being Mentha aquatica L. (Lamiaceae) which contained the highest amount of phenolics (337 mg/g) and of flavonoids (15.75 mg/g). Moreover, the content and the composition of sterols were assessed by GC-MS in the examined plants Borago officinalis L. (Boraginaceae) contained the highest number of sterols.

The chemical composition and antioxidant activities of wild and cultivated Laurus nobilis leaves and Foeniculum vulgare subsp. piperitum seeds were determined. Differences were found in the total phenolic content of fennel. GC-MS analysis of the non polar fractions showed a different composition between wild and cultivated plants. Cultivated laurel had a high content of terpenes such as linool, alpha-terpinol, alpha-terpinyl acetate, thymol, caryophyllene, aromandrene, selinene, farnesene, and cadinene, while wild laurel had a high content of eugenol and methyl eugenol, vitamin E, and sterols. The antioxidant potential of the extracts was determined using three complementary methods. Wild plants showed greater radical scavenging activity than the cultivated plants. The extracts also exhibited a significant antioxidant capacity also in the beta-carotene-linoleic acid test system. A high level of antioxidant activity was observed in wild laurel (IC50 = 1 microg/ml). Significant antioxidant activity measured in bovine brain was observed in wild laurel.

Background: Reelin (RELN) is a glycoprotein secreted preferentially by cortical gamma-aminobutyric acid-ergic (GABAergic) interneurons (layers I and II) that binds to integrin receptors located on dendritic spines of pyramidal neurons or on GABAergic interneurons of layers III through V expressing the disabled-1 gene product (DAB1), a cytosolic adaptor protein that mediates RELN action. To replicate earlier findings that RELN and glutamic acid decarboxylase (GAD)(67), but not DAB1 expression, are down-regulated in schizophrenic brains, and to verify whether other psychiatric disorders express similar deficits, we analyzed, blind, an entirely new cohort of 60 postmortem brains, including equal numbers of patients matched for schizophrenia, unipolar depression, and bipolar disorder with nonpsychiatric subjects., Methods: Reelin, GAD(65), GAD(67), DAB1, and neuron-specific-enolase messenger RNAs (mRNAs) and respective proteins were measured with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analyses. Reelin-positive neurons were identified by immunohistochemistry using a monoclonal antibody., Results: Prefrontal cortex and cerebellar expression of RELN mRNA, GAD(67) protein and mRNA, and prefrontal cortex RELN-positive cells was significantly decreased by 30% to 50% in patients with schizophrenia or bipolar disorder with psychosis, but not in those with unipolar depression without psychosis when compared with nonpsychiatric subjects. Group differences were absent for DAB1,GAD(65) and neuron-specific-enolase expression implying that RELN and GAD(67) down-regulations were unrelated to neuronal damage. Reelin and GAD(67) were also unrelated to postmortem intervals, dose, duration, or presence of antipsychotic medication., Conclusions: The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypothesis that these changes may be liability factors underlying psychosis.

Allopregnanolone [3alpha-hydroxy-5alpha-pregnan-20-one] (ALLO), a potent neurosteroid that positively modulates gamma-aminobutyric acid (GABA) action at various GABA(A) receptor subtypes is synthesized in nanomolar concentrations and stored non uniformly in various brain structures of mammals. We have measured brain ALLO content and its precursors by negative ion chemical ionization-mass-spectrometry after purification and separation of the different steroids with HPLC and gas chromatography. Our procedure measures steroids in the femtomolar range with structural information and unsurpassed selectivity. We were able to establish an association between the decrease in content of ALLO in mouse brain cortex elicited by either long-lasting social isolation or by the administration of 17beta-17 [bis (1-methylethyl) amino carbonyl] androstane-3,5-dilene-3-carboxylic acid (SKF 105111). an inhibitor of Types I and II 5alpha reductases, and the shortening of the righting reflex loss elicited by pentobarbital (PBT). SKF 105111 added to cortical brain slices in concentrations up to 10(-5) M failed per se to alter GABAergic currents or their potentiation by PTB recorded from pyramidal neurons. Fluoxetine (1.45 or 2.9 micromol/kg i.p.) doses that fail to change the PTB-induced loss of righting reflex and the level of brain ALLO in group-housed mice normalized both parameters in socially-isolated mice. In addition, we could detect both fluoxetine actions in socially isolated mice pretreated with doses of p-chlorophenylalanine (1.2 mmol/kg i.p. at 72, 48, and 24 h) that substantially inhibit brain serotonin 5HT synthesis as shown by an 80% drop of brain 5HT content. These studies for the first time have provided evidence suggesting that the endogenous cortical stores of ALLO physiologically upregulate GABAergic tone and by such a mechanism play a permissive or facilitatory role on the PTB-induced loss of the righting reflex. In the absence of such a permissive physiological influence by endogenous ALLO, the righting reflex inhibition by PTB is down regulated.

Postmortem prefrontal cortices (PFC) (Brodmann's areas 10 and 46), temporal cortices (Brodmann's area 22), hippocampi, caudate nuclei, and cerebella of schizophrenia patients and their matched nonpsychiatric subjects were compared for reelin (RELN) mRNA and reelin (RELN) protein content. In all of the brain areas studied, RELN and its mRNA were significantly reduced (approximately 50%) in patients with schizophrenia; this decrease was similar in patients affected by undifferentiated or paranoid schizophrenia. To exclude possible artifacts caused by postmortem mRNA degradation, we measured the mRNAs in the same PFC extracts from gamma-aminobutyric acid (GABA)A receptors alpha1 and alpha5 and nicotinic acetylcholine receptor alpha7 subunits. Whereas the expression of the alpha7 nicotinic acetylcholine receptor subunit was normal, that of the alpha1 and alpha5 receptor subunits of GABAA was increased when schizophrenia was present. RELN mRNA was preferentially expressed in GABAergic interneurons of PFC, temporal cortex, hippocampus, and glutamatergic granule cells of cerebellum. A protein putatively functioning as an intracellular target for the signal-transduction cascade triggered by RELN protein released into the extracellular matrix is termed mouse disabled-1 (DAB1) and is expressed at comparable levels in the neuroplasm of the PFC and hippocampal pyramidal neurons, cerebellar Purkinje neurons of schizophrenia patients, and nonpsychiatric subjects; these three types of neurons do not express RELN protein. In the same samples of temporal cortex, we found a decrease in RELN protein of approximately 50% but no changes in DAB1 protein expression. We also observed a large (up to 70%) decrease of GAD67 but only a small decrease of GAD65 protein content. These findings are interpreted within a neurodevelopmental/vulnerability "two-hit" model for the etiology of schizophrenia.

The combination of in situ hybridization and immunocytochemical technique is an important tool to detail the biochemical phenotype of individual neurons. In this work, we have developed a double fluorescence method to show the presence of reelin mRNA in GABAergic cells. This was achieved by demonstrating the colocalization of glutamic acid decarboxylase67, the synthesizing enzyme for GABA, with the mRNA for reelin, a novel factor involved in brain development and possibly the maintenance of the synaptic organization of layered structures in adult brain. The results demonstrated that reelin is expressed primarily in GABAergic cells in the adult rat cerebrum, but not in the cerebellum., (Copyright 1998 Elsevier Science B.V.)

During embryonic development of brain laminated structures, the protein Reelin, secreted into the extracellular matrix of the cortex and hippocampus by Cajal-Retzius (CR) cells located in the marginal zone, contributes to the regulation of migration and positioning of cortical and hippocampal neurons that do not synthesize Reelin. Soon after birth, the CR cells decrease, and they virtually disappear during the following 3 weeks. Despite their disappearance, we can quantify Reelin mRNA (approximately 200 amol/ g of total RNA) and visualize it by in situ hybridization, and we detect the translated product of this mRNA by immunocytochemistry preferentially in gamma-aminobutyric acid (GABA)ergic neurons of adult rat cortex and hippocampus. In adult rat cerebellum, Reelin is expressed in glutamatergic neurons (granule cells). The translated product of this mRNA is readily exported from the granule cell somata to the parallel fibers, where it has been detected by electron microscopy in axon terminals located presynaptically to Purkinje cell dendrites.

The direct analytical and semipreparative high-performance liquid chromatographic (HPLC) resolution of the enantiomers of IDRA 21 [1,7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide] is reported. (+/-)-IDRA 21 administered orally to rats subjected to a water maze cognition test elicited a performance enhancing effect. Between the two enantiomers, (+)-IDRA 21 was identified as being pharmacologically active in the water maze performance test, whereas (-)-IDRA 21 was completely devoid of activity when given in doses comparable to those of the dextrorotatory (+)-enantiomer. The design and preparation of a new chiral stationary phase (CSP) employed for the liquid chromatographic resolution of the enantiomers of racemic IDRA 21 is presented. This brush-type CSP, which has not been described before, is a "mixed" (pi-donor pi-acceptor) type and is derived from (R)-N-(3,5-dinitrobenzoyl) allylglycine 2,6-dimethylanilide. It is easily prepared and possesses a relatively broad scope of applicability, as determined by its ability to resolve the enantiomers of both pi-acidic and pi-basic compounds.