Monoterpene Indole Alkaloids with Cav3.1 T-Type Calcium Channel Inhibitory Activity from Catharanthus roseus

Catharanthus roseus is a well-known traditional herbal medicine for the treatment of cancer, hypertension, scald, and sore in China. Phytochemical investigation on the twigs and leaves of this species led to the isolation of two new monoterpene indole alkaloids, catharanosines A (1) and B (2), and six known analogues (3–8). Structures of 1 and 2 were established by ¹H-, ¹³C- and 2D-NMR, and HREIMS data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 2 represented an unprecedented aspidosperma-type alkaloid with a 2-piperidinyl moiety at C-10. Compounds 6–8 exhibited remarkable Ca_v3.1 low voltage-gated calcium channel (LVGCC) inhibitory activity with IC₅₀ values of 11.83 ± 1.02, 14.3 ± 1.20, and 14.54 ± 0.99 μM, respectively.     

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

TASK channels belong to the two-pore-domain potassium (K_2P) channels subfamily. These channels modulate cellular excitability, input resistance, and response to synaptic stimulation. TASK-channel inhibition led to membrane depolarization. TASK-3 is expressed in different cancer cell types and neurons. Thus, the discovery of novel TASK-3 inhibitors makes these bioactive compounds very appealing to explore new cancer and neurological therapies. TASK-3 channel blockers are very limited to date, and only a few heterofused compounds have been reported in the literature. In this article, we combined a pharmacophore hypothesis with molecular docking to address for the first time the rational design, synthesis, and evaluation of 5-(indol-2-yl)pyrazolo[3,4-b]pyridines as a novel family of human TASK-3 channel blockers. Representative compounds of the synthesized library were assessed against TASK-3 using Fluorometric imaging plate reader—Membrane Potential assay (FMP). Inhibitory properties were validated using two-electrode voltage-clamp (TEVC) methods. We identified one active hit compound (MM-3b) with our systematic pipeline, exhibiting an IC₅₀ ≈ 30 μM. Molecular docking models suggest that compound MM-3b binds to TASK-3 at the bottom of the selectivity filter in the central cavity, similar to other described TASK-3 blockers such as A1899 and PK-THPP. Our in silico and experimental studies provide a new tool to predict and design novel TASK-3 channel blockers.     

Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA2β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes

Type 1 diabetes (T1D) development, in part, is due to ER stress-induced β-cell apoptosis. Activation of the Ca²⁺-independent phospholipase A₂ beta (iPLA₂β) leads to the generation of pro-inflammatory eicosanoids, which contribute to β-cell death and T1D. ER stress induces iPLA₂β-mediated generation of pro-apoptotic ceramides via neutral sphingomyelinase (NSMase). To gain a better understanding of the impact of iPLA₂β on sphingolipids (SLs), we characterized their profile in β-cells undergoing ER stress. ESI/MS/MS analyses followed by ANOVA/Student’s t-test were used to assess differences in sphingolipids molecular species in Vector (V) control and iPLA₂β-overexpressing (OE) INS-1 and Akita (AK, spontaneous model of ER stress) and WT-littermate (AK-WT) β-cells. As expected, iPLA₂β induction was greater in the OE and AK cells in comparison with V and WT cells. We report here that ER stress led to elevations in pro-apoptotic and decreases in pro-survival sphingolipids and that the inactivation of iPLA₂β restores the sphingolipid species toward those that promote cell survival. In view of our recent finding that the SL profile in macrophages—the initiators of autoimmune responses leading to T1D—is not significantly altered during T1D development, we posit that the iPLA₂β-mediated shift in the β-cell sphingolipid profile is an important contributor to β-cell death associated with T1D.     

Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y₁, Y₂ and Y₅. While Y₁ receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca²⁺ channels such as nifedipine, little is known about the role of such channels in Y₅-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1 µg/kg/min) increased diuresis and natriuresis, and this was attenuated by intraperitoneal injection of nifedipine (3 µg/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30 μg/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100 μg/kg/min i.v.) moderately inhibited these effects. We conclude that Y₅-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y₁-mediated renovascular effects. Whether this reflects a general sensitivity of Y₅ receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.     

TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca²⁺ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca²⁺-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca²⁺ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca²⁺-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without α1_SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in α1_SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or α1_SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca²⁺ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.     

Antispasmodic Effect of Asperidine B,a Pyrrolidine Derivative,through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle

Antispasmodic agents are used for modulating gastrointestinal motility. Several compounds isolated from terrestrial plants have antispasmodic properties. This study aimed to explore the inhibitory effect of the pyrrolidine derivative, asperidine B, isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, on spasmodic activity. Isolated rat ileum was set up in an organ bath. The contractile responses of asperidine B (0.3 to 30 µM) on potassium chloride and acetylcholine-induced contractions were recorded. To investigate its antispasmodic mechanism, CaCl₂, acetylcholine, Nω-nitro-l-arginine methyl ester (l-NAME), nifedipine, methylene blue and tetraethylammonium chloride (TEA) were tested in the absence or in the presence of asperidine B. Cumulative concentrations of asperidine B reduced the ileal contraction by ~37%. The calcium chloride and acetylcholine-induced ileal contraction was suppressed by asperidine B. The effects of asperidine B combined with nifedipine, atropine or TEA were similar to those treated with nifedipine, atropine or TEA, respectively. In contrast, in the presence of l-NAME and methylene blue, the antispasmodic effect of asperidine B was unaltered. These results suggest that the antispasmodic property of asperidine B is probably due to the blockage of the L-type Ca²⁺ channel and is associated with K⁺ channels and muscarinic receptor, possibly by affecting non-selective cation channels and/or releasing intracellular calcium.     

Phosphorylation of cPLA2α at Ser505 Is Necessary for Its Translocation to PtdInsP2-Enriched Membranes

Group IVA cytosolic phospholipase A₂α (cPLA₂α) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLA₂α activity is tightly regulated by multiple factors, including the intracellular Ca²⁺ concentration, phosphorylation reactions, and cellular phosphatidylinositol (4,5) bisphosphate levels (PtdInsP₂). In the present work, we demonstrate that phosphorylation of the enzyme at Ser⁵⁰⁵ is an important step for the translocation of the enzyme to PtdInsP₂–enriched membranes in human cells. Constructs of eGFP-cPLA₂ mutated in Ser⁵⁰⁵ to Ala (S505A) exhibit a delayed translocation in response to elevated intracellular Ca²⁺, and also in response to increases in intracellular PtdInsP₂ levels. Conversely, translocation of a phosphorylation mimic mutant (S505E) is fully observed in response to cellular increases in PtdInsP₂ levels. Collectively, these results suggest that phosphorylation of cPLA₂α at Ser⁵⁰⁵ is necessary for the enzyme to translocate to internal membranes and mobilize arachidonic acid for eicosanoid synthesis.     

Triazolylbenzimidazolthiones and derivatives of the new 1,2,3‐triazolo[ 1,5‐a][ 1,3,5]benzotriazepine heterocycle

Four new triazolylbenzimidazolthione derivatives (2a‐d), analogous to triazolylbenzimidazolone derivatives previously tested as activators of the BK_Ca potassium channels, were prepared and assayed without success. Some derivatives of a new tricyclic nitrogen heterocycle, 1,2,3‐triazolo[1,5‐a][1,3,5]benzo‐triazepine, bearing a carboxamido group in the 3 position, other substituents in the 8 position and a carbonyl (5a‐d) or thione (6a‐c) or methylthio (7a‐c) function in the 5 position were synthesised. The nucleophilic displacement of the methylthio substituent with morpholine or cyclopentylamine provided the 5‐amino‐substituted tricyclic derivatives 8a‐d. Starting from the l‐(2‐nitrophenyl)‐4‐cyano‐5‐amino‐1,2,3‐triazole (9), the 3‐cyano‐triazolobenzotriazepin‐5‐one derivative 12 was also obtained. The majority of the new compounds were tested towards the BK_Ca potassium channels, the benzodiazepine and adenosine A₁ and A_2a receptors, but no remarkable activity was detected.     

Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Na_v1.7 and anti-Na_v1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Na_v targets, could serve as new leads for the development of analgesic medicines.     

In Silico and Ex Vivo Studies on the Spasmolytic Activities of Fenchone Using Isolated Guinea Pig Trachea

Fenchone is a bicyclic monoterpene found in a variety of aromatic plants, including Foeniculum vulgare and Peumus boldus, and is used in the management of airways disorders. This study aimed to explore the bronchodilator effect of fenchone using guinea pig tracheal muscles as an ex vivo model and in silico studies. A concentration-mediated tracheal relaxant effect of fenchone was evaluated using isolated guinea pig trachea mounted in an organ bath provided with physiological conditions. Sustained contractions were achieved using low K⁺ (25 mM), high K⁺ (80 mM), and carbamylcholine (CCh; 1 µM), and fenchone inhibitory concentration–response curves (CRCs) were obtained against these contractions. Fenchone selectively inhibited with higher potency contractions evoked by low K⁺ compared to high K⁺ with resultant EC₅₀ values of 0.62 mg/mL (0.58–0.72; n = 5) and 6.44 mg/mL (5.86–7.32; n = 5), respectively. Verapamil (VRP) inhibited both low and high K⁺ contractions at similar concentrations. Pre-incubation of the tracheal tissues with K⁺ channel blockers such as glibenclamide (Gb), 4-aminopyridine (4-AP), and tetraethylammonium (TEA) significantly shifted the inhibitory CRCs of fenchone to the right towards higher doses. Fenchone also inhibited CCh-mediated contractions at comparable potency to its effect against high K⁺ [6.28 mg/mL (5.88–6.42, n = 4); CCh] and [6.44 mg/mL (5.86–7.32; n = 5); high K⁺]. A similar pattern was obtained with papaverine (PPV), a phosphodiesterase (PDE), and Ca²⁺ inhibitor which inhibited both CCh and high K⁺ at similar concentrations [10.46 µM (9.82–11.22, n = 4); CCh] and [10.28 µM (9.18–11.36; n = 5); high K⁺]. However, verapamil, a standard Ca²⁺ channel blocker, showed selectively higher potency against high K⁺ compared to CCh-mediated contractions with respective EC₅₀ values of 0.84 mg/mL (0.82–0.96; n = 5) 14.46 mg/mL (12.24–16.38, n = 4). The PDE-inhibitory action of fenchone was further confirmed when its pre-incubation at 3 and 5 mg/mL potentiated and shifted the isoprenaline inhibitory CRCs towards the left, similar to papaverine, whereas the Ca²⁺ inhibitory-like action of fenchone pretreated tracheal tissues were authenticated by the rightward shift of Ca²⁺ CRCs with suppression of maximum response, similar to verapamil, a standard Ca²⁺ channel blocker. Fenchone showed a spasmolytic effect in isolated trachea mediated predominantly by K⁺ channel activation followed by dual inhibition of PDE and Ca²⁺ channels. Further in silico molecular docking studies provided the insight for binding of fenchone with Ca²⁺ channel (−5.3 kcal/mol) and K⁺ channel (−5.7), which also endorsed the idea of dual inhibition.     

Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-γ1 pathway

In women with preeclampsia (PE), endothelial cell (EC) dysfunction can lead to altered secretion of paracrine factors that induce peripheral vasoconstriction and proteinuria. This study examined the hypothesis that PE sera may directly or indirectly, through human umbilical vein ECs (HUVECs), stimulate phospholipase C-γ1-1,4,5-trisphosphate (PLC-γ1-IP₃) signaling, thereby increasing protein kinase C-α (PKC-α) activity, collagen I expression and intracellular Ca²⁺ concentrations ([Ca²⁺]_i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-γ1 silencing. Increased PLC-γ1 and IP₃ receptor (IP₃R) phosphorylation was observed in cocultured HUASMCs stimulated with PE sera (P<0.05). In addition, PE serum significantly increased HUASMC viability and reduced their apoptosis (P<0.05); these effects were abrogated with PLC-γ1 silencing. Compared with normal sera, PE sera increased [Ca²⁺]_i in cocultured HUASMCs (P<0.05), which was inhibited by PLC-γ1 and IP₃R silencing. Finally, PE sera-induced PKC-α activity and collagen I expression was inhibited by PLC-γ1 small interfering RNA (siRNA) (P<0.05). These results suggest that vasoactive substances in the PE serum may induce deposition in the extracellular matrix through the activation of PLC-γ1, which may in turn result in thickening and hardening of the placental vascular wall, placental blood supply shortage, fetal hypoxia–ischemia and intrauterine growth retardation or intrauterine fetal death. PE sera increased [Ca²⁺]_i and induced PKC-α activation and collagen I expression in cocultured HUASMCs via the PLC-γ1 pathway.     

Involvement of the γ Isoform of cPLA2 in the Biosynthesis of Bioactive N-Acylethanolamines

Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other N-acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via N-acyl-phosphatidylethanolamine (NAPE). The ɛ isoform of cytosolic phospholipase A₂ (cPLA₂) functions as an N-acyltransferase to form NAPE. Since the cPLA₂ family consists of six isoforms (α, β, γ, δ, ɛ, and ζ), the present study investigated a possible involvement of isoforms other than ɛ in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA₂ isoforms were labeled with [¹⁴C]ethanolamine, the increase in the production of [¹⁴C]NAPE was observed only with the ɛ-expressing cells. Secondly, when the cells co-expressing ɛ and one of the other isoforms were analyzed, the increase in [¹⁴C]N-acyl-lysophosphatidylethanolamine (lysoNAPE) and [¹⁴C]NAE was seen with the combination of ɛ and γ isoforms. Furthermore, the purified cPLA₂γ hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-N-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA₂γ is involved in the biosynthesis of NAE by its phospholipase A₁/A₂ and lysophospholipase activities.     

A Study of the Effect of Sintering Conditions of Mg0.95Ni0.05Ti3 on Its Physical and Dielectric Properties

Mg_0.95Ni_0.05TiO₃ ceramics were prepared by traditional solid-state route using sintering temperatures between 1300 and 1425 °C and holding time of 2–8 h. The sintered samples were characterized for their phase composition, micro-crystalline structure, unit–cell constant, and dielectric properties. A two-phase combination region was identified over the entire compositional range. The effect of sintering conditions was analyzed for various properties. Both permittivity (ε_r) and Q factor (Q_f) were sensitive to sintering temperatures and holding times, and the optimum performance was found at 1350 °C withholding time of 4 h. The temperature coefficient of resonant frequency (τ_f) in a range from −45.2 to −52 (ppm/°C) and unit–cell constant were not sensitive to both the sintering temperature and holding time. An optimized Q factor of 192,000 (GHz) related with a permittivity (ε_r) of 17.35 and a temperature coefficient (τ_f) of −47 (ppm/°C) was realized for the specimen sintered at 1350 °C withholding time of 4 h. For applications of 5G communication device (filter, antennas, etc.), Mg_0.95Ni_0.05TiO₃ is considered to be a suitable candidate for substrate materials.     

Sarcorucinine-D Inhibits Cholinesterases and Calcium Channels: Molecular Dynamics Simulation and In Vitro Mechanistic Investigations

Acetylcholinesterase (AChE) inhibitors and calcium channel blockers are considered effective therapies for Alzheimer’s disease. AChE plays an essential role in the nervous system by catalyzing the hydrolysis of the neurotransmitter acetylcholine. In this study, the inhibition of the enzyme AChE by Sarcorucinine-D, a pregnane type steroidal alkaloid, was investigated with experimental enzyme kinetics and molecular dynamics (MD) simulation techniques. Kinetics studies showed that Sarcorucinine-D inhibits two cholinesterases—AChE and butyrylcholinesterase (BChE)—noncompetitively, with K_i values of 103.3 and 4.66 µM, respectively. In silico ligand-protein docking and MD simulation studies conducted on AChE predicted that Sarcorucinine-D interacted via hydrophobic interactions and hydrogen bonds with the residues of the active-site gorge of AChE. Sarcorucinine-D was able to relax contractility concentration-dependently in the intestinal smooth muscles of jejunum obtained from rabbits. Not only was the spontaneous spasmogenicity inhibited, but it also suppressed K⁺-mediated spasmogenicity, indicating an effect via the inhibition of voltage-dependent Ca²⁺ channels. Sarcorucinine-D could be considered a potential lead molecule based on its properties as a noncompetitive AChE inhibitor and a Ca²⁺ channel blocker.     

An Efficient Synthesis of 2-CF3-3-Benzylindoles

The reaction of α-CF₃-β-(2-nitroaryl) enamines with benzaldehydes afforded effectively α,β-diaryl-CF₃-enones having nitro group. Subsequent reduction of nitro group by NH₄HCO₂-Pd/C system initiated intramolecular cyclization to give 2-CF₃-3-benzylindoles. Target products can be prepared in up to quantitative yields. Broad synthetic scope of the reaction was shown. Probable mechanism of indole formation is proposed.     

PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin α_vβ₃ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin α_vβ₃ tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (¹⁸F, ⁶⁴Cu, and ⁶⁸Ga), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included.     

Nickel and potassium co-modified β-Mo2C catalyst for CO conversion

Nickel and potassium co-modified -Mo2C catalysts were prepared and used for CO hydrogenation reaction. The major products over -Mo2C were C1–C4 hydrocarbons, only few alcohols were obtained. Addition of potassium resulted in remarkable selectivity shift from hydrocarbons to alcohols at the expense of CO conversion over -Mo2C. Moreover, it was found that potassium enhanced the ability of chain propagation with a higher C2+OH production. Modified by nickel, -Mo2C showed a relatively high CO conversion, however, the products were similar to those of pure -Mo2C. When co-modified by nickel and potassium, -Mo2C exhibited high activity and selectivity towards mixed alcohols synthesis, and also the whole chain propagation to produce alcohols especially for the stage of C1OH to C2OH was remarkably enhanced. It was concluded that the Ni and K had, to some extent, synergistic effect on CO conversion.     

Conduction and Ion Transport in LaYO<Subscript>3</Subscript> Doped with CaO

Values of partial conductions (ionic: protonic, oxygen, hole) and their activation energies in LaYO₃ are determined at 700–1050°C, pO₂ ranging from air to 10⁻¹⁵ Pa, and pH₂O = 0.04–13.5 kPa for different versions of doping with calcium (when introduced into the lanthanum or yttrium sublattices, or into both sublattices simultaneously). The conductivity increases in the series La_0.97Ca_0.03YO_{3 − α} < LaY_0.97Ca_0.03O_{3 − α} < La_0.985Y_0.985Ca_0.03O_{3 − α}, which means that the stoichiometric composition with a 1 : 1 ratio between Y and La has the highest conductivity.__________Translated from Elektrokhimiya, Vol. 41, No. 5, 2005, pp. 610–615.Original Russian Text Copyright © 2005 by Balakireva, Stroeva, Gorelov.     

GABAA Receptor-Mediated Sleep-Promoting Effect of Saaz–Saphir Hops Mixture Containing Xanthohumol and Humulone

Hops contain flavonoids that have sedative and sleep-promoting activities such as α-acid, β-acid, and xanthohumol. In this study, the sleep-enhancing activity of a Saaz–Saphir hops mixture was measured. In the caffeine-induced insomnia model, the administration of a Saaz–Saphir mixture increased the sleep time compared to Saaz or Saphir administration alone, which was attributed to the increase in NREM sleep time by the δ-wave increase. Oral administration of the Saaz–Saphir mixture for 3 weeks increased the γ-amino butyric acid (GABA) content in the brain and increased the expression of the GABA_A receptor. As the GABA antagonists picrotoxin and bicuculline showed a decrease in sleep activity, it was confirmed that the GABA_A receptor was involved in the Saaz–Saphir mixture activity. In addition, the GABA_A receptor antagonist also reduced the sleep activity induced by xanthohumol and humulone contained in the Saaz–Saphir mixture. Therefore, xanthohumol and humulone contained in the Saaz–Saphir mixture showed sleep-promoting activity mediated by the GABA_A receptors. The mixture of the Saaz and Saphir hop varieties may thus help mitigate sleep disturbances compared to other hop varieties.     

IR-Spectroscopic Study of Complex Formation of Nitrogen Oxides (NO,N2O) with Cationic Forms of Zeolites and the Reactivity of Adsorbed Species in CO and CH4 Oxidation

The formation of complexes and disproportionation of nitrogen oxides (NO, N₂O) on cationic forms of LTA, FAU, and MOR zeolites was investigated by diffuse-reflectance IR spectroscopy. N₂O is adsorbed on the samples under study in the molecular form and the frequencies of the first overtone of the stretching vibrations ν¹_0–2 and the combination bands of the stretching vibrations with other vibrational modes for N₂O complexes with cationic sites in zeolites (ν³_0–1 + ν¹_0–1, ν¹_0–1 + δ_0–2) are more significantly influenced by the nature of the zeolite. The presence of several IR bands in the region of 2400–2600 cm⁻¹ (the ν¹_0–1 + δ_0–2 transitions) for different zeolite types was explained by the availability of different localization sites for cations in these zeolites. The frequencies in this region also depend on the nature of the cation (its charge and radius). The data can be explained by the specific geometry of the N₂O complex formed, presumably two-point adsorption of N₂O on a cation and a neighboring oxygen atom of the framework. Adsorption of CO or CH₄ on the samples with preliminarily adsorbed N₂O at 20–180 °C does not result in any oxidation of these molecules. NO⁺ and N₂O₃ species formed by disproportionation of NO are capable of oxidizing CO and CH₄ molecules to CO₂, whereas NO_x is reduced simultaneously to N₂ or N₂O. The peculiarities in the behavior of cationic forms of different zeolites with respect to adsorbed nitrogen oxides determined by different density and localization of cations have been established.