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Background: Recently, Europe has seen an emergence of mosquito-borne viruses (MBVs). Understanding citizens' perceptions of and behaviours towards mosquitoes and MBVs is crucial to reduce disease risk. We investigated and compared perceptions, knowledge, and determinants of citizens' behavioural intentions related to mosquitoes and MBVs in the Netherlands and Spain, to help improve public health interventions. Methods: Using the validated MosquitoWise survey, data was collected through participant panels in Spain (N = 475) and the Netherlands (N = 438). Health Belief Model scores measuring behavioural intent, knowledge, and information scores were calculated. Confidence Interval-Based Estimation of Relevance was used, together with potential for change indexes, to identify promising determinants for improving prevention measure use. Results: Spanish participants' responses showed slightly higher intent to use prevention measures compared to those of Dutch participants (29.1 and 28.2, respectively, p 0.03). Most participants in Spain (92.2%) and the Netherlands (91.8%) indicated they used at least one prevention measure, but differences were observed in which types they used. More Spanish participants indicated to have received information on mosquitoes and MBVs compared to Dutch participants. Spanish participants preferred health professional information sources, while Dutch participants favoured government websites. Determinants for intent to use prevention measures included "Knowledge", "Reminders to Use Prevention Measures", and "Information" in the Netherlands and Spain. Determinants for repellent use included "Perceived Benefits" and "Cues to Action", with "Perceived Benefits" having a high potential for behavioural change in both countries. "Self-Efficacy" and "Knowledge" were determinants in both countries for breeding site removal. Conclusion: This study found differences in knowledge between the Netherlands and Spain but similarities in determinants for intent to use prevention measures, intent to use repellents and intent to remove mosquito breeding sites. Identified determinants can be the focus for future public health interventions to reduce MBV risks. [ABSTRACT FROM AUTHOR]

Due to climate change and the expanding geographical ranges of key mosquito species, several mosquito-borne viruses (MBVs) have recently emerged in Europe. Understanding people's perceptions and behaviours towards these viruses and the mosquitoes capable of transmitting them is crucial for implementing effective prevention measures and targeted communication campaigns. However, there is currently no appropriate validated survey for European populations to assess this. This study developed and validated a standardized survey, based on the Health Belief Model (HBM), to assess perceptions of mosquitoes and MBVs among Europe's residents. The survey was distributed online to United Kingdom (UK), Dutch and Spanish participants through panel providers. Survey validity and reliability were tested using confirmatory factor analysis (CFA) and Cronbach's alpha. The optimised survey was completed by 336 UK, 438 Dutch and 475 Spanish residents, respectively, and the HBM items passed our validity and reliability testing in all three countries. The final survey has 57 questions, including 19 validated HBM items, and questions to assess demographic characteristics, knowledge, prevention measures and behavioural determinants. Our MosquitoWise survey bridges researchers' understandings of European residents' perceptions and knowledge as a first step to improve preventive behaviour towards mosquitoes and MBVs and guide prevention and communication initiatives. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to identify nutmeg compounds that indirectly interact with the endocannabinoid system through inhibition of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes. Methods: Thirteen compounds were screened for FAAH and MAGL inhibition. Compounds demonstrating significant FAAH inhibition were evaluated to determine the halfmaximal inhibitory concentration (IC50). The most potent compound was investigated in the elevated plus maze (EPM) rodent anxiety model. Key findings: Three compounds, licarin A (9), 5′‐methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 μm ± 2.02, 4.57 μm ± 0.66 and 38.29 μm ± 6.18, respectively. None of the purified compounds showed significant MAGL inhibition. Because of its relative high potency and selectivity, compound 8 was further evaluated in the EPM animal model of anxiety. The compound showed significant increase in number of open arm entries (P < 0.05) when administered at 120 mg/kg dose. No effect was observed on the locomotor activity. Conclusions: Results collected introduce active nutmeg compounds as potential leads for further development. Of the three compounds, 8 possesses highest potency and FAAH selectivity as well as anxiolytic activity. Furthermore, in vivo testing in appropriate behavioural animal paradigms is warranted. [ABSTRACT FROM AUTHOR]

Green tea (Camellia sinensis) preparations are among the top selling products in the United States dietary supplements market. Numerous manufacturers claim different levels of specific catechin markers in their products while many others use total phenolic concentration instead, or not at all. Limited quality control results have been published for green tea dietary supplements over the past seven years. Thus, the goal of this work was to correlate determined levels of phenolics, catechins, and caffeine with manufacturer label claims for selected dietary supplement products (26 total) purchased in the United States. The Folin-Ciocalteu (FC) method was used to determine the total phenolic content while reversed-phase (RP) HPLC was used to quantify the major catechins: epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG). The developed HPLC method was validated for accuracy and precision. It utilized a C8 column with gradient elution of acetonitrile in 0.1% aqueous formic acid over 11 min total run time. Peak detection was performed at 280 nm. Caffeine was also included in the HPLC method as another non-phenolic alkaloid marker commonly found in green tea. Both methods showed a good correlation between the content of catechins and polyphenolic compounds in the selected products. The ranges of total catechins and polyphenol concentrations were 3.8–70.2% and 3.6–95.8%, respectively, while that of caffeine was 0.8–11.2%. The selected products displayed a wide range of marker levels. A lack of conformity in disclosing the actual levels of marker compounds was also noticed in the labeling of many products. [ABSTRACT FROM AUTHOR]

Abstract: Microbial transformation of silybin (1), the major flavonolignan of milk thistle (Silybum marianum, Asteraceae), resulted in the isolation of four metabolites. The structures of the isolated metabolites were determined by spectroscopic methods. One phase I metabolite was produced by Beauveria bassiana and was characterized as 8-hydroxysilybin (2). Three phase II metabolites were produced by two Cunninghamella species and were identified as 2,3-dehydrosilybin-3-O-β-d-glucoside (3), obtained from Cunninghamella species; and silybin-7-sulfate (4) and 2,3-dehydrosilybin-7-sulfate (5), obtained from Cunninghamella blakesleana. Compared to 1 (IC50 284μg/mL), the generated metabolites displayed varying levels of antioxidant activities in the DPPH free-radical scavenging assay. [Copyright &y& Elsevier]

The enhancing effect of sub-inhibitory concentrations of eugenol and isoeugenol with isoniazid, 6-paradol and 6-shogaol was evaluated in two different strains, Mycobacterium smegmatis and Candida albicans, using the in vitro checkerboard method. With M. smegmatis, isoeugenol (at ½ MIC) was able to lower the MIC (minimum inhibitory concentration) of isoniazid and 6-paradol by 800 percent (10-->1.25 [mu]g/mL) and 400 percent (30-->7.5 [mu]g/mL), respectively. Against C. albicans, Isoeugenol (at ½ MIC) was also able to lower the MIC of 6-paradol by 1600 percent (60-->3.75 [mu]g/mL). Similar synergistic effects were not observed between isoeugenol and 6-shogaol. Eugenol failed to exhibit any of the synergistic effects of isoeugenol under the same experimental conditions. Isoeugenol is a promising enhancing agent for compounds with weak antimycobacterial and anticandidal activities. 6-Paradol may be a potential candidate for further combination studies due to its broader antimicrobial effect against both M. smegmatis and C. albicans. [ABSTRACT FROM AUTHOR]

The enhancing effect of sub-inhibitory concentrations of eugenol and isoeugenol with isoniazid, 6-paradol and 6-shogaol was evaluated in two different strains, Mycobacterium smegmatis and Candida albicans, using the in vitro checkerboard method. With M. smegmatis, isoeugenol (at ½ MIC) was able to lower the MIC (minimum inhibitory concentration) of isoniazid and 6-paradol by 800 percent (10→1.25 μg/mL) and 400 percent (30→7.5 μg/mL), respectively. Against C. albicans, Isoeugenol (at ½ MIC) was also able to lower the MIC of 6-paradol by 1600 percent (60→3.75 μg/mL). Similar synergistic effects were not observed between isoeugenol and 6-shogaol. Eugenol failed to exhibit any of the synergistic effects of isoeugenol under the same experimental conditions. Isoeugenol is a promising enhancing agent for compounds with weak antimycobacterial and anticandidal activities. 6-Paradol may be a potential candidate for further combination studies due to its broader antimicrobial effect against both M. smegmatis and C. albicans. [ABSTRACT FROM AUTHOR]

The caffeine content of selected herbal products and energy drinks available in the Saudi market was determined by HPTLC–UV densitometric analysis. Pre-coated HPTLC silica gel plates (20cm × 10cm) were used for the analysis. The solvent system consisted of ethyl acetate–methanol (85:15, v/v), and caffeine was detected at 275nm. The developed method was validated for specificity, repeatability (C.V. < 5%), recovery (98.90 ± 3.46), and accuracy (99.84 ± 2.87). The levels of caffeine were 4.76–13.29% (w/w) and 0.011–0.032% (w/v), for the herbal products and the energy drinks, respectively. [Copyright &y& Elsevier]

Although the presence of harman alkaloids in the genus Passiflora has been established in a few species, their presence in the medicinally significant P. incarnata (passion flower) is still debatable. Powdered samples from 91 Passiflora species were subjected to accelerated speed extraction and analyzed for their content of five harman alkaloids by reversed-phase HPLC with photodiode array detection. The utilized analytical method was capable of detecting harman alkaloids in more than 50% of the analyzed samples at ppm levels. A library of HPLC chromatograms has also bees generated as a tool for fingerprinting and authentication of the studied Passiflora species. [ABSTRACT FROM AUTHOR]

Describes the high-speed extraction and HPLC fingerprinting of medicinal plants. Samples of different species of genus Passiflora; Availability of unique fingerprints; Generation of characteristics chromatographic profiles.

Aims: Zoonotic arboviruses (arthropod‐borne) of the Orthoflavivirus genus, such as West Nile virus (WNV), Usutu virus (USUV) and Tick‐borne encephalitis virus (TBEV), are emerging in Northwestern Europe and pose a threat to both human and animal health. In the Netherlands, passive symptomatic surveillance (notification of clinical cases) in horses is one of the main pillars for the early detection of WNV. For such passive surveillance to work properly, horse owners and veterinarians need to recognize symptoms and report suspected cases to the authorities. Currently, little is known about the seroprevalence of orthoflaviviruses in domestic animals in the Netherlands. Therefore, this study aims at identifying the seroprevalence of WNV and USUV in horses and dogs in the Netherlands. Additionally, this study seeks to evaluate the knowledge and perceptions of Dutch horse owners towards mosquito‐borne viruses. Methods and Results: A cross‐sectional serosurvey in horses and dogs was conducted between May 2021 and May 2022. Serum samples were screened using an ELISA and doubtful and positive samples were confirmed by Virus Neutralization Tests for WNV, USUV and TBEV. A validated questionnaire, the MosquitoWise survey, was used to assess the knowledge and perceptions of Dutch horse owners towards mosquito‐borne viruses between July and October 2022. The serosurvey revealed a low seroprevalence for WNV in horses and no WNV‐positive dogs were found. Similarly, a low USUV seroprevalence was found in dogs. The MosquitoWise survey revealed a high knowledge level for horse owners and high awareness of WNV vaccination but a more limited intent to vaccinate. Conclusions: The low seroprevalences of WNV and USUV indicate many dogs and horses remain susceptible, offering opportunities for trend analysis and surveillance. However, despite multiple recent detections of WNV, USUV, and TBEV in humans, the role of dogs and horses in early detection of human cases is debatable. High awareness among horse owners and the absence of detected equine WNV cases highlight this uncertainty. Continued surveillance is crucial for detecting increased virus circulation and protecting both animal and human health. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has forced many governments to impose social distancing measures upon its citizens, including in the Netherlands. Motivating adolescents to adhere to measures such as social distancing can be challenging, since adolescents are relatively more affected by them, while experiencing virtually no personal health benefit. In addition, the COVID-19 pandemic seems to impact the social environment of adolescents in schools, as some media sources have reported bullying and stigmatisation of students with an Asian appearance. This study aims to explore the experiences of adolescents regarding their Health-Protective Behaviour (HPB), as well as the prevalence and expression of stigma towards ethnic minorities within the context of the first wave of COVID-19 pandemic. We performed a cross-sectional mixed-methods study, including two independent online questionnaires. An adapted version of the "HPB" questionnaire (n = 528) and the "Measure of Disease-Related Stigma (MDRS)" questionnaire (n = 380), were administered to Dutch adolescents of 10–16 years old, attending primary or secondary school. Furthermore, 15 interviews were held with eight male and seven female adolescents. All data collection took place between March 17 and April 20, 2020. Results show that adolescents perceive COVID-19 as a threat to other peoples' health, rather than their own, and report adherence to public health measures in the interest of older and more vulnerable members of their community. We found no convincing evidence for widespread misinformation or stigmatising of certain ethnic groups among adolescents related to COVID-19 during this study. Participants acknowledged such behaviour happened in the early stages of the pandemic, before this study was initiated. Adolescents are a vital group for public health researchers to engage with during a pandemic, even when reaching them can be challenging. [ABSTRACT FROM AUTHOR]

This study attempts to determine what products health food store employees recommend for depression, to analyze the content of these products based on label claims, and to evaluate employee statements or recommendations for accuracy and safety. Methods: Twelve health food stores were selected for the study. One investigator approached an employee in each store and asked what they recommended for depression plus five additional questions regarding product use. Thirteen products containing St. John's wort were purchased and analyzed for hypericin and pseudohypericin content using high-performance liquid chromatography (HPLC). Total hypericin content was calculated by adding the values for hypericin and pseudohypericin. Results: All 12 health food store employees recommended a St. John's wort supplement for treatment of depression. Furthermore, numerous comments made by employees regarding St. Johns wort and the treatment of depression were unsafe and inaccurate. The HPLC analysis revealed that no product contained ± 10% of the stated label claim for hypericin content, and two products contained 0% hypericin. The total hypericin content (hypericin plus pseudohypericin) of only two products was within ± 10% of tie label claim for hypericin. Conclusions: Health food store employees offer health care advice regarding treatment of depression with dietary supplements without proper scientific and medical training. Their comments could cause significant harm to customers. In addition, the inconsistencies of dietary supplement content continue to raise concern for individuals who use these agents as medical treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE Ambrisentan, an endothelin receptor antagonist FDA-approved for the treatment of pulmonary arterial hypertension in adult patients, lacks an acceptable pediatric dosage form. The objective of this investigation was to determine the stability of an extemporaneously compounded ambrisentan suspension. METHODS Ambrisentan suspension was compounded to a concentration of 1 mg/mL using commercially available suspending agents. The suspension was then evenly split into 2 plastic amber prescription bottles. One bottle was stored at room temperature and under continuous fluorescent light while the other bottle was stored under refrigeration and protection from light. A fast and selective reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of ambrisentan. HPLC analysis was performed on samples withdrawn from the stock bottles at predetermined time intervals, up to 90 days. RESULTS The developed HPLC method enabled the elution and detection of ambrisentan peak at 4.4 minutes. HPLC analysis revealed that all samples from both storage conditions retained >90% potency throughout the study timeframe. There were no signs of any ambrisentan breakdown products on HPLC analysis. Color and odor of the final product was also consistent throughout the 90-day storage period. CONCLUSION Ambrisentan suspension, compounded to 1 mg/mL, is stable at room temperature or under refrigeration for up to 90 days. ABBREVIATIONS FDA, US Food and Drug Administration; HPLC, reversed-phase high-performance liquid chromatography; PAH, pulmonary arterial hypertension; SA, ambrisentan bottle A; SB, ambrisentan bottle B [ABSTRACT FROM AUTHOR]

Lotaustralin was isolated as a mixture of two diastereoisomeric forms from the methanol extract of Rhodiola rosea roots, together with the known compounds rosavin, rosarin, rosin, rosiridin, salidroside, and β-sitosterol. The structure of lotaustralin was established by 1D and 2D-NMR spectroscopy, including 1H–1H COSY, NOESY, HMQC, and HMBC, and FAB and HR MS. [Copyright &y& Elsevier]

Context:Nutmeg [Myristica fragransHoutt. (Myristicaceae)] has a long-standing reputation of psychoactivity. Anecdotal reports of nutmeg use as a cheap marijuana substitute, coupled to previous studies reporting a cannabimimetic-like action, suggest that nutmeg may interact with the endocannabinoid system. Objective:The study evaluates nutmeg fractions for binding capacity with various CNS receptors and their potential interaction with the endocannabinoid system. Materials and methods:Dichloromethane (DF) and ethyl acetate (EF) fractions were prepared from the methanol extract of powdered whole nutmeg. The HPLC-profiled fractions were assayed by the NIMH Psychoactive Drug Screening Program (PDSP) in a panel of CNS targets at a 10 μg/mL concentration. The fractions were also screened for fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition, initially at a concentration of 500 μg/mL, then by concentration-dependent inhibition studies. Results:None of the tested fractions showed significant binding to CNS receptors included in the PDSP panel. However, both fractions exerted significant inhibition of the FAAH and MAGL enzymes. The DF fraction inhibited FAAH and MAGL enzymes at IC50values of 21.06 ± 3.16 and 15.34 ± 1.61 μg/mL, respectively. Similarly, the EF fraction demonstrated FAAH and MAGL inhibition with IC50values of 15.42 ± 3.09 and 11.37 ± 6.15 μg/mL, respectively. Discussion and conclusion:The study provides the first piece of evidence that nutmeg interacts with the endocannabinoid system via inhibition of the endocannabinoid catabolizing enzymes. This mechanism provides insight into reported cannabis-like action as well as expands the potential therapeutic utility of nutmeg. [ABSTRACT FROM AUTHOR]

For the first time, a fast, high-performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of the new ultra-short hypnotic HIE-124 and its metabolite in mice serum. Each compound, together with carbamazepine (internal standard) was extracted from the serum matrix using liquid–liquid extraction (LLE). Chromatographic resolution of the analytes was performed on a Chromolith Speed Rod monolithic silica column (100 mm × 4.6 mm i.d.) under isocratic conditions using a mobile phase of 65 : 35 (v/v), 20 mM phosphate buffer (pH 7.0 adjusted with phosphoric acid)–acetonitrile. The elution of the analytes were monitored at 240 nm and conducted at ambient temperature. Because of high column efficiency the mobile phase was pumped at a flow rate of 2.5 mL min−1. The total run time of the assay was 2 min. The method was validated over the range of 60–2000 ng mL−1for HIE-124 and 200–1600 ng mL−1for the metabolite (r2= 0.99). The limit of detection (LOD) for HIE-124 and its metabolite were 20 ng mL−1and 65 ng mL−1, respectively. The proposed method was validated in compliance with ICH guidelines, in terms of accuracy, precision, limits of detection and quantitation and other aspects of analytical validation. The developed method could be used for the trace analyses of HIE-124 and its metabolite in serum and was finally used for the pharmacokinetic study investigation of HIE-124 in mice serum. [ABSTRACT FROM AUTHOR]

Abstract: Microemulsion electrokinetic capillary chromatography (MEEKC) with sample stacking induced by reverse migrating pseudostationary phase (SRMP) technique in a suppressed electro-osmotic flow (EOF) strategy was investigated for analysing the new ultra-short hypnotic HIE-124 in mice serum. The proposed method utilized fused-silica capillary with a total length of 50cm (effective length 40cm), applied voltages for stacking and separation were 5.0kV for 4.30min and subsequently 25kV, respectively, with a sample injection of 0.5psi for 90s. All the runs were carried out at 25°C and detected at 213nm. The optimum microemulsion background electrolyte (BGE) solution consisted of 0.8% (v/v) ethyl acetate, 6.6% (v/v) butan-2-ol, 1.0% (v/v) acetonitrile, 2.0% (w/v) sodium dodecyl sulfate (SDS), and 89.6mL with 25mM phosphate buffer pH 8. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with changing the voltage with an intermediate polarity switching step. The proposed method was validated carefully with respect to high specificity of the method, good linearity (r =0.9994), fair wide linear concentration range (66–1500ngmL−1), limit of detection and quantitation were 21.6 and 65.5ngmL−1, respectively. The mean relative standard deviation (RSD) of the results of intra- and inter-day precision and accuracy were less than 6.0%, and overall recovery higher than 95% of HIE-124 in mice serum. The developed method could be used for the trace analyses of HIE-124 in serum and was finally used for the pharmacokinetic study investigation of HIE-124 in mice serum. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Nutmeg, the seeds of Myritica fragrans (family Myristicaceae), is a well known kitchen spice with a long-standing reputation as a psychoactive herb. Nutmeg at high doses is considered a cheap substitute to several drugs of abuse. Earlier reports have attributed amphetamine-like activities to nutmeg. Aim of the study: To characterize the neuropharmacological effects of different nutmeg extracts, administered orally and intraperitoneally, in comparison to Δ9-terahydrocannabinol, amphetamine, and morphine. Materials and methods: Methanolic (ME), dichloromethane (DE), and hexane (HE) extracts were obtained from a chromatographically fingerprinted batch of nutmeg. Biological evaluation was conducted in sets of 6–8 mice in the tetrad assay at doses ranging from 100 to 500 and 500 to 1000mg/kg for i.p. and oral administration, respectively. Results: While oral administration of all the nutmeg extracts at 500mg/kg caused a significant increase in locomotor activity, the i.p. administration of DE showed significant reduction in rectal temperature along with a significant increase in tail flick latency at 300mg/kg. A significant decrease in core body temperature was observed with HE at 100mg/kg, while higher doses caused significant increases in hot plate latency. Conclusion: Different behavioral effects were observed that varied by the type of extract as well as by the route of administration. [Copyright &y& Elsevier]

The chemical composition of three essential oil samples (stored aerial parts, fresh aerial parts, and fresh flowering tops) of Commiphora opobalsamum L., obtained by hydrodistillation, was determined using GC-MS analysis. The identified constituents represented 69.5 to 84.4 percent of the total chemical compounds of the three samples. The major components were [alpha]-cadinol in the stored aerial parts, [alpha]-calacorene in the fresh aerial parts, and terpinen-4-ol in the fresh flowering tops. The essential oil from the fresh aerial parts exhibited antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Candida glabrata, C. krusei, Cryptococcus neoformans, and Mycobacterium intracellulare. The same oil sample was non-selectively cytotoxic to four tumor cell lines: SK-MEL, KB, BT549 and SK-OV3. Weak antioxidant activity of the oil from the fresh aerial sample was demonstrated in a DPPH free-radical scavenging assay. [ABSTRACT FROM AUTHOR]

The chemical composition of three essential oil samples (stored aerial parts, fresh aerial parts, and fresh flowering tops) of Commiphora opobalsamum L., obtained by hydrodistillation, was determined using GC-MS analysis. The identified constituents represented 69.5 to 84.4 percent of the total chemical compounds of the three samples. The major components were α-cadinol in the stored aerial parts, α-calacorene in the fresh aerial parts, and terpinen-4-ol in the fresh flowering tops. The essential oil from the fresh aerial parts exhibited antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Candida glabrata, C. krusei, Cryptococcus neoformans, and Mycobacterium intracellulare. The same oil sample was non-selectively cytotoxic to four tumor cell lines: SK-MEL, KB, BT549 and SK-OV3. Weak antioxidant activity of the oil from the fresh aerial sample was demonstrated in a DPPH free-radical scavenging assay. [ABSTRACT FROM AUTHOR]

Phytopharmaceuticals and dietary supplements containing valerian are used as mild sleep-inducing agents. An in vitro radioligand binding assay at A1 and A2A adenosine receptors (ARs) was conducted with a fixed extract combination of valerian and hop (Ze 91019) to investigate a possible mechanism for the pharmacological activity of the extract. Component extracts of valerian and hop were also individually investigated. The fixed combination Ze 91019 as well as the valerian extracts therein exhibited selective affinity to A1ARs (Ki = 0.15–0.37 mg/mL vs [3H]CCPA). The same extracts exhibited partial agonist activity at the A1 adenosine receptor as indicated by a lower degree of stimulation of [35S]GTPγS binding in membrane preparations of CHO-hA1 cells as compared to the full A1 AR agonist N6-cyclopentyladenosine (CPA). In addition valerian extract inhibited cAMP accumulation in CHO-hA1 cell membranes. The partial agonistic activity at A1ARs may thus play a role in the sleep inducing effect of Ze 91019 and the valerian extract therein. [Copyright &y& Elsevier]

The inhibitory activity of 34 natural products of various structural classes on hydroxyphenylpyruvate dioxygenase (HPPD), the target site for triketone herbicides, and the mode of interaction of selected natural products were investigated. Recombinant HPPD from arabidopsis is sensitive to several classes of natural compounds including, in decreasing order of sensitivity, triketones, benzoquinones, naphthoquinones and anthraquinones. The triketone natural products acted as competitive tight-binding inhibitors, whereas the benzoquinones and naphthoquinones did not appear to bind tightly to HPPD. While these natural products may not have optimal structural features required for in vivo herbicidal activity, the differences in their kinetic behavior suggest that novel classes of HPPD inhibitors may be developed based on their structural backbones. [Copyright &y& Elsevier]