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1.
Ecotoxicol Environ Saf ; 228: 113020, 2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34856485

RESUMEN

We were intrigued by reported observations of reduced brood production and a high number of empty brood cells in bee colonies exposed to sublethal pesticide doses, which could suggest an active removal of larvae. Higher numbers of oenocytes, insect cells responsible for lipid processing and detoxification, were also found in pesticide-exposed larvae. Oenocytes are involved in hydrocarbon metabolism and chemical communication, and we hypothesized that these larvae could display altered cuticular hydrocarbon (CHC) profiles when exposed to pesticides as compared to control larvae. In addition, we proposed that these chemical cues could trigger specific behavioral responses in colony nurses. To test these hypotheses, we analyzed the CHC profiles of artificially reared larvae that had been fed sublethal doses of either dimethoate or clothianidin or fed on lipopolysaccharide (LPS) using gas chromatography-mass spectrometry. We found significant differences in the CHC profiles of these differently treated larvae. In a subsequent behavioral experiment, we transferred clothianidin-treated or LPS-treated larvae into the brood combs of surrogate colonies. Larvae that had been fed either the pesticide or LPS were removed at a significantly higher rate than control larvae. Our results demonstrate that larvae exposed to clothianidin possess altered CHC profiles, are detected in the colony by nurse bees via chemical cues and are actively removed.

2.
Eur J Med Chem ; 207: 112837, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33002847

RESUMEN

Malaria and tuberculosis are still among the leading causes of death in low-income countries. The 1,4-naphthoquinone (NQ) scaffold can be found in a variety of anti-infective agents. Herein, we report an optimised, high yield process for the preparation of various 2-arylnaphthoquinones by a palladium-catalysed Suzuki reaction. All synthesised compounds were evaluated for their in-vitro antiprotozoal and antimycobacterial activity. Antiprotozoal activity was assessed against Plasmodium falciparum (P.f.) NF54 and Trypanosoma brucei rhodesiense (T.b.r.) STIB900, and antimycobacterial activity against Mycobacterium smegmatis (M.s.) mc2 155. Substitution with pyridine and pyrimidine rings significantly increased antiplasmodial potency of our compounds. The 2-aryl-NQs exhibited trypanocidal activity in the nM range with a very favourable selectivity profile. (Pseudo)halogenated aryl-NQs were found to have a pronounced effect indicating inhibition of mycobacterial efflux pumps. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. In addition, the physicochemical parameters of the synthesised compounds were discussed.


Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Paladio/química , Quinonas/síntesis química , Quinonas/farmacología , Antibacterianos/química , Antiprotozoarios/química , Catálisis , Técnicas de Química Sintética , Mycobacterium smegmatis/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Quinonas/química , Trypanosoma brucei rhodesiense/efectos de los fármacos
3.
Hum Brain Mapp ; 41(7): 1904-1919, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31904899

RESUMEN

Odors can increase memory performance when presented as context during both encoding and retrieval phases. Since information from different sensory modalities is integrated into a unified conceptual knowledge, we hypothesize that the social information from body odors and faces would be integrated during encoding. The integration of such social information would enhance retrieval more so than when the encoding occurs in the context of common odors. To examine this hypothesis and to further explore the underlying neural correlates of this behavior, we have conducted a functional magnetic resonance imaging study in which participants performed an encoding-retrieval memory task for faces during the presentation of common odor, body odor or clean air. At the behavioral level, results show that participants were less biased and faster in recognizing faces when presented in concomitance with the body odor compared to the common odor. At the neural level, the encoding of faces in the body odor condition, compared to common odor and clean air conditions, showed greater activation in areas related to associative memory (dorsolateral prefrontal cortex), odor perception and multisensory integration (orbitofrontal cortex). These results suggest that face and body odor information were integrated and as a result, participants were faster in recognizing previously presented material.


Asunto(s)
Cara , Recuerdo Mental/fisiología , Odorantes , Reconocimiento en Psicología/fisiología , Adolescente , Adulto , Afecto , Aprendizaje por Asociación , Femenino , Cuerpo Humano , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria Episódica , Percepción Olfatoria/fisiología , Corteza Prefrontal/fisiología , Desempeño Psicomotor/fisiología , Adulto Joven
4.
Cancer Med ; 8(3): 1186-1196, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30793515

RESUMEN

Most BRAF-mutant melanoma patients experience a fulminate relapse after several months of treatment with BRAF/MEK inhibitors. To improve therapeutic efficacy, natural plant-derived compounds might be considered as potent additives. Here, we show that magnolol, a constituent of Magnolia officinalis, induced G1 arrest, apoptosis and cell death in BRAF- and NRAS-mutant melanoma cells at low concentration, with no effect in BRAF- and NRAS wild-type melanoma cells and human keratinocytes. This was confirmed in a 3D spheroid model. The apoptosis-inducing effect of magnolol was completely rescued by activating Akt suggesting a mechanism relying primarily on Akt signaling. Magnolol significantly downregulated the PI3K/Akt pathway which led to a global decrease of the active histone mark H3K4me3. Alongside, the repressive histone mark H3K9me3 was increased as a response to DNA damage. Magnolol-induced alterations of histone modifications are reversible upon activation of the Akt pathway. Magnolol-induced a synergistic effect in combination with either BRAF/MEK inhibitors dabrafenib/trametinib or docetaxel at a lower concentration than usually applied in melanoma patients. Combination of magnolol with targeted therapy or chemotherapy also led to analogous effects on histone marks, which was rescued by Akt pathway activation. Our study revealed a novel epigenetic mechanism of magnolol-induced cell death in melanoma. Magnolol might therefore be a clinically useful addition to BRAF/MEK inhibitors with enhanced efficacy delaying or preventing disease recurrence.


Asunto(s)
Compuestos de Bifenilo/farmacología , Epigénesis Genética/efectos de los fármacos , GTP Fosfohidrolasas/genética , Lignanos/farmacología , Proteínas de la Membrana/genética , Mutación , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Melanoma/genética , Melanoma/metabolismo , Modelos Biológicos , Transducción de Señal/efectos de los fármacos
5.
Molecules ; 23(11)2018 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-30405045

RESUMEN

The cytotoxic and antiprotozoal activities of the phytoquinoide, jacaranone, and related compounds have been an ongoing topic in recent drug discovery. Starting from the natural product-derived cyclohexadienone scaffold, a series of nitrogen-containing derivatives were synthesized and subsequently evaluated for their antiproliferative and antiprotozoal activity. Anticancer potency was analyzed using different types of cancer cell lines: MDA-MB-231 breast cancer, CCRF-CEM leukemia, HCT-116 colon cancer, U251 glioblastoma, and, in addition, non-tumorigenic MRC-5 lung fibroblasts. Antiproliferative activities at micromolar concentrations could be shown. Antiprotozoal activity was assessed against Plasmodium falciparum NF54 and Trypanosoma brucei rhodesiense STIB900. For all compounds, selectivity indices (SI) were calculated based on assessed cytotoxicity towards L6 cells. In addition, the structure-activity-relationships and physicochemical parameters of these compounds are discussed.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Ciclohexenos/síntesis química , Ciclohexenos/farmacología , Antiprotozoarios/química , Productos Biológicos/química , Productos Biológicos/farmacología , Línea Celular , Supervivencia Celular , Ciclohexenos/química , Humanos , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Fitoquímicos/química , Fitoquímicos/farmacología , Relación Estructura-Actividad
6.
Molecules ; 23(10)2018 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-30287800

RESUMEN

In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, Magnolia bark preparations that contain honokiol are thought to primarily interact with γ-aminobutyric acid A (GABAA) receptors. However, stress responses inherently involve the noradrenergic system, which has not been investigated in the pharmacological mechanism of honokiol. We present here interactions of honokiol and other synthesized biphenyl-type neolignans and diphenylmethane analogs with the norepinephrine transporter (NET), which is responsible for the synaptic clearance of norepinephrine and the target of many anxiolytics. Of the synthesized compounds, 16 are new chemical entities, which are fully characterized. The 52 compounds tested show mild, non-potent interactions with NET (IC50 > 100 µM). It is thus likely that the observed anxiolytic effects of, e.g., Magnolia preparations, are not due to direct interaction with the noradrenergic system.


Asunto(s)
Neuronas Adrenérgicas/efectos de los fármacos , Ansiolíticos/farmacología , Sistema Nervioso Central/efectos de los fármacos , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/efectos de los fármacos , Extractos Vegetales/farmacología , Ansiolíticos/química , Compuestos de Bencidrilo/química , Compuestos de Bencidrilo/farmacología , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Sistema Nervioso Central/metabolismo , Células HEK293 , Humanos , Lignanos/química , Lignanos/farmacología , Magnolia/química , Norepinefrina/metabolismo , Corteza de la Planta/química , Extractos Vegetales/química , Receptores de GABA-A/efectos de los fármacos
7.
Mol Ecol ; 26(11): 3062-3073, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28271576

RESUMEN

Recently, evidence has shown that variations in the cuticular hydrocarbons (CHCs) profile allow healthy honeybees to identify diseased nestmates, eliciting agonistic responses in the former. Here, we determined whether these 'immunologic cues' emitted by diseased nestmates were only detected by workers, who consequently took hygienic measures and excluded these individuals from the colony, or whether queens were also able to detect these cues and respond accordingly. Healthy honeybee queens were exposed to (i) healthy, (ii) Ringer-injected and (iii) lipopolysaccharide (LPS)-injected nestmates by allowing direct body contact. Quantitative differences in the CHC profiles of these three groups were measured using GC-MS. The transcript levels of the products of four genes that encode for antimicrobial peptides (AMPs), which are part of the queen's immune response, were measured in bees exposed to direct contact using qPCR. A significant increase in the transcript levels of these AMP genes over baseline levels in queens was observed when body contact was allowed between the queens and the Ringer- and LPS-injected nestmates. These results provide the first evidence that the detection of CHCs contributes to the initiation of an immune response in insects. In an additional experiment, CHCs were extracted from diseased workers and directly presented to queens, which also evoked a similar immune response. A potential mechanism that relied on volatile compounds could be ruled out by conducting a distance experiment. The study helps to expand our knowledge of chemical communication in insects and sheds light on a likely new mechanism of social immunity.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/inmunología , Abejas/efectos de los fármacos , Abejas/inmunología , Hidrocarburos/química , Animales , Péptidos Catiónicos Antimicrobianos/genética , Abejas/genética , Señales (Psicología) , Femenino , Cromatografía de Gases y Espectrometría de Masas , Regulación de la Expresión Génica
8.
Sci Rep ; 7: 40853, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28145462

RESUMEN

Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.


Asunto(s)
Abejas/efectos de los fármacos , Dimetoato/toxicidad , Guanidinas/toxicidad , Neonicotinoides/toxicidad , Nitrilos/toxicidad , Plaguicidas/toxicidad , Piretrinas/toxicidad , Tiazoles/toxicidad , Animales , Abejas/microbiología , Supervivencia Celular , Larva/efectos de los fármacos , Larva/microbiología , Dosificación Letal Mediana , Paenibacillus larvae/patogenicidad
9.
Sci Rep ; 6: 30699, 2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27480379

RESUMEN

Honeybee (Apis mellifera) imagines are resistant to the Gram-positive bacterium Paenibacillus larvae (P. larvae), causative agent of American foulbrood (AFB), whereas honeybee larvae show susceptibility against this pathogen only during the first 48 h of their life. It is known that midgut homogenate of adult honeybees as well as a homogenate of aged larvae exhibit strong anti-P. larvae activity. A bioactivity-guided LC-HRMS analysis of midgut homogenate resulted in the identification of 1-oleoyl-sn-glycero-3-phosphocholine (LPC) pointing to a yet unknown immune defence in adult honeybees against P. larvae. Antimicrobial activity of LPC was also demonstrated against Melissococcus plutonius, causative agent of European Foulbrood. To demonstrate an AFB-preventive effect of LPC in larvae, artificially reared larvae were supplemented with LPC to evaluate its toxicity and to assess whether, after infection with P. larvae spores, LPC supplementation prevents AFB infection. 10 µg LPC per larva applied for 3 d significantly lowered mortality due to AFB in comparison to controls. A potential delivery route of LPC to the larvae in a colony via nurse bees was assessed through a tracking experiment using fluorescent-labelled LPC. This yet undescribed and non-proteinous defense of honeybees against P. larvae may offer new perspectives for a treatment of AFB without the utilization of classic antibiotics.


Asunto(s)
Antiinfecciosos/metabolismo , Abejas/inmunología , Abejas/microbiología , Factores Inmunológicos/metabolismo , Lisofosfatidilcolinas/metabolismo , Paenibacillus larvae/inmunología , Animales , Antiinfecciosos/aislamiento & purificación , Cromatografía Liquida , Enterococcaceae/efectos de los fármacos , Factores Inmunológicos/aislamiento & purificación , Larva/microbiología , Larva/fisiología , Lisofosfatidilcolinas/aislamiento & purificación , Espectrometría de Masas , Paenibacillus larvae/efectos de los fármacos , Paenibacillus larvae/crecimiento & desarrollo
10.
Front Plant Sci ; 7: 961, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27458464

RESUMEN

A new simple phloroglucinol derivative characterized as 1-(6-hydroxy-2,4-dimethoxyphenyl)-2-methyl-1-propanone (1) was isolated from Hypericum cistifolium (Hypericaceae) as a major constituent of the non-polar plant extract. Minor amounts of this new compound, in addition to two known structurally related phloroglucinol derivatives (2 and 3), and two new terpenoid derivatives characterized, respectively, as 2-benzoyl-3,3-dimethyl-4R,6S-bis-(3-methylbut-2-enyl)-cyclohexanone (4a) and 2-benzoyl-3,3-dimethyl-4S,6R-bis-(3-methylbut-2-enyl)-cyclohexanone (4b), were isolated from a related species, H. galioides Lam. The chemical structures were established using 2D-NMR spectroscopy and mass spectrometry. These compounds were evaluated in vitro for antimicrobial activity against a panel of pathogenic microorganisms and anti-inflammatory activity through inhibition of COX-1, COX-2, and 5-LOX catalyzed LTB4 formation.

11.
Apidologie ; 46(2): 238-249, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26412907

RESUMEN

Immune responses of invertebrates imply more than developing a merely unspecific response to an infection. Great interest has been raised to unveil whether this investment into immunity also involves fitness costs associated to the individual or the group. Focusing on the immune responses of honeybees, we use the well-studied insect bumblebee for comparison. Bumblebees are capable of producing specific immune responses to infections whereas this has not been assessed for honeybees so far. We investigated whether a prior bacterial encounter provides protection against a later exposure to the same or a different bacterium in honeybees. Additionally, we studied whether the foraging activities of honeybees and bumblebees are affected upon immune stimulation by assessing the flight performance. Finally, the acceptance behavior of nestmates toward immune-challenged honeybees was determined. Results show that despite stimulating the immune system of honeybees, no protective effects to infections were found. Further, honeybees were not affected by an immune challenge in their flight performance whereas bumblebees showed significant flight impairment. Immune-challenged honeybees showed lower survival rates than naive individuals when introduced into a regular colony. Here, we reveal different immune response-cost scenarios in honeybees and bumblebees for the first time.

12.
Bioorg Med Chem ; 23(20): 6757-62, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26410663

RESUMEN

In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignan honokiol together with its isomer magnolol are the main constituents of Magnolia bark extracts. We have previously identified a nitrogen-containing honokiol derivative (3-acetylamino-4'-O-methylhonokiol, AMH) as a high efficient modulator of GABAA receptors. Here we further elucidate the structure-activity relation of a series of nitrogenated biphenyl-neolignan derivatives by analysing allosteric modulation and agonistic effects on α1ß2γ2S GABAA receptors. The strongest IGABA enhancement was induced by compound 5 (3-acetamido-4'-ethoxy-3',5-dipropylbiphenyl-2-ol, Emax: 123.4±9.4% of IGABA-max) and 6 (5'-amino-2-ethoxy-3',5-dipropylbiphenyl-4'-ol, Emax: 117.7±13.5% of IGABA-max). Compound 5 displayed, however, a significantly higher potency (EC50=1.8±1.1 µM) than compound 6 (EC50=20.4±4.3 µM). Honokiol, AMH and four of the derivatives induced significant inward currents in the absence of GABA. Strong partial agonists were honokiol (inducing 78±6% of IGABA-max), AMH (63±6%), 5'-amino-2-O-methylhonokiol (1) (59±1%) and 2-methoxy-5'-nitro-3',5-dipropylbiphenyl-4'-ol (3) (52±1%). 3-N-Acetylamino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (5) and 3-amino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (7) were less efficacious but even more potent (5: EC50=6.9±1.0 µM; 7: EC50=33.2±5.1 µM) than the full agonist GABA.


Asunto(s)
Regulación Alostérica/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Agonismo Parcial de Drogas , Agonistas de Receptores de GABA-A/farmacología , Lignanos/farmacología , Nitrógeno/química , Receptores de GABA-A/metabolismo , Animales , Compuestos de Bifenilo/síntesis química , Compuestos de Bifenilo/química , Relación Dosis-Respuesta a Droga , Femenino , Agonistas de Receptores de GABA-A/síntesis química , Agonistas de Receptores de GABA-A/química , Lignanos/síntesis química , Lignanos/química , Magnolia/química , Estructura Molecular , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Relación Estructura-Actividad , Xenopus laevis
13.
Nat Prod Commun ; 10(6): 887-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26197509

RESUMEN

During an investigation of the Indian heterosporous fern Selaginella chrysocaulos, two novel C28 spirostene monosides, chrysocauloside A and B were identified. Chrysocauloside A (1ß,3ß-dihydroxy-20S,22R-spirost-5-ene-1-yl ß-D-glucopyranoside) and chrysocauloside B (1ß,3ß-dihydroxy-20S,22R-spirost-5-ene-1-yl ß-D-galactopyranoside) are O-glycosylated at C-1 and each bear a methyl group at C-24 and C-25. Spectroscopic (NMR) and MS data for the new compounds are given and the taxonomic significance of the occurrence of spirostenes in the group of Lycophyta is discussed.


Asunto(s)
Glicósidos/química , Extractos Vegetales/química , Selaginellaceae/química , Espirostanos/química , Espectroscopía de Resonancia Magnética
14.
J Neuroinflammation ; 12: 89, 2015 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-25962384

RESUMEN

BACKGROUND AND PURPOSE: 4'-O-methylhonokiol (MH) is a natural product showing anti-inflammatory, anti-osteoclastogenic, and neuroprotective effects. MH was reported to modulate cannabinoid CB2 receptors as an inverse agonist for cAMP production and an agonist for intracellular [Ca2+]. It was recently shown that MH inhibits cAMP formation via CB2 receptors. In this study, the exact modulation of MH on CB2 receptor activity was elucidated and its endocannabinoid substrate-specific inhibition (SSI) of cyclooxygenase-2 (COX-2) and CNS bioavailability are described for the first time. METHODS: CB2 receptor modulation ([35S]GTPγS, cAMP, and ß-arrestin) by MH was measured in hCB2-transfected CHO-K1 cells and native conditions (HL60 cells and mouse spleen). The COX-2 SSI was investigated in RAW264.7 cells and in Swiss albino mice by targeted metabolomics using LC-MS/MS. RESULTS: MH is a CB2 receptor agonist and a potent COX-2 SSI. It induced partial agonism in both the [35S]GTPγS binding and ß-arrestin recruitment assays while being a full agonist in the cAMP pathway. MH selectively inhibited PGE2 glycerol ester formation (over PGE2) in RAW264.7 cells and significantly increased the levels of 2-AG in mouse brain in a dose-dependent manner (3 to 20 mg kg(-1)) without affecting other metabolites. After 7 h from intraperitoneal (i.p.) injection, MH was quantified in significant amounts in the brain (corresponding to 200 to 300 nM). CONCLUSIONS: LC-MS/MS quantification shows that MH is bioavailable to the brain and under condition of inflammation exerts significant indirect effects on 2-AG levels. The biphenyl scaffold might serve as valuable source of dual CB2 receptor modulators and COX-2 SSIs as demonstrated by additional MH analogs that show similar effects. The combination of CB2 agonism and COX-2 SSI offers a yet unexplored polypharmacology with expected synergistic effects in neuroinflammatory diseases, thus providing a rationale for the diverse neuroprotective effects reported for MH in animal models.


Asunto(s)
Antiinflamatorios/farmacología , Ácidos Araquidónicos/metabolismo , Compuestos de Bifenilo/farmacología , Encéfalo/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Endocannabinoides/metabolismo , Glicéridos/metabolismo , Lignanos/farmacología , Animales , Ácidos Araquidónicos/farmacocinética , Arrestinas/metabolismo , Encéfalo/metabolismo , Células CHO , Línea Celular Transformada , Cricetulus , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Endocannabinoides/farmacocinética , Femenino , Glicéridos/farmacocinética , Guanosina 5'-O-(3-Tiotrifosfato)/farmacocinética , Macrófagos , Ratones , Elastómeros de Silicona/farmacocinética , Isótopos de Azufre/farmacocinética , Tritio/farmacocinética , beta-Arrestinas
15.
Biochim Biophys Acta ; 1840(10): 3017-21, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24973566

RESUMEN

BACKGROUND: Magnolia bark preparations from Magnolia officinalis of Asian medicinal systems are known for their muscle relaxant effect and anticonvulsant activity. These CNS related effects are ascribed to the presence of the biphenyl-type neolignans honokiol and magnolol that exert a potentiating effect on GABAA receptors. 4-O-methylhonokiol isolated from seeds of the North-American M. grandiflora was compared to honokiol for its activity to potentiate GABAA receptors and its GABAA receptor subtype-specificity was established. METHODS: Different recombinant GABAA receptors were functionally expressed in Xenopus oocytes and electrophysiological techniques were used determine to their modulation by 4-O-methylhonokiol. RESULTS: 3µM 4-O-methylhonokiol is shown here to potentiate responses of the α1ß2γ2 GABAA receptor about 20-fold stronger than the same concentration of honokiol. In the present study potentiation by 4-O-methylhonokiol is also detailed for 12 GABAA receptor subtypes to assess GABAA receptor subunits that are responsible for the potentiating effect. CONCLUSION: The much higher potentiation of GABAA receptors at identical concentrations of 4-O-methylhonokiol as compared to honokiol parallels previous observations made in other systems of potentiated pharmacological activity of 4-O-methylhonokiol over honokiol. GENERAL SIGNIFICANCE: The results point to the use of 4-O-methylhonokiol as a lead for GABAA receptor potentiation and corroborate the use of M. grandiflora seeds against convulsions in Mexican folk medicine.


Asunto(s)
Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/farmacocinética , Agonistas de Receptores de GABA-A/farmacología , Fármacos Gastrointestinales/farmacología , Lignanos/farmacología , Lignanos/farmacocinética , Potenciales de la Membrana/efectos de los fármacos , Receptores de GABA-A/metabolismo , Animales , Compuestos de Bifenilo/química , Agonistas de Receptores de GABA-A/química , Fármacos Gastrointestinales/química , Humanos , Lignanos/química , Magnolia/química , Corteza de la Planta/química , Receptores de GABA-A/genética , Xenopus laevis
16.
Proc Biol Sci ; 281(1785): 20140454, 2014 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-24789904

RESUMEN

Maternal immune experience acquired during pathogen exposure and passed on to progeny to enhance resistance to infection is called trans-generational immune priming (TgIP). In eusocial insects like honeybees, TgIP would result in a significant improvement of health at individual and colony level. Demonstrated in invertebrates other than honeybees, TgIP has not yet been fully elucidated in terms of intensity and molecular mechanisms underlying this response. Here, we immune-stimulated honeybee queens with Paenibacillus larvae (Pl), a spore-forming bacterium causing American Foulbrood, the most deadly bee brood disease worldwide. Subsequently, offspring of stimulated queens were exposed to spores of Pl and mortality rates were measured to evaluate maternal transfer of immunity. Our data substantiate the existence of TgIP effects in honeybees by direct evaluation of offspring resistance to bacterial infection. A further aspect of this study was to investigate a potential correlation between immune priming responses and prohaemocytes-haemocyte differentiation processes in larvae. The results point out that a priming effect triggers differentiation of prohaemocytes to haemocytes. However, the mechanisms underlying TgIP responses are still elusive and require future investigation.


Asunto(s)
Abejas/genética , Abejas/inmunología , Epigénesis Genética , Inmunidad Innata , Paenibacillus/fisiología , Animales , Abejas/crecimiento & desarrollo , Abejas/microbiología , Femenino , Larva/genética , Larva/inmunología , Larva/microbiología , Longevidad , Estaciones del Año
17.
Chem Biodivers ; 11(5): 695-708, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24827680

RESUMEN

The in vitro inhibitory potential of 50 extracts from various species of the flowering plant genus Hypericum was investigated using the Kirby-Bauer disk diffusion susceptibility test against Paenibacillus larvae, a spore-forming, Gram-positive bacterial pathogen that causes American foulbrood (AFB), a lethal disease affecting honeybee brood worldwide. Of the tested extracts, 14 were identified as highly active against P. larvae as compared to the activity of the positive control, indicating the presence of highly potent antibacterial compounds in the extracts. Examination of these extracts using TLC and HPLC/MS analyses revealed the presence of acylphloroglucinol and filicinic-acid derivatives. Six pure compounds isolated from these extracts, viz., hyperforin (1), uliginosin B (2), uliginosin A (3), 7-epiclusianone (4), albaspidin AA (5), and drummondin E (6), displayed strong antibacterial activity against the vegetative form of P. larvae (MIC ranging from 0.168-220 µM). Incubation of P. larvae spores with the lipophilic extract of Hypericum perforatum and its main acylphloroglucinol constituent 1 led to the observation of significantly fewer colony forming units as compared to the negative control, indicating that the acylphloroglucinol scaffold represents an interesting lead structure for the development of new AFB control agents.


Asunto(s)
Antibacterianos/farmacología , Abejas/microbiología , Infecciones por Bacterias Grampositivas/veterinaria , Hypericum/química , Paenibacillus/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antibacterianos/química , Infecciones por Bacterias Grampositivas/microbiología , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Paenibacillus/crecimiento & desarrollo , Extractos Vegetales/química
18.
Nat Prod Commun ; 9(1): 57-60, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24660463

RESUMEN

Many names of plant secondary compounds that have been isolated and identified in the course of phytochemical investigations are based either on the vernacular or Latin names of the source plants, are constructed according to rules of chemical nomenclature, or consist of in-between forms. Trivial names, based on the specific epithets of biological organisms, occasionally create confusion because such epithets are used in numerous combinations and, therefore, could potentially be used when naming chemical entities from radically different sources. Such an example of ambiguous naming is represented with the case of corymbosin, a name that was assigned to two chemically distinct compounds that were isolated and reported simultaneously in 1967 from two different spermatophyte taxa: a terpene glucoside from Turbina corymbosa and a flavone from Webera corymbosa. The flavone is more widespread and has been reported so far from 15 taxa, whereas the glucoside has thus far only been isolated from the original source species. Furthermore, glycosides named corymbosins K1-K4 were isolated in 2006 from Knoxia corymbosa. This article emphasizes the need to adhere to strict principles when naming secondary constituents and suggests that a practice should be applied that is similar to the application of the priority rules used in botanical nomenclature for homonyms. The use of the trivial name, corymbosin, should be applied only to the more widespread tricetin-7,3',4',5'-tetramethyl ether by rules of conservation.


Asunto(s)
Productos Biológicos , Glicósidos , Terminología como Asunto , Terpenos , Convolvulaceae/química , Rubiaceae/química
19.
Molecules ; 19(1): 1223-37, 2014 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-24448063

RESUMEN

Biphenyl neolignans such as honokiol and magnolol, which are the major active constituents of the Asian medicinal plant Magnolia officinalis, are known to exert a multitude of pharmacological and biological activities. Among these, cytotoxic and tumor growth inhibitory activity against various tumour cell lines are well-documented. To further elucidate the cytotoxic effects of honokiol derivatives, derivatizations were performed using tetrahydrohonokiol as a scaffold. The derivatizations comprised the introduction of functional groups, e.g., nitro and amino groups, as well as alkylation. This way, 18 derivatives, of which 13 were previously undescribed compounds, were evaluated against CCRF-CEM leukemia cells, U251 glioblastoma and HCT-116 colon cancer cells. The results revealed no significant cytotoxic effects in any of the three tested cell lines at a test concentration of 10 µM.


Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Compuestos de Bifenilo/síntesis química , Lignanos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Compuestos de Bifenilo/farmacología , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon , Ensayos de Selección de Medicamentos Antitumorales , Glioblastoma , Células HCT116 , Humanos , Concentración 50 Inhibidora , Leucemia , Lignanos/farmacología , Metilación , Microondas
20.
Chem Biodivers ; 10(9): 1613-22, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24078595

RESUMEN

The gum resin exuding from the leaf buds of Gardenia gummifera was investigated. Eight new cycloartane triterpenes, 1-6, 8, and 10, together with two known triterpenes, 25-hydroxycycloart-23-en-3-one (7) and cycloartenone (9), were isolated and identified by extensive NMR spectroscopy. For cycloartenone (9), full NMR assignments are given as these data were not available in the literature. Eight compounds possess a C(3)=O group, two are 3,4-secocycloartanes bearing a free C(3)OOH group; in one of the cycloartanes, gummiferartane-9 (10), ring A occurs as a seven-membered lactone.


Asunto(s)
Gardenia/química , Triterpenos/química , Gardenia/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Triterpenos/aislamiento & purificación
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