Effects of Linalool on Glutamate Release and Uptake in Mouse Cortical Synaptosomes

Linalool, a monoterpene compound prevalent in essential oil of plant species traditionally used as sedatives, has been characterized as anticonvulsant in several experimental models. Linalool inhibits the binding of [³H]glutamate and [³H]dizocilpine to brain cortical membranes, indicating a participation of the glutamatergic transmission its mechanism of action. In this study, we investigated the effects of linalool on [³H]glutamate release (basal and potassium-stimulated) and [³H]glutamate uptake in mice cortical synaptosomes. Linalool significantly reduced potassium-stimulated glutamate release as well as glutamate uptake, not interfering with basal glutamate release. The data indicates that linalool may interfere with several relevant elements of the glutamatergic transmission, including detriment of the K⁺-stimulated glutamate release.     

Effect of the Leaf Essential Oil from Cinnamosma madagascariensis Danguy on Pentylenetetrazol‐induced Seizure in Rats

In the Malagasy traditional practices, the smoke from burning leaves of Cinnamosma madagascariensis Danguy is inhaled to treat brain disorders such as dementia, epilepsy, and headache. In the present work, we have evaluated the in vivo anticonvulsant effects of the essential oil from leaves of C. madagascariensis (CMEO). CMEO was isolated by steam distillation. The anticonvulsant activity of CMEO (0.4 and 0.8 ml/kg bw) administered subcutaneously was evaluated on pentylenetetrazol (PTZ)‐induced seizures in Wistar rats; diazepam was used as positive control. Linalool, limonene, and myrcene were the major CMEO constituents. At the dose of 0.8 ml/kg, CMEO completely arrested the PTZ‐induced convulsions with moderate sedative effects. The traditional anticonvulsant use of C. madagascariensis was confirmed allowing us to candidate molecules from CMEO as potential drugs to treat convulsions associated with strong agitation.     

Inhaled linalool-induced sedation in mice

Linalool is a monoterpene often found as a major component of essential oils obtained from aromatic plant species, many of which are used in traditional medical systems as hypno-sedatives. Psychopharmacological evaluations of linalool (i.p. and i.c.v.) revealed marked sedative and anticonvulsant central effects in various mouse models. Considering this profile and alleged effects of inhaled lavender essential oil, the purpose of this study was to examine the sedative effects of inhaled linalool in mice. Mice were placed in an inhalation chamber during 60 min, in an atmosphere saturated with 1% or 3% linalool.Immediately after inhalation, animals were evaluated regarding locomotion, barbiturate-induced sleeping time, body temperature and motor coordination (rota-rod test). The 1% and 3% linalool increased (p<0.01) pentobarbital sleeping time and reduced (p<0.01) body temperature. The 3% linalool decreased (p<0.01) locomotion. Motor coordination was not affected. Hence, linalool inhaled for 1 h seems to induce sedation without significant impairment in motor abilities, a side effect shared by most psycholeptic drugs.     

Floral scents of hawkmoth-pollinated flowers in Japan

Similarity among the floral scents of hawkmoth-pollinated plants was investigated with headspace samplings. Six of seven plant species belonging to different families were found to be rich in isoprenoids, among which linalool was the most common compound. Linalool showed rhythmicity with a nocturnal increase inLonicera japonica. These findings suggest that linalool is a common attractant for nocturnal hawkmoths. However, the composition of other isoprenoids, benzenoids and fatty acid derivatives varied markedly among the plant species examined. There was a significant correlation between species composition of flower-visiting hawkmoths and specific floral scents, suggesting that attractiveness to each hawkmoth species is dependent upon floral scent.     

Anticonvulsant properties of linalool in glutamate-related seizure models.

In order to investigate the pharmacodynamic basis of the previously-established anticonvulsant properties of linalool, we examined the effects of this compound on behavioral and neurochemical aspects of glutamate expression in experimental seizure models. Specifically, linalool effects were investigated to determine its inhibition of (i) L-[3H]glutamate binding at CNS (central nervous system membranes), (ii) N-methyl-D-aspartate (NMDA)-induced convulsions, (iii) quinolinic acid (QUIN)-induced convulsions, and the behavioral and neurochemical correlates of PTZ-kindling. The data indicate that linalool modulates glutamate activation expression in vitro (competitive antagonism of L-[3H]glutamate binding) and in vivo (delayed NMDA convulsions and blockage of QUIN convulsions). Linalool partially inhibited and significantly delayed the behavioral expression of PTZ-kindling, but did not modify the PTZ-kindling-induced increase in L-[3H]glutamate binding.     

Novel spiro[indene-1,2′-quinazolin]-4′(3′H)-one derivatives as potent anticonvulsant agents: One-pot synthesis,in vivo biological evaluation,and molecular docking studies

A new series of spiro[indene-1,2′-quinazolin]-4′(3′H)-one derivatives 4a–m were synthesized via a one-pot method and evaluated for anticonvulsant activities using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. Obtained results demonstrated that these compounds have not anticonvulsant activity in PTZ test while are active in the MES test. Among the synthesized compounds, the best anticonvulsant activity was obtained with compound 4h . This compound also was not neurotoxic. Given that the title new compounds have the pharmacophore requirement for benzodiazepine (BZD) receptor agonist, the most potent compound was assayed in vivo and in silico as BZD receptor agonist. After treatment with flumazenil as a standard BZD receptor antagonist, anticonvulsant activity of compound 4h decreased. Therefore, the involvement of BZD receptors in anticonvulsant activity of this compound confirmed. Furthermore, docking study of compound 4h in the BZD-binding site of GABA_A receptor confirmed that this compound interacted with the important residues.     

Anticonvulsant mechanisms of piperine,a piperidine alkaloid

Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na⁺ and Ca²⁺ channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na⁺ channels. Together, our data suggest Na⁺ channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine.     

Study of the major essential oil compounds of Coriandrum sativum against Acinetobacter baumannii and the effect of linalool on adhesion,biofilms and quorum sensing

Acinetobacter baumannii is a pathogen that has the ability to adhere to surfaces in the hospital environment and to form biofilms which are increasingly resistant to antimicrobial agents. The aim of this work was to study the antimicrobial activity of the major oil compounds of Coriandrum sativum against A. baumannii. The effect of linalool on planktonic cells and biofilms of A. baumannii on different surfaces, as well as its effect on adhesion and quorum sensing was evaluated. From all the compounds evaluated, linalool was the compound with the best antibacterial activity, with minimum inhibitory concentration values between 2 and 8 μl ml^?1. Linalool also inhibited biofilm formation and dispersed established biofilms of A. baumannii, changed the adhesion of A. baumannii to surfaces and interfered with the quorum- sensing system. Thus, linalool could be a promising antimicrobial agent for controlling planktonic cells and biofilms of A. baumannii.     

Anti-convulsant Effect and Mechanism of Astragalus mongholicus Extract In Vitro and In Vivo: Protection Against Oxidative Damage and Mitochondrial Dysfunction

Astragalus mongholicus (AM) is a traditional medicinal herb used as a neuroprotective agent for its anxiolytic, antidepressant, antiamnestic, and antiaggresive effects. However, the mechanisms underlying its anti-convulsant properties are not well studied. In the present study, we examined the anticonvulsant effects on pentylenetetrazol (PTZ)-induced seizures in mice and the possible mechanisms of protection against oxidative damage and mitochondrial dysfunction in vitro. The behavioral studies showed that the root extract of AM had powerful anticonvulsant effects against seizures induced by PTZ and the biochemical studies showed that root extract of AM inhibited PTZ-induced increase in lipid peroxidation, protein oxidation and reactive oxygen species, and enhanced mitochondrial function. Electron spin resonance spectroscopy studies demonstrated that the extracts from the root and aerial parts of AM possess potent effects on scavenging hydroxyl and lipid free radicals. We found that AM extract significantly protected malondialdehyde-induced oxidative damage by ameliorating activities of the mitochondrial complexes I, II, malate dehydrogenase and mitochondrial membrane potential. These data suggest that the anti-convulsant effects of AM extract may be mediated by its protective actions against oxidative damage and amelioration of mitochondrial dysfunction.     

Synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-a](tetrazolo[5,1-a])phthalazine derivatives

With the aim of finding new anticonvulsant drugs, new 6-substituted-[1,2,4]triazolo[3,4-a] (tetrazolo[5,1-a]) phthalazine derivatives (1–34) have been designed and synthesized. All the compounds were evaluated for their anticonvulsant activities using the maximal electroshock test (MES). Most of the synthesized compounds exhibited potent anticonvulsant activities in the MES. The most promising compound 14 showed significant anticonvulsant activity in MES test with ED₅₀ value of 9.3 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drug Carbamazepine. And the potency of compound 14 against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide and 3-Mercaptopropionic acid in the chemical-induced seizure tests suggested that compound 14 displayed wide spectrum of activity in several models.     

Batatasin‐III and the allelopathic capacity of Empetrum nigrum

Batatasin‐III (3,3‐dihydroxy‐5‐methoxybibenzyl) is a phenolic compound associated with the allelopathic effect of the evergreen dwarf shrub Empetrum nigrum, and has been referred to as the causal factor for the species being successful in dominating extensive ecosystems. Yet, only a few plant species have been tested for their response to batatasin‐III, and little is known about whether environmental factors modify this allelopathic effect. In this study, we tested the inhibitory effect of purified batatasin‐III through bioassays on 24 vascular plant species and, for certain species, we tested if this effect depended on growth substrate (mineral vs organic substrate), pH, and fertilization. Moreover, we tested if batatasin‐III predicted the allelopathic effect of E. nigrum by analyzing the inhibitory effect of E. nigrum leaves and humus in relation to their batatasin‐III content. Our results confirmed batatasin‐III as a stable compound capable of inhibiting germination and/or mean root elongation in all of the tested species, but this effect was modified by growth substrate. Surprisingly, the measured batatasin‐III content of E. nigrum leaves (mean value 19.7 ± 10.8 (SE) mg g^?1) and humus (mean value of 1 ± 1.5 (SE) μg g^?1) did not predict the inhibitory effect on mean root elongation. Although batatasin‐III was found to be phytotoxic to all the tested species, we conclude that this substance alone should not be used as a proxy for the allelopathic effect of E. nigrum.     

Differential mediation of the anticonvulsant effects of carbamazepine and diazepam

Possible mechanisms of action of carbamazepine and diazepam on amygdala-kindled seizures were studied using compounds acting at the central and "peripheral-type" benzodiazepine binding sites. Ro-15-1788, a selective antagonist at the central benzodiazepine site, blocked the anticonvulsant effect of diazepam, but not of carbamazepine. In contrast, Ro5-4864, which acts at the "peripheral-type" benzodiazepine site, blocked the anticonvulsant effect of carbamazepine, but not of diazepam. The effect of Ro5-4864 was itself reversed by PK-11195, a compound that displaces Ro5-4864 binding in vitro and in vivo. These data indicate that the anticonvulsant effects of carbamazepine and diazepam on amygdala-kindled seizures are differentially mediated and suggest that the "peripheral-type" benzodiazepine binding site is functionally involved in the anticonvulsant effect of carbamazepine.     

Intra-specific variation in the inhibitory effects of Thymus vulgaris (Labiatae) monoterpenes on seed germination

The ecological role of plant secondary compounds has received a great deal of attention yet little is known regarding variation in the ecological significance of different compounds produced by a single species. This is particularly pertinent to species where variation in compound presence is under genetic control. In this study we have quantified variation in the inhibitory effects of the six dominant monoterpene oils produced by different genotypes (or chemotypes) of Thymus vulgaris on achene germination of an associated species (Brachypodium phoenicoides), and seeds of T. vulgaris itself, in controlled experimental conditions. The experiments involved the germination of seeds of the two species with crushed leaves or pure essences of the six chemotypes, i.e. four experimental trials. A significant inhibitory effect against B. phoenicoides was found for both crushed leaves and the range of concentrations of pure oils used in the trial. The two phenolic compounds had a greater effect than the non-phenolic leaves and pure oils. The significant differences between non-phenols and the controls declined faster over time for crushed leaves and low concentrations of the pure essences than did that between the phenolics and the controls. There was a significant inhibitory effect against the germination of T. vulgaris seeds for the crushed leaves and the pure oils, although the contrast between the non-phenols and the phenols was not significant. The effect of the different oils varied depending on the seed source of the thyme seeds used in the trial. This is suggested to be due to differences in the rates of outcrossing among the sampled populations. The effects of the oils on the associated species, B. phoenicoides, were not found to be greater than their effects on the germination of thyme seeds. The results are discussed in the context of a potential role for such inhibitory effects in relation to the onset of rainfall and suitable germination conditions.     

牡丹组植物的药用民族植物学研究与考证

牡丹干燥根皮自古以来就有入药的传统,尤其在中药和民族药中被广泛使用.为阐明牡丹组植物在古籍中的记载情况和民族药中的利用现状,该文对中国八部经典医学古籍、37部地方志和民族药传统知识进行整理,采用民族植物学编目方法,对牡丹组植物在古籍和民族药中的入药种类、地理分布、入药部位、炮制方法和功效等相关传统知识进行考证和分析研究...     

Floral volatiles fromClarkia breweri andC. concinna (Onagraceae): Recent evolution of floral scent and moth pollination

Clarkia breweri (Onagraceae) is the only species known in its genus to produce strong floral fragrance and to be pollinated by moths. We used gas chromatography-mass spectrometry (GC-MS) to identify 12 abundant compounds in the floral headspace from two inbred lines ofC. breweri. These volatiles are derived from two biochemical pathways, one producing acyclic monoterpenes and their oxides, the other leading from phenylalanine to benzoate and its derivatives. Linalool and linalool oxide (pyran form) were the most abundant monoterpenoids, while linalool oxide (furan form) was present at lower concentrations. Of the aromatic compounds detected, benzyl acetate was most abundant, whereas benzyl benzoate, eugenol, methyl salicylate, and vanillin were present as minor constituents in all floral samples. The two inbredC. breweri lines differed for the presence of the additional benzenoid compounds isoeugenol, methyleugenol, methylisoeugenol, and veratraldehyde. We also analyzed floral headspace fromC. concinna, the likely progenitor ofC. breweri, whose flowers are odorless to the human nose. Ten volatiles (mostly terpenoids) were detected at low concentrations, but only when headspace was collected from 20 or more flowers at a time. Trans--ocimene was the most abundant floral compound identified from this species. Our data are consistent with the hypothesized recent evolution of floral scent production and moth pollination inC. breweri.     

Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats acute seizure models

2,4(1H)-Diarylimidazoles have been previously shown to inhibit hNa(V)1.2 sodium (Na) channel currents. Since many of the clinically used anticonvulsants are known to inhibit Na channels as an important mechanism of their action, these compounds were tested in two acute rodent seizure models for anticonvulsant activity (MES and scMet) and for sedative and ataxic side effects. Compounds exhibiting antiepileptic activity were further tested to establish a dose response curve (ED(50)). The experimental data identified four compounds with anticonvulsant activity in the MES acute seizure rodent model (compound 10, ED(50)=61.7mg/kg; compound 13, ED(50)=46.8mg/kg, compound 17, ED(50)=129.5mg/kg and compound 20, ED(50)=136.7mg/kg). Protective indexes (PI=TD(50)/ED(50)) ranged from 2.1 (compound 10) to greater than 3.6 (compounds 13, 17 and 20). All four compounds were shown to inhibit hNa(V)1.2 in a dose dependant manner. Even if a correlation between sodium channel inhibition and anticonvulsant activity was unclear, these studies identify four Na channel antagonists with anticonvulsant activity, providing evidence that these derivatives could be potential drug candidates for development as safe, new and effective antiepileptic drugs (AEDs).     

两种Eupristina属小蜂对宿主榕果挥发物和合成信息素的行为反应

高榕,雌雄同株,与其共生的形态高度相似的传粉小蜂Eupristina altissima与非传粉小蜂Eupristina sp.均为果内产卵。利用Y型嗅觉仪生物测定法研究E.altissima和Eupristina sp.对不同发育期高榕榕果挥发物以及合成信息素混合物的行为反应差异。结果表明:E.altissima和Eupristina sp.对高榕雌花期榕果挥发物具极显著趋向行为,对高榕雄花期榕果挥发物具极显著驱避行为,表明E.altissima与Eupristina sp.雌蜂能够敏锐辨别高榕雌花期和雄花期榕果的挥发物,快速远离雄花期榕果,并实现对宿主雌花期榕果的定位。但是,E.altissima与Eupristina sp.对其它发育时期榕果挥发物的行为反应具有差异性,前者对雌前期榕果和传粉或产卵后榕果释放的挥发物存在显著的趋避反应,而后者无明显的行为偏向性,表明E.altissima能够识别雌前期榕果和传粉或产卵后榕果,可避免误入其中而无法繁殖后代,Eupristina sp.则不具备这种识别能力。E.altissima和Eupristina sp.小蜂对合成信息素的行为反应也高度相似,表现为芳樟醇、苯乙烯,以及苯乙烯和金合欢醇的交互作用对两种小蜂选择行为影响显著,组合A_1B_2C_2(0.5%Linalool+1%Benzyl ethylene+1%Farnesol)的混合信息素对两种小蜂具有极显著的驱避作用,而组合A_2B_1C_1(1%Linalool+0.5%Benzyl ethylene+0.5%Farnesol),A_2B_1C_2(1%Linalool+0.5%Benzyl ethylene+1%Farnesol),A2B2C1(1%Linalool+1%Benzyl ethylene+0.5%Farnesol)的混合信息素对其具有极显著的吸引作用,但两种小蜂对组合A_1B_1C_1(0.5%Linalool+0.5%Benzyl ethylene+0.5%Farnesol)的行为反应存在差异。两种小蜂对榕果挥发物和合成信息素的反应异同,可能与其触角结构的差异密切相关。研究结果为探究榕-蜂共生体系的化学信号传导机制提供科学依据。     

The effect of nordihydroguaiaretic acid on iodoacetate‐induced toxicity in cultured neurons

Nordihydroguaiaretic acid (NDGA) is present in high concentrations in the desert shrub Creosote bush, Larrea tridentate. This plant has been used in traditional medicine because of its beneficial effects related, at least in part, to its antioxidant properties. Taking into account some evidence about neuroprotective effects elicited by NDGA, we evaluated the effect of this compound on the neurotoxicity induced by iodoacetate (IAA), an inhibitor of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), on cerebellar granule neurons. In addition, as reactive oxygen species play an important role in IAA‐induced cytotoxicity, we also studied the enzymatic antioxidant system in IAA‐treated cells. We found that IAA caused a dose‐dependent decrease in cell viability of cultured neurons with an IC₅₀ of 18.4 µM and induced increased activity of catalase, glutathione peroxidase, and glutathione‐S‐transferase. Moreover, NDGA attenuated the toxicity induced by 18.4, 25, and 30 µM of IAA without abolishing the inhibitory effect of IAA on GAPDH activity. Furthermore, NDGA could prevent the inhibitory effect of IAA on aconitase activity, a marker of oxidative stress, suggesting that the protective effect of NDGA on IAA neurotoxicity was associated with the prevention of oxidative stress. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:137–142, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20278     

Bioactivity‐Guided Isolation of Anti‐Inflammatory Constituents of the Rare Mushroom Calvatia nipponica in LPS‐Stimulated RAW264.7 Macrophages

Calvatia species, generally known as puffball mushrooms, are used both as sources of food and as traditional medicine. Among the Calvatia genus, Calvatia nipponica (Agaricaceae) is one of the rarest species. Using bioassay‐guided fractionation based on anti‐inflammatory effects, five alkaloids ( 1 – 5 ), two phenolics ( 6 and 7 ), and a fatty acid methyl ester ( 8 ) were isolated from the fruiting bodies of C. nipponica. Compound 8 was identified from C. nipponica for the first time, and all isolates ( 1 – 8 ) were tested for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages. Compound 7 showed mild inhibition while compound 8 significantly inhibited NO production with an IC₅₀ value of 27.50 ± 0.08 μm . The mechanism of NO inhibition of compound 7 was simulated by molecular docking analysis against nitric oxide synthase (iNOS), which revealed the interactions of 7 with the key amino acid residue and the heme in the active site. With the most potent inhibition against LPS‐induced inflammation, compound 8 was further investigated with respect to its mechanism of action, and the activity was found to be mediated through the inhibition of iNOS and COX‐2 expression.     

Combination of newly developed high quality <Emphasis Type="Italic">Fuqu</Emphasis> with traditional <Emphasis Type="Italic">Daqu</Emphasis> for <Emphasis Type="Italic">Luzhou-flavor</Emphasis> liquor brewing

Application of a compound starter composed of traditional Daqu, high quality Fuqu developed previously in our lab, and alcohol-producing and aroma-producing yeasts in the brewing of Luzhou-flavor liquor was investigated. Compared with traditional Daqu, the compound starter demonstrated apparently higher starch utilization and alcohol productivity both in flasks and in pits. Flavor ingredient analyses showed that the flavor ingredient compositions of liquors produced with the compound starter were similar to those obtained with the traditional process. With appropriate after treatments, the compound starter may be applied in distilleries for elevating the productivity of traditional liquor or producing high quality new-style distilled liquor. As starch utilization can be increased significantly, using this compound starter in liquor brewing is especially meaningful for lessening environmental pollution. These findings may also be helpful for further understanding the mechanisms of Chinese liquor brewing.