Article

Benzodiazepine-like compounds and GABA in flower heads of Matricaria chamomilla

Abstract

The presence of benzodiazepine-like substances in dried flower heads of Matricaria chamomilla was investigated. After extraction and HPLC purification we tested several fractions for their ability to displace in vitro [3H]Flunitrazepam bound to its receptors in rat cerebellar membranes, [3H]Muscimol linked to GABA receptors in rat cortical membrane preparations and [3H]RO 5-4864 specifically bound to the so-called 'peripheral' benzodiazepine binding sites present in membrane preparations from rat adrenal glands. Few of these fractions displaced both central and peripheral benzodiazepine binding sites and GABA receptors, too. As regards this last activity, by further HPLC analysis we identified GABA as the main agent responsible for the displacing effect. Some of the extracted fractions, not containing GABA, were intracerebronventricularly injected in rats and produced a statistically significant reduction of the locomotor activity. Ongoing experiment by mass spectrometric technique will help in the identification of the benzodiazepine-like compounds present in the extract of Matricaria chamomilla responsible for its sedative effect.
... As a sedative, chamomile tea is often used to reduce anxiety and treat sleep problems. These sedative effects are related to the binding of the flavonoid apigenin in chamomile to benzodiazepine receptors in the brain (Avallone et al., 1996). ...
Article
One of the management problems in aquaculture is the negative impact of operational factors on fish health and welfare. In order not to adversely affect fish welfare, various anesthetic agents are applied in routine aquaculture operations. Alternative extracts are used as anesthetic agents in addition to traditional agents, which will minimally affect fish health. In this study, the hematological, biochemical, oxidative and histopathological effects of chamomile oil on rainbow trout (Oncorhynchus mykiss) were evaluated as an herbal anesthetic. The focus is on the anesthetic effect of chamomile oil at concentrations of 100 μl/L, 150 μl/L and 200 μl/L and its physiological findings on fish after anesthesia. Recovery time was significantly longer for 200 μl/L, while induction time was longer for 100 μl/L. Hematological parameters generally showed an increasing trend until the eighth hour and decreased to normal levels again at the sixteenth hour. The gill histology of the fish treated with 100 μl/L chamomile oil contains low degradation similar to the control group. However, hyperplasia and epithelial lifting were observed especially in the 150 μl/L group, and additional hypertrophy and necrosis symptoms were observed in the 200 μl/L group. As antioxidant activity, catalase and glutathione peroxidase showed higher results in the 100 μl/L group compared to the other groups and similar to the control. Although cortisol decreased for all groups at the first moment after anesthesia, it increased to normal levels in the 150 and 200 μl/L groups at the fourth hour. In the 100 μl/L group, the cortisol level could not reach the control level even at the eighth hour. As a result, even though chamomile oil at a concentration of 100 μl/L causes a relatively high induction time, it has a lower adverse effect on fish health than other groups.
... However, in contrast with previous reports, the study presented by Avallone, Zanoli, Puia, Kleinschnitz, Schreier and showed that the sedative effect of apigenin is not mediated by BZD receptors since the affinity between them is very low. In addition, electrophysiological studies performed on cultured cerebellar granule cells showed that apigenin reduced GABA-activated Cl − currents, suggesting that the sedative effect of M. chamomilla extracts can be ascribed to other compounds with BZD-like activity [134,216]. Similar finding were presented by Zanoli, Avallone and Baraldi (2000), who investigated the sedative and anxiolytic activities of apigenin contained in chamomile [132]. However, in this study apigenin failed to exert anxiolytic activity, it reduced locomotor behavior when injected in rats with a minimal effective dose of 25 mg/kg. ...
Article
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Anxiety and insomnia are among the most common mental health disorders and are a major cause of disability around the world. Traditional herbal medicines are receiving significant attention in global health debates. Several Italian regions maintain rural traditions and are among the most extensively studied areas of Europe regarding medicinal plant uses. The present overview aims to highlight the use of wild and cultivated plants, specifically as sedatives and for insomnia treatment in Italy, and to collect, analyze, and summarize the available literature about their pharmacological activity as well as clinical and pre-clinical studies concerning the most cited plants. In total, 106 wild taxa are used in Italy for sedative purposes. The plant species belong to 76 genera and 32 families, of which the most cited are Asteraceae (24.2%) and Lamiaceae (21.1%). Leaves (29%) and flowers (27%) are the plant parts mostly used as infusion (70%) and decoction (25%). Out of 106 taxa documented, only the most cited are analyzed in this overview (A. arvensis L., C. nepeta L., C. monogyna Jacq., H. lupulus L., L. nobilis L., L. angustifolia Mill., M. sylvestris L., M. chamomilla L., M. officinalis L., O. basilicum L., P. rhoeas L., P. somniferum L., R. officinalis L., T. platyphyllus Scop., and V. officinalis L.). Among the fifteen species selected, only seven have been studied for their pharmacological activity as hypnotic-sedatives. Future pre-clinical and clinical studies are needed to better clarify the mechanism of action of bioactive compounds and confirm the potential of these alternative therapies.
... Además, se han encontrado propiedades neuroprotectoras, especialmente mejorando los procesos mnésicos (48,49,50). La actividad como tranquilizante menor de la Manzanilla fue calificada como excelente o buena en el 68% de los pacientes, además de probada su actividad GABAérgica (51,52). La ansiedad de tipo somática, específicamente aquella que afecta al sistema gastrointestinal, se ve disminuida con el uso de Menta. ...
Article
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El uso de las benzodiazepinas (BZD) ha ido incrementándose en los últimos años. Son los fármacos más utilizados en el ámbito médico para el tratamiento de los trastornos del ritmo sueño-vigilia y en los trastornos de ansiedad. Poseen serios efectos adversos en tanto alteran la arquitectura del sueño, provocan tolerancia y dependencia, incoordinación motora y debilidad muscular, y a mediano y largo plazo altera funciones cognitivas tales como la memoria y la atención. Se analizan las posibles alternativas a éstas medicaciones que pueden dar una respuesta similar o mejorada sin los efectos adversos mencionados. Entre ellas encontramos a las medicinas naturales o fitoterapia. Se plantea como objetivo realizar una revisión bibliográfica que permita determinar los actuales usos de plantas medicinales en los cuadros de insomnio y en los trastornos de ansiedad. Se encontró que ciertas plantas medicinales son una alternativa terapéutica segura y eficaz para suplantar a las BZD en los trastornos del sueño y la ansiedad, cuando su uso es responsable y respaldado con evidencia científica.
... The Calming effects of chamomile essential oil maybe due to its principal components such as flavonoid, apigenin that binds to benzodiazepine receptors in the brain. Studies in pre-clinical models have shown anticonvulsant and CNS depressant effect (Avallone et al., 1996). Another study indicated that inhalation of the vapor of chamomile oil reduced a stress-induced increase in plasma adrenocorticotropic hormone (ACTH) levels (Yamada et al., 1996). ...
... El centro-norte de Buenos Aires se ha transformado en la principal zona de producción de manzanilla común (Matricaria chamomilla L.), una especie medicinal perteneciente a la familia Asteraceae de gran importancia por sus propiedades antiinflamatorias, antiespasmódicas, antibacterianas, antifúngicas (Mc-Kay y Blumberg, 2006), sedantes (Avallone et al., 1996) y antipiréticas (Krishna et al., 2012) entre otras. La incorporación de su cultivo en las rotaciones agrícolas de la Pampa húmeda generó la necesidad de cambios en el paquete agrotecnológico tradicional de manzanilla para permitir su inserción, lo que demandó la evaluación de diferentes aspectos agronómicos de la producción para tomar decisiones acerca del manejo del cultivo. ...
Technical Report
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En el siguiente reporte se exponen los resultados de la caracterizaciónn de cultivares de Manzanilla (Matricaria recutita o M. chamomilla) utilizados para producción extensiva en el centro-norte de la provincia de Buenos Aires.
... The results were consistent after we excluded one study that reported sleep quality outcome using PSQS scale (Chang & Chen, 2016). These effects may be as a result of the presence of flavonoid apigenin, which can directly bind to the brain, specifically the benzodiazepine receptors and result in these tranquilizing effects (R Avallone, Zanoli, Corsi, Cannazza, & Baraldi, 1996b;Srivastava et al., 2010). ...
Article
This systematic review and meta‐analysis aimed to study the efficacy and safety of chamomile for the treatment of state anxiety, generalized anxiety disorders (GADs), sleep quality, and insomnia in human. Eleven databases including PubMed, Science Direct, Cochrane Central, and Scopus were searched to retrieve relevant randomized control trials (RCTs), and 12 RCTs were included. Random effect meta‐analysis was performed by meta package of R statistical software version 3.4.3 and RevMan version 5.3. Our meta‐analysis of three RCTs did not show any difference in case of anxiety (standardized mean difference = −0.15, 95% CI [−0.46, 0.16], P = 0.4214). Moreover, there is only one RCT that evaluated the effect of chamomile on insomnia and it found no significant change in insomnia severity index (P > 0.05). By using HAM‐A scale, there was a significant improvement in GAD after 2 and 4 weeks of treatment (mean difference = −1.43, 95% CI [−2.47, −0.39], P = 0.007), (MD = −1.79, 95% CI [−3.14, −0.43], P = 0.0097), respectively. Noteworthy, our meta‐analysis showed a significant improvement in sleep quality after chamomile administration (standardized mean difference = −0.73, 95% CI [−1.23, −0.23], P < 0.005). Mild adverse events were only reported by three RCTs. Chamomile appears to be efficacious and safe for sleep quality and GAD. Little evidence is there to show its effect on anxiety and insomnia. Larger RCTs are needed to ascertain these findings.
... In the flower head of German chamomile there some bezodizepine like compounds are present, the sedative effect of German chamomile may be due to this compound 96,97 . The main chemical extract of this plant is Apigenin, which is cemically a flavonoid, this may bind to the benzodiazepine receptor in brain and thus producing sedative 98 . ...
Article
About one third of the world's population is affected by insomnia. Insomnia may be due to various reasons such as physiological, psychological, genetic etc. It affects the health as well as the professional and social life of the affected person. There are many treatment of insomnia, among them pharmacological treatment with benzodiazepine and related tricyclic antihistamines are quite popular. But due to several side effects of these drugs, non-pharmacological and herbal treatments of insomnia are becoming popular day by day. Many types of herbs are reported to have sedative properties in the ethnobotanical evidences around the world. Among them Valerian, Kava Kava, Ginseng, St. John's Wort are most common. Besides these plants there are several other plants which are also used in insomnia treatment. Though there are lot of work to be done on herbal treatment of insomnia due to scarcity of reliable data and lack of proper preclinical (using animal models) and/or clinical evidences.
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Throughout history, Matricaria chamomilla L. (M. chamomilla) has had countless applications in traditional medicine. Its extracts, oils and teas have been used for treating diverse ailments, including wounds, rheumatic pain, menstrual cramps, eye and ear infections, gastrointestinal disorders, and respiratory illnesses. These traditional applications guided modern research into its medicinal effects through increasingly detailed in vitro and in vivo studies and clinical trials. A plethora of preclinical studies have assessed the antimicrobial, antioxidant, anti-inflammatory, antiulcer, hypoglycemic, hypolipidemic, cardioprotective, hepatoprotective, neuroprotective, nephroprotective, anti-diarrheal, antispasmodic, wound healing, and anticancer properties of M. chamomilla. These pharmacological properties of M. chamomilla are attributed to its rich reservoir of phytochemical constituents, primarily its flavonoids, such as luteolin, apigenin, and quercetin, as well as its sesquiterpenes, mainly chamazulene and (−)-α-bisabolol. Remarkably, preclinical studies have paved the way for progress towards controlled human clinical trials. M. chamomilla has been clinically evaluated for its effects against anxiety, sleep-deficiency, depression, as well as oral, women-related, inflammatory, metabolic, dermatological, gastrointestinal disorders, and children-related conditions. In this sense, this review elucidates and discusses the recent findings for M. chamomilla development as a therapeutic agent that possesses health-promoting, disease-preventing and even treatment properties. The traditional medicinal uses and evidence-based research studies, which were performed in cell culture, animal models and human subjects to assess the pharmacological activities of M. chamomilla, are extensively highlighted. Particular emphasis is given to some phytochemical constituents of M. chamomilla, which demonstrate great potential in treating various conditions.
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Sedatives manage anxiety and nervous tension as they cause sedation, and sometimes a degree of analgesia, numbed consciousness with sedation, have a tendency to get sleep even at regular therapeutic doses, which distinguishes sedatives from tranquilizers. Herbs are widely used as an alternative medicine in sleep disorders. Currently insomnia is mostly managed by synthetic sedatives-hypnotics, but safety in prolonged use of synthetic sedatives and hypnotics has been raised. Over the past few years, there has been a growing propensity for herbal medicines around the world to prevent insomnia. This paper highlights the need of a natural medicine to treat insomnia and sleep disorder.
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Matricaria chamomilla L. (Fam. – Asteraceae) is an annual plant species, with a height of 15–60 cm, used for healing of external wounds, treatment of gastrointestinal ailments, eczema, gout, neuralgia, sciatica, mastitis, leg ulcers, cracked nipples, chicken pox, conjunctivitis, and skin and respiratory tract inflammations. The essential oils of the aerial parts of this plant species showed antimicrobial effects against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The experimental researches have suggested that this plant species possessed antispasmodic, anxiolytic, anti‐inflammatory, and some antimutagenic and cholesterol‐lowering properties. The formaldehyde observed is believed to be derived from metabolically labile hydroxyl methyl group and opines that some as yet without known hydroxyl methyl‐containing compound in chamomile may play a significant role in the metabolism of M. chamomilla.
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From bovine cerebral cortex extracts, used to isolate n-butyl carboline-3-carboxylate (8), fractions active in displacing [3H] flunitrazepam binding were purified and shown to contain benzodiazepine-like molecules. These were recognized by UV spectra, retention time in HPLC, and interaction with a specific monoclonal antibody. Such molecules were localized in synaptic vesicles and cytosol of synaptosomes. Similar molecules were also found in cow milk. The possible dietary origin of these benzodiazepine-like molecules is discussed.
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