RESUMEN
Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi-target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Enfermedades Neurodegenerativas , Estilbenos , Humanos , Resveratrol , Enfermedades Neurodegenerativas/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológicoRESUMEN
Daily living and functioning under stress can lead to mental health problems such as anxiety or depression. Over the past decades, a number of studies have been conducted to determine the relationship between the central nervous system (CNS), intestinal flora and bidirectional communication along the gut brain axis (GBA) in the maintaining of homeostasis. One of the most important factors regulating GBA functioning in exposure to stress may be a proper diet enriched in the supplementation with pre-, pro-and synbiotics. In the present study, we examined whether a 10-week oral preventive supplementation with natural prebiotics: topinambur powder (TPB) and chicory root inulin (INU) influenced an anxiety, depressive behavior and cognition in mice exposed to the chronic unpredictable mild stress (CUMS). Additionally, a fluoxetine (FLU) has been used as a reference antidepressive drug. Furthermore, we assessed the effect of TPB, INU and FLU administration on neurogenesis in mice exposed to CUMS and finally analyzed fecal microbiota for possible changes after TPB and INU supplementation in CUMS induced mice. Results obtained from the behavioral studies (elevated plaze maze, forced swim and Morris water maze test) indicated, that 10 week supplementation with TPB (250 mg/kg) and INU (66 mg/kg), similarly to FLU (12 mg/kg), significantly mitigated an anxiety and stress as well as protected learning and memory functions in the CUMS induced mice compared to the control stressed group. Additionally, TPB and INU CUMS mice showed significantly higher level of neurogenesis in comparison to control CUMS group. Interestingly, results obtained from the fecal microbiota analysis showed a beneficial effect of TPB and INU supplementation against CUMS-induced intestinal dysbiosis in mice. In conclusion, the obtained results showed that a long-term, preventive supplementation with TPB or INU alleviates the negative effects such as anxiety, cognitive disorders or dysbiosis in mice exposed to chronic unpredictable stress.
Asunto(s)
Inulina , Microbiota , Animales , Ratones , Inulina/farmacología , Disbiosis , Ansiedad/tratamiento farmacológico , Ansiedad/prevención & control , Cognición , Neurogénesis , Fluoxetina , Suplementos DietéticosRESUMEN
The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain-gut-microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB1) bacteria alters brain metabolites' levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.
Asunto(s)
Lacticaseibacillus rhamnosus , Animales , Conducta Animal , Ingestión de Alimentos , Glutatión/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Ratas , Ratas Wistar , Estrés Psicológico , Taurina/metabolismoRESUMEN
Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the in vitro evaluation of potential neuroprotective properties of a new pyrrolidine-2,5-dione derivatives compound C11, as well as the in vivo assessment of the impact on the neurogenesis and cognitive functions of C11 and levetiracetam (LEV) after pilocarpine (PILO)-induced SE in mice. The in vitro results indicated a protective effect of C11 (500, 1000, and 2500 ng/mL) on astrocytes under trophic stress conditions in the MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) test. The results obtained from the in vivo studies, where mice 72 h after PILO SE were treated with C11 (20 mg/kg) and LEV (10 mg/kg), indicated markedly beneficial effects of C11 on the improvement of the neurogenesis compared to the PILO control and PILO LEV mice. Moreover, this beneficial effect was reflected in the Morris Water Maze test evaluating the cognitive functions in mice. The in vitro confirmed protective effect of C11 on astrocytes, as well as the in vivo demonstrated beneficial impact on neurogenesis and cognitive functions, strongly indicate the need for further advanced molecular research on this compound to determine the exact neuroprotective mechanism of action of C11.
Asunto(s)
Anticonvulsivantes/farmacología , Cognición/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Pilocarpina/efectos adversos , Estado Epiléptico/etiología , Animales , Anticonvulsivantes/administración & dosificación , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Biomarcadores , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Ratones , Fármacos Neuroprotectores/farmacología , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológicoRESUMEN
Major depressive disorder is a stress-related disease associated with brain metabolic dysregulation in the glutamine-glutamate/γ-aminobutyric acid (Gln-Glu/GABA) cycle. Recent studies have demonstrated that microbiome-gut-brain interactions have the potential to influence mental health. The hypothesis of this study was that Lactobacillus rhamnosus JB-1 (LR-JB1™) dietary supplementation has a positive impact on neuro-metabolism which can be quantified in vivo using magnetic resonance spectroscopy (MRS). A rat model of depressive-like disorder, chronic unpredictable mild stress (CUMS), was used. Baseline comparisons of MRS and behavior were obtained in a control group and in a stressed group subjected to CUMS. Of the 22 metabolites measured using MRS, stressed rats had significantly lower concentrations of GABA, glutamate, glutamine + glutathione, glutamate + glutamine, total creatine, and total N-acetylaspartate (tNAA). Stressed rats were then separated into 2 groups and supplemented with either LR-JB1™ or placebo and re-evaluated after 4 weeks of continued CUMS. The LR-JB1™ microbiotic diet restored these metabolites to levels previously observed in controls, while the placebo diet resulted in further significant decrease of glutamate, total choline, and tNAA. LR-JB1™ treated animals also exhibited calmer and more relaxed behavior, as compared with placebo treated animals. In summary, significant cerebral biochemical downregulation of major brain metabolites following prolonged stress were measured in vivo using MRS, and these decreases were reversed using a microbiotic dietary supplement of LR-JB1™, even in the presence of continued stress, which also resulted in a reduction of stress-induced behavior in a rat model of depressive-like disorder.
Asunto(s)
Encéfalo/metabolismo , Trastorno Depresivo/dietoterapia , Suplementos Dietéticos , Lacticaseibacillus rhamnosus , Estrés Psicológico/dietoterapia , Animales , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Conducta Animal , Colina/metabolismo , Trastorno Depresivo/metabolismo , Progresión de la Enfermedad , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Glutatión/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas Wistar , Estrés Psicológico/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Jerusalem artichoke (Helianthus tuberosus Linne) is a tuberous perennial plant of the Asteraceae family, which originates from North America, and is also known as wild sunflower or topinambur (TPB). It is characterized by good tolerance to frost, drought and poor soil, strong resistance to pests and plant diseases. For ages it was cultivated due to being both an edible tuber and having healing properties. In folk medicine, TPB leaves are used for the treatment of bone fractures and pain. TPB tubers are rich in sugar and have therefore been used for the production of functional food ingredients, such as inulin. Moreover, TPB is one of the potential crops for bioenergy production, such as bioethanol, biobuthanol and biodiesel, and chemicals (lactic acid, butyric acid). A number of bioactive compounds from the above ground parts of this plant have been isolated which have demonstrating antifungal, antioxidant and anticancer activities. In recent years, a number of animal experiments have been carried out to assess the health properties of TPB. Obtained results show that TPB possess a wide spectrum of medical applications, e.g. reduction in the levels of plasma glucose, total cholesterol and triglyceride. Interestingly, TPB has been shown to be a valuable alternative source of prebiotic compounds. This review article presents recent scientific reports on the chemical and biological properties of TPB and its potential use as a prebiotic diet supplement.
Asunto(s)
Helianthus/química , Prebióticos , Animales , Humanos , Inulina/farmacología , Hojas de la Planta/química , Tubérculos de la Planta/químicaRESUMEN
The aim of this study was to determine the effects of xanthotoxin (8-methoxypsoralen) on the protective action of 5 various second- and third-generation antiepileptic drugs (i.e., lacosamide, lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure model. Seizure activity was evoked in adult male albino Swiss mice by a current (25mA, 500V, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were determined in the chimney, grip-strength and passive avoidance tests. Total brain antiepileptic drug concentrations were measured to confirm pharmacodynamic nature of observed interactions with xanthotoxin. Results indicate that xanthotoxin (100mg/kg, i.p.) significantly enhanced the anticonvulsant action of lacosamide (P<0.01), oxcarbazepine (P<0.05), pregabalin (P<0.01), and topiramate (P<0.001), but not that of lamotrigine in the maximal electroshock-induced seizure test. Moreover, xanthotoxin (50mg/kg) still significantly potentiated the anticonvulsant action of lacosamide (P<0.05), pregabalin (P<0.05), and topiramate (P<0.001) in this seizure test. Xanthotoxin had no significant impact on total brain concentrations of the studied antiepileptic drugs in mice. Furthermore, combinations of xanthotoxin with oxcarbazepine or topiramate produced no adverse effects. However, xanthotoxin in combination with lacosamide, lamotrigine or pregabalin significantly reduced muscular strength in mice in the grip-strength test. In the chimney test, only the combinations of xanthotoxin with pregabalin significantly impaired motor coordination in mice. In conclusion, the combinations of xanthotoxin with oxcarbazepine and topiramate produce beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced seizure test. A special caution is advised when combining xanthotoxin with pregabalin due to appearance of acute adverse effects.