RESUMEN
BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Even with scientific and technological advances, the therapeutic approaches used for the treatment of PD have shown to be largely ineffective in controlling the progression of symptoms in the long term. There is a growing demand for the development of novel therapeutic strategies for PD treatment. Different herbs and supplements have been considered as adjuvant to treat the symptoms of Parkinsonism. The carrot is one of the most consumed vegetable species worldwide, and its root is known for its content of anthocyanins, which possess antioxidant and antiinflammatory properties. This study evaluated the neuroprotective effect of purple carrot extract (CAR) in rats on the reserpine (RES)-induced progressive parkinsonism model. METHODS: Male rats (6-month-old) received orally the CAR (400 mg/kg) or vehicle and subcutaneously RES (0.01 mg/kg) or vehicle for 28 days (Preventive Phase). From the 29th day, rats received CAR or vehicle daily and RES (0.1 mg/kg) or vehicle every other day (for 23 days, Protective phase). Behavioral tests were conducted throughout the treatment. Upon completion, the animals' brain were processed for tyrosine hydroxylase (TH) immunohistochemical assessment. RESULTS: Our results showed that the chronic treatment of CAR protected against motor disabilities, reducing the time of catalepsy behavior and decreasing the frequency of oral movements, possibly by preserving TH levels in the Ventral Tegmental Area (VTA) and SNpc. CONCLUSION: CAR extract is effective to attenuate motor symptoms in rats associated with increased TH+ levels in the Ventral Tegmental Area (VTA) and SNpc, indicating the potential nutraceutical benefits of CAR extract in a progressive parkinsonism model induced by RES.
Asunto(s)
Daucus carota , Fármacos Neuroprotectores , Extractos Vegetales , Reserpina , Tirosina 3-Monooxigenasa , Animales , Reserpina/toxicidad , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Daucus carota/química , Tirosina 3-Monooxigenasa/metabolismo , Ratas Wistar , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , Sustancia Negra/patología , Modelos Animales de Enfermedad , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patologíaRESUMEN
Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.
Asunto(s)
Lippia , Fármacos Neuroprotectores , Aceites Volátiles , Enfermedad de Parkinson , Trastornos Parkinsonianos , beta-Ciclodextrinas , Animales , alfa-Sinucleína/metabolismo , Lippia/metabolismo , Reserpina , Aceites Volátiles/efectos adversos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Antioxidantes/metabolismo , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Enfermedad de Parkinson/metabolismo , Neuronas Dopaminérgicas/metabolismo , Modelos Animales de Enfermedad , beta-Ciclodextrinas/efectos adversos , Sustancia Negra/metabolismoRESUMEN
Epilepsy is a chronic neurological disorder characterized by an abnormal, spontaneous, and synchronized neuronal hyperactivity. Therapeutic approaches for controlling epileptic seizures are associated with pharmacoresistance and side effects burden. Previous studies reported that different natural products may have neuroprotector effects. Sakuranetin (SAK) is a flavanone with antiparasitic, anti-inflammatory, antimutagenic, antiallergic, and antioxidant activity. In the present work, the effect of SAK on seizures in a model of status epilepticus induced by bicuculline (BIC) in mice was evaluated. Male Swiss mice received an intracerebroventricular injection (i.c.v.) of SAK (1, 10, or 20 mg/kg-SAK1, SAK10, or SAK20). Firstly, animals were evaluated in the open field (OF; 20 min), afterwards in the elevated plus maze (EPM) test (5 min). Next, 30 min prior the administration of BIC (1 mg/kg), mice received an injection of SAK (1 or 10 mg/kg, i.c.v.) and were observed in the OF (20 min) for seizures assessment. After behavioral procedures, immunohistochemical analysis of c-Fos was performed. Our main results showed that the lowest doses of SAK (1 and 10 mg/kg) increased the total distance traveled in the OF, moreover protected against seizures and death on the BIC-induced seizures model. Furthermore, SAK treatment reduced neuronal activity on the dentate gyrus of the BIC-treated animals. Taken together, our results suggest an anticonvulsant effect of SAK, which could be used for the development of anticonvulsants based on natural products from herbal source.
Asunto(s)
Anticonvulsivantes , Productos Biológicos , Animales , Anticonvulsivantes/farmacología , Bicuculina/efectos adversos , Productos Biológicos/uso terapéutico , Flavonoides , Masculino , Ratones , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoRESUMEN
Epilepsy is a chronic neuropathology characterized by an abnormal hyperactivity of neurons that generate recurrent, spontaneous, paradoxical and synchronized nerve impulses, leading or not to seizures. This neurological disorder affects around 70 million individuals worldwide. Pharmacoresistance is observed in about 30% of the patients and long-term use of antiepileptics may induce serious side effects. Thus, there is an interest in the study of the therapeutic potential of bioactive substances isolated from natural products in the treatment of epilepsy. Arthropod venoms contain neurotoxins that have high affinity for molecular structures in the neural tissue such as receptors, transporters and ion channels both in glial and neuronal membranes. This study evaluated the potential neuroprotective effect of melittin (MEL), an active compound of bee venom, in the bicuculline-induced seizure model (BIC) in rats. Male Wistar rats (3 months, 250-300 g) were submitted to surgery for the implantation of a unilateral cannula in the lateral ventricle. After the recovery period, rats received a microinjection of saline solution or MEL (0.1 mg per animal). Firstly, rats were evaluated in the open field (20 min) and in the elevated plus maze (5 min) tests after received microinjection of saline or MEL. After, 30 min later animals received BIC (100 mg/ml) or saline, and their behaviors were analyzed for 20 min in the open field according to a seizure scale. At the end, rats were euthanized, brains collected and processed to glial fibrillary acidic protein (GFAP) immunohistochemistry evaluation. No changes were observed in MEL-treated rats in the open field and elevated plus maze. However, 90% of MEL-treated animals were protected against seizures induced by BIC. There was an increase in the latency for the onset of seizures, accompanied by a reduction of GFAP-immunoreactivity cells in the dentate gyrus and CA1. Thus, our study suggests that MEL has an anticonvulsant potential, and further studies are needed to elucidate the mechanisms involved in this action.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Astrocitos/efectos de los fármacos , Venenos de Abeja/uso terapéutico , Hipocampo/efectos de los fármacos , Meliteno/uso terapéutico , Convulsiones/prevención & control , Animales , Anticonvulsivantes/farmacología , Venenos de Abeja/farmacología , Conducta Animal/efectos de los fármacos , Bicuculina , Masculino , Meliteno/farmacología , Ratas , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
Current pharmacological approaches to treat Parkinson's disease have low long-term efficacy and important adverse side effects. The development of new pharmacological therapies has focused on novel plant-derived phytochemicals. The alcoholic monoterpene myrtenol has been isolated from several plant species, and has anxiolytic, analgesic, anti-inflammatory and antioxidant actions. Our study evaluated the neuroprotective potential of myrtenol complexed with ß-cyclodextrin (MYR) on a progressive parkinsonism model induced by reserpine (RES) in mice. The complexation with cyclodextrins enhances the pharmacological action of monoterpenes. Male Swiss mice were treated daily with MYR (5 mg/kg, p.o.) and with RES (0.1 mg/kg, s.c.) every other day during 28 days. Behavioural evaluations were conducted across treatment. At the end of the treatment, immunohistochemistry for tyrosine hydroxylase (TH) and oxidative stress parameters were evaluated. Chronic MYR-treatment protected against olfactory sensibility loss, restored short-term memory and decreased RES-induced motor impairments. Moreover, this treatment prevented dopaminergic depletion and reduced the oxidative status index in the dorsal striatum. Therefore, MYR ameliorated motor and non-motor impairments in the progressive animal model of parkinsonism, possibly by an antioxidant action. Additional research is needed to investigate the mechanisms involved in this neuroprotective effect.
Asunto(s)
ReserpinaRESUMEN
Worldwide, the excessive consumption of fat and/or sugar has increased considerably. Palatable high-fat diets (HFDs) lead to metabolic disturbances and obesity, and impact emotional and cognitive processes. Previous studies in rodent models suggested that HFDs often cause multiple behavioral alterations, such as learning and memory deficits, and anxiety-like behaviors. Different sexes imply different behavioral and cognitive abilities; yet, most of these studies dealt with male or ovariectomized rats. We evaluated HFD effects in female rats submitted to different behavioral tasks, considering the effects of endogenous hormonal variations throughout estrous cycle. Female Wistar rats in each phase of the estrous cycle using commercial chow (CC) or HFD for 32 days. During treatment, behavioral assessments using sucrose preference (SP), elevated plus-maze (EPM), open field (OF) and novel-object recognition (NOR). At the end of the behavioral tests, animals were euthanized, and performed an immunohistochemical analysis of the brains by brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase (TH). The main results demonstrated that (1) HFD-fed rats had higher body mass gain and food intake, without altering caloric intake, (2) rats in diestrus had lower sucrose intake, (3) females in metestrus and diestrus showed deficits in the novel-object recognition memory. Furthermore, TH-immunoreactivity decreased in the dorsal striatum and BDNF in the hippocampus in HFD-fed females. These results suggest that HFD alters neurochemical and metabolic aspects that may induce phase-dependent behavioral changes in female rats.