RESUMO
There is an increasing interest in revisiting plants for drug discovery, proving scientifically their role as remedies. The aim of this review was to give an overview of the ethnopharmacological uses of Pistacia lentiscus L. (PlL) leaves and fruits, expanding the search for the scientific discovery of their chemistry, anti-inflammatory, antioxidative and antimicrobial activities. PlL is a wild-growing shrub rich in terpenoids and polyphenols, the oil and extracts of which have been widely used against inflammation and infections, and as wound healing agents. The more recurrent components in PlL essential oil (EO) are represented by α-pinene, terpinene, caryophyllene, limonene and myrcene, with high variability in concentration depending on the Mediterranean country. The anti-inflammatory activity of the oil mainly occurs due to the inhibition of pro-inflammatory cytokines and the arachidonic acid cascade. Interestingly, the capacity against COX-2 and LOX indicates PlL EO as a dual inhibitory compound. The high content of polyphenols enriching the extracts provide explanations for the known biological properties of the plant. The protective effect against reactive oxygen species is of wide interest. In particular, their anthocyanins content greatly clarifies their antioxidative capacity. Further, the antimicrobial activity of PlL oil and extracts includes the inhibition of Staphylococcus aureus, Escherichia coli, periodontal bacteria and Candida spp. In conclusion, the relevant scientific properties indicate PlL as a nutraceutical and also as a therapeutic agent against a wide range of diseases based on inflammation and infections.
RESUMO
The polyphenol resveratrol (RVT) may drive protective mechanisms of cerebral homeostasis during the hypoperfusion/reperfusion triggered by the transient bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R). This immunochemical study investigates if a single dose of RVT modulates the plasticity-related markers brain-derived neurotrophic factor (BDNF), the tyrosine kinase trkB receptor, Polysialylated-Neural Cell Adhesion Molecule (PSA-NCAM), and Activity-regulated cytoskeleton-associated (Arc) protein in the brain cortex after BCCAO/R. Frontal and temporal-occipital cortical regions were examined in male Wistar rats randomly subdivided in two groups, sham-operated and submitted to BCCAO/R. Six hours prior to surgery, half the rats were gavage fed a dose of RVT (180 mg·kg-1 in 300 µL of sunflower oil as the vehicle), while the second half was given the vehicle alone. In the frontal cortex of BCCAO/R vehicle-treated rats, BDNF and PSA-NCAM decreased, while trkB increased. RVT pre-treatment elicited an increment of all examined markers in both sham- and BCCAO/R rats. No variations occurred in the temporal-occipital cortex. The results highlight a role for RVT in modulating neuronal plasticity through the BDNF-trkB system and upregulation of PSA-NCAM and Arc, which may provide both trophic and structural local support in the dynamic changes occurring during the BCCAO/R, and further suggest that dietary supplements such as RVT are effective in preserving the tissue potential to engage plasticity-related events and control the functional response to the hypoperfusion/reperfusion challenge.
Assuntos
Doenças das Artérias Carótidas/tratamento farmacológico , Córtex Cerebral/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Resveratrol/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Proteínas do Citoesqueleto/metabolismo , Suplementos Nutricionais , Masculino , Proteínas do Tecido Nervoso/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Plasticidade Neuronal , Ratos , Ratos Wistar , Receptor trkB/metabolismo , Ácidos Siálicos/metabolismoRESUMO
BACKGROUND: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP). METHODS: Two groups of adult Wistar rats were used, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half of the rats were gavage-fed with a single dose of BCP (40 mg/per rat in 300 µl of sunflower oil as vehicle), while the second half were pre-treated with the vehicle alone. HPLC, Western Blot and immunohistochemistry were used to analyze cerebral cortex and plasma. RESULTS: After BCCAO/R, BCP prevented the increase of lipoperoxides occurring in the vehicle-treated rats in both cerebral cortex and plasma. In the frontal cortex, BCP further prevented activation of the endocannabinoid system (ECS), spared the docosahexaenoic acid (DHA), appeared to prevent the increase of cyclooxygenase-2 and increased the peroxisome-proliferator activated receptor-alpha (PPAR-alpha) protein levels, while, in plasma, BCP induced the reduction of arachidonoylethanolamide (AEA) levels as compared to vehicle-treated rats. CONCLUSIONS: Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Endocanabinoides/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Hipocampo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos Policíclicos , Ratos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT) in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R) and to investigate RVT's ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle), while the second half received the vehicle alone. In the frontal cortex, RVT pre-treatment prevented the BCCAO/R-induced increase of lipoperoxides, augmented concentrations of palmitoylethanolamide and docosahexaenoic acid, increased relative levels of the cannabinoid receptors type 1 (CB1) and 2 (CB2), and peroxisome-proliferator-activated-receptor (PPAR)-α proteins. Increased expression of CB1/CB2 receptors mirrored that of synaptophysin and post-synaptic density-95 protein. No BCCAO/R-induced changes occurred in the temporal-occipital cortex. Collectively, our results demonstrate that, in the frontal cortex, RVT pre-treatment prevents the BCCAO/R-induced oxidative stress and modulates the endocannabinoid and PPAR-α systems. The increased expression of synaptic structural proteins further suggests the possible efficacy of RVT as a dietary supplement to preserve the nervous tissue metabolism and control the physiological response to the hypoperfusion/reperfusion challenge.
Assuntos
Doenças das Artérias Carótidas , Lobo Frontal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptores de Canabinoides/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Estilbenos/farmacologia , Animais , Arteriopatias Oclusivas , Lobo Frontal/metabolismo , Regulação da Expressão Gênica , Masculino , Ratos , Ratos Wistar , Receptores de Canabinoides/genética , Traumatismo por Reperfusão/metabolismo , Resveratrol , Estilbenos/uso terapêuticoRESUMO
BACKGROUND: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. METHODS: Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. RESULTS: The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. CONCLUSIONS: The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge.
Assuntos
Isquemia Encefálica/metabolismo , Transtornos Cerebrovasculares/metabolismo , Endocanabinoides/metabolismo , Peróxidos Lipídicos/metabolismo , Traumatismo por Reperfusão/metabolismo , Amidas , Animais , Ácidos Araquidônicos/metabolismo , Isquemia Encefálica/fisiopatologia , Artéria Carótida Primitiva/cirurgia , Transtornos Cerebrovasculares/fisiopatologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Etanolaminas/metabolismo , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologia , Regulação da Expressão Gênica , Glicerídeos/metabolismo , Peroxidação de Lipídeos , Masculino , Lobo Occipital/metabolismo , Lobo Occipital/fisiopatologia , Estresse Oxidativo , PPAR alfa/genética , PPAR alfa/metabolismo , Ácidos Palmíticos/metabolismo , Alcamidas Poli-Insaturadas/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Lobo Temporal/metabolismo , Lobo Temporal/fisiopatologiaRESUMO
Spinal cord injury leads to major neurological impairment for which there is currently no effective treatment. Recent clinical trials have demonstrated the efficacy of Fortasyn® Connect in Alzheimer's disease. Fortasyn® Connect is a specific multi-nutrient combination containing DHA, EPA, choline, uridine monophosphate, phospholipids, and various vitamins. We examined the effect of Fortasyn® Connect in a rat compression model of spinal cord injury. For 4 or 9 weeks following the injury, rats were fed either a control diet or a diet enriched with low, medium, or high doses of Fortasyn® Connect. The medium-dose Fortasyn® Connect-enriched diet showed significant efficacy in locomotor recovery after 9 weeks of supplementation, along with protection of spinal cord tissue (increased neuronal and oligodendrocyte survival, decreased microglial activation, and preserved axonal integrity). Rats fed the high-dose Fortasyn® Connect-enriched diet for 4 weeks showed a much greater enhancement of locomotor recovery, with a faster onset, than rats fed the medium dose. Bladder function recovered quicker in these rats than in rats fed the control diet. Their spinal cord tissues showed a smaller lesion, reduced neuronal and oligodendrocyte loss, decreased neuroinflammatory response, reduced astrocytosis and levels of inhibitory chondroitin sulphate proteoglycans, and better preservation of serotonergic axons than those of rats fed the control diet. These results suggest that this multi-nutrient preparation has a marked therapeutic potential in spinal cord injury, and raise the possibility that this original approach could be used to support spinal cord injured patients.
Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Fosfolipídeos , Traumatismos da Medula Espinal/dietoterapia , Animais , Astrócitos/imunologia , Astrócitos/patologia , Morte Celular , Sobrevivência Celular , Cicatriz/dietoterapia , Cicatriz/patologia , Cicatriz/fisiopatologia , Modelos Animais de Doenças , Feminino , Gliose/dietoterapia , Gliose/patologia , Gliose/fisiopatologia , Atividade Motora , Neurônios/imunologia , Neurônios/patologia , Oligodendroglia/imunologia , Oligodendroglia/patologia , Ratos Sprague-Dawley , Ratos Wistar , Recuperação de Função Fisiológica , Medula Espinal/imunologia , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Vértebras Torácicas , Resultado do Tratamento , Bexiga Urinária/fisiopatologiaRESUMO
BACKGROUND: Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. METHODS: Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. RESULTS: BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). CONCLUSIONS: Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.