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1.
Antioxidants (Basel) ; 9(6)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532064

RESUMO

Osteoarthritis is a progressive joint disease characterized by the activation of different molecular mediators, including proinflammatory cytokines, reactive oxygen species, metalloproteinases and nociceptive mediators. Anacardium occidentale L. is a medicinal plant with anti-oxidative and anti-inflammatory properties. In this study we evaluate the effects of cashew nuts (from Anacardium occidentale L.) oral administration on an experimental model of painful degenerative joint disease. Monosodium iodoacetate (MIA) was intraarticularly injected, and cashew nuts were orally administered three times per week for 21 days, starting the third day after MIA injection. Nociception was evaluated by a Von Frey filament test, and motor function by walking track analysis at 3, 7, 14 and 21 days after osteoarthritis. Histological and biochemical alteration were examined at the end of the experiment. Cashew nuts administration reduced pain-like behavior and showed antioxidant activities, restoring biochemical serum parameters: glutathione (GSH), catalase (CAT) levels, glutathione peroxidase (GPx) activity and lipid peroxidation. Moreover, cashew nuts ameliorated radiographic and histological alteration, resulting in decreased cartilage degradation, pro-inflammatory cytokines and metalloproteinases levels and mast cells recruitment. Our results demonstrated that the oral assumption of cashew nuts counteracts the inflammatory and oxidative process involved in osteoarthritis.

2.
Int J Mol Sci ; 21(12)2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32545788

RESUMO

Inflammation is a protective reaction activated in response to detrimental stimuli, such as dead cells, irritants or pathogens, by the evolutionarily conserved immune system and is regulated by the host. The inflammasomes are recognized as innate immune system sensors and receptors that manage the activation of caspase-1 and stimulate inflammation response. They have been associated with several inflammatory disorders. The NLRP3 inflammasome is the most well characterized. It is so called because NLRP3 belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent evidence has greatly improved our understanding of the mechanisms by which the NLRP3 inflammasome is activated. Additionally, increasing data in animal models, supported by human studies, strongly implicate the involvement of the inflammasome in the initiation or progression of disorders with a high impact on public health, such as metabolic pathologies (obesity, type 2 diabetes, atherosclerosis), cardiovascular diseases (ischemic and non-ischemic heart disease), inflammatory issues (liver diseases, inflammatory bowel diseases, gut microbiome, rheumatoid arthritis) and neurologic disorders (Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis and other neurological disorders), compared to other molecular platforms. This review will provide a focus on the available knowledge about the NLRP3 inflammasome role in these pathologies and describe the balance between the activation of the harmful and beneficial inflammasome so that new therapies can be created for patients with these diseases.

3.
Int J Mol Sci ; 21(10)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429243

RESUMO

Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum-Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), was given by oral gavage daily for 14 days after SNI. PEAum-Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum-Paracetamol could act in a synergistic manner through the inhibition of the NF-κB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs.

4.
Nutrients ; 12(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32245085

RESUMO

BACKGROUND: Anacardium occidentale L. is a tropical plant used for the treatment of inflammatory diseases. The goal of the present work was to investigate the anti-inflammatory and anti-oxidant potential of oral administration of cashew nuts (from Anacardium occidentale L.) in a mouse model of colitis. METHODS: Induction of colitis was performed by intrarectally injection of dinitrobenzene sulfonic acid (DNBS). Cashew nuts were administered daily orally (100 mg/kg) in DNBS-injected mice. RESULTS: Four days after DNBS, histological and macroscopic colon alterations as well as marked clinical signs and increased cytokine production were observed. Neutrophil infiltration, measured by myeloperoxidase (MPO) positive immunostaining, was correlated with up-regulation of adhesion molecules ICAM-1 and P-selectin in colons. Oxidative stress was detected with increased malondialdehyde (MDA) levels, nitrotyrosine, and poly ADP-ribose polymerase (PARP) positive staining in inflamed colons. Oral treatment with cashew nuts reduced histological, macroscopic damage, neutrophil infiltration, pro-inflammatory cytokines and MDA levels, as well as nitrotyrosine, PARP and ICAM-1, and P-selectin expressions. Colon inflammation could be related to nuclear factor (NF)-kB pathway activation and reduced manganese superoxide dismutase (MnSOD) antioxidant activity. Cashew nuts administration inhibited NF-kB and increased MnSOD antioxidant expressions. CONCLUSIONS: The results suggested that oral assumption of cashew nuts may be beneficial for the management of colitis.

5.
Int J Mol Sci ; 21(6)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244997

RESUMO

Chronic rejection is the major leading cause of morbidity and mortality after lung transplantation. Bronchiolitis obliterans syndrome (BOS), a fibroproliferative disorder of the small airways, is the main manifestation of chronic lung allograft rejection. We investigated, using transgenic mice, the mechanisms through which the deficiency of IL-1ß/IL-18, Casp-1, or Fpr-1 genes could be protective in an experimental model of BOS, induced in mice by allogeneic heterotopic tracheal transplantation. Fpr-1 KO mice showed a marked reduction in histological markers of BOS and of mast cell numbers compared to other groups. Molecular analyses indicated that the absence of the Fpr-1 gene was able to decrease NF-κB nuclear translocation and modulate NLRP3 inflammasome signaling and the mitogen-activated protein kinase (MAPK) pathway in a more significant way compared to other groups. Additionally, Fpr-1 gene deletion caused a reduction in resistance to the apoptosis, assessed by the TUNEL assay. Immunohistochemical analyses indicated changes in nitrotyrosine, PARP, VEGF, and TGF-ß expression associated with the pathology, which were reduced in the absence of the Fpr1 gene more so than by the deletion of IL-1ß/IL-18 and Casp-1. We underline the importance of the NLRP3 inflammasome and the pathogenic role of Fpr-1 in experimental models of BOS, which is the result of the modulation of immune cell recruitment together with the modulation of local cellular activation, suggesting this gene as a new target in the control of the pathologic features of BOS.

6.
Biomed Pharmacother ; 125: 110023, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32092830

RESUMO

Several studies demonstrated the pharmacological actions of carnosine as well as hyaluronic acid (HA) during joint inflammation. In that regard, the aim of this study was to investigate the protective effect of a new HA -Carnosine conjugate (FidHycarn) on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by two intradermal injections of 100 µl of an emulsion of collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail on day 0 and 21. At 35 day post CIA induction, the animals were sacrificed. CII injection caused erythema and edema in the hind paws, histological alterations with erosion of the joint cartilage as well as behavioral changes. Oral treatment with FidHycarn starting at the onset of arthritis (day 25) ameliorated the clinical signs, improved behavioral deficits as well as decreased histological and radiographic alterations. The degree of oxidative damage evaluated by inducible nitric oxide synthase (iNOS), nitrotyrosine, poly-ADP-ribose (PAR) expressions and malondialdehyde (MDA) levels, was also significantly reduced in Carnosine+HA association and FidHycarn treated mice. Moreover, the levels of proinflammatory cytokines and chemokines and cyclo-oxygenase COX-2 enzyme were also more significantly reduced by Carnosine+HA and FidHycarn compared to carnosine alone. However, interestingly, in some cases, the effects of FidHycarn were more important than Carnosine+HA association and not statistically different to methotrexate (MTX) used as positive control. Thus, the conjugation of Carnosine with HA (FidHycarn) could represent an interesting therapeutic strategy to combat arthritis disorders.

7.
BMC Vet Res ; 16(1): 13, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931804

RESUMO

BACKGROUND: Leishmaniasis is a emergent disease characterized by different clinical manifestations in both humans and dogs. Predominant clinical features of cutaneous leishmaniasis are ulcerative painless skin lesions. Several data reported that pain is associated with human and dog leishmaniasis, out with areas of painless ulcerative lesions per se. Actually, current medications used for leishmaniasis management are characterized by several side effects and, in addition, some cases of the disease are refractory to the treatment. On this background it is mandatory the identification of new and safe candidates for designing less toxic and low-cost remedies. Therefore, the search for new leishmanicidal compounds is indispensable. METHODS: In the present paper we investigated the effect of orally N-acetyl-L-cysteine (NAC) supplementation at dose of 200 mg/Kg for 10 weeks, in subcutaneous Leishmania (L). amazonensis infected BALB/c mice. And evaluating the effect of NAC on inflammatory response such as TNF-α, IL-6, IL-1ß levels, and on thermal and mechanical hyperalgesia. RESULTS: In the present paper we showed how NAC supplementation affected parameters of oxidative stress (GSH, MDA, SOD), inflammation such as cytokines levels (IL-1ß, IL-6, TNFα) and mast cell activation and consequently on induced pain, during leishmaniosis in BALB\c mice. CONCLUSIONS: The findings of our study provided the scientific data demonstrating that L. amazonensis infection induces inflammation and pain in BALB/c mice that are reversed by administration of NAC.

8.
CNS Neurol Disord Drug Targets ; 19(1): 27-43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914916

RESUMO

BACKGROUND: The activity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is commonly dysregulated in stress-related psychiatric disorders. Annexin A1 (ANXA1), an endogenous ligand of Formyl Peptide Receptor (FPR) 2/3, is a member of the family of phospholipid- and calcium-binding proteins with a well-defined role in the delayed early inhibitory feedback of Glucocorticoids (GC) in the pituitary gland and implicated in the occurrence of behavioural disorders such as anxiety. OBJECTIVE: The present study aimed to evaluate the potential role of ANXA1 and its main receptor, as a cellular mediator of behavioural disorders, in a model of Corticosterone (CORT)-induced depression and subsequently, the possible correlation between the depressive state and impairment of hippocampal memory. METHODS: To induce the depression model, Wild-Type (WT), ANXA1 Knockout (KO), and FPR2/3 KO mice were exposed to oral administration of CORT for 28 days dissolved in drinking water. Following this, histological, biochemical and behavioural analyses were performed. RESULTS: FPR2/3 KO and ANXA1 KO mice showed improvement in anxiety and depression-like behaviour compared with WT mice after CORT administration. In addition, FPR2/3 KO and ANXA1 KO mice showed a reduction in histological alterations and neuronal death in hippocampal sections. Moreover, CORT+ FPR2/3 KO and ANXA1 KO, exhibited a higher expression of Brain-Derived Neurotrophic Factor (BDNF), phospho-ERK, cAMP response element-binding protein (pCREB) and a decrease in Serotonin Transporter Expression (SERT) compared to WT(CORT+) mice. CONCLUSION: In conclusion, the absence of the ANXA1 protein, even more than the absence of its main receptor (FPR 2/3), was fundamental to the inhibitory action of GC on the HPA axis; it also maintained the hippocampal homeostasis by preventing neuronal damage associated with depression.

9.
FASEB J ; 34(3): 4085-4106, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31950563

RESUMO

Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal (GI) tract, and it is associated with different neurological disorders. Recent evidence has demonstrated that the gut-brain-axis has a central function in the perpetuation of IBS, and for this reason, it can be considered a possible therapeutic target. N-Palmitoylethanolamine-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects on the gut-brain axis during colitis. The aim of this study is to explore the mechanism and the effect of PEA-OXA on the gut-brain axis in rats subjected to experimental colitis induced by oral administration of dextran sulfate sodium (DSS). Daily oral administration of PEA-OXA (10 mg/kg daily o.s.) was able to decrease the body weight loss, macroscopic damage, colon length, histological alteration, and inflammation after DSS induction. Additionally, PEA-OXA administration enhanced neurotrophic growth factor release and decreased the astroglial and microglial activation induced by DSS. Moreover, PEA-OXA restored intestinal permeability and tight junctions (TJs) as well as reduced apoptosis in the colon and brain. In our work, we demonstrated, for the first time, the action of PEA-OXA on the gut-brain axis in a model of DSS-induced colitis and its implication on the "secondary" effects associated with colonic disturbance.

10.
FASEB J ; 34(1): 1576-1590, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914614

RESUMO

Inflammatory bowel diseases (IBDs) are characterized by an inflammatory and oxidative stress condition in the intestinal tissue. In this study, we evaluated the effect of plumericin, one of the main bioactive components of Himatanthus sucuuba (Woodson) bark, on intestinal inflammation and oxidative stress, both in vitro and in vivo. The effect of plumericin (0.5-2 µM) in vitro was evaluated in rat intestinal epithelial cells (IEC-6) treated with lipopolysaccharides from E. coli (10 µg/mL) plus interferon-γ (10 U/mL). Moreover, a 2,4,6-dinitrobenzene sulfonic acid (DNBS)-induced colitis model was used to evaluate the anti-inflammatory and antioxidant activity of plumericin (3 mg/kg) in vivo. The results showed that plumericin significantly reduces intestinal inflammatory factors such as tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase expression, and nitrotyrosine formation. Plumericin also inhibited nuclear factor-κB translocation, reactive oxygen species (ROS) release, and inflammasome activation. Moreover, plumericin activated the nuclear factor erythroid-derived 2 pathway in IEC-6. Using the DNBS-induced colitis model, a significant reduction in the weight loss and in the development of the macroscopic and histologic signs of colon injury, together with a reduced inflammatory and oxidative stress state, were observed in plumericin-treated mice. These results indicate that plumericin exerts a strong anti-inflammatory and antioxidant activity. Thus, it might be a candidate for the development of a new pharmacologic approach for IBDs treatment.

11.
Arch Physiol Biochem ; : 1-11, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31835914

RESUMO

Several in vitro and in vivo investigations have already proved that cells and tissues, when pre-exposed to low oxidative stress by different stimuli such as chemical, physical agents and environmental factors, display more resistance against subsequent stronger ischaemic injuries, resulting in an adaptive response known as ischaemic preconditioning (IPC). The aim of this review is to report the most recent knowledge about the complex adaptive mechanisms, including signalling transduction pathways, antioxidant systems, apoptotic and inflammation pathways, underlying cell protection against oxidative damage. In addition, an update about in vivo adaptation strategies in response to ischaemic/reperfusion episodes and brain trauma is also given.

12.
J Ocul Pharmacol Ther ; 35(10): 571-577, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31825758

RESUMO

Purpose: Inflammatory corneal diseases such as bacterial keratitis provoke severe injury to the visual functions and physical structure, leading to opaqueness, wounding, damage to the cornea, and even long-lasting vision loss. Usually antioxidant substances have been of great attention as candidate therapies in the management of keratitis in both humans and animals. Based on the findings, the aim of our research was to examine the effects of Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a membrane-permeable free radical scavenger with exclusive antioxidant properties, on in vitro model of eye inflammation of rabbit corneal cells stimulated with lipopolysaccharide (LPS) (Seruminstitute Rabbit Cornea). Methods: The cells were pretreated with Tempol and incubated with LPS for 24 h. LPS stimulation triggered increased cellular mortality, oxidative stress, cytokine levels expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, and also enhanced prostaglandin E2 (PGE2) levels and cyclooxygenase-2 (COX-2) expression. Results: Pretreatment with Tempol (3 mM) significantly increased cell viability and antioxidant activity as well as decreased reactive oxygen species production, cytokines, PGE2 levels, and COX-2 expression. Conclusions: Taken together, Tempol could be a new therapeutic strategy for management of ocular inflammatory disorders for clinical and veterinary use.

13.
Antioxidants (Basel) ; 8(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817734

RESUMO

BACKGROUND: Fibromyalgia is a chronic condition characterized by increased sensory perception of pain, neuropathic/neurodegenerative modifications, oxidative, and nitrosative stress. An appropriate therapy is hard to find, and the currently used treatments are able to target only one of these aspects. METHODS: The aim of this study is to investigate the beneficial effects of melatonin plus folic acid administration in a rat model of reserpine-induced fibromyalgia. Sprague-Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days and later administered with melatonin, folic acid, or both for twenty-one days. RESULTS: Administration of reserpine led to a significant decrease in the nociceptive threshold as well as a significant increase in depressive-like symptoms. These behavioral changes were accompanied by increased oxidative and nitrosative stress. Lipid peroxidation was significantly increased, as well as nitrotyrosine and PARP expression, while superoxide dismutase, nonprotein thiols, and catalase were significantly decreased. Endogenously produced oxidants species are responsible for mast cell infiltration, increased expression pro-inflammatory mediators, and microglia activation. CONCLUSION: Melatonin plus acid folic administration is able to ameliorate the behavioral defects, oxidative and nitrosative stress, mast cell infiltration, inflammatory mediators overexpression, and microglia activation induced by reserpine injection with more efficacy than their separate administration.

14.
Arthritis Res Ther ; 21(1): 254, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779692

RESUMO

BACKGROUND: Osteoarthritis is increasingly recognized as the result of a complex interplay between inflammation, chrondrodegeneration, and pain. Joint mast cells are considered to play a key role in orchestrating this detrimental triad. ALIAmides down-modulate mast cells and more generally hyperactive cells. Here we investigated the safety and effectiveness of the ALIAmide N-palmitoyl-D-glucosamine (PGA) in inflammation and osteoarthritis pain. METHODS: Acute toxicity of micronized PGA (m-PGA) was assessed in rats following OECD Guideline No.425. PGA and m-PGA (30 mg/kg and 100 mg/kg) were orally administered to carrageenan (CAR)-injected rats. Dexamethasone 0.1 mg/kg was used as reference. Paw edema and thermal hyperalgesia were measured up to 6 h post-injection, when also myeloperoxidase activity and histological inflammation score were assessed. Rats subjected to intra-articular injection of sodium monoiodoacetate (MIA) were treated three times per week for 21 days with PGA or m-PGA (30 mg/kg). Mechanical allodynia and motor function were evaluated at different post-injection time points. Joint histological and radiographic damage was scored, articular mast cells were counted, and macrophages were immunohistochemically investigated. Levels of TNF-α, IL-1ß, NGF, and MMP-1, MMP-3, and MMP-9 were measured in serum using commercial colorimetric ELISA kits. One- or two-way ANOVA followed by a Bonferroni post hoc test for multiple comparisons was used. RESULTS: Acute oral toxicity of m-PGA resulted in LD50 values in excess of 2000 mg/kg. A single oral administration of PGA and m-PGA significantly reduced CAR-induced inflammatory signs (edema, inflammatory infiltrate, and hyperalgesia), and m-PGA also reduced the histological score. Micronized PGA resulted in a superior activity to PGA on MIA-induced mechanical allodynia, locomotor disability, and histologic and radiographic damage. The MIA-induced increase in mast cell count and serum level of the investigated markers was also counteracted by PGA and to a significantly greater extent by m-PGA. CONCLUSIONS: The results of the present study showed that PGA is endorsed with anti-inflammatory, pain-relieving, and joint-protective effects. Moreover, it proved that particle size reduction greatly enhances the activity of PGA, particularly on joint pain and disability. Given these results, m-PGA could be considered a valuable option in the management of osteoarthritis.

15.
Front Pharmacol ; 10: 1114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611796

RESUMO

Astrocytes are a population of cells with distinctive morphological and functional characteristics that differ within specific areas of the brain. Postnatally, astrocyte progenitors migrate to reach their brain area and related properties. They have a regulatory role of brain functions that are implicated in neurogenesis and synaptogenesis, controlling blood-brain barrier permeability and maintaining extracellular homeostasis. Mature astrocytes also express some genes enriched in cell progenitors, suggesting they can retain proliferative potential. Considering heterogeneity of cell population, it is not surprising that their disorders are related to a wide range of different neuro-pathologies. Brain diseases are characterized by the active inflammatory state of the astrocytes, which is usually described as up-regulation of glial fibrillary acidic protein (GFAP). In particular, the loss of astrocytes function as a result of cellular senescence could have implications for the neurodegenerative disorders, such as Alzheimer disease and Huntington disease, and for the aging brain. Astrocytes can also drive the induction and the progression of the inflammatory state due to their Ca2+ signals and that it is strongly related to the disease severity/state. Moreover, they contribute to the altered neuronal activity in several frontal cortex pathologies such as ischemic stroke and epilepsy. There, we describe the current knowledge pertaining to astrocytes' role in brain pathologies and discuss the possibilities to target them as approach toward pharmacological therapies for neuro-pathologies.

16.
Int J Mol Sci ; 20(19)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569558

RESUMO

Diabetes causes various macrovascular and microvascular alterations, often culminating in major clinical complications (first of all, stroke) that lack an effective therapeutic intervention. N-palmitoylethanolamide-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects in treating cerebral ischemia. METHODS: Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAo) in the right hemisphere. Middle cerebral artery (MCA) occlusion was provided by introducing a 4-0 nylon monofilament (Ethilon; Johnson & Johnson, Somerville, NJ, USA) precoated with silicone via the external carotid artery into the internal carotid artery to occlude the MCA. RESULTS: A neurological severity score and infarct volumes were carried out to assess the neuroprotective effects of PEA-OXA. Moreover, we observed PEA-OXA-mediated improvements in tissue histology shown by a reduction in lesion size and an improvement in apoptosis level (assessed by caspases, Bax, and Bcl-2 modulation and a TUNEL assay), which further supported the efficacy of PEA-OXA therapy. We also found that PEA-OXA treatment was able to reduce mast cell degranulation and reduce the MCAo-induced expression of NF-κB pathways, cytokines, and neurotrophic factors. CONCLUSIONS: based on these findings, we propose that PEA-OXA could be useful in decreasing the risk of impairment or improving function in ischemia/reperfusion brain injury-related disorders.


Assuntos
Complicações do Diabetes , Etanolaminas/farmacologia , Infarto da Artéria Cerebral Média/etiologia , Infarto da Artéria Cerebral Média/metabolismo , Ácidos Palmíticos/farmacologia , Substâncias Protetoras/farmacologia , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Isquemia Encefálica/etiologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Degranulação Celular , Citocinas/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , NF-kappa B/metabolismo , Ratos , Sirtuína 1/genética , Proteína Desacopladora 2
17.
Nutrients ; 11(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514292

RESUMO

The use of a complete nutritional approach seems increasingly promising to combat chronic inflammation. The choice of healthy sources of carbohydrates, fats, and proteins, associated with regular physical activity and avoidance of smoking is essential to fight the war against chronic diseases. At the base of the analgesic, anti-inflammatory, or antioxidant action of the diets, there are numerous molecules, among which some of a lipidic nature very active in the inflammatory pathway. One class of molecules found in diets with anti-inflammatory actions are ALIAmides. Among all, one is particularly known for its ability to counteract the inflammatory cascade, the Palmitoylethanolamide (PEA). PEA is a molecular that is present in nature, in numerous foods, and is endogenously produced by our body, which acts as a balancer of inflammatory processes, also known as endocannabionoid-like. PEA is often used in the treatment of both acute and chronic inflammatory pathologies, either alone or in association with other molecules with properties, such as antioxidants or analgesics. This review aims to illustrate an overview of the different diets that are involved in the process of opposition to the inflammatory cascade, focusing on capacity of PEA and new formulations in synergy with other molecules.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Dieta Saudável , Suplementos Nutricionais , Etanolaminas/uso terapêutico , Inflamação/prevenção & controle , Ácidos Palmíticos/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Sinergismo Farmacológico , Etanolaminas/efeitos adversos , Etanolaminas/metabolismo , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Ácidos Palmíticos/efeitos adversos , Ácidos Palmíticos/metabolismo , Transdução de Sinais
18.
FASEB J ; 33(10): 11364-11380, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31344333

RESUMO

Diabetic peripheral neuropathy (DPN) is a complication of diabetes connected with morbidity and mortality. DPN presents deterioration of peripheral nerves with pain, feebleness, and loss of sensation. Particular medications might display their remedial potential by controlling neuroinflammation. Palmitoylethanolamide (PEA) is an autacoid local injury antagonist distinguished for its neuroprotective, analgesic, and anti-inflammatory properties in numerous experimental models of neuroinflammation. Based on these findings, the goal of this work was to better test the neuroprotective effects of a formulation of micronized PEA (PEA-m) and the probable mechanism of action in a mouse model of DPN induced by streptozotocin (STZ) injection. Diabetic and control animals received PEA-m (10 mg/kg) by oral gavage daily starting 2 wk from STZ injection. After 16 wk, the animals were euthanized, and blood, urine, spinal cord, and sciatic nerve tissues were collected. Our results demonstrated that after diabetes induction, PEA-m was able to reduce mechanical, thermal hyperalgesia, and motor alterations as well as reduce mast cell activation and nerve growth factor expression. In addition, PEA-m decreased neural histologic damage, oxidative and nitrosative stress, cytokine release, angiogenesis, and apoptosis. Moreover, spinal microglia activation (IBA-1), phospho-P38 MAPK, and nuclear factor NF-κB inflammatory pathways were also inhibited. The protective effects of PEA-m could be correlated at least in part to peroxisome proliferator-activated receptor-α activation. In summary, we demonstrated that PEA-m represents a new therapeutic strategy for neuroinflammation pain associated with mixed neuropathies.-Impellizzeri, D., Peritore, A. F., Cordaro, M., Gugliandolo, E., Siracusa, R., Crupi, R., D'Amico, R., Fusco, R., Evangelista, M., Cuzzocrea, S., Di Paola, R. The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice.

19.
CNS Neurol Disord Drug Targets ; 18(7): 530-554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244434

RESUMO

BACKGROUND: Delirium is a disorder in awareness, attention and cognition. Pathophysiologically it is a response to stress. Postoperative delirium (POD) is a usual complication in aged patients following hip fracture surgery. Neuroinflammation is an important factor linked with the progress of POD. Though there are no efficient cures for delirium the endocannabinoid system may have a role in neuropsychiatric disorders. OBJECTIVE: Therefore, we examined the effects of co-ultramicronized PEALut (co-ultraPEALut) in the LPS murine model of delirium and in elderly hip fractured patients. METHODS: In the preclinical study, mice were injected intraperitoneally (i.p.) with Escherichia coli LPS (10 mg/kg). Co-ultraPEALut (1 mg/kg o.s.) was administered 1h before LPS injection or 1h and 6h after LPS injection or 1h before LPS injection and 1h and 6h after LPS. In the clinical study, the effects of Glialia® (co-ultramicronized 700 mg PEA + 70 mg luteolin) administration was evaluated in elderly hip fractured patients with an interventional, randomized, single-blind, monocentric study. RESULTS: Administration of co-ultraPEALut to LPS-challenged mice ameliorated cognitive dysfunctions and locomotor activity; moreover, it reduced inflammation and apoptosis, while stimulating antioxidant response and limiting the loss of neurotrophins. In the clinical study, the results obtained demonstrated that administration of Glialia® to these surgical patients prevented the onset of POD and attenuated symptom intensity and their duration. CONCLUSION: Therefore, the results obtained enhanced the idea that co-ultraPEALut may be a potential treatment to control cognitive impairment and the inflammatory and oxidative processes associated with delirium.

20.
Phytomedicine ; 54: 27-42, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30668378

RESUMO

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is the principal cause of death, happens after prolonged obstruction of the coronary arteries.  The first intervention to limit myocardial damage is directed to restoration of perfusion, to avoid inflammatory response and a significant oxidative stress triggered by infarction. Palmitoylethanolamide (PEA), is a well-known fatty acid amide-signaling molecule that possess an important anti-inflammatory and analgesic effects. PEA does not hold the ability to inhibit free radicals formation. Baicalein, a bioactive component isolated from a Chinese herbal medicine, has multiple pharmacological activities, such as a strong anti-oxidative effects. PURPOSE: A combination of PEA and Baicalein could have beneficial effects on oxidative stress produced by inflammatory response. STUDY DESIGN: In the present study we explored the effects of composite containing PEA and Baicalein in a model of myocardial I/R injury. METHODS: Myocardial ischemia/reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-Baicalein (9:1), was administered (10 mg/kg) 5 min before the end of ischemia and 1 h after reperfusion. RESULTS: In this study, we clearly demonstrated that PEA-Baicalein treatment decreases myocardial tissue injury, neutrophils infiltration, markers for mast cell activation expression as chymase and tryptase and pro-inflammatory cytokines production (TNF-α, IL-1ß). Moreover, PEA-Baicalein treatment reduces stress oxidative and modulates Nf-kB and apoptosis pathways. CONCLUSION: These results support the idea that the association between PEA and Baicalein should be a potent candidate for the treatment of myocardial I/R injury.


Assuntos
Etanolaminas/farmacologia , Flavanonas/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ácidos Palmíticos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocardite/tratamento farmacológico , Miocardite/etiologia , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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