Anti-inflammatory Effects of Compounds Extracted from Marine Sponge s: A Systematic Review.

BACKGROUND: Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs. AIMS: Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential. METHODS: This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included. RESULTS: The results were based on in vivo and in vitro assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals. CONCLUSION: In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.

The bee venom active compound melittin protects against bicuculline-induced seizures and hippocampal astrocyte activation in rats.

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.

Different Phenotypes in Asthma: Clinical Findings and Experimental Animal Models.

Asthma is a respiratory allergic disease presenting a high prevalence worldwide, and it is responsible for several complications throughout life, including death. Fortunately, asthma is no longer recognized as a unique manifestation but as a very heterogenic manifestation. Its phenotypes and endotypes are known, respectively, as pathologic and molecular features that might not be directly associated with each other. The increasing number of studies covering this issue has brought significant insights and knowledge that are constantly expanding. In this review, we intended to summarize this new information obtained from clinical studies, which not only allowed for the creation of patient clusters by means of personalized medicine and a deeper molecular evaluation, but also created a connection with data obtained from experimental models, especially murine models. We gathered information regarding sensitization and trigger and emphasizing the most relevant phenotypes and endotypes, such as Th2-high asthma and Th2-low asthma, which included smoking and obesity-related asthma and mixed and paucigranulocytic asthma, not only in physiopathology and the clinic but also in how these phenotypes can be determined with relative similarity using murine models. We also further investigated how clinical studies have been treating patients using newly developed drugs focusing on specific biomarkers that are more relevant according to the patient's clinical manifestation of the disease.

Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

Characterization and Biological Performance of Marine Sponge Collagen

Abstract This study characterized the morphological aspects of marine collagen - spongin (SPG) extract from marine sponges, as well as, evaluating its in vitro and in vivo biological performance. Aplysina fulva marine sponge was used for the SPG extraction. It was investigated the physicochemical and morphological properties of SPG by using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and compared to PMMA and bovine collagen. Additionally, the SPG cytotoxicity and its influence on cell proliferation, through in vitro tests. Moreover, the in vivo biological response was investigated using an experimental model of tibial bone defect. The results demonstrated that SPG presented an irregular granular aspect, with a composition of OH, C=O, NH, CN and an amorphous profile. Also, in vitro viability results for the L929 and MC3T3 cell lines cultured with SPG extracts demonstrated normal growth in comparison to controls, except for MC3T3 viability at day 3. For in vivo analysis, using tibial bone defects in rats, SPG treated animals presented an increased rate of material resorption and higher granulation and bone formation deposition in the region of the defect, mainly after 45 days. As a conclusion, SPG was successfully extracted. The in vitro and in vivo studies pointed out that SPG samples produced an increase in L929 and MC3T3 viability and improved the performance in tibial bone defects. It can be concluded that SPG can be used as a bone graft for bone regeneration.

Characterization of ß-cyclodextrin/myrtenol complex and its protective effect against nociceptive behavior and cognitive impairment in a chronic musculoskeletal pain model.

Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with ß-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into ß-cyclodextrin cavity. The interaction between myrtenol and ß-cyclodextrin was confirmed by molecular docking. Hence, the SC ß-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and ß-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the ß-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, ß-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.

Eplingiella fruticosa (Lamiaceae) essential oil complexed with ß-cyclodextrin improves its anti-hyperalgesic effect in a chronic widespread non-inflammatory muscle pain animal model.

Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with ßCD (HypEO-ßCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, ß-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-ßCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-ßCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with ß-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.

Memory impairment induced by different types of prolonged stress is dependent on the phase of the estrous cycle in female rats.

A growing body of evidence demonstrates that estrogen and corticosterone (CORT) impact on cognition and emotion. On the one hand, ovarian hormones may have beneficial effects on several neurophysiological processes, including memory. On the other hand, chronic exposure to stressful conditions has negative effects on brain structures related to learning and memory. In the present study, we used the plus-maze discriminative avoidance task (PMDAT) to evaluate the influence of endogenous variations of sex hormones and exposure to different types of prolonged stressors on learning, memory, anxiety-like behavior and locomotion. Female Wistar rats were submitted to seven consecutive days of restraint stress (4 h/day), overcrowding (18 h/day) or social isolation (18 h/day) and tested in different phases of the estrous cycle. The main results showed that: (1) neither stress conditions nor estrous cycle modified PMDAT acquisition; (2) restraint stress and social isolation induced memory impairments; (3) this impairment was observed particularly in females in metestrus/diestrus; (4) stressed females in estrus displayed less risk assessment behavior, suggesting reduced anxiety-like behavior; (5) restraint stress and social isolation, but not overcrowding, elevated corticosterone levels. Taken together, our findings suggest that the phase of the estrous cycle is an important modulatory factor of the cognitive processing disrupted by stress in female rats. Negative effects were observed in metestrus/diestrus, indicating that the peak of sex hormones may protect females against stress-induced memory impairment.

Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone.

Studies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women.

Estrogen levels modify scopolamine-induced amnesia in gonadally intact rats.

Previous studies suggested that estrogen plays a role in cognitive function by modulating the cholinergic transmission. However, most of the studies dealing with this subject have been conducted using ovariectomized rats. In the present study we evaluated the effects of physiological and supra-physiological variation of estrogen levels on scopolamine-induced amnesia in gonadally intact female rats. We used the plus-maze discriminative avoidance task (PMDAT) in order to evaluate anxiety levels and motor activity concomitantly to the memory performance. In experiment 1, female Wistar rats in each estrous cycle phase received scopolamine (1 mg/kg) or saline i.p. 20 min before the training session in the PMDAT. In experiment 2, rats in diestrus received estradiol valerate (1 mg/kg) or sesame oil i.m., and scopolamine (1 mg/kg) or saline i.p., 45 min and 20 min before the training, respectively. In experiment 3, rats in diestrus received scopolamine (1 mg/kg) or saline i.p. 20 min before the training, and estradiol valerate (1 mg/kg) or sesame oil i.m. immediately after the training session. In all experiments, a test session was performed 24 h later. The main results showed that: (1) scopolamine impaired retrieval and induced anxiolytic and hyperlocomotor effects in all experiments; (2) this cholinergic antagonist impaired acquisition only in animals in diestrus; (3) acute administration of estradiol valerate prevented the learning impairment induced by scopolamine and (4) interfered with memory consolidation process. The results suggest that endogenous variations in estrogen levels across the estrous cycle modulate some aspects of memory mediated by the cholinergic system. Indeed, specifically in diestrus, a stage with low estrogen levels, the impairment produced by scopolamine on the acquisition was counteracted by exogenous administration of the hormone, whereas the posttraining treatment potentiated the negative effects of scopolamine during the consolidation phase of memory.

Estresse e ansiedade em pacientes renais crônicos submetidos à hemodiálise / Stress and anxiety in chronic renal patients undergoing hemodialysis

A deficiência renal crônica é uma doença sistêmica que provoca a perda da autonomia do paciente, levando-o a limitações físicas, restrições laborais e também a perdas sociais. Pacientes com esse tipo de patologia geralmente são submetidos a sessões regulares de hemodiálise, um tratamento rigoroso e debilitante. O objetivo deste estudo foi investigar o nível de estresse e a ansiedade de pacientes submetidos à hemodiálise no Instituto do Rim de Natal, no estado do Rio Grande do Norte, Brasil. Para a coleta de dados, foram utilizados dois instrumentos: Inventário de Sintomas para Stress para Adultos de Lipp e Inventário de Ansiedade Traço-Estado. A amostra (n=100) apresentou homogeneidade em relação ao sexo, com média de idade de 46 anos e predominância de indivíduos casados, aposentados e com renda familiar baixa. Os resultados obtidos no primeiro instrumento revelaram que 71% dos pacientes encontravam-se estressados, dos quais 47% estavam na fase de resistência. Todos os pacientes entrevistados apresentaram ansiedade com níveis de moderado (66%) a severo (34%). Esses dados levam a descrever esse grupo de pacientes como altamente sujeitos ao estresse e à ansiedade.

Chronic renal failure is a systemic disease that provokes the loss of autonomy of the patient leading to physical limitations, work restrictions, and social losses. Patients with this type of pathology are usually treated by hemodialysis, a rigorous and debilitating treatment. The goal of this study was to assess levels of stress and anxiety in patients undergoing hemodialysis at the Instituto do Rim clinic in Natal in the state of Rio Grande do Norte, Brazil. The Lipp Stress Symptoms Inventory and the Trait-State Anxiety Inventory were used for the data collection. The sample (n=100) showed homogeneity in relation to gender, with a mean age of 46 and a predominance of married and retired individuals, with low family incomes. The results showed that the majority of the patients (71%) suffered high levels of stress, specifically in the resistance phase, and the incidence of psychological symptoms was greater than the physical manifestations. Furthermore, all the individuals presented moderate (66%) or high levels (34%) of anxiety. According to these data patients with chronic renal failure showed high levels of stress and anxiety.

Effects of regular meditative practice on psychological measures of healthy subjects

Introduction: Meditation is described as a method for improving attention and promoting psychological and emotional stability, presenting favorable results on cognitive functions and stress tolerance as well. Recently, studies have shown differences on psychological measurements between meditators and non-meditators. The aim of this study was to investigate the influence of regular practice of meditation on psychological measures of healthy participants in basal conditions or after experimental stress-induction. Methods: Forty-four healthy participants (20 meditators and 24 non-meditators) were evaluated by inventories of life quality, anxiety, mood, sleep quality, depression, and stress. Furthermore, all participants were submitted to working memory tasks (Hanoy tower and Digit Spam) before and after two stress-induction procedures: Stroop Color-word and Serial Subtraction tests. The research protocol was approved by the institutional ethics committee (204/09 - CEP/UFRN, CAAE 0221.0.051.000-09). Results: Our results showed that meditators presented better inventories scores when compared with non-meditators in parameters such as life quality (score 15.6 versus 14.9, p = 0.04), mood (score 6.0 versus 22.5, p = 0.02), and depression (score 2.5 versus 7.0, p = 0.01). Regarding stress levels, 10 % of meditators (against 37.5% of non-meditators) presented low levels of stress (p = 0.04). Moreover, there was an improvement in performance of meditators (23.3 ± 0.8) in relation to non-meditators (19.0 ± 1.0) on digit span task and in Hanoi tower of meditators (165.2 ± 6.1 ) in relation to non-meditation (224.1 ± 13.1) after stress induction. Conclusion: These findings corroborate other studies showing that meditation can provide an improvement in general quality of life as well as the performance of practitioners in memory tasks.

Influência da prática do yoga sobre os sintomas do climatério / Influence of yoga practice on climacteric symptoms

Introdução: Yoga vem sendo praticado há mais de três mil anos e atualmente seu conjunto de técnicas de controle do corpo e da mente tem sido adotado por milhares de pessoas em todo o mundo. Um número crescente de estudos têm atribuído ao yoga benefícios significativos para a reabilitação da saúde do indivíduo. Na mulher, o processo de envelhecimento é marcado pela suspensão da atividade folicular ovariana (menopausa) durante o período do climatério, este caracterizado por uma série de alterações fisiológicas e neuroendócrinas que podem ser acompanhadas por sintomas desconfortáveis e muitas vezes debilitantes. Objetivo: o objetivo deste estudo é investigar os efeitos psicofisiológicos da prática regular do yoga em mulheres que apresentam sintomas do climatério. Método: Noventa mulheres na faixa etária entre 45 e 65 anos, já em menopausa há pelo menos um ano foram divididas em três grupos: Grupo Controle (não participaram das atividades, n = 19), Grupo ginástica suave (2 vezes por semana, n = 31) e Grupo yoga (2 vezes por semana, n = 40). Todas as participantes foram avaliadas antes e ao final do período da intervenção (12 semanas) através dos inventários de síndrome climatérica (MRS: Menopause Rating Scale), depressão (Inventário de Depressão de Beck), estresse (Inventário de Sintomas de Stress para Adultos de Lipp) e medidas de cortisol salivar. O protocolo de pesquisa foi aprovado pelo comitê de ética (582/11/CEP/HUOL, CAAE 09930.000.294-11). Resultados: Nossos resultados mostraram que as voluntárias que praticaram yoga apresentaram redução do índice referente aos sintomas climatéricos após 12 semanas de prática (8,65 ± 1,05) em relação as voluntárias que praticaram ginástica suave (15,13 ± 1,24) e ao grupo controle que não praticou nenhuma atividade (18,58 ± 2,59), esta redução indica uma melhora nos sintomas. Além disso, os grupos ginástica suave (11,65 ± 0,95) e yoga (9,85 ± 1,17) apresentaram uma melhora significativa com relação aos níveis de depressão quando comparados ao grupo controle (18,95 ± 2,66). Após 12 semanas de pratica, os níveis de estresse também foram reduzidos no grupo yoga (0,55 ± 0,14) com relação ao controle (1,74 ± 0,31) e grupo ginástica suave (1,35 ± 0,19). Conclusões: Nossos resultados mostram que a prática deyogapode ser eficazna redução dos sintomas do climatério, além de diminuir os níveis de estresse dessas mulheres, podendo ser considerado como terapia alternativa para o manejo dos sintomas da menopausa.