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Linalool-rich Rosewood oil (Aniba rosaeodora Ducke) is a natural compound widely used in perfumery industry. Evidence suggests that linalool exerts antidepressant and anxiolytic effects. Conversely, ethanol binge drinking (i.e., intermittent and episodic consumption) during adolescence elicits neurobehavioral alterations associated with brain damage. Here, we investigated whether linalool-rich Rosewood oil administration can improve the emotional and molecular impairments associated with ethanol binge-like exposure during adolescence in female rats. Rosewood oil was obtained by hydrodistillation and posteriorly analyzed. Adolescent female Wistar rats received four-cycles of ethanol binge-like pattern (3 g/kg/day, 3 days on/4 days off) and daily Rosewood oil (35 mg/kg, intranasally) for 28 days. Twenty-four hours after treatments, it was evaluated the impact of ethanol exposure and Rosewood oil treatment on the putative emotional impairments assessed on the splash and forced swimming tests, as well as the levels of brain-derived neurotrophic factor (BDNF), S100B, oxidative parameters, and inflammatory cytokines in prefrontal cortex and hippocampus. Results indicated that Rosewood oil intranasal administration mitigated emotional impairments induced by ethanol exposure accompanied by a marked increase in BDNF, S100B, glutathione (GSH), and antioxidant activity equivalent to Trolox (TEAC) levels in brain areas. Rosewood oil treatment also prevented the ethanol-induced increase of interleukin-1ß, interleukin-6, tumor necrosis factor α (TNF-α), and neurofilament light chain (NFL) levels. These findings provide the first evidence that Rosewood oil intranasal administration exerts protective effects against emotional and molecular impairments associated with adolescent ethanol binge-like exposure, possibly due to linalool actions triggering neurotrophic factors, rebalancing antioxidant status, and attenuating proinflammatory process.

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Ethanol is one of the psychoactive substances most used by young individuals, usually in an intermittent and episodic manner, also called binge drinking. In the adolescent period, brain structures undergo neuromaturation, which increases the vulnerability to psychotropic substances. Our previous studies have revealed that ethanol binge drinking during adolescence elicits neurobehavioral alterations associated with brain damage. Thus, we explored the persistence of motor function impairment and cerebellum damage in the context of ethanol withdrawal periods (emerging adulthood and adult life) in adolescent female rats. Female Wistar rats (35 days old) received orally 4 cycles of ethanol (3.0 g/kg/day) or distilled water in 3 days on-4 days off paradigm (35th until 58th day of life). Motor behavioral tests (open field, grip strength, beam walking, and rotarod tests) and histological assays (Purkinje's cell density and NeuN-positive cells) were assessed on the 1-, 30-, and 60-days of binge alcohol exposure withdrawal. Our findings demonstrate that the adolescent binge drinking exposure paradigm induced cerebellar cell loss in all stages evaluated, measured through the reduction of Purkinje's cell density and granular layer neurons. The cerebellar tissue alterations were accompanied by behavioral impairments. In the early withdrawal, the reduction of spontaneous movement, incoordination, and unbalance was seen. However, the grip strength reduction was found at long-term withdrawal (60 days of abstinence). The cerebellum morphological changes and the motor alterations persisted until adulthood. These data suggest that binge drinking exposure during adolescence causes motor function impairment associated with cerebellum damage, even following a prolonged withdrawal, in adult life.

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Petiveria alliacea L. (Phytolaccaceae) holds significant importance in the Amazon region, where it has been traditionally utilized in folk medicine. In this study, we conducted a comprehensive bibliometric analysis using conventional metrics, combined with a critical content review of its pharmacological and toxicological properties, to identify gaps in the existing literature that require further investigation. Our investigation identified a total of 55 articles that met the inclusion criteria for this study. Remarkably, Brazil emerged as the primary contributor within the scope of this review, indicating a strong presence of research from this country. Furthermore, professional scientific societies have played a pivotal role in facilitating the dissemination of scientific findings through specialist journals, fostering the sharing of research work within the community. Analysis of keyword co-occurrence revealed that "Petiveria alliacea", "plant extract", and "guatemala" were the most frequently encountered terms, indicating their significance within the literature. In terms of study designs, in vivo and in vitro were the predominant types observed, highlighting their prevalence in this field of study. Our study also identified a lack in knowledge yet to be investigated.

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Amitriptyline was first introduced as a medication to treat depression. Over time, this substance has been used to treat other conditions, such as gastrointestinal disorders, fibromyalgia, neuropathic pain, and analgesia, among others. However, there are no published studies that provide a broad view of the possible motivations that have led to changes in the use of amitriptyline. In this study, we have identified the landscape of use for amitriptyline based on knowledge mapping of the 100 most-cited articles about this drug. We searched Web of Science Core Collection without time and language restrictions. We obtained 14,446 results, but we only used the 100 most-cited articles that had amitriptyline as the object of study. We collected the following information from each article: authors, country of the corresponding authors, year of publication, citation count, citation density (number of citations per year), and keywords. In addition, we seek to map in the chosen articles study design and research findings. We found that since 1980, the use of amitriptyline has expanded beyond depression, moving to off-label use to treat a variety of diseases and conditions, including post-herpetic neuralgia, neuropathic pain, primary fibrosis, fibromyalgia, and migraine, can be considered a drug with more clinical applicability than its original clinical indication.

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The developing central nervous system is vulnerable to several stimuli, especially psychotropic drugs. Sedation procedures during the developmental period are frequent in pediatric intensive care units (PICUs), in which the use of the sedative agent is still a challenge for the PICU team. Ketamine has been indicated for sedation in critically ill children with hemodynamic and ventilatory instabilities, but the possible neurobehavioral consequences related to this use are still uncertain. Here, we performed a bibliometric analysis with conventional metrics and a critical review of clinical findings to reveal a gap in the literature that deserves further investigation. We revealed that only 56 articles corresponded to the inclusion criteria of the study. The United States of America emerges as the main country within the scope of this review. In addition, professional clinical societies play a key role in the publications of scientific clinical findings through the specialist journals, which encourages the sharing of research work. The co-occurrence of keywords evidenced that the terms "sedation", "ketamine", and "pediatric" were the most frequent. Case series and review articles were the most prevalent study design. In the critical evaluation, the scarce studies highlight the need of use and post-use monitoring, which reinforces the importance of additional robust clinical studies to characterize the possible adverse effects resulting from ketamine anesthetic protocol in critically ill children.

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Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf's ethanolic extract is determined by ultra-performance liquid chromatography-high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals' consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.

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Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups. The protocol administration was performed for 3 consecutive days (binge-like pattern). Behavioral assays of open field, elevated plus maze, and forced swim test were performed. After that, the prefrontal cortex and hippocampus were collected to evaluate oxidative biochemistry (reactive oxygen species-ROS; Antioxidant capacity against peroxyl radicals-ACAP; and lipid peroxidation). We found that isolated or combined ethanol and ketamine exposure displayed anxiety- and depressive-like profile, in a non-synergistically manner during early withdrawal. However, oxidative damage was aggravated in the co-administered animals than in isolated exposed subjects. We concluded that ethanol plus ketamine co-abuse may intensify oxidative damage in the hippocampus and prefrontal cortex in the early withdrawal of adolescent female rats, which was not reflected in the emotional behavioral phenotype. DATA AVAILABILITY STATEMENT: The datasets used and/or analyzed during the current investigation are available upon reasonable request from the corresponding author.

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Ganoderma lucidum is a mushroom that has been widely used for centuries in Asian countries for its antiaging properties. It is popularly known as "Ling Zhi," "Reishi," and "Youngzhi," and because of its benefits, it is known as the "immortality mushroom." Pharmacological assays have revealed that G. lucidum ameliorates cognitive impairments through inhibition of ß-amyloid and neurofibrillary tangle formation, antioxidant effect, reduction of inflammatory cytokine release and apoptosis, genic expression modulation, among other activities. Chemical investigations on G. lucidum have revealed the presence of metabolites such as triterpenes, which are the most explored in this field, as well as flavonoids, steroids, benzofurans, and alkaloids; in the literature, these have also been reported to have mnemonic activity. These properties of the mushroom make it a potential source of new drugs to prevent or reverse memory disorders, as actual medications are able to only alleviate some symptoms but are unable to stop the progress of cognitive impairments, with no impact on social, familiar, and personal relevance. In this review, we discuss the cognitive findings of G. lucidum reported in the literature, converging the proposed mechanisms through the several pathways that underlie memory and cognition processes. In addition, we highlight the gaps that deserve particular attention to support future studies.

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Binge drinking intake is the most common pattern of ethanol consumption by adolescents, which elicits emotional disturbances, mainly anxiety and depressive symptoms, as well as cognitive alterations. Ethanol exposure may act on the adenosine neuromodulation system by increasing adenosine levels, consequently increasing the activation of adenosine receptors in the brain. The adenosine modulation system is involved in the control of mood and memory behavior. However, there is a gap in the knowledge about the exact mechanisms related to ethanol exposure's hazardous effects on the immature brain (i.e., during adolescence) and the role of the adenosine system thereupon. The present review attempts to provide a comprehensive picture of the role of the adenosinergic system on emotional and cognitive disturbances induced by ethanol during adolescence, exploring the potential benefits of caffeine administration in view of its action as a non-selective antagonist of adenosine receptors.

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Ketamine, also called 'K-powder' by abusers, an analog of phencyclidine, primarily acts as an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, therapeutically used as an anesthetic agent. Ketamine also stimulates the limbic system, inducing hallucinations and dissociative effects. At sub-anesthetic doses, ketamine also displays hallucinatory and dissociative properties, but not loss of consciousness. These behavioral consequences have elicited its recreational use worldwide, mainly at rave parties. Ketamine is generally a drug of choice among teenagers and young adults; however, the harmful consequences of its recreational use on adolescent central nervous systems are poorly explored. Thus, the aim of the present study was to characterize the behavioral and biochemical consequences induced by one binge-like cycle of ketamine during the early withdrawal period in adolescent female rats. Adolescent female Wistar rats (n = 20) received intraperitoneally administered ketamine (10 mg/kg/day) for 3 consecutive days. Twenty-four hours after the last administration of ketamine, animals were submitted to behavioral tests in an open field, elevated plus-maze, and forced swimming test. Then, animals were intranasally anesthetized with 2% isoflurane and euthanized to collect prefrontal cortex and hippocampus to assess lipid peroxidation, antioxidant capacity against peroxyl radicals, reactive oxygen species, reduced glutathione, and brain-derived neurotrophic factor (BDNF) levels. Our results found that 24 h after recreational ketamine use, emotional behavior disabilities, such as anxiety- and depression-like profiles, were detected. In addition, spontaneous ambulation was reduced. These negative behavioral phenotypes were associated with evidence of oxidative stress on the prefrontal cortex and hippocampus.

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Alcohol consumption is spread worldwide and can lead to an abuse profile associated with severe health problems. Adolescents are more susceptible to addiction and usually consume ethanol in a binge drinking pattern. This form of consumption can lead to cognitive and emotional disorders, however scarce studies have focused on long-term hazardous effects following withdrawal periods after binge drinking in adolescents. Thus, the present study aims at investigating whether behavioral and cognitive changes persist until mid and late adulthood. Female Wistar rats (9-10 animals/group) received intragastric administration of four cycles of ethanol binge-like pattern (3.0 g/kg/day, 20% w/v; 3 days-on/4 days-off) from 35th to 58th days old, followed withdrawal checkpoints 1 day, 30 days, and 60 days. At each checkpoint period, behavioral tests of open field, object recognition test, elevated plus maze, and forced swimming test were performed, and blood and hippocampus were collected for oxidative biochemistry and brain-derived neurotrophic factor (BDNF) levels analysis, respectively. The results demonstrated that adolescent rats exposed to binge drinking displayed anxiogenic- and depressive-like phenotype in early and midadulthood, however, anxiety-like profile persisted until late adulthood. Similarly, short-term memory was impaired in all withdrawal periods analysed, including late adult life. These behavioral data were associated with oxidative damage in midadulthood but not BDNF alterations. Taken together, the present work highlights the long-lasting emotional and cognitive alterations induced by ethanol binge drinking during adolescence, even after a long period of abstinence, which might impact adult life.

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The present study aimed to investigate the antioxidant activity of Aniba canelilla (kunth) Mez (Lauraceae) essential oil (AcEO), exploring its potential for prevention and/or treatment of oxidative stress and associated inflammatory process. With this aim, Wistar rats (n = 6/group) were pre-treated intraperitoneally with saline (0.9%) or AcEO (2 or 5 mg/kg) for 5 days. One hour after the last dose, inflammation and oxidative stress were induced by carrageenan (0.3 mg/kg; ip.) administration. Total antioxidant capacity, reduced glutathione (GSH) and lipid peroxidation levels, protein concentration, and leukocyte migration were evaluated in peritoneal fluid. Lipid peroxidation was also evaluated in plasma. Carrageenan strongly reduced the peritoneal antioxidant capacity and GSH concentration, increasing peritoneal and plasma lipid peroxidation. It also promoted increased plasma leakage and leukocyte migration. Treatment with AcEO (2 and 5 mg/kg), whose major constituent was 1-nitro-2-phenylethane (77.5%), increased the peritoneal antioxidant capacity and GSH concentrations, and reduced lipid peroxidation, both peritoneal and plasma, thus inhibiting the carrageenan-induced oxidative imbalance. AcEO also reduced the carrageenan-induced plasma leakage and leukocyte migration. These data demonstrate the AcEO antioxidant activity and its ability to modulate plasma leakage and leukocyte migration, confirming its potential for treating diseases associated with inflammation and oxidative stress.

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Margaritaria nobilis is a shrubby species widely distributed in Brazil from the Amazon to the Atlantic Rainforest. Its bark and fruit are used in the Peruvian Amazon for disinfecting abscesses and as a tonic in pregnancy, respectively, and its leaves are used to treat cancer symptoms. From analyses via UHPLC-MS/MS, we sought to determine the chemical profile of the ethanolic extract of M. nobilis leaves by means of putative analyses supported by computational tools and spectral libraries. Thus, it was possible to annotate 44 compounds, of which 12 are phenolic acid derivatives, 16 are O-glycosylated flavonoids and 16 hydrolysable tannins. Among the flavonoids, although they are known, except for kaempferol, which has already been isolated from this species, the other flavonoids (10, 14, 15, 21, 24-26, 28-30, 33-35, 40 and 41) are being reported for the first time in the genus. Among the hydrolysable tannins, six ellagitannins present the HHDP group (6, 19, 22, 31, 38 and 43), one presents the DHHDP group (5), and four contain oxidatively modified congeners (12, 20, 37 and 39). Through the annotation of these compounds, we hope to contribute to the improved chemosystematics knowledge of the genus. Furthermore, supported by a metric review of the literature, we observed that many of the compounds reported here are congeners of authentically bioactive compounds. Thus, we believe that this work may help in understanding future pharmacological activities.

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Drug abuse has become a public health concern. The misuse of ketamine, a psychedelic substance, has increased worldwide. In addition, the co-abuse with alcohol is frequently identified among misusers. Considering that ketamine and alcohol share several pharmacological targets, we hypothesize that the consumption of both psychoactive substances may synergically intensify the toxicological consequences, both under the effect of drugs available in body systems and during withdrawal. The aim of this review is to examine the toxicological mechanisms related to ketamine plus ethanol co-abuse, as well the consequences on cardiorespiratory, digestive, urinary, and central nervous systems. Furthermore, we provide a comprehensive discussion about the probable sites of shared molecular mechanisms that may elicit additional hazardous effects. Finally, we highlight the gaps of knowledge in this area, which deserves further research.

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This case report describes the long-term behavioral and cognitive alterations in a critically ill pediatric patient submitted to a ketamine sedation and analgesia protocol for 7 consecutive days in a pediatric intensive care unit. The infant exhibited withdrawal syndrome in the early withdrawal period, as measured using the Withdrawal Assessment Tool-1 (WAT-1). In the days following ketamine withdrawal, behavioral, motor, and cognitive impairment was observed, even after hospital discharge. At 20 days after admission to hospital, the infant still displayed language deficits compatible with the at-risk category for the appropriate age group on the development assessment (Denver-II Developmental Screening Test). The infant's mother reported that these impairments were not present before ketamine sedation. We therefore suggest that prolonged ketamine use may have contributed to the long-lasting behavioral and cognitive impairments observed in the critically ill infant. These adverse effects may be attributable to ketamine's pharmacological mechanism of action, by which the N-methyl-D-aspartate receptor-the central nervous system excitatory receptor responsible for memory and learning domains-is blockaded, disrupting long-term potentiation events. Our case highlights the need for clinical evaluation of ketamine agents and their associated risks in intensive care units to better clarify appropriate sedative and analgesic agents during neurodevelopmental periods of life.

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Depression is a prevalent disease worldwide, limiting psychosocial functioning and thequality of life. Linalool is the main constituent of some essential oils from aromatic plants, representing about 70% of these volatile concentrates. Evidence of the linalool activity on the central nervous system, mainly acting as an antidepressant agent, is increasingly abundant. This review aimed to extend the knowledge of linalool's antidepressant action mechanisms, which is fundamental for future research, intending to highlight this natural compound as a new antidepressant phytomedication. A critical analysis is proposed here with probable hypotheses of the synergic mechanisms that support the evidence of antidepressant effects of the linalool. The literature search has been conducted in databases for published scientific articles before December 2020, using relevant keywords. Several pieces of evidence point to the anticonvulsant, sedative, and anxiolytic actions. In addition to these activities, other studies have revealed that linalool acts on the monoaminergic and neuroendocrine systems, inflammatory process, oxidative stress, and neurotrophic factors, such as BDNF, resulting in considerable advances in the knowledge of the etiology of depression. In this context, linalool emerges as a promising bioactive compound in the therapeutic arsenal, capable of interacting with numerous pathophysiological factors and acting on several targets. This review claims to contribute to future studies, highlighting the gaps in the linalool knowledge, such as its kinetics, doses, routes of administration, and multiple targets of interaction, to clarify its antidepressant activity.

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Mercury is a heavy metal found in organic and inorganic forms that represents an important toxicant with impact on human health. Mercury can be released in the environment by natural phenoms (i.e., volcanic eruptions), industrial products, waste, or anthropogenic actions (i.e., mining activity). Evidence has pointed to mercury exposure inducing neurological damages related to emotional disturbance, such as anxiety, depression, and insomnia. The mechanisms that underlie these emotional disorders remain poorly understood, although an important role of glutamatergic pathways, alterations in HPA axis, and disturbance in activity of monoamines have been suggested. Ethanol (EtOH) is a psychoactive substance consumed worldwide that induces emotional alterations that have been strongly investigated, and shares common pathophysiological mechanisms with mercury. Concomitant mercury and EtOH intoxication occur in several regions of the world, specially by communities that consume seafood and fish as the principal product of nutrition (i.e., Amazon region). Such affront appears to be more deleterious in critical periods of life, such as the prenatal and adolescence period. Thus, this review aimed to discuss the cellular and behavioral changes displayed by the mercury plus EtOH exposure during adolescence, focused on emotional disorders, to answer the question of whether mercury plus EtOH exposure intensifies depression, anxiety, and insomnia observed by the toxicants in isolation.

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Psychoactive substances during pregnancy and lactation is a key problem in contemporary society, causing social, economic, and health disturbance. In 2010, about 30 million people used opioid analgesics for non-therapeutic purposes, and the prevalence of opioids use during pregnancy ranged from 1% to 21%, representing a public health problem. This study aimed to evaluate the long-lasting neurobehavioral and nociceptive consequences in adult offspring rats and mice exposed to morphine during intrauterine/lactation periods. Pregnant rats and mice were exposed subcutaneously to morphine (10 mg/kg/day) during 42 consecutive days (from the first day of pregnancy until the last day of lactation). Offspring were weighed on post-natal days (PND) 1, 5, 10, 15, 20, 30, and 60, and behavioral tasks (experiment 1) or nociceptive responses (experiment 2) were assessed at 75 days of age (adult life). Morphine-exposed female rats displayed increased spontaneous locomotor activity. More importantly, both males and female rats perinatally exposed to morphine displayed anxiety- and depressive-like behaviors. Morphine-exposed mice presented alterations in the nociceptive responses on the writhing test. This study showed that sex difference plays a role in pain threshold and that deleterious effects of morphine during pre/perinatal periods are nonrepairable in adulthood, which highlights the long-lasting clinical consequences related to anxiety, depression, and nociceptive disorders in adulthood followed by intrauterine and lactation morphine exposure.

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Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well-explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro-inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.

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Peperomia pellucida (PP) belongs to the Peperomia genus, which has a pantropic distribution. PP is used to treat a wide range of symptoms and diseases, such as pain, inflammation, and hypertension. Intriguingly, PP extract is used by different tropical countries for its anti-inflammatory and antinociceptive effects. In fact, these outcomes have been shown in animal models, though the exact bioactive products of PP that exert such results are yet to be discovered. To determine and elucidate the mechanism of action of one of these compounds, we evaluated the antinociceptive effect of the novel dimeric ArC2 compound, Pellucidin A by using in vivo and in silico models. Animals were then subjected to chemical, biphasic and thermal models of pain. Pellucidin A induced an antinociceptive effect against chemical-induced pain in mice, demonstrated by the decrease of the number of writhes, reaching a reduction of 43% and 65% in animals treated with 1 and 5 mg/kg of Pellucidin A, respectively. In the biphasic response (central and peripheral), animals treated with Pellucidin A showed a significant reduction of the licking time exclusively during the second phase (inflammatory phase). In the hot-plate test, Pellucidin A did not have any impact on the latency time of the treated animals. Moreover, in vivo and in silico results show that Pellucidin A's mechanism of action in the inflammatory pain occurs most likely through interaction with the nitric oxide (NO) pathway. Our results demonstrate that the antinociceptive activities of Pellucidin A operate under mechanism(s) of peripheral action, involving inflammatory mediators. This work provides insightful novel evidence of the biological properties of Pellucidin A, and leads to a better understanding of its mechanism of action, pointing to potential pharmacological use.

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