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Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.
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Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Limoneno/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/prevenção & controle , Masculino , Camundongos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Aristolochia trilobata L. is an aromatic plant, popularly known as "mil-homens", and its essential oil (EO) is generally used to treat colic, diarrhea and dysentery disorders. We evaluated the antinociceptive effect of A. trilobata stem EO and of its major compound, the (R)-(-)-6-methyl-5-hepten-2-yl acetate (sulcatyl acetate: SA), using acetic acid (0.85%)-induced writhing response and formalin-induced (20 µL of 1%) nociceptive behavior in mice. We also evaluated the EO and SA effect on motor coordination, using the rota-rod apparatus. EO (25, 50 and 100 mg/kg) or SA (25 and 50 mg/kg) reduced nociceptive behavior in the writhing test (p<0.001). EO (100 mg/kg) and SA (25 and 50 mg/kg) decreased the nociception on the first phase of the formalin test (p<0.05). On the second phase, EO (25: p<0.01; 50: p<0.05 and 100 mg/kg: p<0.001) and SA (25 and 50 mg/kg; p<0.001) reduced the nociceptive response induced by formalin. EO and SA were not able to cause changes in the motor coordination of animals. Together, our results suggest that EO has an analgesic profile and SA seems to be one of the active compounds in this effect.
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Analgésicos/farmacologia , Aristolochia/química , Heptanol/farmacologia , Óleos Voláteis/isolamento & purificação , Caules de Planta/química , Acetatos/antagonistas & inibidores , Acetatos/farmacologia , Analgésicos/isolamento & purificação , Animais , Heptanol/análogos & derivados , Heptanol/isolamento & purificação , Masculino , Camundongos , Óleos Voláteis/química , Medição da Dor , Extratos Vegetais/química , Desempenho Psicomotor/efeitos dos fármacos , Teste de Desempenho do Rota-RodRESUMO
CONTEXT: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment. OBJECTIVE: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.
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Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Citocinas , Hiperalgesia/tratamento farmacológico , Monoterpenos/farmacologia , Receptores Opioides , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Cimenos , Citocinas/fisiologia , Relação Dose-Resposta a Droga , Hiperalgesia/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Camundongos , Monoterpenos/uso terapêutico , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Receptores Opioides/agonistas , Receptores Opioides/fisiologiaRESUMO
BACKGROUND: Given the impact of the pandemic in Brazil, vaccination is essential to prevent illness and death. Thus, this study sought to compare, after vaccination, the circulation of SARS-CoV-2 and the response to vaccination in the least and most vaccinated municipalities of a Brazilian state during the height of the pandemic when the Omicron variant was dominant. METHODS: We tested for the SARS-CoV-2 antigen and confirmed infection using an RT-qPCR and measured IgM and IgG antibodies in fully vaccinated participants from municipalities with higher and lower vaccination rates. RESULTS: We showed that participants from the least vaccinated municipalities were more likely to have detectable IgM antibodies and a positive antigen/RT-qPCR result for SARS-CoV-2 than participants from the most vaccinated municipalities. There were no differences between the vaccines used (BNT162b2, Ad26.COV2.S, AZD1222, and CoronaVac) and antibody production. CONCLUSIONS: Our study evaluated municipal vaccination coverage and its effects on mortality, infections, and anti-SARS-CoV-2 antibodies during a critical phase of the pandemic. The results suggest that higher vaccination coverage reduces acute cases and confers higher memory antibody levels against SARS-CoV-2. Even with a full vaccination schedule, individuals living in places with low vaccination rates are more susceptible to infection.
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BACKGROUND: Diabetes Mellitus (DM) is an important chronic disease that occurs worldwide. AIMS: This study aims to investigate how the use of the FreeStyle® Libre system in Unified Health System (SUS) patients impacts diabetes parameters in patients who receive education on proper insulin administration and the use of the continuous monitoring device, as well as how this affects patients without any concomitant multidisciplinary support in Sergipe, Brazil. METHODS: We conducted a prospective randomized study in a diabetes clinic in Sergipe, Brazil, using the flash method FreeStyle® Libre (Abbott). The participants were divided into two groups: one receiving diabetes education on CGM (continuous glucose monitoring), while the other did not. Before the intervention, the patient's treatment motivation and quality of life were assessed using a questionnaire, and baseline levels of glycated hemoglobin were measured using high-performance liquid chromatography (HPLC) and the point of care AlereTM Afinion with boronate fixation. We compared first- and second-phase data with respect to glycated hemoglobin, mean interstitial blood glucose, time on and above target for hypoglycemic and hyperglycemic events, and mean hypoglycemic duration. RESULTS: In group A, which received the diabetes education intervention, there was a significant reduction in average HbA1c levels from 8.6% to 7.9% after 3 months (p = 0.001). However, there was no significant difference in average glycemic values. Time above target decreased significantly from 50.62% to 29.43% (p = 0.0001), while time below target decreased from 22.90% to 20.21% (p = 0.002). There was no significant change in the number of hypoglycemic events, but the duration of hypoglycemia decreased significantly from 130.35 min to 121.18 min after 3 months (p = 0.0001). In Group B, there was no significant difference in mean HbA1c levels before (7.07%) and after (7.28%) sensor installation. This group maintained lower HbA1c levels compared to the other group. Average blood glucose levels also remained similar before (148.37 mg/dL) and after (154.65 mg/dL) the intervention. Although the time above the target glucose level increased significantly from 35.94% to 48.17%, the time at target decreased from 50.40% to 37.97%. No significant changes were observed in the time below target, the number of hypoglycemic events, or the duration of hypoglycemia. CONCLUSIONS: Our findings indicate that utilizing continuous glucose monitoring technology can enhance glycemic control, particularly in motivated, educated, low-income patients dependent on the SUS. To achieve positive results with FreeStyle Libre, it is imperative to allocate resources for multidisciplinary support.
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BACKGROUND: COVID-19 led to the suspension academic activities worldwide, affecting millions of students and staff. METHODS: In this study, we evaluated the presence of IgM and IgG anti-SARS-CoV-2 antibodies in an academic population during the return to classes after a one-year suspension. The study took place over five months at a Brazilian university and included 942 participants. RESULTS: We found that most participants had reactive IgG and non-reactive IgM. All received at least one dose, and 940 received two or more doses, of different COVID-19 vaccines. We obtained a higher average of memory antibodies (IgG) in participants who received the CoronaVac/ChAdOx1 combination. IgG was consistently distributed for each vaccine group, but individuals who completed the vaccination schedule had higher levels. There were no differences between antibodies and gender, presence of symptoms, and previous COVID-19 infection, but older participants (>53 years) and contacts of infected individuals had higher IgM levels. CONCLUSION: This study makes significant contributions to the assessment of antibodies in the academic environment, allowing us to infer that most participants had memory immunity and low indications of recent infection when returning to face-to-face classes, as well as demonstrating the need to monitor immunity and update vaccinations.
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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition.
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Background: It is estimated that one in five people worldwide faces a diagnosis of a malignant neoplasm during their lifetime. Carvacrol and its isomer, thymol, are natural compounds that act against several diseases, including cancer. Thus, this systematic review aimed to examine and synthesize the knowledge on the antitumor effects of carvacrol and thymol. Methods: A systematic literature search was carried out in the PubMed, Web of Science, Scopus and Lilacs databases in April 2020 (updated in March 2021) based on the PRISMA 2020 guidelines. The following combination of health descriptors, MeSH terms and their synonyms were used: carvacrol, thymol, antitumor, antineoplastic, anticancer, cytotoxicity, apoptosis, cell proliferation, in vitro and in vivo. To assess the risk of bias in in vivo studies, the SYRCLE Risk of Bias tool was used, and for in vitro studies, a modified version was used. Results: A total of 1,170 records were identified, with 77 meeting the established criteria. The studies were published between 2003 and 2021, with 69 being in vitro and 10 in vivo. Forty-three used carvacrol, 19 thymol, and 15 studies tested both monoterpenes. It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity, and also displayed different antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR). Conclusions: Carvacrol and thymol exhibited antitumor and antiproliferative activity through several signaling pathways. In vitro, carvacrol appears to be more potent than thymol. However, further in vivo studies with robust methodology are required to define a standard and safe dose, determine their toxic or side effects, and clarify its exact mechanisms of action. This systematic review was registered in the PROSPERO database (CRD42020176736) and the protocol is available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176736.
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The objective of the present study was to evaluate the renal function of rural workers in a city of northeastern Brazil. A cross-sectional study was carried out with 208 workers in Boquim, Sergipe, Brazil. Renal function markers and butyrylcholinesterase (BChE) were evaluated and the glomerular filtration rate (GFR) was determined. The sample consisted mainly of illiterate males with a low usage of personal protective equipment and no training. Approximately 40% had some level of renal failure. Relative risk (1.59) of GFR alteration was higher in workers with more than 5 yr of exposure, mainly to organophosphates. Workers more than 60 yr of age presented a 17.06 greater risk for manifesting acute intoxication. Butyrylcholinesterase reduction was associated with reports of intoxication (relative risk of 11.36). We concluded that exposure to pesticides represented a risk factor for the development of nephrotoxic effects and alteration of renal function, which reinforced the need to implement measures to protect rural workers. Environ Toxicol Chem 2021;40:1132-1138. © 2020 SETAC.
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Nefropatias , Doenças Profissionais , Exposição Ocupacional , Praguicidas , Agroquímicos , Brasil , Butirilcolinesterase , Estudos Transversais , Humanos , Nefropatias/induzido quimicamente , Masculino , Doenças Profissionais/induzido quimicamenteRESUMO
Even with the current advances that have been made in regard to COVID-19, such as a better understanding of the disease and the steady growth in the number of vaccinated individuals, it remains a challenge for humanity. Dealing with the disease in prison settings has been particularly difficult. This study sought to discover whether in-person visiting affected the number of cases of SARS-CoV-2 infection in the penitentiaries in the state of Sergipe (Brazil). We conducted a two-phase study (when visiting was suspended and after it recommenced) in seven penitentiaries in Sergipe using immunochromatography and nasopharyngeal swab testing to evaluate whether visiting affects the number of COVID-19 cases. In the first phase (n = 778), 57.6% of inmates reported risk factors and 32.5% were positive for COVID-19 (18.9% IgM, 24.2% IgG, 1% antigen). In the second phase, 19.6% tested positive (13.9% IgM, 7.9% IgG, 0.2% antigen). The occurrence of positive cases of COVID-19 and positive results (IgM and IgG) were significantly higher in the first phase. In the second phase, 56.7% of inmates had received visits and 18.7% were positive for COVID-19 (14% IgM, 7% IgG). Among those who had not received visits, 20.9% tested positive (13.8% IgM, 9.2% IgG, 0.5% antigen). There was no significant difference in positive cases/results between inmates that had and had not received visits. These findings suggest that, under the conditions assessed, visiting does not seem to affect the number of COVID-19 cases in prisons and reinforces the importance of sanitary measures to control dissemination.
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The emergence of a new coronavirus (SARS-CoV-2) outbreak represents a challenge for the diagnostic laboratories responsible for developing test kits to identify those infected with SARS-CoV-2. Methods with rapid and accurate detection are essential to control the sources of infection, to prevent the spread of the disease and to assist decision-making by public health managers. Currently, there is a wide variety of tests available with different detection methodologies, levels of specificity and sensitivity, detection time, and with an extensive range of prices. This review therefore aimed to conduct a patent search in relation to tests for the detection of SARS-CoV, MERS-CoV, and SARS-CoV-2. The greatest number of patents identified in the search were registered between 2003 and 2011, being mainly deposited by China, the Republic of Korea, and the United States. Most of the patents used the existing RT-PCR, ELISA, and isothermal amplification methods to develop simple, sensitive, precise, easy to use, low-cost tests that reduced false-negative or false-positive results. The findings of this patent search show that an increasing number of materials and diagnostic tests for the coronavirus are being produced to identify infected individuals and combat the growth of the current pandemic; however, there is still a question in relation to the reliability of the results of these tests.
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COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , China , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Reprodutibilidade dos Testes , República da Coreia , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
Farnesol is a sesquiterpene found in several plants, with multiple pharmacological activities. However, pharmacological actions of farnesol in the treatment of cardiac hypertrophy are not yet reported. This study aimed to investigate the effect and regulatory mechanisms of farnesol against isoproterenol-induced pathological cardiac hypertrophy. Male Wistar rats were treated for 8 days with isoproterenol (4.5 mg/kg; i. p.) and with farnesol (50 µM; i. p.). Hearts were subjected to evaluation of left ventricular developed pressure (LVDP), coronary pressure, electrocardiogram, histopathological analysis, reactive oxygen species (ROS) generation, antioxidant enzyme activity, and pro- and anti-apoptosis protein expression. The results showed that severe impairment of LVDP induced by cardiac hypertrophy was significantly prevented by farnesol treatment. Moreover, farnesol attenuated electrocardiographic changes that are characteristic of cardiac hypertrophy, as well as prevented the increase of fibrosis and migration of inflammatory cells in cardiac tissue. Additionally, farnesol treatment prevented the increase of cardiac ROS generation and restored the activity of endogenous antioxidant enzymes, such as SOD and catalase. It was also evidenced that farnesol decreased the ERK1/2, Bax and Caspase 3 activation, and an increase of AKT and Bcl-2 protein expression, which can be associated with the pathological cardiac remodeling and also with cardioprotection mediated by farnesol, respectively. These results suggest that farnesol is a novel therapeutic agent for amelioration of cardiac hypertrophy in rats.
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Cardiomegalia/prevenção & controle , Farneseno Álcool/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Agonistas Adrenérgicos beta , Animais , Antioxidantes/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/induzido quimicamente , Eletrocardiografia/efeitos dos fármacos , Isoproterenol , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
BACKGROUND: Cancer is the leading cause of death in the world and one of the main symptoms affecting these individuals is chronic pain, which must be evaluated and treated in its various components. Several drugs are currently used, but beyond the high cost, they have harmful side effects to patients or are transitorily effective. Ergo, there is a need to look for new options for cancer pain relief. Natural products (NPs) present themselves as strong candidates for the development of new drugs for the treatment of chronic pain, such as cancer pain. PURPOSE: This systematic review aimed to summarize current knowledge about the analgesic profile of NPs in cancer pain. METHODS: The search included PubMed, Scopus and Web of Science (from inception to June 2018) sought to summarize the articles studying new proposals with NPs for the management of oncological pain. Two independent reviewers extracted data on study characteristics, methods and outcomes. RESULTS: After an extensive survey, 21 articles were selected, which described the analgesic potential of 15 natural compounds to relieve cancer pain. After analyzing the data, it can be suggested that these NPs, which have targets in central and peripheral mechanisms, are interesting candidates for the treatment of cancer pain for addressing different pharmacological mechanisms (even innovative), but ensuring the safety of these compounds is still a challenge. Likewise, the cannabinoids compounds leave the front as the most promising compounds for direct applicability due to the clinical studies that have already been developed and the background already established about these effects on chronic pain. CONCLUSION: Regarding these findings, it can be concluded that the variability of possible biological sites of action is strategic for new perspectives in the development of therapeutic proposals different from those available in the current market.
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Analgésicos/farmacologia , Produtos Biológicos/farmacologia , Dor do Câncer/tratamento farmacológico , Manejo da Dor/métodos , Alcaloides/farmacologia , Analgésicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Canabinoides/farmacologia , Dor Crônica/etiologia , Flavonoides/farmacologia , Humanos , Terpenos/farmacologiaRESUMO
OBJECTIVES: The treatment of wounds accounts for a considerable fraction of health expenses as well as serious socioeconomic problems. The use of natural substances stands out as a source of new therapeutic discoveries for the wound healing. Thus, this review compiled scientific findings on the applicability of carvacrol and thymol, or essential oils containing at least one of these compounds, for the treatment of wounds. METHODS: This review was performed at PubMed, SCOPUS, Web of Science databases using keywords as wound healing, thymol/carvacrol and essential oils. Thirteen studies were selected for discussion. KEY FINDINGS: Thymol/carvacrol was able to act in the three phases of wound healing. In the first phase, they showed modulatory effect of the inflammatory cytokines, oxidative stress and antimicrobial power. In the second phase, they promoted re-epithelialization, angiogenesis and development of granulation tissue. Finally, in the third phase, they improve the collagen deposition and modulated the growth of fibroblasts and keratinocytes. CONCLUSIONS: These compounds present a high potential for the development of new therapeutic for wound repair. However, dose, efficacy and safety of these compounds for the treatment of wounds, as well as the mechanisms by which those effects can be observed, are challenges for future studies.
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Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Cimenos , Citocinas/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Timol/farmacologiaRESUMO
Skin diseases have a notable impact on the life of the affected and in their health conditions. In order to allow a more effective and economical treatment for such disorders, new therapeutic approaches have been continuously investigated. Due to its high therapeutic and phytochemical potential, Matricaria species emerges as a pleasant alternative, since it is an important source of bioactive secondary metabolites suitable for the treatment of varied skin diseases. Therefore, this review aimed to catalog inventions that have used Matricaria species as the active component for skin disease treatment in order to assess the status of the technological development of the fitomedicines. For this, a search of patents was performed in four specialized patent database, which have reported the discovery of pharmaceutical bioproducts that used Matricaria species in its composition for skin treatment. Therefore, it is possible to notice that the pharmaceutical industry has driven efforts and investment to produce medicines for the dermatopathies, using species of this genus as an active principle. Besides, a trend of growth has been identified for the last years, which is accompanied by the continuous publication of scientific articles on the subject. It is known that a long journey is traversed between the scientific findings and their applications in the pharmaceutical market, creating the perspective that new Matricaria-based medicines may reach the pharmaceutical market in the coming years.
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Matricaria/química , Fitoterapia , Extratos Vegetais/farmacologia , Dermatopatias/tratamento farmacológico , Humanos , Patentes como Assunto , Compostos Fitoquímicos/farmacologiaRESUMO
Macrophages are immune system cells that respond to various pathogenic insults. The recognition of antigens is performed through receptors such as TLR4 and RAGE, which recognize pathogen-associated patterns (PAMPs), including lipopolysaccharide (LPS) from Gram-negative bacteria. Carvacrol (CAR) is a phenolic compound found in some essential oils commonly used in folk medicine for treatment of inflammation-related diseases. Previous works observed strong antioxidant actions and some anti-inflammatory effects by CAR in in vivo and in vitro assays. However, the potential pharmacological application of CAR remains limited as details on its mechanisms of action are still missing. Here we investigated the molecular pathways by which CAR acts on LPS-mediated pro-inflammatory activation of RAW 264.7 macrophages. CAR 100⯵M protected cells against loss of cell viability induced by LPS (1⯵g/mL). Pre-incubation with CAR prevented LPS-induced ERK1/2 phosphorylation, but it had no effect on p38 and JNK activation. The effect of LPS on NF-kB (p65) translocation from cytoplasm to nucleus was inhibited by CAR, as well as NF-kB transcriptional activation. Moreover, LPS-elicited release of TNF-α and IL-1ß were inhibited by CAR, as well as activation of phagocytic activity. Such effects may be related to the antioxidant effect of CAR, as the LPS-induced increase in reactive species (RS) production (assessed by DCFH oxidation) and nitric oxide (NO) production (assessed by nitrite quantification) were inhibited by CAR. Altogether, these results demonstrate that CAR exerts relevant anti-inflammatory actions through a cellular mechanism involving ERK1/2 and NF-kB inhibition and possibly related to the antioxidant properties of this phenolic compound.
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Anti-Inflamatórios/farmacologia , Cimenos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , NF-kappa B/metabolismo , Animais , Lipopolissacarídeos , Camundongos , Nitritos/metabolismo , Fagocitose/efeitos dos fármacos , Células RAW 264.7RESUMO
Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with ß-cyclodextrin (ßCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-ßCD (50â¯mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in ßCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-ßCD reduced (pâ¯<â¯0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-ßCD inhibited (pâ¯<â¯0.05) TNF-α production in the spinal cord and stimulated (pâ¯<â¯0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-ßCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-ßCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in ßCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.
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Citocinas/metabolismo , Gliose/tratamento farmacológico , Hiperalgesia/induzido quimicamente , Inflamação/tratamento farmacológico , Sesquiterpenos Monocíclicos/uso terapêutico , Neuralgia/tratamento farmacológico , beta-Ciclodextrinas/uso terapêutico , Animais , Proteínas de Ligação ao Cálcio/biossíntese , Adjuvante de Freund , Temperatura Alta , Hiperalgesia/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , Proteínas dos Microfilamentos/biossíntese , Força Muscular/efeitos dos fármacos , Neuralgia/induzido quimicamente , Neuralgia/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Medula Espinal/metabolismo , EstereoisomerismoRESUMO
Agriculture accountsfor an important economic activity worldwide and the search for the increased productivity incorporated the use of pesticides in this practice. Such compounds have significant environmental and human health effects, especially for workers exposed to them. Among the main health problems caused by pesticides are the renal alterations, which in more advanced stages comprise an important public health problem. For this reason, this systematic review aimed at gathering evidence of the risk of renal changes induced by occupational exposure to pesticides. The search was made in PubMed, Scopus, Lilacs and Scielo in December 2017, using keywords as pesticides, poisoning, kidney, renal insufficiency. After the application of inclusion criteria, 11 studies were selected. It was possible to gather evidence on the prevalence and risk (3.12-6.71) of renal injury from the occupational exposure of agricultural workers and its association with the exposure to agrichemicals, as organophosphates and herbicides.
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Doenças dos Trabalhadores Agrícolas/fisiopatologia , Praguicidas/toxicidade , Insuficiência Renal/induzido quimicamente , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Herbicidas/toxicidade , Humanos , Testes de Função Renal , Exposição Ocupacional , Organofosfatos/toxicidade , Insuficiência Renal/fisiopatologiaRESUMO
The toxicological assessment of plant products and pharmaceutical chemicals is a necessary requirement to ensure that all compounds are safe to be exposed to humans. Many countries are trying to reduce the use of animals; thus, alternative techniques, such as ex vivo tests, in vitro assays, and ex uteri embryos, are used. Toxicological assays using zebrafish embryos are an advantageous technique because they are transparent, have rapid embryonic development, and do not require invasive techniques. This paper comprehensively reviews how toxicity testing with plant products is conducted in zebrafish embryos. The search terms zebra fish, Danio rerio, zebrafish, zebra danio, Brachydanio rerio, zebrafish, and embryos were used to search for English-language articles in PUBMED, SCOPUS, and WEB OF SCIENCE. Twelve articles on plant product toxicity studies using zebrafish were selected for reading and analysis. After analyzing the articles and comparing with results in mammals, it was possible to prove the similarity among the results and thus corroborate the further development of zebrafish as a valid tool in toxicity tests.