RESUMO
The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1-10-year-old (yo); adolescents:11-20 yo; adults 21-40 yo; and older adults: 41-75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1ß, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1-10 yo and 11-20 yo), whereas in older ages (21-40 yo and 41-75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases.
Assuntos
Vírus da Dengue , Dengue , Viroses , Adolescente , Idoso , Criança , Pré-Escolar , Humanos , Lactente , Citocinas , Vírus da Dengue/fisiologia , Imunidade , Interleucina-12 , Interleucina-6 , Sorogrupo , Fator de Necrose Tumoral alfa , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
Obesity causes low-grade inflammation that results in the development of comorbidities. In people with obesity, exacerbation of gastric lesion severity and delayed healing may aggravate gastric mucosal lesions. Accordingly, we aimed to evaluate the citral effects on gastric lesion healing in eutrophic and obese animals. C57Bl/6 male mice were divided into two groups: animals fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Gastric ulcers were induced using acetic acid (80%) in both groups. Citral (25, 100, or 300 mg/kg) was administered orally for 3 or 10 days. A vehicle-treated negative control (1% Tween 80, 10 mL/kg) and lansoprazole-treated (30 mg/kg) were also established. Lesions were macroscopically examined by quantifying regenerated tissue and ulcer areas. Matrix metalloproteinases (MMP-2 and -9) were analyzed by zymography. The ulcer base area between the two examined periods was significantly reduced in HFD 100 and 300 mg/kg citral-treated animals. In the 100 mg/kg citral-treated group, healing progression was accompanied by reduced MMP-9 activity. Accordingly, HFD could alter MMP-9 activity, delaying the initial healing phase. Although macroscopic changes were undetectable, 10-day treatment with 100 mg/kg citral exhibited improved scar tissue progression in obese animals, with reduced MMP-9 activity and modulation of MMP-2 activation.
Assuntos
Metaloproteinase 2 da Matriz , Úlcera Gástrica , Camundongos , Animais , Masculino , Úlcera Gástrica/patologia , Metaloproteinase 9 da Matriz/farmacologia , Úlcera/patologia , Dieta Hiperlipídica , Obesidade/patologia , Mucosa Gástrica/patologiaRESUMO
Ischaemia and reperfusion (I/R)-induced gastrointestinal disorders are caused by free radicals, resulting in organ damage and functional disarrangement. This study aimed to investigate the healing effects of hydroalcoholic extracts from the leaves of Eugenia punicifolia (Kunth) DC. (HEEP) in male and female Wistar rats with I/R-induced peptic injuries, and the role of antioxidants in improving this response. After I/R-induced gastric and duodenal injuries, male and female [intact (INT) and ovariectomized (OVZ)] rats were orally treated with HEEP for 6 days. Biochemical analysis was used to determine the catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities, as well as malondialdehyde and reduced glutathione levels, to measure the gastric and duodenal healing process. Six days of HEEP treatment significantly decreased the I/R-induced gastric [male (73.68%), INT (52.83%), and OVZ (43.13%)] and duodenal damage [male (57.03%), INT (56.04%), and OVZ (54.83%)] in all groups. In OVZ rats, the healing effect of HEEP occurred because of the increased activity of SOD (2x) and CAT (1.16x) in the gastric mucosa. In the duodenal mucosa of INT rats, the extract reduced MPO (20.83%) activity. The 6-day HEEP treatment improved the healing of I/R-induced peptic ulcer injury, with the system acting differently in males and females. The antioxidant system is an important component of the HEEP activity during post-I/R mucosal recovery. This result revealed the importance of antioxidant compounds in minimizing the severity of I/R-related events.
Assuntos
Eugenia , Úlcera Péptica , Traumatismo por Reperfusão , Úlcera Gástrica , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Eugenia/química , Eugenia/metabolismo , Feminino , Mucosa Gástrica , Isquemia/metabolismo , Masculino , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/metabolismo , Extratos Vegetais , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismoRESUMO
Single-domain antibodies (sdAbs) offer the affinity and therapeutic value of conventional antibodies, with increased stability and solubility. Unlike conventional antibodies, however, sdAbs do not benefit from a platform manufacturing process. While successful production of a variety of sdAbs has been shown in numerous hosts, purification methods are often molecule specific or require affinity tags, which generally cannot be used in clinical manufacturing due to regulatory concerns. Here, we have developed a broadly applicable production and purification process for sdAbs in Komagataella phaffii (Pichia pastoris) and demonstrated the production of eight different sdAbs at a quality appropriate for nonclinical studies. We developed a two-step, integrated purification process without the use of affinity resins and showed that modification of a single process parameter, pH of the bridging buffer, was required for the successful purification of a variety of sdAbs. Further, we determined that this parameter can be predicted based only on the biophysical characteristics of the target molecule. Using these methods, we produced nonclinical quality sdAbs as few as 5 weeks after identifying the product sequence. Nonclinical studies of three different sdAbs showed that molecules produced using our platform process conferred protection against viral shedding of rotavirus or H1N1 influenza and were equivalent to similar molecules produced in Escherichia coli and purified using affinity tags.
Assuntos
Anticorpos Antivirais , Vírus da Influenza A Subtipo H1N1/imunologia , Rotavirus/imunologia , Saccharomycetales/crescimento & desenvolvimento , Anticorpos de Cadeia Única , Animais , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Anticorpos de Cadeia Única/biossíntese , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/isolamento & purificaçãoRESUMO
BACKGROUND: Neonatal diarrhea remains one of the main causes of morbi-mortality in dairy calves under artificial rearing. It is often caused by infectious agents of viral, bacterial, or parasitic origin. Cows vaccination and colostrum intake by calves during the first 6 h of life are critical strategies to prevent severe diarrhea but these are still insufficient. Here we report the field evaluation of a product based on IgY antibodies against group A rotavirus (RVA), coronavirus (CoV), enterotoxigenic Escherichia coli, and Salmonella sp. This product, named IgY DNT, has been designed as a complementary passive immunization strategy to prevent neonatal calf diarrhea. The quality of the product depends on the titers of specific IgY antibodies to each antigen evaluated by ELISA. In the case of the viral antigens, ELISA antibody (Ab) titers are correlated with protection against infection in calves experimentally challenged with RVA and CoV (Bok M, et al., Passive immunity to control bovine coronavirus diarrhea in a dairy herd in Argentina, 2017), (Vega C, et al., Vet Immunol Immunopathol, 142:156-69, 2011), (Vega C, et al., Res Vet Sci, 103:1-10, 2015). To evaluate the efficiency in dairy farms, thirty newborn Holstein calves were randomly assigned to IgY DNT or control groups and treatment initiated after colostrum intake and gut closure. Calves in the IgY DNT group received 20 g of the oral passive treatment in 2 L of milk twice a day during the first 2 weeks of life. Animals were followed until 3 weeks of age and diarrhea due to natural exposure to infectious agents was recorded during all the experimental time. RESULTS: Results demonstrate that the oral administration of IgY DNT during the first 2 weeks of life to newborn calves caused a delay in diarrhea onset and significantly reduced its severity and duration compared with untreated calves. Animals treated with IgY DNT showed a trend towards a delay in RVA infection with significantly shorter duration and virus shedding compared to control calves. CONCLUSIONS: This indicates that IgY DNT is an effective product to complement current preventive strategies against neonatal calf diarrhea in dairy farms. Furthermore, to our knowledge, this is the only biological product available for the prevention of virus-associated neonatal calf diarrhea.
Assuntos
Anticorpos Antibacterianos/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Doenças dos Bovinos/terapia , Diarreia/veterinária , Imunoglobulinas/uso terapêutico , Imunoterapia , Animais , Animais Recém-Nascidos , Anticorpos Antiprotozoários , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/virologia , Criptosporidiose/prevenção & controle , Indústria de Laticínios , Diarreia/microbiologia , Diarreia/terapia , Diarreia/virologia , Imunização Passiva/métodos , Imunização Passiva/veterináriaRESUMO
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice. We also investigated the involvement of TRPV1 (transient receptor potential vanilloid 1), TRPA1 (transient receptor potential ankyrin 1), TRPM8 (transient receptor potential melastatin 8), and ASIC (acid-sensing ion channel), as well as the opioidergic, glutamatergic, and supraspinal pathways. Moreover, the nociceptive response was reduced (30 mg/kg) in the early and late phase of the formalin test. DEAB activity appears to involve the opioid system, TRPM8, and ASIC receptors, clearly showing that the DEAB alleviates acute pain in mice and suggesting the involvement of the TRPM8 and ASIC receptors and the opioid system in acute pain relief.
Assuntos
Canais Iônicos Sensíveis a Ácido/metabolismo , Analgésicos/uso terapêutico , Bignoniaceae/química , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Canais de Cátion TRPM/metabolismo , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Plantas Medicinais/químicaRESUMO
The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antidiarreicos/administração & dosagem , Cissus/química , Edema/tratamento farmacológico , Intestinos/patologia , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antidiarreicos/química , Antidiarreicos/farmacologia , Dinoprostona/metabolismo , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/metabolismo , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Xilenos/efeitos adversosRESUMO
Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.
Assuntos
Anti-Inflamatórios/administração & dosagem , Dilleniaceae/química , Edema/tratamento farmacológico , Metanol/química , Extratos Vegetais/administração & dosagem , Taninos/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Carragenina , Edema/induzido quimicamente , Injeções Intraperitoneais , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Taninos/farmacologiaRESUMO
Background: Central nervous system (CNS) infections are important causes of mortality and morbidity in children, and they are related to severe problems such as hearing loss, neurological sequelae, and death. The objective was to describe clinical and laboratory exam profiles of children who were diagnosed with CNS infections. Methods: We conducted a cross-sectional study based on medical records, which included pediatric patients aged from 3 months to 15 years, with a clinical suspicion of CNS infection between January 2014 to December 2019. The pathogens were confirmed in cerebrospinal fluid (CSF) samples using Gram staining, cell culture, molecular diagnostics (PCR and qPCR), and serology. Results: Out of the 689 enrolled patients, 108 (15.6%) had laboratory-confirmed infections in CSF. The most common bacterial pathogens isolated from the culture were Neisseria meningitidis serogroup C in 19, Streptococcus pneumoniae in 11, and Haemophilus influenzae in seven samples. The viruses identified were Enterovirus, Cytomegalovirus, Varicella-zoster virus, Epstein-Barr virus, and arbovirus. No patient was found to be positive for Herpes simplex virus 1 and 2. Patients with viral infections showed altered levels of consciousness (p = 0.001) when compared to bacterial infections. Conclusion: This study shows the presence of important vaccine-preventable pathogens, and different families of viruses causing CNS infections in the pediatric patients of Manaus.
Assuntos
Infecções do Sistema Nervoso Central , Infecções por Vírus Epstein-Barr , Humanos , Criança , Estudos Transversais , Herpesvirus Humano 4 , Afeto , Infecções do Sistema Nervoso Central/epidemiologiaRESUMO
BACKGROUND: The gold-standard techniques for measuring insulin sensitivity and secretion are well established. However, they may be perceived as invasive and expensive for use in dietary intervention studies. Thus, surrogate markers have been proposed as alternative markers for insulin sensitivity and secretion. This systematic review aimed to identify markers of insulin sensitivity and secretion in response to dietary intervention and assess their suitability as surrogates for the gold-standard methodology. METHODS: Three databases, PubMed, Scopus, and Cochrane were searched, intervention studies and randomised controlled trials reporting data on dietary intake, a gold standard of analysis of insulin sensitivity (either euglycaemic-hyperinsulinaemic clamp or intravenous glucose tolerance test and secretion (acute insulin response to glucose), as well as surrogate markers for insulin sensitivity (either fasting insulin, area under the curve oral glucose tolerance tests and HOMA-IR) and insulin secretion (disposition index), were selected. RESULTS: We identified thirty-five studies that were eligible for inclusion. We found insufficient evidence to predict insulin sensitivity and secretion with surrogate markers when compared to gold standards in nutritional intervention studies. CONCLUSIONS: Future research is needed to investigate if surrogate measures of insulin sensitivity and secretion can be repeatable and reproducible in the same way as gold standards.
Assuntos
Diabetes Mellitus , Resistência à Insulina , Biomarcadores , Glicemia , Técnica Clamp de Glucose , Humanos , Insulina , Resistência à Insulina/fisiologiaRESUMO
A panoramic analysis of chemokines, pro-inflammatory/regulatory cytokines, and growth factors was performed in serum samples from patients with acute DENV infection (n=317) by a high-throughput microbeads array. Most soluble mediators analyzed were increased in DENV patients regardless of the DENV serotype. The substantial increase (≥10-fold) of CXCL10, IL-6, and IFN-γ, and decreased levels of PDGF (<0.4-fold) was universally identified in all DENV serotypes. Of note, increased levels of CXCL8, CCL4, and IL-12 (≥3-9-fold) were selectively observed in DENV2 as compared to DENV1 and DENV4. Heatmap and biomarker signatures further illustrated the massive release of soluble mediators observed in DENV patients, confirming the marked increase of several soluble mediators in DENV2. Integrative correlation matrices and networks showed that DENV infection exhibited higher connectivity among soluble mediators. Of note, DENV2 displayed a more complex network, with higher connectivity involving a higher number of soluble mediators. The timeline kinetics (Day 0-1, D2, D3, D4-6) analysis additionally demonstrated differences among DENV serotypes. While DENV1 triggers a progressive increase of soluble mediators towards D3 and with a decline at D4-6, DENV2 and DENV4 develop with a progressive increase towards D4-6 with an early plateau observed in DENV4. Overall, our results provided a comprehensive overview of the immune response elicited by DENV infection, revealing that infection with distinct DENV serotypes causes distinct profiles, rhythms, and dynamic network connectivity of soluble mediators. Altogether, these findings may provide novel insights to understand the pathogenesis of acute infection with distinct DENV serotypes.
Assuntos
Vírus da Dengue , Dengue , Anticorpos Antivirais , Humanos , Sorogrupo , SoroRESUMO
Bovine viral diarrhoea virus (BVDV) is a major cause of economic loss in the cattle industry, worldwide. Infection results in reduced productive performance, growth retardation, reduced milk production and increased susceptibility to other diseases leading to early culling of animals. There are two primary methods used to control the spread of BVDV: the elimination of persistently infected (PI) animals and vaccination. Currently, modified live or inactivated vaccines are used in BVDV vaccination programmes, but there are safety risks or insufficient protection, respectively, with these vaccines. Here, we report the development and efficacy of the first targeted subunit vaccine against BVDV. The core of the vaccine is the fusion of the BVDV structural protein, E2, to a single-chain antibody, APCH, together termed, APCH-E2. The APCH antibody targets the E2 antigen to the major histocompatibility type II molecule (MHC-II) present on antigen-presenting cells. Industrial production of the vaccine is carried out using the baculovirus expression vector system (BEVS) using single-use manufacturing technologies. This new subunit vaccine induces strong BVDV-specific neutralizing antibodies in guinea pigs and cattle. Importantly, in cattle with low levels of natural BVDV-specific neutralizing antibodies, the vaccine induced strong neutralizing antibody levels to above the protective threshold, as determined by a competition ELISA. The APCH-E2 vaccine induced a rapid and sustained neutralizing antibody response compared with a conventional vaccine in cattle.
Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina , Doenças dos Bovinos , Vírus da Diarreia Viral Bovina , Vacinas Virais , Animais , Anticorpos Antivirais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Bovinos , Cobaias , Vacinas de Subunidades AntigênicasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC known as "carqueja" in Brazil has been acknowledged as a medicinal plant in folk medicine for the treatment of stomach aches and gastrointestinal disorders. AIM OF THE STUDY: The present study aimed to evaluate the gastroprotective and healing effects of essential oil from B. trimera (EOBT) against gastric ulcer lesions caused by absolute ethanol and acetic acid, respectively, and to identify the mechanism of action of this essential oil in male Wistar rats. MATERIALS AND METHODS: The plant material used to obtain EOBT was collected in the southern region of Brazil and was analyzed by chromatography-mass spectrometry (GCMS) demonstrate its characteristic chemical composition, with carquejyl acetate as its main component. Different doses of EOBT (50, 100, and 200 mg/kg) were administered orally in male Wistar rats as an acute treatment against absolute ethanol-induced gastric lesions. The gastric healing effect of EOBT (100 mg/kg) was evaluated once a day after 7, 10, and 14 days of treatment. After treatment, the stomachs of rats from all groups were collected to measure the lesion area (mm2), the activity of myeloperoxidase (MPO), and the relative expression of caspases -3, -8, -9, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). The zymography method was used to elucidate the activity of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in the healing action of EOBT. We also analyzed toxicological parameters (body weight evolution and biochemical parameters) that could result after treatment with this essential oil for 14 days. RESULTS: Pretreatment with EOBT (100 and 200 mg/kg) significantly decreased the severity of gastric damage induced by absolute ethanol and decreased MPO activity in gastric tissue. After 10 and 14 days of treatment with EOBT (100 mg/kg) once a day, the lesion area was significantly reduced by 61% and 65.5%, respectively, compared to the negative control group. The gastric healing effect of EOBT was followed by a decrease in the expression of COX-1 compared to that in the negative control group. Notably, treatment with EOBT for 14 days increased the expression of VEGF compared to that using an anti-ulcer drug (lansoprazole). Additionally, analyses of MMP-2 and MMP-9 activities in the gastric mucosa confirmed the accelerated gastric healing effect of EOBT, with a significant decrease in the activity of pro-MMP-2. No sign of toxicity was observed after treatment with EOBT for 14 consecutive days. CONCLUSION: These findings indicated that EOBT was effective in preventing and accelerating ulcer healing by decreasing MPO activity, increasing VEGF expression, and decreasing MMP-2 activity. These actions collectively contribute to the rapid recovery of gastric mucosa following treatment with EOBT, without any observed toxicity.
Assuntos
Antiulcerosos/farmacologia , Baccharis/química , Metaloproteinase 2 da Matriz/metabolismo , Óleos Voláteis/farmacologia , Úlcera Gástrica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ácido Acético/toxicidade , Animais , Antiulcerosos/uso terapêutico , Antiulcerosos/toxicidade , Brasil , Caspases/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Lansoprazol/farmacologia , Lansoprazol/uso terapêutico , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional , Proteínas de Membrana/metabolismo , Óleos Voláteis/uso terapêutico , Óleos Voláteis/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologiaRESUMO
Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the understanding of PUD has changed a lot with the discovery of Helicobacter pylori infection. However, this disease continues to be a challenge due to side-effects, incidence of relapse from use of various anti-ulcer medicines, and the rapid appearance of antimicrobial resistance with current H. pylori therapies. Consequently, there is the need to identify more effective and safe anti-ulcer agents. The search for new therapies with natural products is a viable alternative and has been encouraged. The literature reports the importance of monoterpenes based on the extensive pharmacological action of this class, including wound healing and anti-ulcerogenic agents. In the present study, 20 monoterpenes with anti-ulcerogenic properties were evaluated by assessing recent in vitro and in vivo studies. Here, we review the anti-ulcer effects of monoterpenes against ulcerogenic factors such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori, highlighting challenges in the field.
Assuntos
Monoterpenos/farmacologia , Úlcera Péptica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/patogenicidade , Humanos , Monoterpenos/metabolismo , Úlcera Péptica/epidemiologia , Úlcera Péptica/etiologia , Fatores de RiscoRESUMO
Citral is a mixture of monoterpenes present in the essential oil of several plants, such as Cymbopogon citratus and Zingiber officinale, possessing anti-inflammatory, anti-ulcerogenic, and antipyretic actions. We investigated the action of citral on body temperature (Tb) and inflammatory signaling in eutrophic and obese mice during Systemic Inflammation (SI) induced by Lipopolysaccharide (LPS). Thus, we assessed the effect of citral (25, 100, and 300 mg/kg) and ibuprofen in LPS-induced SI in Swiss male mice fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Following SI induction, we measured Tb and collected the serum, hypothalamus, and gastric mucosa for biochemical measurements. Acute treatment with citral decreased the Tb of both SD and HFD-fed animals. Citral (300 mg/kg) treatment caused a significantly lower Tb variation in HFD-fed animals than in those fed the SD. Citral reduced peripheral levels of tumor necrosis factor (TNF)-α in SD and HFD mice and decreased serum leptin concentration in HFD mice 90 min after the LPS challenge. Furthermore, citral also reduced interleukin (IL)-6 levels in the hypothalamus of obese mice. In summary, citral effectively reduced Tb during SI by reducing inflammatory mediators with a distinct action profile in HFD mice when compared with SD.
Assuntos
Monoterpenos Acíclicos/farmacologia , Inflamação/tratamento farmacológico , Leptina/sangue , Fator de Necrose Tumoral alfa/sangue , Monoterpenos Acíclicos/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Zingiber officinale/química , Humanos , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/sangue , Leptina/genética , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Obesos , Óleos Voláteis/química , Óleos Voláteis/farmacologiaRESUMO
:Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as "jacaranda de espinho" or "espinheira santa nativa" is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, L-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, ß-amyrin, allantoin, apigenin-7-methoxy-6-C-ß-D-glucopyranoside, and apigenin-6-C-ß-D-glucopyranosyl-8-C-ß-D-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.
Assuntos
Dor Aguda/tratamento farmacológico , Fabaceae/química , Inflamação/tratamento farmacológico , Dor Aguda/complicações , Analgésicos Opioides/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Araquidônico , Arginina/metabolismo , Peso Corporal/efeitos dos fármacos , Dinoprostona/metabolismo , Edema/tratamento farmacológico , Etanol , Feminino , Formaldeído , Glutamatos/metabolismo , Indometacina/efeitos adversos , Inflamação/complicações , Canais Iônicos/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Óxido Nítrico/metabolismo , Nociceptividade/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda , Úlcera/induzido quimicamente , Úlcera/complicações , Úlcera/tratamento farmacológico , XilenosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia punicifolia (Kunth) DC. (Myrtaceae), an Amazonian medicinal plant known as "pedra-ume-caá," is popularly used as a natural remedy for inflammation, wounds, infections, diabetes, fever, and flu. Its anti-inflammatory, antinociceptive, and gastroprotective effects have already been characterized. We evaluated the gastric healing effect of the hydroalcoholic extract of the leaves of E. punicifolia (HEEP) in male and female Wistar rats against nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol. MATERIALS AND METHODS: The healing effect of HEEP on the gastric mucosa of adult male and female Wistar rats was measured after the chronic application of aggressive factors such as NSAIDs or 80% ethanol. Male, and intact and ovariectomized (OVZ) female rats were treated with HEEP for two days (NSAIDs) or one, two, four, and six days (80% ethanol). The stomachs were analyzed macroscopically for ulcerative lesions (mm2), and the healing process was measured using biochemical analysis with anti-inflammatory and antioxidant parameters. RESULTS: Macroscopic evaluation of the gastric mucosa showed that gastric lesions induced by NSAIDs were significantly healed (66%) and pro-inflammatory interleukin 5 cytokine level was decreased after two-day oral treatment with HEEP compared with those in the negative control group (pâ¯<â¯0.05). However, the gastric lesions induced by NSAIDs did not heal in HEEP-treated female rats (pâ¯>â¯0.05). In addition, four-day treatment with HEEP significantly healed the gastric lesions induced by ethanol in male and female rats (63% and 78%, respectively) compared to those of the negative control group (pâ¯<â¯0.05). However, the OVZ group required six days of HEEP treatment to heal gastric ulcers (67% compared to the control group). HEEP exerts the healing effect against ethanol by significantly reducing neutrophil infiltration into the gastric mucosa by decreasing myeloperoxidase activity in male and OVZ rats after four and six days of treatment, respectively (pâ¯<â¯0.05). Four-day treatment with HEEP also increased the level of a non-enzymatic antioxidant, reduced glutathione in intact females compared to that of the negative control group (pâ¯<â¯0.05). CONCLUSION: These findings indicated that HEEP was effective in promoting the healing of gastric ulcers induced by NSAIDs or ethanol. The gastric healing effects of this extract could be affected by female sex hormone interference; in future, comprehensive studies should be performed by considering sex differences.
Assuntos
Antiulcerosos/farmacologia , Eugenia/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/isolamento & purificação , Antioxidantes/metabolismo , Modelos Animais de Doenças , Etanol/toxicidade , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Masculino , Folhas de Planta , Ratos , Ratos Wistar , Fatores Sexuais , Úlcera Gástrica/patologia , Cicatrização/efeitos dos fármacosRESUMO
Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti-Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine. Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-ß and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Malpighiaceae/química , Úlcera Péptica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Glutationa/metabolismo , Masculino , Medicina Tradicional/métodos , Úlcera Péptica/metabolismo , Compostos Fitoquímicos/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Medicinais/química , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: This study was undertaken to assess the relationship between physical abuse during pregnancy and preterm delivery. STUDY DESIGN: We conducted a hospital-based survey on physical abuse during pregnancy, which included 2660 women with consecutive live births. Women were interviewed and violence was assessed using the Abuse Assessment Screen. Data on sociodemographic, behavioral, and obstetric variables were also obtained. Mothers of preterm (<37 weeks; n = 217) were contrasted with mothers of term newborn infants (n = 2428). Logistic regression analysis was performed to estimate adjusted odds ratios. RESULTS: Twenty-four percent of mothers of preterm newborn infants had experienced physical abuse during pregnancy compared with 8% of mothers of term newborn infants (P < .0001). Violence was associated with preterm birth even after controlling for age, marital status, education, income, parity, planned pregnancy, antenatal care, smoking, alcohol, and illicit drugs use (odds ratio = 3.14, 95% confidence interval, 2.00-4.93). CONCLUSION: Women who have had physical abuse during pregnancy present a large increase in the risk of preterm delivery, independently from a large set of sociodemographic and behavioral characteristics usually recognized as determinants of preterm birth.
Assuntos
Trabalho de Parto Prematuro/epidemiologia , Maus-Tratos Conjugais/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Trabalho de Parto Prematuro/etiologia , Trabalho de Parto Prematuro/prevenção & controle , Portugal/epidemiologia , Gravidez , Cuidado Pré-Natal , Prevalência , Classe Social , Inquéritos e QuestionáriosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological survey indicated leaves of Byrsonima fagifolia Nied. (Malpighiaceae) against gastrointestinal disorders. AIM OF THE STUDY: The methanolic extract from the leaves of Byrsonima fagifolia (denominated BF) was evaluated for toxic, mutagenic, gastroprotective, antidiarrheal, antibacterial and immunomodulatory activities. MATERIALS AND METHODS: The preventive and healing action of BF against gastric ulcer was evaluated in experimental models in rodents. We evaluated immunomodulatory (by murine peritoneal macrophages), antidiarrheal (by induced diarrhea with castor oil and intestinal motility) and antibacterial action of BF against standard strain of Escherichia coli, Staphylococcus aureus and Helicobacter pylori. The safety of use of BF was also evaluated by mutagenic (Ames assay) and by analyses of toxicity parameters. RESULTS: Phytochemical BF profile indicated the presence of phenolic compounds with antioxidant and radical-scavenging properties. BF significantly inhibited gastric lesions induced by ethanol and HCl/ethanol and endogenous mucosal sulphydryl groups (SHs) participated efficaciously in BF gastroprotection. BF blocked development of inflammation process and also has antidiarrheal actions. This extract accelerated the healing of the gastric ulcerated mucosa by stimulating proliferative factors and by increasing production of gastric mucus with no toxic action. The substances responsible for the protective action are concentrated in the ethyl acetate fraction that demonstrated no mutagenic action in vitro. CONCLUSIONS: Byrsonima fagifolia presents gastroprotective, healing and antidiarrheal activities supporting previous claims that its traditional use by Brazilians can treat these gastrointestinal ailments.