RESUMEN
Hypertension is a chronic disease and a global health problem. Due to its high prevalence, it constitutes the most important risk factor for cardiovascular disease. Fruit peels from Passiflora edulis fo. flavicarpa are rich in bioactive natural compounds that may have action in hypertension. This study aimed to perform a fingerprinting analysis of Passiflora edulis fruit peel extract and evaluate its actions on the cardiovascular system in an in vivo model. The extract was obtained from the dried and powdered fruit peels of Passiflora edulis. Glycoside flavonoids were identified in the extract by HPLC-ESI-MSn. The extract showed a significant hypotensive effect after 28 days of treatment and improved vascular function in the mesenteric artery. This effect was verified by decreased vascular hypercontractility and increased vasorelaxant in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction, which can be attributed to nitric oxide's increased bioavailability. Thus, we hypothesize that all these effects contributed to a reduction in peripheral vascular resistance, leading to a significant hypotensive effect. These results are novel for fruit peels from P. edulis. Also, there was a decrease in plasma and cardiac malondialdehyde levels and an increase in glutathione, suggesting a reduction in oxidative stress, as well as an increase of anti-inflammatory cytokines such as IL-10 in the plasma. This study demonstrated that the extract can be a new source of raw material to be applied as food or medicine adjuvant for treating hypertension.
Asunto(s)
Sistema Cardiovascular , Hipertensión , Passiflora , Animales , Cromatografía Líquida de Alta Presión , Frutas/química , Hipertensión/tratamiento farmacológico , Passiflora/química , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Análisis EspectralRESUMEN
BACKGROUND: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. METHODS: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. RESULTS: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). CONCLUSION: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.
Asunto(s)
Densidad Ósea/genética , Periodontitis/genética , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 2/genética , Animales , Modelos Animales de Enfermedad , Lipopolisacáridos/toxicidad , Masculino , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo II/genética , Periodontitis/inducido químicamente , Periodontitis/diagnóstico por imagen , Periodontitis/patología , Porphyromonas gingivalis/patogenicidad , Ligando RANK/metabolismo , Microtomografía por Rayos XRESUMEN
Reactive oxygen species (ROS) are aerobic products generated during cellular respiration, but in the case of oxidative stress, they become key factors in the development of inflammatory processes and chronic diseases such as diabetes and rheumatoid arthritis. In this work, Euterpe oleracea oil (EOO), as well as the complexes produced by slurry (S) and kneading (K), were analyzed for antioxidant capacity in vitro, while only the ß-cyclodextrin complex obtained by kneading (EOO-ßCD-K), which showed better complexation, was selected for anti-inflammatory assays in vivo. In the scavenging activity of OH·, the hydroxypropyl-ß-cyclodextrin complex obtained by kneading (EOO-HPßCD-K) exhibited an activity 437% higher than the pure oil. In the paw edema assay, EOO-ßCD-K reduced edema by 200% and myeloperoxidase (MPO) activity by 112%. In an air pouch model, this treatment showed a reduction in leukocyte, MPO, and Interleukin-1ß (IL-1ß) levels; meanwhile those of glutathione and IL-10 were increased, demonstrating its ability to potentiate the anti-inflammatory effect of EOO.
Asunto(s)
Euterpe/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , 2-Hidroxipropil-beta-Ciclodextrina/administración & dosificación , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Edema/tratamiento farmacológico , Femenino , Técnicas In Vitro , Masculino , Ratones , Fitoquímicos/administración & dosificación , Fitoquímicos/química , Fitoquímicos/farmacología , Aceites de Plantas/administración & dosificación , Plantas Medicinales/química , beta-Ciclodextrinas/administración & dosificaciónRESUMEN
A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.
Asunto(s)
Pérdida de Hueso Alveolar/metabolismo , Enfermedades Mandibulares/metabolismo , Periodontitis/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Pérdida de Hueso Alveolar/genética , Pérdida de Hueso Alveolar/patología , Angiotensina II/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Enfermedades Mandibulares/genética , Enfermedades Mandibulares/patología , Ratones , Ratones Noqueados , Periodontitis/genética , Periodontitis/patología , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 2/genéticaRESUMEN
CONTEXT: Metformin is an important oral anti-hyperglycemic used in diabetes. Polylactic-co-glycolic acid (PLGA) has been widely used due to its reliability in controlling the release of drugs. OBJECTIVE: This study evaluates the in vitro-in vivo availability of metformin hydrochloride-loaded polylactic-co-glycolic acid. MATERIAL AND METHODS: In vitro metformin release (Met-free or PLGA + Met-12.5 mg/mL per 360 min) was evaluated using static Franz vertical diffusion cells. The in vivo study was performed with two control groups (validation bioanalytical method) and two experimental groups of diabetic male Wistar rats treated with PLGA + Met 10 mg/kg or Met 100 mg/kg by oral gavage. Diabetes was induced by streptozotocin (40 mg/kg) through the penile vein. Blood samples were collected 0.5, 1, 4, 7, 10, 12, 18, 24, 36, 48 and 72 h and analysed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: PLGA + Met 10 mg/kg was released in the in vitro assay suggesting a parabolic diffusion kinetic model (K -0.0619-0.5h) with a 100% release profile in 10 h by controlled diffusion. The in vivo assay showed the apparent volume of distribution Vz/F (PLGA + Met 10 mg/kg, 40971.8 mL/kg vs. Met 100 mg/kg, 2174.58 mL/kg) and mean residence time MRTinf (PLGA + Met 10 mg/kg, 37.66 h vs. Met 100 mg/kg, 3.34 h). DISCUSSION AND CONCLUSIONS: The formulation modifies pharmacokinetics parameters such as apparent distribution volume and mean residence time. The PLGA + Met 10 mg/kg had a slower elimination rate compared to Met 100 mg/kg in diabetic rats in a periodontal disease experimental model.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Enfermedades Periodontales/tratamiento farmacológico , Animales , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/química , Liberación de Fármacos , Hipoglucemiantes/farmacocinética , Masculino , Metformina/farmacocinética , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas , Ratas Wistar , Estreptozocina , Espectrometría de Masas en Tándem , Distribución TisularRESUMEN
p-Cymene (p-C) and rosmarinic acid (RA) are secondary metabolites that are present in medicinal herbs and Mediterranean spices that have promising anti-inflammatory properties. This study aimed to evaluate their intestinal anti-inflammatory activity in the trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. p-C and RA (25-200 mg/kg) oral administration reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. Both compounds (200 mg/kg) decreased malondialdehyde (MDA) and myeloperoxidase (MPO), restored glutathione (GSH) levels, and enhanced fluorescence intensity of superoxide dismutase (SOD). They also decreased interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and maintained IL-10 basal levels. Furthermore, they modulated T cell populations (cluster of differentiation (CD)4+, CD8+, or CD3+CD4+CD25+) analyzed from the spleen, mesenteric lymph nodes, and colon samples, and also decreased cyclooxigenase 2 (COX-2), interferon (IFN)-γ, inducible nitric oxide synthase (iNOS), and nuclear transcription factor kappa B subunit p65 (NFκB-p65) mRNA transcription, but only p-C interfered in the suppressor of cytokine signaling 3 (SOCS3) expression in inflamed colons. An increase in gene expression and positive cells immunostained for mucin type 2 (MUC-2) and zonula occludens 1 (ZO-1) was observed. Altogether, these results indicate intestinal anti-inflammatory activity of p-C and RA involving the cytoprotection of the intestinal barrier, maintaining the mucus layer, and preserving communicating junctions, as well as through modulation of the antioxidant and immunomodulatory systems.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Cinamatos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Cimenos/uso terapéutico , Depsidos/uso terapéutico , Mucina 2/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Cinamatos/farmacología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Cimenos/farmacología , Depsidos/farmacología , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucina 2/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Wistar , Linfocitos T/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteína de la Zonula Occludens-1/genética , Ácido RosmarínicoRESUMEN
BACKGROUND: Libidibia ferrea (L. ferrea) has been used in folk medicine to treat several conditions and to prevent cancer. This study performed a chromatographic analysis of the crude aqueous extract of Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz (LfAE) leaves and evaluated its in vivo antioxidant and anti-inflammatory potential. METHODS: Polyphenols present in LfAE were characterized by high performance liquid chromatography (HPLC). Anti-inflammatory activity was studied in an experimental model of zymosan-induced intra-articular inflammation, conducted in Wistar rats treated with LfAE at the doses of 100, 200 and 300 mg/kg by gavage. Synovial fluid was collected for global leukocyte count, for spectrocopical UV/VIS analysis of myeloperoxidase (MPO) activity, total glutathione and malondialdehyde (MDA), and for quantification of inflammatory cytokines IL1-ß and TNF-α by enzyme-linked immunosorbent assay. Synovial membrane was collected for histological analysis. The level of statistical significance was p < 0.05. RESULTS: HPLC detected concentrations of 1.56 (0.77) %m/m for ellagic acid and 1.20 (1.38) %m/m for gallic acid in LfAE leaves. Treatment with LfAE at all doses significantly decreased the leukocyte influx into the synovial fluid (p < 0.001) and myeloperoxidase activity (p < 0.001), an important marker of neutrophils. LfAE at doses of 100 (p < 0.05), 200 and 300 mg/kg (p < 0.001) also reduced the levels of MDA. LfAE at doses of 200 and 300 mg/kg significantly decreased the levels of IL-1ß (p < 0.05) and TNF-α (p < 0.001). All doses of LfAE resulted in increased levels of total glutathione (p < 0.001). Histopathological findings confirmed a reduction of the inflammatory infiltrate in the rats treated with LfAE at a dose of 200 mg/kg (p < 0.05). CONCLUSION: LfAE has an important anti-oxidant and anti-inflammatory effect on intra-articular inflammation.
Asunto(s)
Antiinflamatorios/farmacología , Caesalpinia/química , Inflamación/metabolismo , Extractos Vegetales/farmacología , Animales , Antioxidantes/metabolismo , Artritis Experimental/inducido químicamente , Artritis Experimental/metabolismo , Citocinas/metabolismo , Inflamación/inducido químicamente , Masculino , Hojas de la Planta/química , Ratas , Ratas Wistar , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/patología , ZimosanRESUMEN
BACKGROUND: The aim of this study was to evaluate the effect of olmesartan medoxomil (Olme), an angiotensin II receptor antagonist, on oral mucositis (OM) experimental model. METHODS: Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg day 1 and 40 mg/kg day 2). Animals (n = 10/group) were pretreated with oral Olme (1, 5, or 10 mg/kg) or vehicle 30 minutes before 5-FU injection and daily, until day 10. Cheek pouch samples were subjected to histopathological and immunostaining analysis of IL-1ß, TNF-α, IL-10, TGF-ß, macrophage migration inhibitory factor (MIF), SOD, MMP-2 and FGF-2. In addition, IL-1ß and TNF-α levels were evaluated by ELISA. Myeloperoxidase activity (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were investigated by spectroscopic UV/VIS analysis. Reverse transcriptase polymerase chain reactions (RT-PCRs) were used to quantify the expression of IL-1ß, TNF-α, NF-κBp65, MKP1 and ACE2. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2 protein levels were analysed by Western blot. RESULTS: Treatment with 10 mg/kg Olme reduced ulceration, inflammatory cell infiltration, MPO activity, MDA levels, iNOS and ERK1/2 proteins levels, MIF expression and TNF-α and IL-1ß of levels and gene expression. These findings were associated with a significant increase in the immunostaining of IL-10, FGF-2 and TGF-ß. In addition, gene expression of IL-1ß, TNF-α, NF-κBp65 MKP1 and ACE2 was decreased. CONCLUSION: Olmesartan at a dose of 10 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.
Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Olmesartán Medoxomilo/farmacología , Olmesartán Medoxomilo/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Estomatitis/tratamiento farmacológico , Estomatitis/metabolismo , Animales , Antimetabolitos Antineoplásicos/efectos adversos , Cricetinae , Fluorouracilo/efectos adversos , Masculino , Mesocricetus , Modelos Animales , Estomatitis/inducido químicamenteRESUMEN
BACKGROUND: This study showed phytochemical composition and evaluates the anti-inflammatory, and analgesic activities of crude extract (CE) and fractions from E. uniflora Linn leaves. METHODS: Polyphenols present in crude extract (CE), in aqueous fraction (AqF), and ethyl acetate (EAF) treated fractions from E. uniflora Linn leaves were shown by chromatographic analysis in order to conduct a phytochemical characterization. Antibacterial activity was evaluated based on minimum inhibitory concentrations (MICs) determined using the agar dilution method. Doses of 50, 100, and 200 mg/kg of the CE and fractions were applied for conducting in vivo models (male Swiss mice, 8-10 weeks old). The peritonitis experimental model was induced by carrageenan following of Myeloperoxidase activity (MPO), Total glutathione and malondialdehyde (MDA), IL-1ß and TNF-α levels by spectroscopic UV/VIS analysis. Antinociceptive activity was evaluated based on an abdominal writhing model and hot plate test. The results were statistically evaluated using one-way analysis of variance (ANOVA), followed by Bonferroni's post-hoc test. The level of statistical significance was p < 0.05. RESULTS: High-performance liquid chromatography with photodiode array detection (HPLC-DAD) detected varying concentrations of gallic acid, ellagic acid, and myricitrin in the CE and fractions obtained from E. uniflora Linn leaves (0.05-0.87%w/w, 0.20-0.32%w/w, and 1.71-6.56%w/w, respectively). In general, the CE had lower MIC values than the fractions, including the lowest MIC against the MRSA strain. The CE and AqF also significantly reduced leukocyte migration and MPO activity (p < 0.05). In addition, AqF significantly reduced IL-1ß and TNF-α levels (p < 0.05). Furthermore, the CE and fractions exhibited an antioxidant effect (p < 0.05) and peripheral analgesic activity (p < 0.05). CONCLUSIONS: The CE and fractions from the studied E. uniflora Linn leaves exhibited antibacterial, anti-inflammatory, antioxidant, and analgesic activity in the performed assays.
Asunto(s)
Antibacterianos/administración & dosificación , Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Eugenia/química , Peritonitis/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Analgésicos/administración & dosificación , Analgésicos/química , Analgésicos/aislamiento & purificación , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Glutatión/inmunología , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Masculino , Malondialdehído/inmunología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología , Ratones , Peritonitis/genética , Peritonitis/inmunología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine for treating peptic ulcers and inflammatory problems. In this context, this study aims to characterize the chemical constituents and evaluate the gastroprotective activity of the leaf juices of the two species in acute gastric lesions models. Thin Layer Chromatography (TLC) and Ultra High Performance Liquid Chromatography coupled to Mass Spectrometer (UHPLC-MS) were performed for chemical characterization. Wistar rats were pre-treated orally with leaf juices (125, 250 and 500 mg/kg) or ranitidine (50 mg/kg). The peaks observed in the chromatogram of K. brasiliensis showed similar mass spectra to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed mass spectra similar to compounds derived from quercetin, patuletin, eupafolin and kaempferol. K. brasiliensis at all doses and K. pinnata at doses of 250 mg/kg and 500 mg/kg significantly reduced the lesions in the ethanol induction model. In the indomethacin induction model, both species showed significant results at doses of 250 and 500 mg/kg. Also, the pre-treatment with leaf juices increased the antioxidant defense system, glutathione (GSH), whereas malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were significantly decreased. Treatment with leaf juices led to the upregulation of zone occludes-1 (ZO-1) and the downregulation of inducible nitric oxide synthase (iNOS) and factor nuclear-κβ transcription (NF-κB-p65), while also showing a cytoprotective effect and maintaining mucus production. These findings show that the leaf juices of the two species showed gastroprotective effects on ethanol and gastric indomethacin injury which were a consequence of gastric inflammation suppression, antioxidant activity and the maintenance of cytoprotective defenses and mucosal structure architecture.
Asunto(s)
Antioxidantes/farmacología , Etanol/efectos adversos , Gastritis/etiología , Gastritis/patología , Indometacina/efectos adversos , Kalanchoe/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Sustancias Protectoras/farmacología , Animales , Antioxidantes/química , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Gastritis/tratamiento farmacológico , Gastritis/metabolismo , Glutatión/metabolismo , Glicoproteínas/metabolismo , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Malondialdehído/metabolismo , Espectrometría de Masas , Peroxidasa/metabolismo , Extractos Vegetales/química , Sustancias Protectoras/química , Ratas , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Úlcera Gástrica/patologíaRESUMEN
Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as "salsa" or "brave salsa", belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κß-p65, STAT3, and decreased levels of TNFα, IL-1ß, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κß-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.
Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Intestinos/patología , Ipomoea/química , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Colitis/patología , Citocinas/metabolismo , Dinitrofluorobenceno/análogos & derivados , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Proteína Quinasa 8 Activada por Mitógenos/genética , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Tamaño de los Órganos , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Extractos Vegetales/farmacología , Ratas Wistar , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
Tabernaemontana catharinensis (Apocynaceae) has been popularly used by folk medicine because of its anti-inflammatory, analgesic, and antiophidic properties. This study aims to analyze the flavonoids composition of the hydroethanolic extract and of the ethyl acetate (EtOAc) and butanol (BuOH) fractions of T. catharinensis leaves, as well as to evaluate their anti-inflammatory activity using in vivo models. The phytochemical profile, determined by High-Performance Liquid Chromatography-High-Resolution Electrospray Ionization-Mass Spectrometry (HPLC-HRESI-MS), showed the presence of flavonoids mainly having an isorhamnetin nucleus. The anti-inflammatory activity was evaluated in carrageenan-induced paw edema (pre- and post-treatment) with oral administration of a T. catharinensis hydroethanolic extract (50, 100, and 150 mg/kg) and of organic fractions (50 mg/kg). The extract and fractions showed antiedematogenic activity by decreasing myeloperoxidase (MPO) production. In the zymosan-air-pouch model, the extract and fractions inhibited leukocyte migration and significantly decreased the levels of various proteins, such as MPO, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α. The cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed no cytotoxicity of the extract and the fractions. These results suggest that the hydroethanolic extract and organic fractions of T. catharinensis leaves have sufficient anti-inflammatory activity to support the popular use of this plant in the treatment of inflammatory disorders.
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Antiinflamatorios/química , Antiinflamatorios/farmacología , Fitoquímicos/análisis , Fitoquímicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Tabernaemontana/química , Animales , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Citocinas/metabolismo , Modelos Animales de Enfermedad , Edema/tratamiento farmacológico , Edema/etiología , Edema/patología , Flavonoides/análisis , Flavonoides/química , Ratones , Peroxidasa/metabolismo , Hojas de la Planta/química , Células RAW 264.7 , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The aim of this cross-sectional study was to analyse quality of life, socio-demographic characteristics, family support, satisfaction with health services, and effect of integrative community therapy among non-institutionalised elderly adults with and without symptoms of depression in the state of Rio Grande do Norte, Brazil. Data from elderly adults with (n = 59) and without (n = 61) depressive symptoms were compared. The instruments used were the Mini-Mental State Examination, the short version of the Geriatric Depression Scale, a clinical socio-demographic questionnaire, the abbreviated version of the World Health Organisation Quality of Life questionnaire, the Family Assessment Device, and the Patient Satisfaction with Mental Health Services Rating Scale. Elderly adults with depressive symptoms had lower quality of life in the social relations domain than did those without depressive symptoms (p = 0.003). In addition, compared with those without depression, fewer elderly adults with depressive symptoms attended integrative community therapy (p = 0.04); they also reported a low degree of family involvement in problem solving (p = 0.04) and showed apathy regarding their satisfaction with health services (p = 0.007). These results have important implications in the decision-making process with regard to strategies for improving the health status of elderly adults with depressive symptoms.
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Relaciones Familiares/psicología , Satisfacción del Paciente , Psicoterapia , Calidad de Vida/psicología , Anciano , Estudios de Casos y Controles , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Masculino , Servicios de Salud Mental , Cooperación del Paciente/psicologíaRESUMEN
The objective of this study was to study the effect of olmesartan medoxomil (OLM), an antihypertensive drug, on intra-articular inflammation induced by zymosan (Zy) in Wistar rats. Intra-articular inflammation was induced in the right knees of rats by 1 mg Zy dissolved in saline. The animals were divided into the following groups: saline only (oral saline and intra-articular saline); Zy only (intra-articular Zy and oral saline), and intra-articular Zy and oral OLM (5, 15, or 30 mg/kg) or diclofenac sodium (SD; 100 mg/kg). Twenty-four hours after Zy injection, synovial fluid was collected for total leukocyte counts, blood was collected for biochemical measurements, and synovial tissue was collected for histopathology, immunohistochemistry, immunofluorescence and myeloperoxidase (MPO), malonaldehyde (MDA), and non-protein sulphydryl (NPSH) assays. OLM doses of 15 and 30 mg/kg had protective effects, as evidenced by improved histopathological parameters of synovium, reduced total leukocyte counts, reduced MPO and MDA levels, and increased NPSH group levels compared with the Zy group. OLM reduced immunostaining for cyclooxygenase 2, tumour necrosis factor and interleukin 17 and increased immunostaining for superoxide dismutase and glutathione peroxidase. SD produced similar results. The drugs studied caused no change in biochemical parameters of the animals. OLM showed protective effects in this model of Zy-induced intra-articular inflammation.
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Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Imidazoles/uso terapéutico , Tetrazoles/uso terapéutico , Alanina Transaminasa/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Experimental/metabolismo , Artritis Experimental/patología , Aspartato Aminotransferasas/sangre , Creatinina/sangre , Ciclooxigenasa 2/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Imidazoles/farmacología , Interleucina-17/metabolismo , Recuento de Leucocitos , Masculino , Malondialdehído/metabolismo , Peroxidasa/metabolismo , Ratas Wistar , Superóxido Dismutasa/metabolismo , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Tetrazoles/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Urea/sangre , ZimosanRESUMEN
Complementary or alternative medicine is of great interest for the treatment of inflammatory bowel disease, with the aim of ameliorating the side effects of the drugs commonly used or improving their efficacy. In this study, we evaluated the ability of goat whey to prevent intestinal inflammation in the experimental model of acetic acid-induced rats and compared it to sulfasalazine. Pretreatment with goat whey (1, 2, and 4g/kg) and sulfasalazine (250mg/kg) on colitic rats improved colonic inflammatory markers, including myeloperoxidase activity, leukotriene B4 levels, as well as the production of proinflammatory cytokines IL-1ß and tumor necrosis factor-α. Furthermore, the administration of goat whey significantly reduced the colonic oxidative stress by reducing malondialdehyde levels and increased total glutathione content, a potent antioxidant peptide. The histological evaluation of the colonic specimens from colitic rats confirmed these beneficial effects, as goat whey preserved the colonic tissue, especially in those rats treated with the highest dose of goat whey or with sulfasalazine. The immunohistochemistry analysis of the colonic tissue evaluation also revealed a reduction in the expression of cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-9, together with an increased expression of suppressor of cytokine signaling-1. These results suggest that goat whey exerted a preventive effect against the intestinal damage induced by acetic acid, showing a similar efficacy to that shown by sulfasalazine, therefore making it a potential treatment for human inflammatory bowel disease.
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Cabras/metabolismo , Ácido Trinitrobencenosulfónico/farmacología , Suero Lácteo , Ácido Acético , Animales , Colitis/inducido químicamente , Colon , Humanos , Inflamación/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas WistarRESUMEN
This cross-sectional study compared quality of life and side effects in 108 users of olanzapine or risperidone suffering schizophrenia and being attended at psychiatric ambulatory services in Rio Grande do Norte, Brazil. Economic, socio-demographic, anthropometric, biochemical, and hormonal variables were compared. The EuroQoL Five-Dimension Scale (EQ-5D) was used to evaluate quality of life, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ(2) test and Student's t test, with a significance level of 5 %.The household incomes of approximately 80 % of patients were <2.0 minimum wages ($678). Anthropometric variables (waist circumference, hip circumference, weight, waist-to-hip ratio) and systolic and diastolic blood pressure were noted among male olanzapine users (all p < 0.05). EQ-5D scores showed that olanzapine use significantly impacted self-help ability (p < 0.001). Risperidone users had a mean quality-adjusted life year value of 1. Mean total Simpson-Angus Scale scores was 0.38 for olanzapine users and 0.11 for risperidone users (p < 0.02). Significant differences in UKU were observed for the following items: asthenia/lassitude/fatigue (higher among olanzapine users, p = 0.02), dystonia (higher among olanzapine users, p = 0.01), tremors (higher among olanzapine users, p = 0.03), gynecomastia (higher among risperidone users, p < 0.02), and ejaculatory dysfunction (higher among risperidone users, p < 0.02). Olanzapine users had impaired quality of life, which can be explained in part by adverse motor, biochemical, and hormonal effects characteristic of metabolic syndrome.
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Benzodiazepinas/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Calidad de Vida , Risperidona/efectos adversos , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Pesos y Medidas Corporales , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Olanzapina , Esquizofrenia/sangreRESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.
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Dinitrofluorobenceno/análogos & derivados , Enfermedades Inflamatorias del Intestino , Extractos Vegetales , Ratones , Animales , Extractos Vegetales/efectos adversos , Commiphora , Interleucina-17 , Factor de Necrosis Tumoral alfa , FN-kappa B , Interleucina-6 , Lipopolisacáridos/farmacología , Ciclooxigenasa 2 , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Fitoquímicos/uso terapéuticoRESUMEN
This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.
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Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Calidad de Vida , Risperidona/efectos adversos , Esquizofrenia/tratamiento farmacológico , Actividades Cotidianas , Adulto , Atención Ambulatoria/estadística & datos numéricos , Brasil , Estudios Transversales , Empleo , Femenino , Humanos , Relaciones Interpersonales , Masculino , Olanzapina , Participación SocialRESUMEN
Osteosarcopenia is a complex geriatric syndrome characterized by the presence of both sarcopenia and osteopenia/osteoporosis. This condition increases rates of disability, falls, fractures, mortality, and mobility impairments in older adults. The purpose of this study was to analyze the Fourier-transform infrared (FTIR) spectroscopy diagnostic power for osteosarcopenia in community-dwelling older women (n = 64; 32 osteosarcopenic and 32 non-osteosarcopenia). FTIR is a fast and reproducible technique highly sensitive to biological tissues, and a mathematical model was created using multivariate classification techniques that denoted the graphic spectra of the molecular groups. Genetic algorithm and support vector machine regression (GA-SVM) was the most feasible model, achieving 80.0% of accuracy. GA-SVM identified 15 wave numbers responsible for class differentiation, in which several amino acids (responsible for the proper activation of the mammalian target of rapamycin) and hydroxyapatite (an inorganic bone component) were observed. Imaging tests and low availability of instruments that allow the observation of osteosarcopenia involve high health costs for patients and restrictive indications. Therefore, FTIR can be used to diagnose osteosarcopenia due to its efficiency and low cost and to enable early detection in geriatric services, contributing to advances in science and technology that are potential "conventional" methods in the future.
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Fracturas Óseas , Osteoporosis , Sarcopenia , Humanos , Femenino , Anciano , Vida Independiente , Espectroscopía Infrarroja por Transformada de Fourier , Osteoporosis/diagnóstico por imagen , Sarcopenia/diagnósticoRESUMEN
Donkey milk (DM) is a source of bioactive compounds that can benefit neural functioning. In the present study, we investigated the effects of DM consumption on anxiolytic-related, despair-like, locomotion and coordination behaviors, as well as the provision of protection from oxidative damage to lipids and proteins in brain tissues and melatonin plasma levels. To achieve this, male mice orally received DM (4 g.kg-1) or vehicle for 18 days. Their behavior was assessed in the following tests: elevated plus maze (EPM), open field and rotarod tests (OF, RR) and forced swimming test (FST). Acute treatments with diazepam (DZP, 1.5 mg.kg-1, v.o.), fluoxetine (FLX, 20 mg.kg-1, i.p.) and nortriptyline (NTP, 20 mg.kg-1, i.p.) were used as positive controls. On the eighteenth day, the animals were euthanized and brain tissue and blood were collected to measure oxidative damage, and melatonin plasma levels. Similar to DZP, repeated DM consumption reduced exploration to open areas in the EPM test. Under our experimental conditions, conventional antidepressants reduced immobility time in the FST, and the benzodiazepine treatment impaired motor coordination in mice. No significant differences in locomotion, motor coordination and despair-related behaviors were observed in the mice treated with DM when assessed in the EPM, OF, RR and FST, respectively. Biochemical assays showed that repeated DM exposition protected against oxidative damage to lipids and increased plasma levels of melatonin. These findings suggest consumption of DM may be a promising food for the treatment of anxiety-related disorders, without depressant effects on the central nervous system.