Publications by authors named "Adriano Francisco Alves"

17 Publications

  • Page 1 of 1

MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice.

Int Immunopharmacol 2021 Apr 13;96:107590. Epub 2021 Apr 13.

Laboratory of Immunopharmacology, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, PB, Brazil; Department of Physiology and Pathology, Federal University of Paraíba, João Pessoa, PB, Brazil. Electronic address:

The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with MHTP by intranasal or oral routes. Treated animals showed a decrease (p < 0.05) of sneezing, nasal rubbings, and histamine nasal hyperactivity. Besides, MHTP presented binding energy and favorable interaction for adequate anchoring in the histamine H1 receptor. MHTP treatment inhibited the eosinophil migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids. Histological analysis showed that the alkaloid decreased the inflammatory cells in the subepithelial and perivascular regions of nasal tissue and in the peribronchiolar and perivascular regions of lung tissue. The MHTP treatment also reduced the pulmonary hyperactivity by decreasing the smooth muscle layer hypertrophy and the collagen fiber deposition in the extracellular matrix. The immunomodulatory effect of the alkaloid was due to the decrease of cytokines like IL-5 and IL-17A (type 2 and 3), TSLP (epithelial), and the immunoregulatory cytokine, TGF-β. These MHTP effects on granulocytes were dependent on the p38/ERK1/2 MAP kinase signaling pathway axis. Indeed, the synthetic alkaloid reduced the frequency of activation of both kinases independent of the NF-κB (p65) pathway indicating that the molecule shut down the intracellular transduction signals underlie the cytokine gene transcription.
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http://dx.doi.org/10.1016/j.intimp.2021.107590DOI Listing
April 2021

Administration Minimizes Neuroinflammation and Shows Anxiolytic, Antidepressant and Slimming Effects in Obese Rats.

Molecules 2020 Nov 26;25(23). Epub 2020 Nov 26.

Experimental Nutrition Laboratory, Department of Nutrition, Federal University of Paraíba, Cidade Universitária, s/n-Castelo Branco III, João Pessoa 58051-085, Brazil.

This study evaluated the effect of (MP) administration on neuroinflammation and behavioral and murinometric parameters in obese rats. Proximate composition, oligosaccharide and phenolic compound profile of MP were determined. Wistar adult male rats were randomized into healthy (HG) and obese group (OG). The HG consumed a control chow diet while OG consumed a cafeteria diet for eight weeks. Then, they were subdivided into: Healthy (HG); Healthy with MP administration (HGMP); Obese (OG); Obese with MP administration (OGMP), with the consumption of the respective diets remaining for another eight weeks, in addition to gavage with MP extract to supplemented groups (750 mg/kg weight). MP presented a composition rich in proteins and phenolic compounds, especially catechin, in addition to 1-kestose and levodopa. Supplementation reduced food intake, body weight, and thoracic and abdominal circumferences in obese rats. MP showed anxiolytic and antidepressant effects and reduced morphological damage and expression of interleukin 6 in the hippocampus of obese rats. MP treatment showed satietogenic, slimming, anxiolytic and antidepressant effects, besides to minimizing hippocampal neuroinflammation in obese rats. Our results demonstrated the potential anti-obesity of MP which are probably related to the high content of bioactive compounds present in this plant extract.
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http://dx.doi.org/10.3390/molecules25235559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730813PMC
November 2020

4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis.

Int Immunopharmacol 2020 Nov 10;88:106938. Epub 2020 Sep 10.

Department of Physiology and Pathology, Federal University of Paraíba, Laboratory of Immunopharmacology, João Pessoa, PB, Brazil. Electronic address:

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 μg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 μL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5-50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.
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http://dx.doi.org/10.1016/j.intimp.2020.106938DOI Listing
November 2020

Potentially obesogenic diets alter metabolic and neurobehavioural parameters in Wistar rats: a comparison between two dietary models.

J Affect Disord 2021 01 17;279:451-461. Epub 2020 Oct 17.

Laboratory of Experimental Nutrition, Department of Nutrition, Federal University of Paraíba (UFPB), João Pessoa, Paraíba, Brazil. Electronic address:

Background: Clinical studies related to the obesity pandemic have intensified in recent years, being the animal studies are also considered of great relevance. However, despite the fact that many diets have been reported in the literature to induce obesity in animal models, there is still a gap regarding evidence of the efficacy of these models, considering not only changes in somatic parameters, but also the triggering of comorbidities associated with obesity. In this scenario, the aim of this study was to compare the effectiveness of western and cafeteria diets as obesity-inducing protocols, focusing on the evaluation of metabolic, somatic, oxidative, histological and behavioural parameters of Wistar rats.

Methods: The rats were fed a control (CON), western (WTD) or cafeteria (CAF) diet for 16 weeks.

Results: The CAF diet caused anxiogenic-like behaviour. Body mass (BMI), Lee and adiposity indices increased in the CAF group. CAF and WTD diets reduced glucose and insulin tolerance, caused dyslipidemia, increased lipid peroxidation and decrease antioxidant capacity in the liver, kidneys and brain. The WTD and CAF groups shows greater IL-6 protein expression in adipose tissue, developed hepatic steatosis and ischaemic neurons, whereas interstitial nephritis was observed only in the CAF group.

Conclusion: The CAF diet was most effective in inducing obesity, as shown both by the somatic parameters and by the greater number of obesity-related metabolic and neurobehavioural disorders in the evaluated rats.
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http://dx.doi.org/10.1016/j.jad.2020.10.034DOI Listing
January 2021

Antidepressant, Anxiolytic and Neuroprotective Activities of Two Zinc Compounds in Diabetic Rats.

Front Neurosci 2019 21;13:1411. Epub 2020 Jan 21.

Programa de Pós Graduação em Ciências da Nutrição, Universidade Federal da Paraíba, João Pessoa, Brazil.

Behavioral disorders affect most diabetic patients and Zinc (Zn) has been used among adjuvant therapies for involvement in the etiology of depression and anxiety, however, the results are still controversial. The objective of this study was to compare the antidepressant, anxiolytic and neuroprotective activity of the supplementation of two Zn compounds in an animal model of Diabetes Mellitus type 1 (DM1). Thirty-eight (38) adult rats were randomized into four groups: Control (C; = 8); Diabetic (D; = 10); Diabetic Zn Sulfate Supplement (DSZ; = 10) and Diabetic Zn Gluconate Supplement (DGZ; = 10). The DSZ group received Zn sulfate supplementation and the DGZ group received Zn gluconate supplementation at a dose of 15 mg/kg for 4 weeks. Data (mean ±SEM) were analyzed by the Mann-Whitney test with a significance level of < 0.05. The results indicate that Zn gluconate supplementation in diabetic animals presented an antidepressant effect demonstrated through the results obtained in the Forced Swim Test, and neuroprotective effect by attenuating alterations in the cerebral cortex; while Zn sulfate supplementation in diabetic animals showed an anxiolytic effect demonstrated by the results obtained in the open field test and the elevated plus maze test. Considering the set of results, supplementation with both zinc compounds showed neurobehavioral benefits in diabetic animals with different effects depending on the type of anion associated with Zn.
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http://dx.doi.org/10.3389/fnins.2019.01411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985554PMC
January 2020

Qualification of tropical fruit-derived Lactobacillus plantarum strains as potential probiotics acting on blood glucose and total cholesterol levels in Wistar rats.

Food Res Int 2019 10 15;124:109-117. Epub 2018 Aug 15.

Laboratory of Microbial Processes in Foods, Department of Food Engineering, Federal University of Paraíba, João Pessoa, Brazil. Electronic address:

Tropical fruit and their industrial processing byproducts have been considered sources of probiotic Lactobacillus. Sixteen tropical fruit-derived Lactobacillus strains were assessed for growth-promoting effects using a host-commensal nutrient scarcity model with Drosophila melanogaster (Dm). Two Lactobacillus strains (L. plantarum 49 and L. plantarum 201) presenting the most significant effects (p ≤ .005) on Dm growth were selected and evaluated for their safety and beneficial effects in adult male Wistar rats during 28 days of administration of 9 log CFU/day, followed by 14 days of wash-out. Daily administration of L. plantarum 49 and L. plantarum 201 did not affect (p > .05) food intake or morphometric parameters. Both strains were associated with reduction (p ≤ .05) in blood glucose levels after 28 days of administration and after wash-out period; glucose levels remained reduced only in the group that received L. plantarum 49. Both strains were able to reduce (p ≤ .05) total cholesterol levels after 14 days of administration; after the wash-out period these levels remained reduced only in the group that received L. plantarum 201. L. plantarum 49 and L. plantarum 201 were detected in the intestine and did not cause alteration or translocate to spleen, kidneys or liver during the experimental or wash-out period. These results indicate that L. plantarum 49 and L. plantarum 201 present potential for use as probiotics with intrinsic abilities to modulate biochemical parameters of interest for the management of metabolic diseases.
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http://dx.doi.org/10.1016/j.foodres.2018.08.035DOI Listing
October 2019

Maternal dyslipidaemic diet induces sex-specific alterations in intestinal function and lipid metabolism in rat offspring.

Br J Nutr 2019 04 23;121(7):721-734. Epub 2019 Jan 23.

1Laboratório de Nutrição Experimental,Departamento de Nutrição,Universidade Federal da Paraíba (UFPB),João Pessoa,58051-900,Paraíba,Brazil.

This study investigated the effects of a maternal dyslipidaemic (DLP) diet on lipid metabolism, microbial counts in faeces and hepatic and intestinal morphology in rat offspring with respect to sex during different phases of life. Wistar rats (dams) were fed a control (CTL) or DLP during gestation and lactation. After weaning, CTL and DLP offspring were fed a standard diet. The effects of a maternal DLP on body composition, biochemical parameters, faecal microbiota and intestinal and hepatic histomorphometric characteristics in rat offspring were evaluated at 30 and 90 d of age. The DLP diet during gestation and lactation caused lower birth weight and a greater weight gain percentage at the end of the 90-d period in both male and female offspring. Female pups from DLP dams had higher liver fat levels compared with CTL (P≤0·001) at 90 d of age. Males from DLP dams had greater visceral fat weight and lower Lactobacillus spp. faecal counts at 90 d of age (P≤0·001) as well as lower faecal fat excretion (P≤0·05) and Bacteroides spp. faecal counts (P≤0·001) at 30 d of age when compared with pups from CTL dams. However, both dams and DLP pups showed damage to intestinal villi. A maternal DLP alters intestinal function and lipid metabolism in a sex-specific manner and is a potential predisposing factor for health complications in offspring from the juvenile period to the adult period.
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http://dx.doi.org/10.1017/S0007114519000011DOI Listing
April 2019

SB-83, a 2-Amino-thiophene derivative orally bioavailable candidate for the leishmaniasis treatment.

Biomed Pharmacother 2018 Dec 11;108:1670-1678. Epub 2018 Oct 11.

Departamento de Biologia Molecular, Centro de Ciências Exatas e da Natureza, Universidade Federal da Paraíba, João Pessoa, Paraíba, CEP 58059-900, Brazil.

Leishmaniasis, affecting more than 12 million people worldwide has become a severe public-health problem. The therapeutic arsenal against leishmaniasis is mainly administered by parenteral route; it is toxic, expensive, and associated with recurrence risk. The need for further therapeutic compounds research is pressing. In previous studies, we demonstrated the antileishmanial activities of ten 2-amino-thiophene derivatives, which evidenced the action of a compound, called SB-83, having expressive antileishmania activity in an in vitro infection model. In the present work, we describe preclinical studies of the thiophenic derivative SB-83, such as acute toxicity, genotoxicity, in vivo oral efficacy in a murine model, and in vitro antileishmanial activity against an L. amazonensis Sb-resistant strain. Determining acute preclinical toxicity, the LD of SB-83 was estimated at 2500 mg/kg orally, with few behavioral changes in Swiss mice. Further, treatment with 2000 mg/kg of SB-83 did not induce in vivo genotoxic activity in the peripheral blood micronucleus assay. In 7 weeks of oral treatment, SB-83 reduced paw lesion size in L. amazonensis infected mice by 52.47 ± 5.32%, and decreased the parasite load of the popliteal lymph node and spleen at the highest dose tested (200 mg/kg) respectively by 42.57 ± 3.14%, and 100%, without presenting weight change or other changes of clinical importance in the biochemical and hematological profiles. The treatment of promastigotes and intracellular amastigotes of Sb sensitive and resistant strains with SB-83 did not produce differences in antileishmania activity, which suggests no cross-resistance. Thus, this work demonstrated that SB-83 has potential as a new active drug candidate even when orally administered, which may become a new therapeutic alternative for the treatment of leishmaniasis.
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http://dx.doi.org/10.1016/j.biopha.2018.10.012DOI Listing
December 2018

Effects of honey from Mimosa quadrivalvis L. (malícia) produced by the Melipona subnitida D. (jandaíra) stingless bee on dyslipidaemic rats.

Food Funct 2018 Aug;9(8):4480-4492

Departamento de Nutrição, Universidade Federal da Paraíba, João Pessoa, 58051-900, Paraíba, Brazil.

This study assessed the effects of supplementation with honey from Mimosa quadrivalvis L. (malícia) (MH) produced by jandaíra stingless bees (Melipona subnitida D.) on the lipid metabolism, antioxidant status and some intestinal health parameters of rats with diet-induced dyslipidaemia. Rats were randomly divided into four groups: healthy control (HC), dyslipidaemic control (DC), healthy experimental (EHH) and dyslipidaemic experimental (EDH). Malícia honey (MH) was administered (1000 mL kg-1) via orogastric feeding for 35 days. Dyslipidaemic rats supplemented with MH showed lower food consumption, increased glucose tolerance and superoxide dismutase (SOD) activity, and decreased total cholesterol, LDL and AST blood levels. Counts of Bifidobacterium spp. and Lactobacillus spp. and excretion of organic acids in faeces increased in dyslipidaemic rats supplemented with MH. MH supplementation protected the colon and liver from tissue damage induced by the dyslipidaemic diet. These results show the beneficial effects of MH on the lipid metabolism, antioxidant status and intestinal health of rats with diet-induced dyslipidaemia.
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http://dx.doi.org/10.1039/c8fo01044gDOI Listing
August 2018

MHTP, 2-Methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol, a Synthetic Alkaloid, Induces IFN-γ Production in Murine Model of Ovalbumin-Induced Pulmonary Allergic Inflammation.

Inflammation 2018 Dec;41(6):2116-2128

Department of Physiology and Pathology, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, PB, Brazil.

MHTP [2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol], a synthetic isoquinolinic alkaloid, presented anti-inflammatory activity in several experimental models of acute inflammation as lipopolysaccharide (LPS)-induced acute lung injury and phlogistic agent-induced edema and presented low preclinical toxicity. The aim of this study was to determine the MHTP effect on ovalbumin (OVA)-induced pulmonary allergic inflammation. In other to realize this study, female BALFB/c mice were sensitized and challenged with OVA (OVA group) and treated with MHTP (MHTP group) by nasal instillation. Inflammatory, allergic, and immunomodulatory parameters such as migration of inflammatory cells to the lung tissue, pulmonary histological analysis, serum level of IgE-allergen specific, cytokine secretion, and lung T cell population characterization were analyzed and the data were considered statistically significant with p < 0.05. OVA-sensitized and OVA-challenged and MHTP (5.0 mg/kg)-treated mice presented reduction on total leukocyte migration into the bronchoalveolar lavage (BALF) dependent of lymphocyte and eosinophil migration (p < 0.001 and p < 0.01) as compared with the OVA group. Flow cytometric analysis showed that MHTP treatment decreased the percentage of granulocytes (p < 0.001) into the BALF and lung tissue histological analyzes demonstrated that the MHTP treatment decreased leukocyte migration and mucus production. In addition, treatment with MHTP decreased the number of CD3CD4 T cells independently of CD8 T cell reduction into the BALF. The treatment also reduced significantly (p < 0.05) the serum level of IgE-OVA specific followed by reduction of IL-4, IL-13, and IL-17 production. Surprisingly, the MHTP treatment increased significantly (p < 0.05) the IFN-γ production in the BALF of these animals. Therefore, the results presented here showed that MHTP treatment, by nasal instillation, in a mouse model of OVA-induced pulmonary allergy has anti-allergic and immunomodulatory effects dependent on a Th1-skewed cytokine production that ameliorate the pulmonary allergic inflammation.
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http://dx.doi.org/10.1007/s10753-018-0855-yDOI Listing
December 2018

Comparison of behavioral, neuroprotective, and proinflammatory cytokine modulating effects exercised by (+)-cis-EC and (-)-cis-EC stereoisomers in a PTZ-induced kindling test in mice.

Fundam Clin Pharmacol 2018 Oct 8;32(5):507-515. Epub 2018 May 8.

Programa de Pós-graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos, Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, Paraíba, Brazil.

Epoxy-carvone (EC) has chiral centers that allow generation of stereoisomers, including (+)-cis-EC and (-)-cis-EC, whose effects in the kindling tests have never been studied. Accordingly, this study aims to comparatively investigate the effect of stereoisomers (+)-cis-epoxy-carvone and (-)-cis-epoxy-carvone on behavioral changes measured in scores, in the levels of cytokines (IL-1β, IL-6, and TNFα) and neuronal protection in the face of continuous treatment with pentylenetetrazol. Swiss mice were divided into five groups (n = 10), receiving vehicle, (+) - cis-EC, (-) - cis-EC (both at the dose of 30 mg/kg), and diazepam (4 mg/kg). Thirty minutes after the respective treatment was administered to the animals one subconvulsive dose of PTZ (35 mg/kg). Seven subconvulsives treatments were made on alternate days, in which each treatment several parameters were recorded. In the eighth treatment, the animals receiving the highest dose of PTZ (75 mg/kg) and were sacrificed for quantification of cytokines and histopathologic analysis. All drugs were administered by intraperitoneal route. In the kindling test, (+)-cis-EC and (-)-cis-EC reduced the average scores. The stereoisomer (+)-cis-EC decreased levels of proinflammatory cytokines IL-1β, IL-6, and TNFα, whereas comparatively (-)-cis-EC did not reduce IL-1β levels. Histopathological analysis of the mice hippocampi undergoing this methodology showed neural protection for treated with (+)-cis-EC. The results suggest that the anticonvulsant effect of (+)-cis-EC possibly takes place due to reduction of proinflammatory cytokines involved in the epileptogenic process, besides neuronal protection, yet further investigation of the mechanisms involved is required.
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http://dx.doi.org/10.1111/fcp.12366DOI Listing
October 2018

Beneficial effects of consumption of acerola, cashew or guava processing by-products on intestinal health and lipid metabolism in dyslipidaemic female Wistar rats.

Br J Nutr 2018 01;119(1):30-41

1Departamento de Nutrição,Universidade Federal da Paraíba,João Pessoa 58051-900,Paraíba,Brazil.

This study assessed the effects of diet supplementation with industrial processing by-products of acerola (Malpighia emarginata D.C.), cashew (Anacardium occidentale L.) and guava (Psidium guajava L.) fruit on the intestinal health and lipid metabolism of female Wistar rats with diet-induced dyslipidaemia. Female rats were randomly divided into five groups: healthy control, dyslipidaemic control and dyslipidaemic experimental receiving acerola, cashew or guava processing by-products. Fruit processing by-products were administered (400 mg/kg body weight) via orogastric administration for 28 consecutive days. Acerola, cashew and guava by-products caused body weight reduction (3·42, 3·08 and 5·20 %, respectively) in dyslipidaemic female rats. Dyslipidaemic female rats receiving fruit by-products, especially from acerola, presented decreased faecal pH, visceral fat, liver fat and serum lipid levels, as well as increased faecal moisture, faecal fat excretion, faecal Bifidobacterium spp. and Lactobacillus spp. counts and amounts of organic acids in faeces. Administration of the tested fruit processing by-products protected colon and liver from tissue damage (e.g. destruction of liver and colon cells and increased fat deposition in hepatocytes) induced by dyslipidaemic diet. Dietary fibres and phenolic compounds in tested fruit by-products may be associated with these positive effects. The industrial fruit processing by-products studied, mainly from acerola, exert functional properties that could enable their use to protect the harmful effects on intestinal health and lipid metabolism caused by dyslipidaemic diet.
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http://dx.doi.org/10.1017/S0007114517003282DOI Listing
January 2018

Author Correction: Ouabain attenuates ovalbumin-induced airway inflammation.

Inflamm Res 2018 03;67(3):277

Laboratório de Imunobiotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba (UFPB), João Pessoa, Brazil.

In the original publication, author missed to include the financial support from CAPES/PROCAD-2013. The complete funding text should read as follows.
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http://dx.doi.org/10.1007/s00011-018-1130-2DOI Listing
March 2018

Ouabain attenuates ovalbumin-induced airway inflammation.

Inflamm Res 2017 Dec 13;66(12):1117-1130. Epub 2017 Sep 13.

Laboratório de Imunobiotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba (UFPB), João Pessoa, Brazil.

Purpose: Ouabain, an Na/K-ATPase inhibitor hormone, presents immunomodulatory actions, including anti-inflammatory effect on acute inflammation models.

Methods: In the present study, the effect of ouabain in a model of allergic airway inflammation induced by ovalbumin (OVA) was assessed.

Results: Initially, it was observed that ouabain treatment inhibited cellular migration induced by OVA on bronchoalveolar lavage fluid (BALF), mostly granulocytes, without modulating macrophage migration. In addition, it was observed, by flow cytometry, that ouabain reduces CD3 lymphocytes cells on BALF. Furthermore, treatment with ouabain decreased IL-4 and IL-13 levels on BALF. Ouabain also promoted pulmonary histological alterations, including decreased cell migration into peribronchiolar and perivascular areas, and reduced mucus production in bronchioles regions observed through hematoxylin-eosin (HE) and by periodic acid-Schiff stain, respectively. Allergic airway inflammation is characterized by high OVA-specific IgE serum titer. This parameter was also reduced by the treatment with ouabain.

Conclusions: Therefore, our data demonstrate that ouabain negatively modulates allergic airway inflammation induced by OVA.
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http://dx.doi.org/10.1007/s00011-017-1092-9DOI Listing
December 2017

Milonine, an Alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae) Inhibits Histamine Release of Activated Mast Cells.

Inflammation 2017 Dec;40(6):2118-2128

Laboratory of Immunopharmacology, Health Sciences Centre, Federal University of Paraíba, João Pessoa, PB, Brazil.

Milonine is an alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae), a plant used in the northeast of Brazil to treat allergies such as asthma, rhinitis, and other conditions. Previously, several alkaloids were isolated from its roots and leaves with pharmacological properties in asthma and acute inflammation models. Therefore, the aim of this study was to evaluate the milonine effect on mast cells degranulation in vivo and in vitro. Swiss mice (n = 8) were used in models of paw edema induced by carrageenan, compound 48/80, or histamine. One hour before challenge, the animals were treated with milonine (at different doses) or standard drugs and, at different time points, the edema formation was measured. In addition, other different methods, such as anaphylactic shock reaction and scratching behavior models both induced by compound 48/80, a mast cell degranulator, were used to assess milonine effect histamine release in vivo. Moreover, milonine effect on mast cell degranulation in vitro was also carried out. Firstly, it was observed that milonine significantly decreased the carrageenan edema formation only at the beginning of the reaction (i.e., up to 2 h after challenge). Furthermore, this alkaloid decreased the edema induced by compound 48/80, maintained the paw tissue integrity, without modulating histamine-induced paw edema. In anaphylactic shock reaction, milonine increased the time of animal survival when compared with compound 48/80 group. Milonine also significantly decreased the scratching behavior induced by compound 48/80 with decreasing of mast cell degranulation in vitro. Therefore, these data indicated that milonine presents anti-allergic properties by decreasing mast cell degranulation rather than acting on histamine effect.
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http://dx.doi.org/10.1007/s10753-017-0652-zDOI Listing
December 2017

Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1β Production.

Inflammation 2017 Dec;40(6):2074-2085

Laboratory of Immunopharmacology, Department of Physiology and Pathology, Federal University of Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.

Milonine is a morphinandienone alkaloid from Cissampelos sympodialis Eichl (Menispermaceae), a plant used in Brazil to treat inflammatory disorders. In this study, we evaluated the anti-inflammatory and analgesic activity of milonine (MIL) by using classical experimental models of inflammation and nociception. The results showed that MIL reduced the paw edema formation induced by lipopolysaccharide, prostaglandin E, and bradykinin, without interfering with the serotonin-induced edema. With respect to the nociception experiments, MIL decreased the exudate into the peritoneum induced by acetic acid, maintaining the tissue morphology. The alkaloid was able to inhibit the peritonitis induced by carrageenan, decreasing mainly the migration of polymorphonuclear cells, without altering the mononuclear cell number, and reduced the levels of TNF-α and IL-1β in the peritoneum. In addition, MIL was able to decrease the frequency of abdominal writhing induced by acetic acid but did not increase the latency time of the animals in the hot plate test. MIL significantly reduced the nociceptive behavior of paw licking induced by formalin only at the second phase of the test. In conclusion, we demonstrate that milonine has anti-inflammatory and anti-nociceptive activities by inhibiting mediators essential for the inflammatory process.
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http://dx.doi.org/10.1007/s10753-017-0647-9DOI Listing
December 2017

Managing murine food allergy with Cissampelos sympodialis Eichl (Menispermaceae) and its alkaloids.

Int Immunopharmacol 2013 Oct 25;17(2):300-8. Epub 2013 Jun 25.

Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba, Paraíba, Brazil.

Food allergy is a severe human disease with imminent risk of life. Cissampelos sympodialis (Menispermaceae) is a native Brazilian plant used in Brazilian folk medicine for the treatment of respiratory allergies. In this study the experimental model of food allergy induced by ovalbumin (OVA) was used to determine whether the alcoholic extract of the plant (AFL) and its alkaloids match a therapeutic approach for this disease. Animal weight, diarrhea, OVA-specific IgE levels, inflammatory cell and cytokine profiles, mucus production and proportion of T cells on the mesenteric lymph node (MLN) were evaluated. Warifteine (W) or methyl-warifteine (MW) alkaloids slightly improve diarrhea score independently of AFL and all treatments decreased the OVA-specific IgE levels. Stimulated mesenteric lymph node (MLN) cells in the presence of the alkaloids diminished the IL-12p70 levels independently of IFN-γ or IL-13 secretion. The alkaloids increased the number of Treg cells on MLN and reduced the number of eosinophils and mast cells as well as mucus production in the gut. Therefore, the alkaloids modulate the immune response in food allergy by increasing regulatory T cells in MLN independently of Th1 or Th2 profiles.
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http://dx.doi.org/10.1016/j.intimp.2013.05.024DOI Listing
October 2013