Publications by authors named "Josean F Tavares"

27 Publications

  • Page 1 of 1

Antidiarrheal Effect of Vogel (Leguminosae) on Mice Involves Adrenergic Pathway Activation.

Evid Based Complement Alternat Med 2021 28;2021:1385606. Epub 2021 Feb 28.

Programa de Pós-graduação Em Produtos Naturais e Sintéticos Bioativos/Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Several secondary metabolites have been isolated from (Leguminosae), mainly flavonoids. These compounds are known for many pharmacological actions, such as antispasmodic and antidiarrheal. Therefore, we evaluated the antidiarrheal effect of the ethanolic extract obtained from aerial parts (ZB-EtOH), as well as its underlying mechanisms. Castor-oil-induced diarrhea, fluid accumulation, and intestinal transit (normal and castor oil induced) were performed to assess the antidiarrheal, antisecretory, and antipropulsive activities of the extract. The involvement of opioid and adrenergic pathways was also investigated. ZB-EtOH inhibited, in a dose-dependent manner, both total defecation frequency and the number of watery stools. The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the marker in the small intestine. Investigation of the involvement of opioid and adrenergic systems showed that the pharmacological potency of the extract did not change in the presence of naloxone, but it was reduced in the presence of yohimbine. The data indicate that has an antidiarrheal effect due to inhibition of the intestinal motility through adrenergic pathway activation.
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http://dx.doi.org/10.1155/2021/1385606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939745PMC
February 2021

Aflatoxin M in Brazilian goat milk and health risk assessment.

J Environ Sci Health B 2021 3;56(4):415-422. Epub 2021 Mar 3.

Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Brazil.

Contamination of goat milk with aflatoxin M (AFM) is a public health concern. This study investigated filamentous fungi in goat feed and quantified AFM in milk samples (n = 108) from goat fed forage and concentrate. Based on the detected AFM concentration, risk assessment analyses were performed concerning the Estimated Daily Intake (EDI) for one-year-old children and adults. Filamentous fungi were found in goat feed samples in a range of 3.1 ± 1.9 to 4.2 ± 0.2 log CFU/g. Five genera were identified, to cite and species comprised and . All goat milk samples were contaminated with AFM (5.60-48.20 ng/L; mean 21.90 ± 10.28 ng/L) in amounts below the limits imposed by regulatory agencies. However, EDI values for AFM through goat milk estimated for one-year-old children were above the Tolerable Daily Intake. The calculated Hazard Index for one-year-old children indicated potential risk of liver cancer due to goat milk consumption. The Margin of Exposure values to AFM in one-year-old children and adults consuming goat milk as the unique milk source indicated increased health risk. Therefore, contamination of goat milk with AFM should be considered a high priority for Brazil's risk management actions.
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http://dx.doi.org/10.1080/03601234.2021.1892434DOI Listing
June 2021

In vitro and in silico studies of 8(17),12E,14-labdatrien-18-oic acid in airways smooth muscle relaxation: new molecular insights about its mechanism of action.

Naunyn Schmiedebergs Arch Pharmacol 2021 05 18;394(5):885-902. Epub 2020 Nov 18.

Pharmaceutical Technology Laboratory (LTF), Federal University of Paraíba (UFPB), Cidade Universitária, Castelo Branco, PO Box 5009, João Pessoa, PB, 58051-970, Brazil.

In the field of experimental pharmacology, researchers continuously investigate new relaxant agents of the airway smooth muscle cells (ASMCs), since the pathophysiology of respiratory illnesses, such as asthma, involves hyperresponsiveness and changes in ASMC homeostasis. In this scenario, labdane-type diterpenes, like forskolin (FSK), are a class of compounds known for their relaxing action on smooth muscle cells (SMCs), being this phenomenon related to the direct activation of AC-cAMP-PKA pathway. Considering the continuous effort of our group to study the mechanism of action and prospecting for compounds isolated from natural sources, in this paper, we presented how the diterpene 8(17),12E,14-labdatrien-18-oic acid (LBD) promotes relaxant effect on ASMC, performing in vitro experiments using isolated guinea pig trachea and in silico molecular docking/dynamics simulations. In vitro experiments showed that in the presence of aminophylline, FSK and LBD had their relaxant effect potentiated (EC from 1.4 ± 0.2 × 10 M to 1.5 ± 0.3 × 10 M for LBD and from 2.0 ± 0.2 × 10 M to 6.4 ± 0.4 × 10 M for FSK) while in the presence of Rp-cAMPS this effect was attenuated (EC from 1.4 ± 0.2 × 10 M to 3 × 10 M for LBD and from 2.0 ± 0.2 × 10 to 3.1 ± 1.0 × 10 M for FSK). Additionally, in silico simulations evidenced that the lipophilic character of LBD is probably responsible for its stability on AC binding site. LBD presented two preferential orientations, where the double bonds of the isoprene moiety as well as the unique polar group (carboxylic acid) in this compound form important anchoring points. In this sense, we consider that the LBD can interact stabilizing the catalytic dimmer of AC as the FSK, although less efficiently.
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http://dx.doi.org/10.1007/s00210-020-02010-0DOI Listing
May 2021

Dereplication and quantification of the ethanol extract of Miconia albicans (Melastomaceae) by HPLC-DAD-ESI-/MS/MS, and assessment of its anti-hyperalgesic and anti-inflammatory profiles in a mice arthritis-like model: Evidence for involvement of TNF-α, IL-1β and IL-6.

J Ethnopharmacol 2020 Aug 5;258:112938. Epub 2020 May 5.

Multiuser Health Center Facility (CMulti-Saúde), Federal University of Sergipe, São Cristóvão-SE, CEP 49.100-000, Brazil; Laboratory of Neuroscience and Pharmacological Assays (LANEF), Depatment of Pharmacy, Federal University of Sergipe, São Cristóvão-SE, CEP 49.100-000, Brazil. Electronic address:

Ethnopharmacological Relevance: Miconia albicans (Sw) Triana (Melastomataceae), a medicinal plant widely used by practitioners of folk medicine in the northeast of Brazil, has been used to treat chronic inflammatory disorders, such as rheumatoid arthritis (RA) and other joint conditions. Oddly, there is little research on the species.

Aim Of The Study: We aimed to evaluate the anti-arthritic and anti-inflammatory profile of the ethanolic leaf extract of M. albicans (EEMA), as well as to perform dereplication and quantification by HPLC-DAD-ESI-/MS/MS.

Materials And Methods: The compounds present in the extracts were identified by HPLC-DAD-ESI-MS/MS. The possible anti-inflammatory effect of EEMA (50 and 100 mg/kg, p.o) was evaluated using the pleurisy model induced by carrageenan and its action on IL-1β and TNF-α levels was also evaluated. The RA model was induced through the intra-articular injection of complete Freund's adjuvant (CFA).

Results: HPLC-DAD-ESI-MS/MS analysis identified 23 compounds, with glycoside flavonoids mainly derived from quercetin, and rutin being the main compounds. EEMA significantly reduced (p < 0.001) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1β levels in pleural lavage (p < 0.001). In the CFA animal model, EEMA significantly reduced the nociceptive and hyperalgesic behaviors demonstrated by the rearing test (p < 0.01 or p < 0.05) and decreased mechanical hyperalgesia (p < 0.001). EEMA produced a significant improvement in mobility in the open-field test (only at the higher dose, p < 0.05). EEMA significantly (p < 0.01) increased hindpaw grip strength. The diameter of CFA-induced ipsilateral knee edema was significantly reduced (p < 0.001) by EEMA, which was related to reduced levels of IL-6 and TNF-α in the joint knee (p < 0.01). No indication of hepatic injury after chronic treatment was found.

Conclusion: Taken together, these results contribute to the chemical and pharmacological knowledge of M. albicans and demonstrated that this medicinal plant appears to be able to mitigate deleterious symptoms of RA, which supports its use in folk medicine.
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http://dx.doi.org/10.1016/j.jep.2020.112938DOI Listing
August 2020

Bioactive Compounds from the Aerial Parts of .

J Nat Prod 2020 05 4;83(5):1515-1523. Epub 2020 May 4.

Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraı́ba, João Pessoa, Brazil.

Three new caryophyllane-type sesquiterpenoids, linariophyllenes A-C (-), two new hamamelitol derivatives, linaritols A ( and B (), two new chromones, linariosides A () and B (), and three known chromones, cnidimol C (), monnieriside A (), and undulatoside A (), were identified from the aerial parts of . The structures of these compounds were elucidated by NMR, MS, and IR data. The absolute configurations of compounds - and were established via electronic circular dichroism data. The anti-inflammatory potential of compounds - and - was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and proinflammatory cytokine IL-1β by stimulated J774 macrophages. Compounds tested at noncytotoxic concentrations inhibited NO production by macrophages, exhibiting IC values between 17.8 and 66.2 μM, and inhibited IL-1β production by stimulated macrophages by 72.7-96.2%.
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http://dx.doi.org/10.1021/acs.jnatprod.9b01189DOI Listing
May 2020

Flavonoids from (Taroda) J.S. Mill (cordiaceae) and the evaluation of spasmolytic activity of its crude ethanolic extract.

Nat Prod Res 2020 Apr 27:1-5. Epub 2020 Apr 27.

Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, Brazil.

Pharmacological studies show spasmolytic activity for various species of . Thus, based on the taxonomy criteria, the aim of this study was to contribute to chemical and biological knowledge, especially regarding the evaluation of spasmolytic activity of the ethanolic extract from leaves (VD-EtOH) on rat aorta and trachea, guinea-pig ileum and rat uterus. Were used High and Medium Performance Liquid Chromatography. Wistar rats and guinea-pigs were used for pharmacological assays. All experimental protocols were approved by Animal Ethics Committee of UFPB (126/2017). Two chalcones (pinostrobin chalcone and gymnogrammene), five flavanones (pinocembrin, isosakuranetin, pinostrobin, sakuranetin 4'-methyl ether, naringenin) and a flavonoid glycosilated (astragalin) were identified based on data of H and C Nuclear Magnetic Resonance. This study also showed that VD-EtOH has a non-selective spasmolytic activity, presenting greater relaxing potency in rat uterus, suggesting that flavonoids isolated from VD-EtOH may be responsible for spasmolytic activity of this extract.
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http://dx.doi.org/10.1080/14786419.2020.1753737DOI Listing
April 2020

Inactivation of Spoilage Yeasts by L. and . × Huds. Essential Oils in Cashew, Guava, Mango, and Pineapple Juices.

Front Microbiol 2018 25;9:1111. Epub 2018 May 25.

Laboratorio de Microbiologia de Alimentos, Departamento de Nutrição, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Brazil.

This study evaluated the efficacy of the essential oil from L. (MSEO) and . × Huds. (MVEO) to inactivate and in Sabouraud dextrose broth and cashew, guava, mango, and pineapple juices during 72 h of refrigerated storage. The effects of the incorporation of an anti-yeast effective dose of MSEO on some physicochemical and sensory characteristics of juices were evaluated. The incorporation of 3.75 μL/mL MSEO or 15 μL/mL MVEO caused a ≥5-log reductions in counts of , and in Sabouraud dextrose broth. In cashew and guava juices, 1.875 μL/mL MSEO or 15 μL/mL MVEO caused ≥5-log reductions in counts of and . In pineapple juice, 3.75 μL/mL MSEO caused ≥5-log reductions in counts of and ; 15 μL/mL MVEO caused ≥5-log reductions in counts of in mango juice. The incorporation of 1.875 μL/mL MSEO did not affect the physicochemical parameters of juices and did not induce negative impacts to cause their possible sensory rejection. These results show the potential of MSEO and MVEO, primarily MSEO, to comprise strategies to control spoilage yeasts in fruit juices.
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http://dx.doi.org/10.3389/fmicb.2018.01111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981176PMC
May 2018

Anti-Trypanosoma cruzi Activity in vitro of Phases and Isolated Compounds from Excoecaria lucida Leaves.

Med Chem 2018 ;14(6):556-562

Pharmacy Department, Faculty of Natural and Exact Sciences, Universidad de Oriente, Santiago de Cuba, Cuba.

Background: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. This illness is found mainly in 21 Latin American countries and an estimated 8 million people are infected worldwide. The unsatisfactory chemotherapy provokes severe toxicity and resistant strains. Medicinal plants constitute a promising source of new drugs and remedies against all kinds of disorders, mainly infectious diseases arousing interest worldwide.

Objective: The aim of this study is the isolation, structural identification and evaluation of the trypanocidal activity of samples present in the Excoecaria lucida Sw. leaves.

Methods: Total extract (TE) of E. lucida Sw. leaves was obtained by ethanol extract therefore fractionated sequentially with hexane, ethyl acetate and n-butanol, to obtain three phases: Hex, EA and But, respectively. Ellagic acid (EL1) was purified from both EA and But phases, while EL2; a 1:1 stigmasterol-3-O-β-D-glucopyranoside plus sitosterol-3-O-β-D-glucopyranoside mixture was obtained from the Hex phase. Activity assays were performed using bloodstream and intracellular forms of T. cruzi and cytotoxicity assays using L929 fibroblasts.

Results: The EL1 and EL2 samples were more active against bloodstream trypomastigote forms with EC50 of 53.0±3.6 and 58.2±29.0 µg/mL, respectively; at 100 µg/mL. These samples also showed 70% of inhibition of L929 cells infection. Toxicity assays demonstrated that after 96 h of treatment only the fractions Hex and EA presented detectable cytotoxicity.

Conclusion: Ellagic acid, stigmasterol-3-O-β-D-glucopyranoside and sitosterol-3-O-β-Dglucopyranoside are reported for the first time in E. lucida Sw. leaves as well as their biological activity studies supporting further investigations for Chagas disease treatment.
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http://dx.doi.org/10.2174/1573406414666180112112154DOI Listing
September 2018

HPLC-DAD analysis, antinociceptive and anti-inflammatory properties of the ethanolic extract of Hyptis umbrosa in mice.

EXCLI J 2017 2;16:14-24. Epub 2017 Jan 2.

Department of Physiology. Laboratory of Neurosciences and Pharmacological Assays Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.

(syn. ) (Lamiaceae Family) has been used to treat several conditions such as gastrointestinal disorders, skin infections, nasal congestion, fever and cramps. The objective of this study was to evaluate the chemical composition, analgesic and anti-inflammatory profiles of ethanol extract from leaves of (EEB). HPLC-DAD was used to determine the fingerprint chromatogram of the extract. Male Swiss mice were orally pretreated with EEB (100, 200 or 400 mg/kg; 60 min before initiating algesic stimulation) and antinociceptive activity was assessed using the acetic acid-induced writhing model, formalin test and hyperalgesia induced by glutamate or capsaicin. Also, peritonitis was induced by the intrathoracic injection of carrageenan to quantify the total number of leukocytes. The presence of phenolic compounds in the extract was confirmed using HPLC-DAD. The treatment with EEB, at all doses, produced a significant analgesic effect against acetic acid-induced antinociceptive activity. In the formalin test, only the 400-mg/kg-dose of EEB had a significant effect in the first phase. However, all doses tested were able to reverse nociception in the second phase. The effect of all doses of EEB also showed a significant antinociceptive effect in the glutamate and capsaicin tests and inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. The present study suggests that the EEB possesses peripheral analgesic action and showed potential in reducing the spreading of the inflammatory processes. Also, it seems to be related with vanilloid and glutamate receptors.
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http://dx.doi.org/10.17179/excli2016-698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318689PMC
January 2017

In silico and In vivo Toxicological Evaluation of Cissampelos Sympodialis Secondary Metabolites in Rattus Norvegicus.

Curr Drug Metab 2017 ;18(6):566-576

Federal University of Paraiba, João Pessoa - PB, Brazil.

Cissampelos sympodialis is a plant in northeastern Brazil used by the populace for treating respiratory diseases. Several studies have shown that ethanol leaf extracts have immunomodulatory and anti-inflammatory activities. Infusions are widely used, popular, and an ancient technique in traditional medicine, using hot water alone as the means of extraction. This study aimed to investigate acute toxicological potential of leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg to Rattus norvegicus, combined with an in silico study of 117 alkaloids present in the Cissampelos genus; five (5) of which were determined to have high toxicity (21, 8, 93, 32 and 88), and five (5) having both low toxicity (57, 77, 28, 25 and 67) and low liver metabolism. The in vivo toxicological evaluation showed that male water consumption decreased, and the feed intake decreased in both sexes. Yet, the figures as to change in weight gain of the animals were not statistically sufficient. As for the biochemical parameters, there was an increase in urea, and decreases in uric acid and AST in males. In females, there was a decrease in albumin and globulin which consequently leads to a total protein decrease. Despite biochemical changes suggestive of kidney damage, the histological sections revealed no kidney or liver changes. The results therefore indicate that despite presenting alkaloids which may be toxic, the genus Cissampelos, or leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg present low toxicity.
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http://dx.doi.org/10.2174/1389200218666170301110806DOI Listing
September 2018

Modulation of the antibiotic activity against multidrug resistant strains of coumarins isolated from Rutaceae species.

Microb Pathog 2017 Mar 19;104:151-154. Epub 2017 Jan 19.

Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Brazil. Electronic address:

The first occurrences and dissemination of resistant microorganisms led to the inefficacy of many antibiotics, available in the market nowadays, therefore, the search for new substances with antimicrobial activity from natural sources has gained a great importance. The purpose of this work is to evaluate the antibacterial activity and modulation of drug resistance in Staphylococcus aureus by coumarins such as bergapten, xantotoxin, isopimpinellin and imperatorin obtained from two Rutaceae species (Metrodorea mollis and Pilocarpus spicatus). The antimicrobial activity was assessed based on the minimum inhibitory concentration (MIC), using the microdilution method. The MIC was >256 g/mL for all coumarins tested. Regarding the modulation of drug resistance assay, the isopimpinellin reducted the MIC of erytromicin by 4 times, whereas imperatorin exhibited the best result, reducing the MIC of tetracycline (2 times), erytomicin (4 times) and norfloxacin (4 times). By reducing the MIC of ethidium bromide, the imperatorin is consider in fact, as a putative efflux pump inhibitor of bacteria.
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http://dx.doi.org/10.1016/j.micpath.2017.01.028DOI Listing
March 2017

Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla.

Z Naturforsch C J Biosci 2015 ;70(5-6):129-37

The chemical composition, antitumor activity and toxicity of the essential oil from Lippia microphylla leaves (OEL) were investigated. The major constituents were thymol (46.5%), carvacrol (31.7%), p-cymene (9%), and γ-terpinene (2.9%). To evaluate the toxicity of OEL in non-tumor cells, the hemolytic assay with Swiss mice erythrocytes was performed. The concentration producing 50% hemolysis (HC50) was 300 μg/mL. Sarcoma 180 tumor growth was inhibited in vivo 38% at 50 mg/kg, and 60% at 100 mg/kg, whereas 5-FU at 50 mg/kg caused 86% inhibition. OEL displays moderate gastrointestinal and hematological toxicity along with causing some alteration in liver function and morphology. However, the changes were considered reversible and negligible in comparison to the effects of several anticancer drugs. In summary, OEL displays in vivo antitumor activity and a moderate toxicity, which suggests further pharmacological study.
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http://dx.doi.org/10.1515/znc-2014-4138DOI Listing
November 2015

Essential oil from the leaves of Xylopia langsdorfiana (Annonaceae) as a possible spasmolytic agent.

Nat Prod Res 2015 16;29(10):980-4. Epub 2014 Oct 16.

a Center for Health Sciences (CCS), Federal University of Paraíba (UFPB) , Campus I, 58.051-970, PO Box 5009, João Pessoa , Paraíba , Brazil.

Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 μg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 μg/mL) inhibited carbachol or histamine-induced phasic contractions (1 μM) in a significant and concentration-dependent manner. In addition, XL-OE (81 μg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.
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http://dx.doi.org/10.1080/14786419.2014.964706DOI Listing
July 2015

Theoretical research into anticancer activity of diterpenes isolated from the paraiban flora.

Nat Prod Commun 2014 Jul;9(7):911-4

Many studies of the scientific literature discuss the anticancer activity of diterpenes inhibiting the Akt/IKK/NF-kappaB pro-survival signaling cascade, mainly by the activation of serine/threonine phosphatase PP2A. The aim of this work was to evaluate and compare the anticancer potential of three atisane, three kaurane and three trachylobane diterpenes extracted from the roots of Xylopia langsdorffiana. Thus, we investigated the reactivity (H-L(GAP) parameter), HOMO atmosphere favorable to neutralize the radical reactivity, and the docking of compounds with PP2A. With all approaches, this theoretical study showed that atisane diterpenes have favorable characteristics for antitumor activity, like electron donating ability and greater hydrophilic interactions with the enzyme, by inhibition of Akt/IKK/NF-kappaB, and activation of PP2A.
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July 2014

Prediction of anticancer activity of diterpenes isolated from the paraiban flora through a PLS model and molecular surfaces.

Nat Prod Commun 2014 May;9(5):609-12

The aim of this work was to predict the anticancer potential of 3 atisane, and 3 trachylobane diterpene compounds extracted from the roots of Xylopia langsdorffiana. The prediction of anticancer activity as expressed against PC-3 tumor cells was made using a PLS model built with 26 diterpenes in the training set. Significant statistical measures were obtained. The six investigated diterpenes were applied to the model and their activities against PC-3 cells were calculated. All the diterpenes were active, with atisane diterpenes showing the higher pICso values. In human prostate carcinoma PC-3 cells, the apoptosis mechanism is related to an inhibition of IKK/NF-KB. Antioxidant potential implies a greater electronic molecular atmosphere (increased donor electron capacity), which can reduce radical reactivity, and facilitate post donation charge accommodation. Molecular surfaces indicated a much greater electronic cloud over atisane diterpenes.
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May 2014

Relaxant effect of Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle.

J Smooth Muscle Res 2013 ;49:15-25

Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil.

Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca(2+)-calmodulin complex was eliminated as chlorpromazine (10(-6) M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K(+) channels. This was confirmed, as in the presence of 10 mM TEA(+) (a non-selective K(+) channel blocker), diterpene relaxation potency was significantly reduced (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K(+) channels, particularly the KATP, KV, SKCa and BKCa subtypes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137274PMC
http://dx.doi.org/10.1540/jsmr.49.15DOI Listing
October 2013

Antinociceptive effect of 7-methoxyflavone isolated from Zornia brasiliensis.

Nat Prod Res 2013 21;27(18):1695-9. Epub 2013 Feb 21.

a Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa , Paraíba , Brazil.

In this study, we investigated the antinociceptive effect of 7-methoxyflavone (7MF) in mice using the following tests: acetic acid-induced writhing, glutamate- and formalin-induced nociception and hotplate. 7MF (30, 50, 100 and 300 μmol/kg, i.p.) reduced the number of writhes, with ID₅₀ = 82.5 ± 11.7 μmol/kg and E max = 58.4%. 7MF treatment (100 μmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin pain response (65.6%) and did not decrease the nociceptive response in the inflammatory phase. In addition, in glutamate-induced nociception, 7MF inhibited 26% of the nociceptive answer. On the other hand, 7MF did not increase the latency time of the animals in the hotplate test. These results suggest that 7MF has peripheral antinociceptive activity.
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http://dx.doi.org/10.1080/14786419.2013.768988DOI Listing
April 2014

Synthesis, structure-activity relationships (SAR) and in silico studies of coumarin derivatives with antifungal activity.

Int J Mol Sci 2013 Jan 10;14(1):1293-309. Epub 2013 Jan 10.

Pharmaceutical Science Department, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil.

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO(2) and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2(cv) of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.
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http://dx.doi.org/10.3390/ijms14011293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565321PMC
January 2013

Antimicrobial, antiproliferative and proapoptotic activities of extract, fractions and isolated compounds from the stem of Erythroxylum caatingae plowman.

Int J Mol Sci 2012 29;13(4):4124-40. Epub 2012 Mar 29.

Antibiotics of Departament, Federal University of Pernambuco, 50670-901, Recife, PE, Brasil; E-Mails: (J.S.A.); (R.O.A.); (M.D.R.); (K.X.F.R.S.); (S.C.N.).

In the study, we have examined the antitumor and antimicrobial activities of the methanol extract, the fractions, a fraction of total alkaloids and two alkaloids isolated from the stem of Erythroxylum caatingae Plowman. All test fractions, except the hexane fractions, showed antimicrobial activity on gram-positive bacteria and fungi. The acetate: methanol (95:5), acetate, chloroform and hexane fractions show the highest cytotoxicity activity against the NCI-H292, HEp-2 and K562 cell lines using MTT. The absence of hemolysis in the erythrocytes of mice was observed in these fractions and 6β-Benzoyloxy-3α-(3,4,5- trimethoxybenzoyloxy) tropane (catuabine B). Staining with Annexin V-FITC and JC-1 was used to verify the mechanism of action of the compounds of E. caatingae that showed cytotoxicity less than 30 μg/mL in leukemic cells. After 48 h of incubation, we observed that the acetate: methanol (95:5), acetate, and chloroform fractions, as well as the catuabine B, increased in the number of cells in early apoptosis, from 53.0 to 74.8%. An analysis of the potential of the mitochondrial membrane by incorporation of JC-1 showed that most cells during incubation of the acetate: methanol (95:5) and acetate fractions (63.85 and 59.2%) were stained, suggesting the involvement of an intrinsic pathway of apoptosis.
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http://dx.doi.org/10.3390/ijms13044124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344205PMC
August 2015

Spasmolytic activity of trachylobanes ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid isolated from Xylopia langsdorfiana A. St-Hil. & Tul. (Annonaceae).

Nat Prod Res 2012 31;26(24):2335-9. Epub 2012 Jan 31.

Laboratório de Tecnologia Farmacêutica Prof. Delby Fernandes de Medeiros, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.
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http://dx.doi.org/10.1080/14786419.2011.653974DOI Listing
April 2013

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K(+) and Ca(2+) channels to reduce cytosolic calcium concentration on guinea pig ileum.

Eur J Pharmacol 2012 Mar 27;678(1-3):39-47. Epub 2011 Dec 27.

Departamento de Bioquímica e Farmacologia, Universidade Federal do Piauí (UFPI), Teresina, Piauí, Brazil.

In this study we investigated the mechanism underlying the spasmolytic action of ent-7α-acetoxytrachyloban-18-oic acid (trachylobane-360) and ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5±0.9 and 4.4±0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl(2)-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca(v)). The Ca(v) participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC(50)=3.5±0.7×10-(5) and 1.1±0.2×10-(5)M) and KCl (EC(50)=5.5±0.3×10-(5) and 1.4±0.2×10-(5)M). K(+) channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5mM tetraethylammonium (TEA(+)) (EC(50)=0.5±0.04×10-(4) and 2.0±0.5×10-(5)M). ATP-sensitive K(+) channel (K(ATP)), voltage activated K(+) channels (K(V)), small conductance calcium-activated K(+) channels (SK(Ca)) or big conductance calcium-activated K(+) channels (BK(Ca)) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K(ATP), K(V) and SK(Ca) (EC(50)=1.1±0.3×10-(5), 0.7±0.2×10-(5) and 0.7±0.2×10-(5)M), but not BK(Ca). A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca(2+)](c)) induced by both trachylobanes in ileal myocytes. In conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K(+) channel positive modulation and Ca(2+) channel blockade, which results in [Ca(2+)](c) reduction at cellular level leading to smooth muscle relaxation.
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http://dx.doi.org/10.1016/j.ejphar.2011.12.028DOI Listing
March 2012

Antioxidant, antinociceptive, and anti-inflammatory properties of the ethanolic extract of Combretum duarteanum in rodents.

J Med Food 2011 Nov 11;14(11):1389-96. Epub 2011 Jun 11.

Department of Physiology, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil.

The antioxidant, antinociceptive, and anti-inflammatory activities of the ethanolic extract from leaves of Combretum duarteanum (EEC) were assessed in rodents through in vitro tests. The antioxidant activity was investigated by using thiobarbituric acid reactive species (TBARS), hydroxyl radical-scavenging, and scavenging activity of nitric oxide assays. The antinociceptive activity was investigated by using acetic acid-induced writhing, formalin, and hot-plate tests in mice. The anti-inflammatory activity was assessed in rats by using the carrageenan-induced hind-paw edema test and arachidonic acid-induced paw edema test. EEC possesses a strong antioxidant potential according to the TBARS, nitric oxide, and hydroxyl radical-scavenging assays; it also presented scavenger activity in all in vitro tests. After intraperitoneal injection, EEC (100, 200, and 400 mg/kg) significantly reduced the number of writhes (38.1%, 90.6%, and 97.8%, respectively) in a writhing test and the number of paw licks during phase 1 (30.5% and 69.5%, higher doses) and phase 2 (38.1%, 90.6%, and 97.8%, all doses) of a formalin test when compared with the control group. Naloxone (1.5 mg/kg, intraperitoneally) antagonized the antinociceptive action of EEC (400 mg/kg), and this finding suggests participation of the opioid system. Administration of 200 and 400 mg/kg (intraperitoneally) of EEC exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis. This finding was confirmed by the arachidonic acid test. Together, these results indicate that properties of EEC might be further explored in the search for newer tools to treat painful inflammatory conditions, including those related to pro-oxidant states.
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http://dx.doi.org/10.1089/jmf.2010.0212DOI Listing
November 2011

Tropane alkaloids from Erythroxylum caatingae Plowman.

Chem Biodivers 2011 Jan;8(1):155-65

Departamento de Ciências Farmacêuticas, Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Three tropane alkaloids, 1-3, were isolated from Erythroxylum caatingae, i.e., 6β-benzoyloxy-3α-[(4-hydroxy-3,5-dimethoxybenzoyl)oxy]tropane (1), a new tropane alkaloid, along with the known alkaloids 3α,6β-dibenzoyloxytropane (2) and 6β-benzoyloxy-3α-[(3,4,5-trimethoxybenzoyl)oxy]tropane (catuabine B; 3). Their structures were determined by 2D- ((1) H and (13) C) NMR. By LC/ESI-MS/MS analysis of the fractions of alkaloids 1-3, it was possible to detect five more alkaloids, 4-8, two of these, 4 and 8, possibly being new natural products. X-Ray crystallography of the chloride derivate of 1, i.e., 6β-benzoyloxy-3α-(4-hydroxy-3,5-dimethoxybenzoyloxy)tropane hydrochloride (1a) confirmed the structure of 1. Cytotoxicity was tested against the cell lines HEp-2, NCI-H292, and KB for the MeOH extract and alkaloid 3, and antitumor activity was tested against Sarcoma 180 only for the MeOH extract.
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http://dx.doi.org/10.1002/cbdv.200900400DOI Listing
January 2011

Tropane alkaloids from Erythroxylum genus: distribution and compilation of 13C-NMR spectral data.

Chem Biodivers 2010 Feb;7(2):302-26

Universidade Federal da Paraíba, Laboratório de Tecnologia Farmacêutica, Caixa Postal 5009, 58051-970, João Pessoa-PB, Brazil.

Erythroxylum, the most representative genus of the Erythroxylaceae family, presents tropane alkaloids as main constituents. This class of compounds greatly contributes to the chemotaxonomic characterization of plants of this genus, and it has important medical uses and shows toxic effects. This review describes 186 tropane alkaloids in the 35 species of Erythroxylum distributed worldwide. In addition, a compilation of their (13)C-NMR spectral data is presented.
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http://dx.doi.org/10.1002/cbdv.200800290DOI Listing
February 2010

Diterpenes from Xylopia langsdorffiana inhibit cell growth and induce differentiation in human leukemia cells.

Z Naturforsch C J Biosci 2009 Sep-Oct;64(9-10):650-6

Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, CP 5009, João Pessoa, Paraíba, 58051-970, Brazil.

Two new diterpenes were isolated from stems and leaves of Xylopia langsdorffiana, ent-atisane-7alpha,16alpha-diol (xylodiol) and ent-7alpha-acetoxytrachyloban-18-oic acid (trachylobane), along with the known 8(17),12E,14-labdatrien-18-oic acid (labdane). We investigated their antitumour effects on HL60, U937 and K562 human leukemia cell lines. We found that xylodiol was the most potent diterpene in inhibiting cell proliferation of HL60, U937 and K562 cells, with mean IC50 values of 90, 80 and 50 microM, respectively. Based on the nitroblue tetrazolium (NBT) reduction assay, all the diterpenes were found to induce terminal differentiation in HL60 and K562 cells, with xylodiol being the most effective. NBT reduction was increased by almost 120% after 12 h exposure of HL60 cells to xylodiol at a concentration lower than the IC50 (50 microM). Thus, xylodiol inhibited human leukemia cell growth in vitro partly by inducing cell differentiation, and merits further studies to examine its mechanism of action as a potential antitumoural agent.
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http://dx.doi.org/10.1515/znc-2009-9-1008DOI Listing
January 2010

Ecdysteroids from Vitex species: distribution and compilation of their 13C-NMR spectral data.

Chem Biodivers 2008 May;5(5):707-13

Universidade Federal da Paraíba, Laboratório de Tecnologia Farmacêutica, Caixa Postal 5009, 58051-970, João Pessoa, PB, Brazil.

Iridoids and ecdysteroids are found in some genera of the family Verbenaceae. In such cases, they are used as chemotaxonomic markers for the difficult task of taxonomic identification by using morphological characteristics of plants belonging to this family. The present work describes the distribution of ecdysteroids in plants from the genus Vitex from a review of previous work on seventeen Vitex species. In addition, (13)C-NMR data of the main ecdysteroids found in this genus are described. This study attempted to summarize previous research on ecdysteroids distribution in Vitex species with the addition of (13)C-NMR analysis to further refine the characterization of these compounds in the Verbenaceae family.
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http://dx.doi.org/10.1002/cbdv.200890067DOI Listing
May 2008

Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302).

Vascul Pharmacol 2006 May 9;44(5):338-44. Epub 2006 Mar 9.

Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Cidade Universitária, Campus I, Caixa Postal 5009, CEP 58.051-900, João Pessoa, PB, Brazil.

The cardiovascular effects induced by labdane-302, a diterpene isolated from the stems of Xylopia langsdorffianna St. Hill and Tull, were evaluated in male Wistar rats. In normotensive, conscious animals, labdane-302 produced dose-dependent hypotension and tachycardia. These effects were significantly attenuated after pre-treatment with L-NAME (20 mg/kg, i.v.). In isolated mesenteric artery rings, labdane-302 (10(-10)-10(-4)M) elicited concentration-dependent relaxation of phenylephrine-induced contractions (IC50 = 5.4 +/- 1.4 microM). Endothelium removal, and pre-treatment with L-NAME (100 microM) or indomethacin (10 microM) caused significant reductions in sensitivity. Labdane-302 also caused concentration-dependent relaxation in arterial rings pre-contracted with high extracellular KCl (80 mM). In Ca2+-free depolarized preparations, labdane-302 inhibited contractions produced by cumulative increases in extracellular Ca2+ concentration. In GH3 cells, labdane-302 (100 microM) inhibited whole-cell L-type Ca2+ currents by approximately 50%. These results demonstrate that labdane-302 causes hypotension through peripheral vasodilation, mediated in part by NO and PGI2 and by blockade of Ca2+ entry through L-type Ca2+ channels.
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http://dx.doi.org/10.1016/j.vph.2006.01.009DOI Listing
May 2006