Publications by authors named "Damião Pergentino de Sousa"

113 Publications

Cytotoxic and Antifungal Amides Derived from Ferulic Acid: Molecular Docking and Mechanism of Action.

Biomed Res Int 2021 1;2021:3598000. Epub 2021 Nov 1.

Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-900 João Pessoa, PB, Brazil.

Amides derived from ferulic acid have a wide spectrum of pharmacological activities, including antitumor and antifungal activity. In the present study, a series of ten amides were obtained by coupling reactions using the reagents (benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and 'dicyclohexylcarbodiimide (DCC). All the compounds were identified on the basis of their IR, H- and C-NMR, HRMS data, and with yields ranging from 43.17% to 91.37%. The compounds were subjected to cytotoxic tests by the alamar blue technique and antifungal screening by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The amides and displayed the best result in both biological evaluations, and compound was the most potent and selective in HL-60 cancer cells, with no cytotoxicity on healthy cells. This amide had antifungal activity in all strains and had the lowest MIC against and . The possible mechanism of antifungal action occurs via the fungal cell wall. Molecular modeling suggested that compounds and interact with the enzymes GWT1 and GSC1, which are essential for the development of . The findings of the present study demonstrated that compounds and may be used as a platform in drug development in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/3598000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575619PMC
November 2021

Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury.

Molecules 2021 Sep 30;26(19). Epub 2021 Sep 30.

Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-970, PB, Brazil.

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26195951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512361PMC
September 2021

Anticoronavirus and Immunomodulatory Phenolic Compounds: Opportunities and Pharmacotherapeutic Perspectives.

Biomolecules 2021 08 23;11(8). Epub 2021 Aug 23.

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

In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11081254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394099PMC
August 2021

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission.

Heliyon 2021 Apr 16;7(4):e06620. Epub 2021 Apr 16.

Postgraduate Programs in Pharmaceutical Sciences and Laboratory of Research in Experimental Neurochemistry (LAPNEX), Federal University of Piauí, 64049-550, Teresina, Brazil.

Rose oxide (RO) is a monoterpene found in rose oil fragrances. This monoterpene has been reported to possess anti-inflammatory activity, however, little is known regarding its pharmacological activity. The present study was carried out to evaluate its antidepressant action and possible mechanisms of action. Analysis of ADMET pharmacokinetic properties (absorption, distribution, metabolism, excretion and toxicity) of rose oxide was performed by computational prediction analysis. Behavioral tests were performed to assess the interaction between rose oxide and the central nervous system and antidepressant effect that includes: forced swim test (FST), tail suspension test (TST), open field test (OFT) and rota-rod test. The results of pharmacokinetic and toxicological properties indicate that rose oxide could be used orally, since it has good intestinal absorption as well as pharmacological and toxicological properties that can be similar to pharmacological compounds (regular hepatic metabolism and low toxicity). Treatment with 50 mg/kg of rose oxide was able to decrease the immobility time of animals not affected by FST and TST and was not able to alter the motor activity of the OFT and rota-rod test, suggesting modulation and antidepressant activity. Docking data suggest that rose oxide can bind to receptors in the serotonergic pathway. The results described here suggest that rose oxide has antidepressant activity, modulating the serotonergic pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2021.e06620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080052PMC
April 2021

Breakpoints for the Classification of Anti- Compounds in Antifungal Screening.

Biomed Res Int 2021 6;2021:6653311. Epub 2021 Apr 6.

Department of Clinic and Social Dentistry, Graduate Program in Natural and Synthetic Bioactive Products (PgPNSB), Center for Health Sciences, Federal University of Paraiba, João Pessoa, PB, Brazil.

Introduction: The absence of a standardized classification scheme for the antifungal potency of compounds screened against species may hinder the study of new drugs. This systematic review proposes a scheme of interpretative breakpoints for the minimum inhibitory concentration (MIC) of bioactive compounds against species in tests.

Materials And Methods: A literature search was conducted in the PubMed, Scopus, Web of Science, Lilacs, and SciFinder databases for the period from January 2015 to April 2020. The following inclusion criterion was used: organic compounds tested by the microdilution technique according to the Clinical and Laboratory Standards Institute protocol against reference strains of the genus . A total of 545 articles were retrieved after removing duplicates. Of these, 106 articles were selected after applying the exclusion criteria and were evaluated according to the number of synthesized molecules and their chemical classes, the type of strain (reference or clinical) used in the antifungal test, the species, and the MIC (in g/mL) used.

Results: The analysis was performed based on the median, quartiles (25% and 75%), maximum, and minimum values of four groups: all strains, ATCC strains, strains, and ATCC strains. The following breakpoints were proposed to define the categories: MIC < 3.515 g/mL (very strong bioactivity); 3.516-25 g/mL (strong bioactivity); 26-100 g/mL (moderate bioactivity); 101-500 g/mL (weak bioactivity); 500-2000 g/mL (very weak bioactivity); and >2000 g/mL (no bioactivity).

Conclusions: A classification scheme of the antifungal potency of compounds against species is proposed that can be used to identify the antifungal potential of new drug candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6653311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046529PMC
May 2021

, and investigation of antioxidant potential and toxicity of ethyl ferulate.

Drug Chem Toxicol 2021 Feb 25:1-11. Epub 2021 Feb 25.

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

By submitting this manuscript, each author certifies that they have made a direct and substantial contribution to the work reported in the manuscript. In this manuscript the conception, design, investigation, acquisition of data and analysis, interpretation of data and writing of the article were conducted by author Camila Bomfim de Sá under the guidance of professors Margareth de Fátima Formiga Melo Diniz, Hilzeth de Luna Freire Pessôa and Caliandra Maria Bezerra Luna Lima, who also approved the final version of the manuscript. Professor Damião Pergentino de Sousa and his student Mayara Castro de Morais performed the production, synthesis and chemical characterization of ethyl ferulate (EF). Professor Abrahão Alves de Oliveira Filho assessed the tests. PhD student Andressa Brito Lira participated in the critical review of the text for important intellectual content and assisted in the antioxidant activity and cytotoxicity tests. Kardilandia Mendes de Oliveira participated in acute oral toxicity tests evaluating the biochemical parameters. Students, Tafaela Dias and Cinthia Rodrigues Melo also assisted in the acute oral toxicity testing and preparing of slides for histopathological analysis. Pathologist Alexandre Rolim da Paz analyzed the histopathology results. EF, a phenolic compound of the large class of phenylpropanoids, is derived from ferulic acid and is produced both naturally and synthetically. Its principal pharmacological activities are: anti-inflammatory and antioxidant activity. This study aimed to investigate the , and toxicity and antioxidant activity of EF. The prediction showed more than 20 biological activities as well as good absorption at the biological membranes and no theoretical toxicity. However, EF presented high environmental toxicity. EF presented low hemolytic potential and exerted protective activity for the erythrocyte membrane for only blood type O. EF presented antioxidant activity against HO at all concentrations and all blood types, but no effect against phenylhydrazine, being unable to prevent its oxidative effects. In the acute nonclinical toxicological trial, the treated animals presented behavioral changes (e.g., sedation). Feed intake was higher for the 2000 mg/kg group, but with no significant difference in weight change. The biochemical parameters presented no differences between treated and control animals, and the organs remained intact with no change. Thus, EF presents a low toxic profile and this study provides important information about the toxicity of this compound, suggesting future safe use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01480545.2021.1878207DOI Listing
February 2021

Bioactive Terpenes and Their Derivatives as Potential SARS-CoV-2 Proteases Inhibitors from Molecular Modeling Studies.

Biomolecules 2021 Jan 7;11(1). Epub 2021 Jan 7.

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

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Millions of cases and deaths to date have resulted in a global challenge for healthcare systems. COVID-19 has a high mortality rate, especially in elderly individuals with pre-existing chronic comorbidities. There are currently no effective therapeutic approaches for the prevention and treatment of COVID-19. Therefore, the identification of effective therapeutics is a necessity. Terpenes are the largest class of natural products that could serve as a source of new drugs or as prototypes for the development of effective pharmacotherapeutic agents. In the present study, we discuss the antiviral activity of these natural products and we perform simulations against the M and PL enzymes of SARS-CoV-2. Our results strongly suggest the potential of these compounds against human coronaviruses, including SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11010074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825698PMC
January 2021

Ferulic Acid and Cardiovascular Health: Therapeutic and Preventive Potential.

Mini Rev Med Chem 2021 ;21(13):1625-1637

Department of Pharmaceutical Sciences, Federal University of Paraiba, Joao Pessoa, Brazil.

Bioactive compounds found in food and medicinal plants contribute to maintaining health and treating illnesses. For example, hydroxycinnamic acids, such as ferulic acid, are widely present in nature and have several pharmacological properties, including antioxidant, anti-inflammatory, and beneficial effects in parameters of diabetes and hyperlipidemia. The results of studies in animal models and in vitro experiments of ferulic acid suggest its high therapeutic and preventive potential against several pathological disorders, such as cardiovascular diseases. Therefore, in this review, the bioactivities of ferulic acid on the cardiovascular system are described, including the discussion of the mechanisms of action in the various components of the system. In this review, we discuss the pharmacological properties of this versatile natural product in aspects of cardiovascular health, including cardioprotective and antihypertensive actions, and on the metabolism of lipids, diabetes, and thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389557521666210105122841DOI Listing
October 2021

Antiviral Role of Phenolic Compounds against Dengue Virus: A Review.

Biomolecules 2020 12 24;11(1). Epub 2020 Dec 24.

Department of Pharmaceutical Sciences, Federal University of Paraíba, CEP 58051-970 João Pessoa, PB, Brazil.

Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823413PMC
December 2020

Mechanistic Aspects and Therapeutic Potential of Quercetin against COVID-19-Associated Acute Kidney Injury.

Molecules 2020 Dec 7;25(23). Epub 2020 Dec 7.

Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-970 João Pessoa, PB, Brazil.

The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25235772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730372PMC
December 2020

Carvone Enantiomers Differentially Modulate IgE-Mediated Airway Inflammation in Mice.

Int J Mol Sci 2020 Dec 3;21(23). Epub 2020 Dec 3.

Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa 58051-900, Brazil.

Carvone is a monoterpene found in nature in the form of enantiomers (S- and R-). While previous research has demonstrated the anti-inflammatory and anti-allergic effects of carvone, the influence of carvone enantiomeric composition on its anti-allergic activity remains to be investigated. This study aimed to evaluate the anti-allergic activity of carvone enantiomers in a murine model of airway allergic inflammation induced by sensitization and challenge with ovalbumin (OVA). The oral treatment with R-carvone or S-carvone 1 h before each challenge inhibited the number of leukocytes and eosinophils in the bronchoalveolar lavage (BAL). R-carvone inhibited leukocyte infiltration and mucus production in the lung, which was correlated with decreased production of OVA-specific IgE in the serum and increased concentrations of IL-10 in the BAL. On the other hand, the administration of S-carvone had little inhibitory effect on inflammatory infiltration and mucus production in the lung, which might be associated with increased production of IFN-γ in the BAL. When administered 1 h before each sensitization, both enantiomers inhibited eosinophil recruitment to the BAL but failed in decreasing the titers of IgE in the serum of allergic mice. Our data indicate that carvone enantiomers differentially modulated IgE-mediated airway inflammation in mice. In conclusion, unlike S-carvone, R-carvone has the potential to be used in anti-allergic drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21239209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731315PMC
December 2020

Alkaloids: Therapeutic Potential against Human Coronaviruses.

Molecules 2020 Nov 24;25(23). Epub 2020 Nov 24.

Department of Pharmaceutical Sciences, Federal University of Paraíba, Paraíba 58051-900, Brazil.

Alkaloids are a class of natural products known to have wide pharmacological activity and have great potential for the development of new drugs to treat a wide array of pathologies. Some alkaloids have antiviral activity and/or have been used as prototypes in the development of synthetic antiviral drugs. In this study, eleven anti-coronavirus alkaloids were identified from the scientific literature and their potential therapeutic value against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is discussed. In this study, in silico studies showed an affinity of the alkaloids for binding to the receptor-binding domain of the SARS-CoV-2 spike protein, putatively preventing it from binding to the host cell. Lastly, several mechanisms for the known anti-coronavirus activity of alkaloids were discussed, showing that the alkaloids are interesting compounds with potential use as bioactive agents against SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25235496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727683PMC
November 2020

Trypanocidal Essential Oils: A Review.

Molecules 2020 Oct 6;25(19). Epub 2020 Oct 6.

Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-900 João Pessoa, Paraíba, Brazil.

Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus . In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25194568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583723PMC
October 2020

Natural Antioxidants: A Review of Studies on Human and Animal Coronavirus.

Oxid Med Cell Longev 2020 12;2020:3173281. Epub 2020 Aug 12.

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

The outbreaks of viruses with wide spread and mortality in the world population have motivated the research for new therapeutic approaches. There are several viruses that cause a biochemical imbalance in the infected cell resulting in oxidative stress. These effects may be associated with the development of pathologies and worsening of symptoms. Therefore, this review is aimed at discussing natural compounds with both antioxidant and antiviral activities, specifically against coronavirus infection, in an attempt to contribute to global researches for discovering effective therapeutic agents in the treatment of coronavirus infection and its severe clinical complications. The contribution of the possible action of these compounds on metabolic modulation associated with antiviral properties, in addition to other mechanisms of action, is presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/3173281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443229PMC
September 2020

The Prowess of Andrographolide as a Natural Weapon in the War against Cancer.

Cancers (Basel) 2020 08 4;12(8). Epub 2020 Aug 4.

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.

There has been a paradigm shift in our understanding about the multifaceted nature of cancer, and a wealth of information has revealed that single-target drugs are not good enough to provide satisfactory clinical outcomes and therapeutic effects for complex diseases which involve multiple factors. Therefore, there has been a reignition to search for natural products having premium pharmacological activities aim to efficiently target multiple deregulated cellular signaling pathways. Andrographolide, a diterpene lactone from was brought into to the limelight because of its ability to inhibit cancer cell proliferation and induce apoptosis. Here we reviewed andrographolide on cellular pathways regulation including Wnt/β-catenin, mTOR, VEGF-mediated intracellular signaling, as well as TRAIL-mediated apoptosis to inhibit cancer development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12082159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465495PMC
August 2020

Ethyl ferulate/β-cyclodextrin inclusion complex inhibits edema formation.

Mater Sci Eng C Mater Biol Appl 2020 Oct 13;115:111057. Epub 2020 May 13.

RENORBIO, Focal Point - Federal University of Piauí, Av. Nossa Senhora de Fátima s/n, 64049-550 Teresina, PI, Brazil. Electronic address:

Ethyl ferulate, a phenylpropanoid derived from rice hulls has aroused interest because of its antioxidant, anti-inflammatory and neuroprotective properties. However, it has low solubility in water which compromises the absorption in the gastrointestinal tract, decreases the bioavailability and compromises the reproducibility of the effects in vivo. To increase the solubility of ethyl ferulate, inclusion complexes were obtained by physical mixing, malaxing, lyophilization and spray drying and characterized using thermal analysis, XRD and FTIR. The complexes obtained were evaluated for ethyl ferulate content, stability, dissolution profile and evaluation of anti-inflammatory activity in vivo through carrageenan-induced paw edema model in rats. The inclusion complexes obtained resulted in increased solubility and stability compared to the isolated ethyl ferulate. In addition, the complexes obtained by malaxage, lyophilization and spray drying showed greater inhibition of the edema formation induced by carrageenan compared to ethyl ferulate 100 mg/kg v.o. The inclusion of ethyl ferulate in B-cyclodextrin resulted in the formation of stable inclusion complexes with potent antidematogenic activity possibly attributed to the increased solubility, dissolution profile of the active.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2020.111057DOI Listing
October 2020

Methyl 3,4,5-trimethoxycinnamate suppresses inflammation in RAW264.7 macrophages and blocks macrophage-adipocyte interaction.

Inflammopharmacology 2020 Oct 16;28(5):1315-1326. Epub 2020 May 16.

Laboratory of Pharmaceutical Chemistry, Federal University of Paraíba, João Pessoa, 58051-085, Brazil.

Methyl 3,4,5-trimethoxycinnamate (MTC) is a bioactive natural phenylpropanoid. We evaluated anti-inflammatory effects of synthetic MTC in RAW264.7 macrophages and RAW264.7-3T3-L1 adipocytes co-culture. Levels of cytokines and chemokines, as well as NO and PGE in cell supernatants were analysed using ELISAs, Griess assay and enzyme immunoassays, respectively. In-cell cytoblot was used to assess levels of proteins; while DNA binding and reporter gene assays were used to measure transcription factor DNA binding and transcriptional activities, respectively. Glucose uptake in adipocytes was evaluated with 2-deoxy-2-[(7-nitro-2, 1, 3-benzoxadiazol-4-yl) amino]-D-glucose uptake. MTC (5-20 µM) suppressed LPS + IFNγ-induced release of TNFα, IL-6 and IL-1β, as well as NO/iNOS and PGE/COX-2 levels in RAW264.7 cells. Furthermore, there was a reduction in phospho-IκB and phospho-p65 proteins, accompanied by a reduction in total IκB in RAW264.7 cells. Further studies showed that MTC also produced a reduction in NF-κB DNA binding and luciferase activity. Treatment of RAW264.7 cells with MTC (5-20 µM) resulted in enhanced DNA binding of Nrf2 and an increase in ARE-luciferase activity. In a macrophage-adipocyte co-culture, the compound reduced the release of TNFα, IL-6, IL-1β, MCP-1 and RANTES, while enhancing glucose uptake and activation of AMPKα. Our results suggest that MTC produced anti-inflammatory and antioxidant activities in macrophages. MTC also prevented inflammation in macrophage-adipocyte co-culture. The effect of MTC on glucose uptake in adipocytes is proposed to be linked to activation of AMPK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10787-020-00720-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524821PMC
October 2020

(-)--Carveol, a Natural Compound, Improves -Amyloid-Peptide 1-42-Induced Memory Impairment and Oxidative Stress in the Rat Hippocampus.

Biomed Res Int 2020 22;2020:8082560. Epub 2020 Apr 22.

Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-970 João Pessoa, PB, Brazil.

Alzheimer's disease (AD) could be considered a multifactorial neurodegenerative disorder characterized by the accumulation of the -amyloid-peptide (A) within the brain leading to cognitive deficits, oxidative stress, and neuroinflammation. The present work was carried out to investigate the neuroprotective effect of (-)--carveol (1% and 3%, for 21 days) against the -amyloid-peptide 1-42- (A1-42-) induced AD. Twenty-five rats were divided into five groups ( = 5/group): the first group-control (sham-operated); the second group-A1-42 (1 mM) that received donepezil treatment (5 mg/kg, as the positive reference drug in the Y-maze and the radial arm maze tests); the third group-A1-42 (1 mM); the fourth and fifth groups-A1-42 (1 mM) that received (-)--carveol treatment groups (1% and 3%). The results of this study demonstrated that (-)--carveol improved A1-42-induced memory deficits examined by using Y-maze and radial arm maze tests. Also, the biochemical analyses of the hippocampus homogenates showed that (-)--carveol reduced hippocampal oxidative stress caused by A1-42. Our results suggested that the use of (-)--carveol may be suitable for decreasing AD-related symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8082560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196140PMC
February 2021

A New Ferulic Acid-Nicotinamide Cocrystal With Improved Solubility and Dissolution Performance.

J Pharm Sci 2020 03 7;109(3):1330-1337. Epub 2019 Dec 7.

Department of Pharmacy, Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal 59010-115, Brazil. Electronic address:

Among the various strategies for increasing aqueous solubility of pharmaceutical substances, cocrystals have been emerging as a promising alternative. The ferulic acid (FEA) is a molecule with limited aqueous solubility, but with an interesting pharmacological activity, highlighting its antitumor potential. This study presents the characterization and physicochemical properties of a new cocrystal based on FEA and nicotinamide (NIC). The FEA-NIC cocrystal was obtained by solvent evaporation technique and physicochemically characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance and scanning electron microscopy. The content determination and dissolution profile in different media were analyzed by high-performance liquid chromatography. The results obtained with the characterization techniques indicated the obtainment of an anhydrous cocrystal of FEA and NIC at a 1:1 molar ratio. The method was reproducible and obtained a high yield, of approximately 99%. In addition, a 70% increase in the FEA solubility in the cocrystal and a better dissolution performance than the physical mixture in pH 6.8 were achieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xphs.2019.12.002DOI Listing
March 2020

Anticonvulsant Essential Oils and Their Relationship with Oxidative Stress in Epilepsy.

Biomolecules 2019 12 6;9(12). Epub 2019 Dec 6.

Department of Pharmaceutical Sciences, Universidade Federal da Paraíba, João Pessoa, PB, CEP 58051-970, Brazil.

Epilepsy is a most disabling neurological disorder affecting all age groups. Among the various mechanisms that may result in epilepsy, neuronal hyperexcitability and oxidative injury produced by an excessive formation of free radicals may play a role in the development of this pathology. Therefore, new treatment approaches are needed to address resistant conditions that do not respond fully to current antiepileptic drugs. This paper reviews studies on the anticonvulsant activities of essential oils and their chemical constituents. Data from studies published from January 2011 to December 2018 was selected from the PubMed database for examination. The bioactivity of 19 essential oils and 16 constituents is described. Apiaceae and Lamiaceae were the most promising botanical families due to the largest number of reports about plant species from these families that produce anticonvulsant essential oils. Among the evaluated compounds, β-caryophyllene, borneol, eugenol and nerolidol were the constituents that presented antioxidant properties related to anticonvulsant action. These data show the potential of these natural products as health promoting agents and use against various types of seizure disorders. Their properties on oxidative stress may contribute to the control of this neurological condition. However, further studies on the toxicological profile and mechanism of action of essential oils are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom9120835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995584PMC
December 2019

Antidepressant Potential of Cinnamic Acids: Mechanisms of Action and Perspectives in Drug Development.

Molecules 2019 Dec 6;24(24). Epub 2019 Dec 6.

Departament of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa PB 58051-970, Brazil.

Depression is a health problem that compromises the quality of life of the world's population. It has different levels of severity and a symptomatic profile that affects social life and performance in work activities, as well as a high number of deaths in certain age groups. In the search for new therapeutic options for the treatment of this behavioral disorder, the present review describes studies on antidepressant activity of cinnamic acids, which are natural products found in medicinal plants and foods. The description of the animal models used and the mechanisms of action of these compounds are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24244469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943791PMC
December 2019

NFBTA: A Potent Cytotoxic Agent against Glioblastoma.

Molecules 2019 Jun 29;24(13). Epub 2019 Jun 29.

Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, PB 58051-085, Brazil.

Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; ()-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24132411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651752PMC
June 2019

Amides Derived from Vanillic Acid: Coupling Reactions, Antimicrobial Evaluation, and Molecular Docking.

Biomed Res Int 2019 15;2019:9209676. Epub 2019 Apr 15.

Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-900 João Pessoa, PB, Brazil.

A series of amides derived from vanillic acid were obtained by coupling reactions using PyBOP ((Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate) and DCC (Dicyclohexylcarbodiimide) coupling reagents. These were submitted to biological evaluation for species of , , and . The microdilution method in broth was used for the antimicrobial testing to determine the Minimum Inhibitory Concentration (MIC) and to verify the likely mechanism of action for antifungal activity. The ten amides were obtained with yields ranging from 28.81 to 86.44%, and three compounds were novel. In the antibacterial evaluation, the amides (in their greatest concentrations) were bioactive against strain ATCC 25925. Meanwhile, all of the tested amides presented antifungal activity against at least one strain. The amide with best antifungal profile was compound , which featured an MIC of 0.46 mol/mL, and a mechanism of action involving the plasma membrane and fungal cell wall. The presence of a methyl group in the position of the aromatic ring is suggested which enhances the activity of the compound against fungi. Docking studies of the ten compounds using the protein 14-demethylase as a biological target were also performed. The biological results presented good correlation with molecular docking studies demonstrating that a possible site of antifungal action for bioactive amides is the enzyme 14-demethylase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/9209676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500666PMC
November 2019

Inhibition of neutrophil migration and reduction of oxidative stress by ethyl p-coumarate in acute and chronic inflammatory models.

Phytomedicine 2019 Apr 27;57:9-17. Epub 2018 Sep 27.

Medicinal Plants Research Center, Federal University of Piauí, Av. Nossa Senhora de Fátima s/n, 64049-550 Teresina, Piauí, Brazil. Electronic address:

Background: It is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested.

Purpose: The aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters.

Study Design: This is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation.

Methods: The anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 μl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100  µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 μg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20  mg/kg, p.o.).

Results: After treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions.

Conclusion: Taken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2018.09.034DOI Listing
April 2019

An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol.

Oxid Med Cell Longev 2018 22;2018:3957262. Epub 2018 Oct 22.

Department of Pharmaceutical Sciences, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil.

The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/3957262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217746PMC
December 2018

Piperlongumine as anticancer agent: The story so far about killing many birds with one stone.

Cell Mol Biol (Noisy-le-grand) 2018 Aug 30;64(11):102-107. Epub 2018 Aug 30.

Department of Pharmacology, Southwest Medical Univerisity, Luzhou, Sichuan 646000, China.

Piperlongumine is a biologically and pharmacologically active constituent of the plant Piper longum. This compound is gradually gaining attention because of its ability to inhibit/prevent different cancers. Modern era of molecular oncology is incomplete without ground-breaking discoveries made in the field of cell signaling pathways. High-throughput technologies have considerably improved our understanding about wide ranging signal transduction cascades which play crucial role in cancer development and progression. It is exciting to note that piperlongumine has been shown to pleiotropically modulate different oncogenic signaling pathways. We partition this multi-component review into discrete sections and categorically summarize key findings related to excellent ability of piperlongumine to therapeutically target JAK-STAT, NF-kB and PI3K/AKT/mTOR pathways. We also set spotlight on regulation of TRAIL pathway and autophagy by piperlongumine in different cancers. On the basis of the current understanding of piperlongumine, molecular biologists and pharmacologists will develop the next generation of translational studies, which will prove to be helpful in improving the clinical outcome and getting a step closer to personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2018

A Comparative Evaluation of the Cytotoxic and Antioxidant Activity of Essential Oil, Its Major Constituent Rotundifolone, and Analogues on Human Glioblastoma.

Oxid Med Cell Longev 2018 2;2018:2083923. Epub 2018 Jul 2.

Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-970 João Pessoa-PB, Brazil.

Cancer is a major public health problem around the globe. This disorder is affected by alterations in multiple physiological processes, and oxidative stress has been etiologically implicated in its pathogenesis. Glioblastoma (GBM) is considered the most common and aggressive brain tumor with poor prognosis despite recent improvements in surgical, radiation, and chemotherapy-based treatment approaches. The purpose of this study was to evaluate antitumor activity from essential oil (MCEO), its major constituent rotundifolone (ROT), and a series of six analogues on the human U87MG glioblastoma cell line. Cytotoxic effects of the compounds on the human U87MG-GBM cell line were assessed using cell viability and oxidative and molecular genetic assays. In addition, biosafety assessment tests were performed on cultured human blood cells. Our findings revealed that MCEO, 1,2-perillaldehyde epoxide (EPER1), and perillaldehyde (PALD) were the most cytotoxic compounds against U87MG cells, with IC50 values of 16.263, 15.087, and 14.888 g/mL, respectively. Further, these compounds increased the expressions of , , , , , , , , , and genes at different degrees and decreased the expression of some genes such as , , , and . Finally, treatment with MCEO, EPER1, and PALD did not lead to genotoxic damage in blood cells. Taken together, our findings reveal antiproliferative potential of MCEO, its major component ROT, and its tested analogues. Some of these chemical analogues may be useful as prototypes for the development of novel chemotherapeutic agents for treating human brain cancer and/or other cancers due to their promising activities as well as nonmutagenic property and safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/2083923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051078PMC
October 2018

Effects of isopulegol in acute nociception in mice: Possible involvement of muscarinic receptors, opioid system and l-arginine/NO/cGMP pathway.

Chem Biol Interact 2018 Sep 24;293:55-60. Epub 2018 Jul 24.

Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil. Electronic address:

Previous studies have shown that isopulegol has anxiolytic, anticonvulsant, gastro-protective and antioxidant activities in rodents, but until now there are no studies showing activity of isopulegol in animal models of nociception and inflammation. The objective of this study was to evaluate the antinociceptive effect of isopulegol and to propose possible mechanisms involved in its effects observed in mice. Groups of male and female Swiss mice (20-35 g, n = 5-8) were used in this test under the authorization of Ethics Committee on Animal Experimentation (CEEA/UFPI N° 82/2014). In order to evaluate the antinociceptive activity of isopulegol, nociception was induced using formalin test, capsaicin and glutamate in hind paw licking model, followed by the investigation of the involvement of opioid mechanisms, K + ATP channels, muscarinic, L arginine-nitric oxide and cGMP. The oral administration of isopulegol showed antinociceptive effect in both phases of the formalin test at doses from 0.78 to 25 mg/kg (first phase) and 1.56-25 mg/kg (second phase) and also produced significant results before capsaicin test at doses from 1.56 to 12.5 mg/kg and glutamate test at doses from 3.12 to 6.25 mg/kg with a dose-dependent effect. The antinociception activity of isopulegol was inhibited in the presence of naloxone (2 mg / kg, ip), glibenclamide (3 mg/kg, ip), atropine (1 mg/kg, ip), l-arginine (600 mg/kg, ip) and methylene blue (20 mg/kg, ip). The results suggested that acute antinociceptive action of opioid isopulegol seems to be related to the K + ATP channels system, through the involvement of muscarinic receptors, inhibiting nitric oxide and cGMP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2018.07.019DOI Listing
September 2018

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma.

Molecules 2018 Jun 8;23(6). Epub 2018 Jun 8.

Laboratory of Pharmaceutical Chemistry, Universidade Federal da Paraíba, João Pessoa 58051-085, Brazil.

Piplartine () is an alkamide extracted from plants of the genus which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound ()-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules23061382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099735PMC
June 2018

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

J Dermatolog Treat 2019 Sep 16;30(6):617-626. Epub 2019 Apr 16.

a Universidade Tiradentes - UNIT , Aracaju , Brazil.

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility, and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09546634.2018.1479726DOI Listing
September 2019
-->