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1.
Sci Rep ; 13(1): 12491, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37528129

RESUMO

Animal venoms are rich sources of neuroactive compounds, including anti-inflammatory, antiepileptic, and antinociceptive molecules. Our study identified a protonectin peptide from the wasp Parachartergus fraternus' venom using mass spectrometry and cDNA library construction. Using this peptide as a template, we designed a new peptide, protonectin-F, which exhibited higher antinociceptive activity and less motor impairment compared to protonectin. In drug interaction experiments with naloxone and AM251, Protonectin-F's activity was decreased by opioid and cannabinoid antagonism, two critical antinociception pathways. Further experiments revealed that this effect is most likely not induced by direct action on receptors but by activation of the descending pain control pathway. We noted that protonectin-F induced less tolerance in mice after repeated administration than morphine. Protonectin-F was also able to decrease TNF-α production in vitro and modulate the inflammatory response, which can further contribute to its antinociceptive activity. These findings suggest that protonectin-F may be a potential molecule for developing drugs to treat pain disorders with fewer adverse effects. Our results reinforce the biotechnological importance of animal venom for developing new molecules of clinical interest.


Assuntos
Peptídeos , Venenos de Vespas , Camundongos , Animais , Venenos de Vespas/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Morfina/farmacologia , Analgésicos Opioides , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dor/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico
2.
J Venom Anim Toxins Incl Trop Dis ; 27: e20200171, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34194483

RESUMO

BACKGROUND: Solitary wasp venoms may be a rich source of neuroactive substances, since their venoms are used for paralyzing preys. We have been exploring bioactive constituents of solitary wasp venoms and, in this study, the component profile of the venom from a solitary scoliid wasp, Scolia decorata ventralis, was investigated through a comprehensive analysis using LC-MS. Two peptides were synthesized, and their neuroprotective properties were evaluated. METHODS: A reverse-phase HPLC connected to ESI-MS was used for LC-MS analyses. Online mass fingerprinting was performed from TIC, and data-dependent tandem mass spectrometry gave the MS/MS spectra. The sequences of two major peptide components were determined by MALDI-TOF/TOF MS analysis, confirmed by solid phase synthesis. Using the synthetic peptides, biological activities were assessed. Cell integrity tests and neuroprotection analyzes using H2O2 as an oxidative stress inducer were performed for both peptides. RESULTS: Online mass fingerprinting revealed that the venom contains 123 components, and the MS/MS analysis resulted in 33 full sequences of peptide components. The two main peptides, α-scoliidine (DYVTVKGFSPLR) and ß-scoliidine (DYVTVKGFSPLRKA), present homology with the bradykinin C-terminal. Despite this, both peptides did not behave as substrates or inhibitors of ACE, indicating that they do not interact with this metallopeptidase. In further studies, ß-scoliidine, but not α -scoliidine, showed protective effects against oxidative stress-induced neurotoxicity in PC12 cells through integrity and metabolism cell assays. Interestingly, ß-scoliidine has the extension of the KA dipeptide at the C-terminal in comparison with α-scoliidine. CONCLUSION: Comprehensive LC-MS and MS/MS analyses from the Scolia decorata ventralis venom displayed the component profile of this venom. ß-scoliidine showed an effective cytoprotective effect, probably due to the observed increase in the number of cells. This is the first report of solitary wasp venom peptides showing neuroprotective activity.

3.
J. venom. anim. toxins incl. trop. dis ; 27: e20200171, 2021. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1279405

RESUMO

Background Solitary wasp venoms may be a rich source of neuroactive substances, since their venoms are used for paralyzing preys. We have been exploring bioactive constituents of solitary wasp venoms and, in this study, the component profile of the venom from a solitary scoliid wasp, Scolia decorata ventralis, was investigated through a comprehensive analysis using LC-MS. Two peptides were synthesized, and their neuroprotective properties were evaluated. Methods A reverse-phase HPLC connected to ESI-MS was used for LC-MS analyses. Online mass fingerprinting was performed from TIC, and data-dependent tandem mass spectrometry gave the MS/MS spectra. The sequences of two major peptide components were determined by MALDI-TOF/TOF MS analysis, confirmed by solid phase synthesis. Using the synthetic peptides, biological activities were assessed. Cell integrity tests and neuroprotection analyzes using H2O2 as an oxidative stress inducer were performed for both peptides. Results Online mass fingerprinting revealed that the venom contains 123 components, and the MS/MS analysis resulted in 33 full sequences of peptide components. The two main peptides, α-scoliidine (DYVTVKGFSPLR) and β-scoliidine (DYVTVKGFSPLRKA), present homology with the bradykinin C-terminal. Despite this, both peptides did not behave as substrates or inhibitors of ACE, indicating that they do not interact with this metallopeptidase. In further studies, β-scoliidine, but not α -scoliidine, showed protective effects against oxidative stress-induced neurotoxicity in PC12 cells through integrity and metabolism cell assays. Interestingly, β-scoliidine has the extension of the KA dipeptide at the C-terminal in comparison with α-scoliidine. Conclusion Comprehensive LC-MS and MS/MS analyses from the Scolia decorata ventralis venom displayed the component profile of this venom. β-scoliidine showed an effective cytoprotective effect, probably due to the observed increase in the number of cells. This is the first report of solitary wasp venom peptides showing neuroprotective activity.(AU)


Assuntos
Animais , Peptídeos/classificação , Venenos de Vespas , Vespas/metabolismo , Neuroproteção , Estresse Oxidativo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
4.
Toxins (Basel) ; 11(10)2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554187

RESUMO

Solitary wasps use their stinging venoms for paralyzing insect or spider prey and feeding them to their larvae. We have surveyed bioactive substances in solitary wasp venoms, and found antimicrobial peptides together with some other bioactive peptides. Eumenine mastoparan-AF (EMP-AF) was the first to be found from the venom of the solitary eumenine wasp Anterhynchium flavomarginatum micado, showing antimicrobial, histamine-releasing, and hemolytic activities, and adopting an α-helical secondary structure under appropriate conditions. Further survey of solitary wasp venom components revealed that eumenine wasp venoms contained such antimicrobial α-helical peptides as the major peptide component. This review summarizes the results obtained from the studies of these peptides in solitary wasp venoms and some analogs from the viewpoint of (1) chemical and biological characterization; (2) physicochemical properties and secondary structure; and (3) channel-like pore-forming properties.


Assuntos
Anti-Infecciosos/química , Conformação Proteica em alfa-Hélice , Venenos de Vespas/análise , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Venenos de Vespas/química , Venenos de Vespas/farmacologia
5.
Toxins (Basel) ; 11(3)2019 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-30857348

RESUMO

Comprehensive LC-MS and MS/MS analysis of the crude venom extract from the solitary eumenine wasp Eumenes micado revealed the component profile of this venom mostly consisted of small peptides. The major peptide components, eumenine mastoparan-EM1 (EMP-EM1: LKLMGIVKKVLGAL-NH2) and eumenine mastoparan-EM2 (EMP-EM2: LKLLGIVKKVLGAI-NH2), were purified and characterized by the conventional method. The sequences of these new peptides are homologous to mastoparans, the mast cell degranulating peptides from social wasp venoms; they are 14 amino acid residues in length, rich in hydrophobic and basic amino acids, and C-terminal amidated. Accordingly, these new peptides can belong to mastoparan peptides (in other words, linear cationic α-helical peptides). Indeed, the CD spectra of these new peptides showed predominantly α-helix conformation in TFE and SDS. In biological evaluation, both peptides exhibited potent antibacterial activity, moderate degranulation activity from rat peritoneal mast cells, and significant leishmanicidal activity, while they showed virtually no hemolytic activity on human or mouse erythrocytes. These results indicated that EMP-EM peptides rather strongly associated with bacterial cell membranes rather than mammalian cell membranes.


Assuntos
Anti-Infecciosos , Peptídeos e Proteínas de Sinalização Intercelular , Venenos de Vespas/química , Animais , Anti-Infecciosos/análise , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Eritrócitos/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Leishmania major/efeitos dos fármacos , Leishmania major/crescimento & desenvolvimento , Mastócitos/efeitos dos fármacos , Camundongos , Ratos Sprague-Dawley , Análise de Sequência de Proteína , Espectrometria de Massas em Tandem , Venenos de Vespas/análise , Venenos de Vespas/farmacologia , Vespas
6.
Artigo em Inglês | MEDLINE | ID: mdl-28855917

RESUMO

BACKGROUND: Among the hymenopteran insect venoms, those from social wasps and bees - such as honeybee, hornets and paper wasps - have been well documented. Their venoms are composed of a number of peptides and proteins and used for defending their nests and themselves from predators. In contrast, the venoms of solitary wasps and bees have not been the object of further research. In case of solitary bees, only major peptide components in a few venoms have been addressed. Therefore, the aim of the present study was to explore the peptide component profile of the venom from the solitary bee Xylocopa appendiculata circumvolans by peptidomic analysis with using LC-MS. METHODS: A reverse-phase HPLC connected to ESI-OrbiTrap MS was used for LC-MS. On-line mass fingerprinting was made from TIC, and data-dependent tandem mass spectrometry gave MSMS spectra. A major peptide component was isolated by reverse-phase HPLC by conventional way, and its sequence was determined by Edman degradation, which was finally corroborated by solid phase synthesis. Using the synthetic specimen, biological activities (antimicrobial activity, mast cell devaluation, hemolysis, leishmanicidal activity) and pore formation in artificial lipid bilayer were evaluated. RESULTS: On-line mass fingerprinting revealed that the crude venom contained 124 components. MS/MS analysis gave 75 full sequences of the peptide components. Most of these are related to the major and novel peptide, xylopin. Its sequence, GFVALLKKLPLILKHLH-NH2, has characteristic features of linear cationic α-helical peptides; rich in hydrophobic and basic amino acids with no disulfide bond, and accordingly, it can be predicted to adopt an amphipathic α-helix secondary structure. In biological evaluation, xylopin exhibited broad-spectrum antimicrobial activity, and moderate mast cell degranulation and leishmanicidal activities, but showed virtually no hemolytic activity. Additionally, the peptide was able to incorporate pores in artificial lipid bilayers of azolectin, confirming the mechanism of the cytolytic activity by pore formation in biological membranes. CONCLUSIONS: LC-ESI-MS and MS/MS analysis of the crude venom extract from a solitary bee Xylocopa appendiculata circumvolans revealed that the component profile of this venom mostly consisted of small peptides. The major peptide components, xylopin and xylopinin, were purified and characterized in a conventional manner. Their chemical and biological characteristics, belonging to linear cationic α-helical peptides, are similar to the known solitary bee venom peptides, melectin and osmin. Pore formation in artificial lipid bilayers was demonstrated for the first time with a solitary bee peptide.

7.
PLoS One ; 12(6): e0178785, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28570651

RESUMO

The rapid spread of multi-drug resistant pathogens represents a serious threat to public health, considering factors such as high mortality rates, treatment restrictions and high prevalence of multi-drug resistant bacteria in the hospital environment. Antimicrobial peptides (AMPs) may exhibit powerful antimicrobial activity against different and diverse microorganisms, also presenting the advantage of absence or low toxicity towards animal cells. In this study, the evaluation of the antimicrobial activity against multi-drug resistant bacteria of a recently described AMP from wasp, Polydim-I, was performed. Polydim-I presented activity against standard strains (non-carriers of multi-resistant genes) that are susceptible to commercial antimicrobials, and also against multi-drug resistant strains at concentrations bellow 1µg/ml (0.41 µM). This is a rather low concentration among those reported for AMPs. At this concentration we found out that Polydim-I inhibits almost 100% of the tested pathogens growth, while with the ATCC strains the minimum inhibitory concentration (MIC100) is 400 times higher. Also, in relation to in vitro activity of conventional drugs against multi-drug resistant bacteria strains, Polydim-I is almost 10 times more efficient and with broader spectrum. Cationic AMPs are known as multi-target compounds and specially for targeting the phospholipid matrix of bacterial membranes. Exploring the interactions of Polydim-I with lipid bilayers, we have confirmed that this interaction is involved in the mechanism of action. Circular dichroism experiments showed that Polydim-I undergoes a conformational transition from random coil to a mostly helical conformation in the presence of membrane mimetic environments. Zeta potential measurements confirmed the binding and partial charge neutralization of anionic asolectin vesicles, and also suggested a possible aggregation of peptide molecules. FTIR experiments confirmed that some peptide aggregation occurs, which is minimized in the presence of strongly anionic micelles of sodium dodecyl sulfate. Also, Polydim-I induced channel-like structures formation to asolectin lipid bilayers, as demonstrated in the electrophysiology experiments. We suggest that cationic Polydim-I targets the membrane lipids due to electrostatic attraction, partially accumulates, neutralizing the opposite charges and induces pore formation. Similar mechanism of action has already been suggested for other peptides from wasp venoms, especially mastoparans.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Dicroísmo Circular , Bicamadas Lipídicas , Micelas , Testes de Sensibilidade Microbiana , Modelos Teóricos , Conformação Molecular , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Int J Antimicrob Agents ; 49(2): 167-175, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28108242

RESUMO

Mastoparans, a class of peptides found in wasp venom, have significant effects following a sting as well as useful applications in clinical practice. Among these is their potential use in the control of micro-organisms that cause infectious diseases with a significant impact on society. Thus, the present study describes the isolation and identification of a mastoparan peptide from the venom of the social wasp Pseudopolybia vespiceps and evaluated its antimicrobial profile against bacteria (Staphylococcus aureus and Mycobacterium abscessus subsp. massiliense), fungi (Candida albicans and Cryptococcus neoformans) and in vivo S. aureus infection. The membrane pore-forming ability was also assessed. The mastoparan reduced in vitro and ex vivo mycobacterial growth by 80% at 12.5 µM in infected peritoneal macrophages but did not affect the shape of bacterial cells at the dose tested (6.25 µM). The peptide also showed potent action against S. aureus in vitro (EC50 and EC90 values of 1.83 µM and 2.90 µM, respectively) and reduced the in vivo bacterial load after 6 days of topical treatment (5 mg/kg). Antifungal activity was significant, with EC50 and EC90 values of 12.9 µM and 15.3 µM, respectively, for C. albicans, and 11 µM and 22.70 µM, respectively, for C. neoformans. Peptides are currently attracting interest for their potential in the design of antimicrobial drugs, particularly due to the difficulty of micro-organisms in developing resistance to them. In this respect, Polybia-MPII proved to be highly effective, with a lower haemolysis rate compared with peptides of the same family.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Peptídeos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Venenos de Vespas/farmacologia , Vespas/química , Administração Tópica , Animais , Anti-Infecciosos/isolamento & purificação , Modelos Animais de Doenças , Feminino , Voluntários Saudáveis , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Macrófagos Peritoneais/microbiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Peptídeos/isolamento & purificação , Resultado do Tratamento , Venenos de Vespas/isolamento & purificação
9.
Artigo em Inglês | MEDLINE | ID: mdl-28074089

RESUMO

Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.

10.
Curr Protein Pept Sci ; 18(1): 72-91, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27226199

RESUMO

Depsipeptides are a group of biologically active peptides that have at least one of the amide bonds replaced by an ester bond. These peptides sometimes present additional chemical modifications, including unusual amino acid residues in their structures. Depsipeptides are known to exhibit a large array of bioactivities, such as anticancer, antiproliferative, antimicrobial, antiviral and antiplasmodial properties. They are commonly found in marine organisms: bacteria, tunicates, mollusks, sponges, and others. Herein, we summarize the latest insights about marine depsipeptides, their mechanisms of action and potential as therapeutic agents.


Assuntos
Organismos Aquáticos/química , Depsipeptídeos/química , Depsipeptídeos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Depsipeptídeos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Humanos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico
11.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1484691

RESUMO

Abstract Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.

12.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1484718

RESUMO

Abstract Background: Among the hymenopteran insect venoms, those from social wasps and bees - such as honeybee, hornets and paper wasps - have been well documented. Their venoms are composed of a number of peptides and proteins and used for defending their nests and themselves from predators. In contrast, the venoms of solitary wasps and bees have not been the object of further research. In case of solitary bees, only major peptide components in a few venoms have been addressed. Therefore, the aim of the present study was to explore the peptide component profile of the venom from the solitary bee Xylocopa appendiculata circumvolans by peptidomic analysis with using LC-MS. Methods: A reverse-phase HPLC connected to ESI-OrbiTrap MS was used for LC-MS. On-line mass fingerprinting was made from TIC, and data-dependent tandem mass spectrometry gave MSMS spectra. A major peptide component was isolated by reverse-phase HPLC by conventional way, and its sequence was determined by Edman degradation, which was finally corroborated by solid phase synthesis. Using the synthetic specimen, biological activities (antimicrobial activity, mast cell devaluation, hemolysis, leishmanicidal activity) and pore formation in artificial lipid bilayer were evaluated. Results: On-line mass fingerprinting revealed that the crude venom contained 124 components. MS/MS analysis gave 75 full sequences of the peptide components. Most of these are related to the major and novel peptide, xylopin. Its sequence, GFVALLKKLPLILKHLH-NH2, has characteristic features of linear cationic -helical peptides; rich in hydrophobic and basic amino acids with no disulfide bond, and accordingly, it can be predicted to adopt an amphipathic -helix secondary structure. In biological evaluation, xylopin exhibited broad-spectrum antimicrobial activity, and moderate mast cell degranulation and leishmanicidal activities, but showed virtually no hemolytic activity. Additionally, the peptide was able to incorporate pores in artificial lipid bilayers of azolectin, confirming the mechanism of the cytolytic activity by pore formation in biological membranes. Conclusions: LC-ESI-MS and MS/MS analysis of the crude venom extract from a solitary bee Xylocopa appendiculata circumvolans revealed that the component profile of this venom mostly consisted of small peptides. The major peptide components, xylopin and xylopinin, were purified and characterized in a conventional manner. Their chemical and biological characteristics, belonging to linear cationic -helical peptides, are similar to the known solitary bee venom peptides, melectin and osmin. Pore formation in artificial lipid bilayers was demonstrated for the first time with a solitary bee peptide.

13.
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-954848

RESUMO

Background: Among the hymenopteran insect venoms, those from social wasps and bees - such as honeybee, hornets and paper wasps - have been well documented. Their venoms are composed of a number of peptides and proteins and used for defending their nests and themselves from predators. In contrast, the venoms of solitary wasps and bees have not been the object of further research. In case of solitary bees, only major peptide components in a few venoms have been addressed. Therefore, the aim of the present study was to explore the peptide component profile of the venom from the solitary bee Xylocopa appendiculata circumvolans by peptidomic analysis with using LC-MS. Methods: A reverse-phase HPLC connected to ESI-OrbiTrap MS was used for LC-MS. On-line mass fingerprinting was made from TIC, and data-dependent tandem mass spectrometry gave MSMS spectra. A major peptide component was isolated by reverse-phase HPLC by conventional way, and its sequence was determined by Edman degradation, which was finally corroborated by solid phase synthesis. Using the synthetic specimen, biological activities (antimicrobial activity, mast cell devaluation, hemolysis, leishmanicidal activity) and pore formation in artificial lipid bilayer were evaluated. Results: On-line mass fingerprinting revealed that the crude venom contained 124 components. MS/MS analysis gave 75 full sequences of the peptide components. Most of these are related to the major and novel peptide, xylopin. Its sequence, GFVALLKKLPLILKHLH-NH2, has characteristic features of linear cationic α-helical peptides; rich in hydrophobic and basic amino acids with no disulfide bond, and accordingly, it can be predicted to adopt an amphipathic α-helix secondary structure. In biological evaluation, xylopin exhibited broad-spectrum antimicrobial activity, and moderate mast cell degranulation and leishmanicidal activities, but showed virtually no hemolytic activity. Additionally, the peptide was able to incorporate pores in artificial lipid bilayers of azolectin, confirming the mechanism of the cytolytic activity by pore formation in biological membranes. Conclusions: LC-ESI-MS and MS/MS analysis of the crude venom extract from a solitary bee Xylocopa appendiculata circumvolans revealed that the component profile of this venom mostly consisted of small peptides. The major peptide components, xylopin and xylopinin, were purified and characterized in a conventional manner. Their chemical and biological characteristics, belonging to linear cationic α-helical peptides, are similar to the known solitary bee venom peptides, melectin and osmin. Pore formation in artificial lipid bilayers was demonstrated for the first time with a solitary bee peptide.(AU)


Assuntos
Animais , Peptídeos , Venenos de Abelha , Produtos Biológicos
14.
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-954807

RESUMO

Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.(AU)


Assuntos
Animais , Antivirais , Peptídeos , Venenos , Produtos Biológicos , Fauna Marinha/análise
15.
Toxicon ; 120: 15-21, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27417686

RESUMO

Analgesic therapy is based on the sequential treatment of pain, in which opioids are drugs of last resource and known to be highly effective, but are also responsible for undesirable side effects, tolerance and addiction. There is a need for new drugs with alternative targets in order to minimize side effects and improve treatment efficacy. Mastoparans are an abundant class of peptides in wasp venom and have shown great potential as new drugs, as well as being excellent tools for the study of G-protein-coupled receptors. The objective of this study was to investigate the antinociceptive activity of the mastoparan Agelaia-MP I and the mechanisms involved. Agelaia-MP I (MW 1565 Da) showed dose-dependent antinociceptive activity in mice submitted to i.c.v. injection in two different models. The highest dose produced a maximum effect for up to 4 h, and nociception remained low three days after injection. Further experiments showed that Agelaia-MPI induced partial and reversible blockade of the amplitude of action potential, probably interacting with voltage-gated sodium channels. These results revealed the significant potential impact of compounds isolated from wasp venom on the central nervous system (CNS). In addition, the antinociceptive effect described here is a novel activity for mastoparans.


Assuntos
Analgésicos/farmacologia , Comportamento Animal , Peptídeos/farmacologia , Venenos de Vespas/química , Potenciais de Ação/efeitos dos fármacos , Sequência de Aminoácidos , Analgésicos/administração & dosagem , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Camundongos , Peptídeos/administração & dosagem , Teste de Desempenho do Rota-Rod , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Venenos de Vespas/administração & dosagem , Venenos de Vespas/farmacologia , Vespas
16.
Toxicon ; 101: 55-62, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25911957

RESUMO

Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by P. maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 µg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 µg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus.


Assuntos
Mordeduras e Picadas/fisiopatologia , Peixes-Gato/metabolismo , Edema/fisiopatologia , Venenos de Peixe/toxicidade , Inflamação/fisiopatologia , Dor/fisiopatologia , Animais , Brasil , Permeabilidade Capilar/efeitos dos fármacos , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/etiologia , Feminino , Venenos de Peixe/química , Água Doce , Hemorragia/etiologia , Hemorragia/fisiopatologia , Inflamação/etiologia , Isoenzimas/metabolismo , Masculino , Camundongos , Nociceptores/efeitos dos fármacos , Nociceptores/patologia , Dor/etiologia , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Ratos Wistar
17.
Mar Drugs ; 12(1): 508-24, 2014 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-24451192

RESUMO

Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the centrilobular vein, and disorganization of the hepatic parenchyma. Some areas also exhibited an inflammatory infiltrate and calcified tissue inside blood vessels. Necrosis and rupture of the convoluted tubule cells were observed in the kidneys. Further analysis of the both extracts indicated the lack of hemolytic activity, and the presence of two unknown anti-AChE substances in the AE of G. splendidum. Thus, P. galeata and G. splendidum are producers of novel toxins that affect mammals when administered orally.


Assuntos
Cianobactérias/química , Toxinas Marinhas/química , Toxinas Marinhas/toxicidade , Animais , Biomassa , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Técnicas In Vitro , Rim/patologia , Fígado/patologia , Pulmão/patologia , Masculino , Camundongos , Intoxicação/patologia
18.
Rev. bras. farmacogn ; 23(3): 471-480, May-June 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-676287

RESUMO

An investigation was directed towards the antiacetylcholinesterase activity of the acid aqueous and methanolic extracts of five cyanobacterial taxa, which encompasses an enzymatic inhibition essay and the evaluation of the physiological responses of mice to cyanobacterial extracts along with toxicological observations. The strains Calothrix sp. CCIBt 3320, Tolypothrix sp. CCIBt 3321, Phormidium cf. amoenum CCIBt 3412, Phormidium sp. CCIBt 3265, and Geitlerinema splendidum CCIBt 3223 were from the São Paulo Botanical Institute Cyanobacterial Culture Collection and all of them showed inhibitory effect on acetylcholinesterase activity (in vitro) and caused systemic effects similar to those described for anticholinesterase drugs (in vivo). With the exception of G. splendidum and Tolypothrix sp. strains, all extracts produced reversible antiacetylcolinesterase effects in mice. Complementary histopathological studies were carried out on tissues from animals administered with Phormidium sp. and P. cf. amoenum.

19.
Toxicon ; 58(6-7): 464-70, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21867725

RESUMO

Toxic cyanobacteria in public water reservoirs may cause severe health issues for livestock and human beings. Geitlerinema amphibium, which is frequently found in São Paulo City's drinking water supplies, showed toxicity in the standard mouse bioassay, while displaying signs of intoxication and post-mortem findings different from those showed by animals intoxicated by known cyanotoxins. We report here the alterations caused by G. amphibium methanolic extract on mouse microcirculatory network, as seen by in vivo intravital microscopy, besides observations on leukocyte migration, cytokine quantitation, and results of toxicological essays. Our data showed that G. amphibium methanolic extract displayed time- and dose-dependent pro-inflammatory activity, and that at lower doses [125 and 250 mg/kg body weight (b.w.)] increased the leukocyte rolling, caused partial venular stasis, as well as induced an increase in leukocyte counts in the peripheral blood and peritoneal washings. At higher doses (500 and 1000 mg/kg b.w.), the extract caused ischemic injury leading to animal death. As confirmed by mass spectrometric studies and polymyxin B test, the G. amphibium methanolic extract did not contain lipopolysaccharides.


Assuntos
Cianobactérias/patogenicidade , Água Potável/microbiologia , Inflamação/etiologia , Animais , Cianobactérias/química , Citocinas/biossíntese , Leucócitos/fisiologia , Masculino , Camundongos , Microcirculação
20.
Toxicon ; 57(7-8): 1081-92, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21549739

RESUMO

Four novel peptides were isolated from the venoms of the solitary eumenine wasps Eumenes rubrofemoratus and Eumenes fraterculus. Their sequences were determined by MALDI-TOF/TOF (matrix assisted laser desorption/ionization time-of-flight mass spectrometry) analysis, Edman degradation and solid-phase synthesis. Two of them, eumenitin-R (LNLKGLIKKVASLLN) and eumenitin-F (LNLKGLFKKVASLLT), are highly homologous to eumenitin, an antimicrobial peptide from a solitary eumenine wasp, whereas the other two, EMP-ER (FDIMGLIKKVAGAL-NH(2)) and EMP-EF (FDVMGIIKKIAGAL-NH(2)), are similar to eumenine mastoparan-AF (EMP-AF), a mast cell degranulating peptide from a solitary eumenine wasp. These sequences have the characteristic features of linear cationic cytolytic peptides; rich in hydrophobic and basic amino acids with no disulfide bond, and accordingly, they can be predicted to adopt an amphipathic α-helix secondary structure. In fact, the CD (circular dichroism) spectra of these peptides showed significant α-helical conformation content in the presence of TFE (trifluoroethanol), SDS (sodium dodecylsulfate) and asolectin vesicles. In the biological evaluation, all the peptides exhibited a significant broad-spectrum antimicrobial activity, and moderate mast cell degranulation and leishmanicidal activities, but showed virtually no hemolytic activity.


Assuntos
Peptídeos/farmacologia , Peçonhas/farmacologia , Vespas/metabolismo , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Cátions/química , Dicroísmo Circular , Espectrometria de Massas , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/isolamento & purificação , Estrutura Secundária de Proteína , Peçonhas/química , Vespas/química
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