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1.
Sci Rep ; 14(1): 15363, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965389

RESUMO

The therapeutic potential of insect-derived bioactive molecules as anti-SARS-CoV-2 agents has shown promising results. Hymenopteran venoms, notably from Apis mellifera (honeybee) and Vespa orientalis (oriental wasp), were examined for the first time in an in vitro setting for their potential anti-COVID-19 activity. This assessment utilized an immunodiagnostic system to detect the SARS-CoV-2 nucleocapsid antigen titer reduction. Further analyses, including cytotoxicity assays, plaque reduction assays, and in silico docking-based screening, were performed to evaluate the efficacy of the most potent venom. Results indicated that bee and wasp venoms contain bioactive molecules with potential therapeutic effects against SARS-CoV-2.Nevertheless, the wasp venom exhibited superior efficacy compared to bee venom, achieving a 90% maximal (EC90) concentration effect of antigen depletion at 0.184 mg/mL, in contrast to 2.23 mg/mL for bee venom. The cytotoxicity of the wasp venom was assessed on Vero E6 cells 48 h post-treatment using the MTT assay. The CC 50 of the cell growth was 0.16617 mg/mL for Vero E6 cells. The plaque reduction assay of wasp venom revealed 50% inhibition (IC50) at a 0.208 mg/mL concentration. The viral count at 50% inhibition was 2.5 × 104 PFU/mL compared to the initial viral count of 5 × 104 PFU/mL. In silico data for the wasp venom revealed a strong attraction to binding sites on the ACE2 protein, indicating ideal interactions. This substantiates the potential of wasp venom as a promising viral inhibitor against SARS-CoV-2, suggesting its consideration as a prospective natural preventive and curative antiviral drug. In conclusion, hymenopteran venoms, particularly wasp venom, hold promise as a source of potential therapeutic biomolecules against SARS-CoV-2. More research and clinical trials are needed to evaluate these results and investigate their potential for translation into innovative antiviral therapies.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Simulação de Acoplamento Molecular , SARS-CoV-2 , Venenos de Vespas , Células Vero , SARS-CoV-2/efeitos dos fármacos , Chlorocebus aethiops , Animais , Humanos , Antivirais/farmacologia , COVID-19/virologia , Venenos de Vespas/farmacologia , Venenos de Vespas/química , Venenos de Abelha/farmacologia , Venenos de Abelha/química , Egito , Abelhas , Vespas
2.
Allergy Asthma Proc ; 45(3): 195-200, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38755779

RESUMO

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.


Assuntos
Dessensibilização Imunológica , Himenópteros , Humanos , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/efeitos adversos , Animais , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Himenópteros/imunologia , Hidróxido de Alumínio , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/terapia , Resultado do Tratamento , Adulto Jovem , Alérgenos/imunologia , Alérgenos/administração & dosagem , Adolescente , Hipersensibilidade/terapia , Hipersensibilidade/imunologia , Venenos de Artrópodes/imunologia , Idoso , Venenos de Abelha/imunologia , Venenos de Abelha/administração & dosagem , Venenos de Abelha/efeitos adversos
3.
Biofouling ; 40(3-4): 235-244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584359

RESUMO

The association between dysbiotic microbiota biofilm and colon cancer has recently begun to attract attention. In the study, the apitherapeutic effects of bee products (honey, bee venom, royal jelly, pollen, perga and propolis) obtained from the endemic Yigilca ecotype of Apis mellifera anatoliaca were investigated. Antibiofilm activity were performed by microplate assay using crystal violet staining to measure adherent biofilm biomass of Escherichia coli capable of forming biofilms. Bee venom showed the highest inhibition effect (73.98%) at 50% concentration. Honey, perga and royal jelly reduced biofilm formation by >50% at all concentrations. The antiproliferation effect on the HCT116 colon cancer cell line was investigated with the water­soluble tetrazolium salt­1 assay. After 48 h of honey application at 50% concentration, cell proliferation decreased by 86.51%. The high cytotoxic effects of royal jelly and bee venom are also remarkable. Additionally, apoptotic pathway analysis was performed by ELISA using caspase 3, 8 and 9 enzyme-linked immunosorbent assay kits. All bee products induced a higher expression of caspase 9 compared with caspase 8. Natural products that upregulate caspase proteins are promising therapeutic targets for proliferative diseases.


Assuntos
Antineoplásicos , Venenos de Abelha , Biofilmes , Neoplasias do Colo , Escherichia coli , Ácidos Graxos , Própole , Biofilmes/efeitos dos fármacos , Humanos , Animais , Venenos de Abelha/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Neoplasias do Colo/tratamento farmacológico , Abelhas/efeitos dos fármacos , Células HCT116 , Própole/farmacologia , Própole/química , Ácidos Graxos/farmacologia , Antineoplásicos/farmacologia , Mel , Proliferação de Células/efeitos dos fármacos , Pólen/química , Antibacterianos/farmacologia , Apoptose/efeitos dos fármacos
4.
Artigo em Inglês | MEDLINE | ID: mdl-38649084

RESUMO

Melittin is a powerful toxin present in honeybee venom that is active in a wide range of animals, from insects to humans. Melittin exerts numerous biological, toxicological, and pharmacological effects, the most important of which is destruction of the cell membrane. The phospholipase activity of melittin and its ability to activate phospholipases in the venom contribute to these actions. Using analytical methods, we discovered that the honeybee Apis mellifera produces melittin not only in the venom gland but also in its fat body cells, which remain resistant to this toxin's effects. We suggest that melittin acts as an anti-bacterial agent, since its gene expression is significantly upregulated when honeybees are infected with Escherichia coli and Listeria monocytogenes bacteria; additionally, melittin effectively kills these bacteria in the disc diffusion test. We hypothesize that the chemical and physicochemical properties of the melittin molecule (hydrophilicity, lipophilicity, and capacity to form tetramers) in combination with reactive conditions (melittin concentration, salt concentration, pH, and temperature) are responsible for the targeted destruction of bacterial cells and apparent tolerance towards own tissue cells. Considering that melittin is an important current and, importantly, potential broad-spectrum medication, a thorough understanding of the observed phenomena may significantly increase its use in clinical practice.


Assuntos
Antibacterianos , Venenos de Abelha , Escherichia coli , Corpo Adiposo , Meliteno , Animais , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Venenos de Abelha/farmacologia , Venenos de Abelha/toxicidade , Abelhas , Escherichia coli/efeitos dos fármacos , Corpo Adiposo/metabolismo , Proteínas de Insetos/metabolismo , Listeria monocytogenes/efeitos dos fármacos , Meliteno/farmacologia , Meliteno/toxicidade
5.
BMC Immunol ; 25(1): 23, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678193

RESUMO

BACKGROUND: Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagents while a new development involves the use of tubes with dried antibody reagents. The aim of this pilot study was to compare these two techniques in patients with insect venom allergy. METHODS: Seventeen patients with an insect venom allergy were included in the study. The established "BAT 1" utilizes conventional antibody solutions of anti-CCR3 for basophil identification and anti-CD63 to assess basophil activation, whereas "BAT 2" uses dried anti-CD45, anti-CD3, anti-CRTH2, anti-203c and anti-CD63 for identification and activation measurement of basophils. Negative and positive controls as well as incubations with honey bee venom and yellow jacket venom at three concentrations were performed. RESULTS: Seven patients had to be excluded due to low basophil counts, high values in negative controls or negative positive controls. For the remaining 10 patients the overall mean (± SD) difference in activated basophils between the two tests was 0.2 (± 12.2) %P. In a Bland-Altman plot, the limit of agreement (LoA) ranged from 24.0 to -23.7. In the qualitative evaluation (value below/above cut-off) Cohen's kappa was 0.77 indicating substantial agreement. BAT 2 took longer to perform than BAT 1 and was more expensive. CONCLUSION: The BAT 2 technique represents an interesting innovation, however, it was found to be less suitable compared to an established BAT for the routine diagnosis of insect venom allergies.


Assuntos
Basófilos , Citometria de Fluxo , Humanos , Basófilos/imunologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Citometria de Fluxo/métodos , Venenos de Artrópodes/imunologia , Projetos Piloto , Animais , Hipersensibilidade/imunologia , Hipersensibilidade/diagnóstico , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/diagnóstico , Venenos de Abelha/imunologia , Adulto Jovem , Idoso , Anticorpos/imunologia , Adolescente , Teste de Degranulação de Basófilos/métodos , Hipersensibilidade a Veneno
6.
Toxicon ; 242: 107711, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583578

RESUMO

Crotalus neutralizing factor (CNF) is an endogenous glycoprotein from Crotalus durissus terrificus snake blood that inhibits secretory phospholipases A2 (sPLA2) from the Viperid but not from Elapid venoms (subgroups IA and IIA, respectively). In the present study, we demonstrated that CNF can inhibit group III-PLA2 from bee venom by forming a stable enzyme-inhibitor complex. This finding opens up new possibilities for the potential use of CNF and/or CNF-based derivatives in the therapeutics of bee stings.


Assuntos
Venenos de Abelha , Crotalus , Serpentes Peçonhentas , Animais , Venenos de Abelha/farmacologia , Inibidores de Fosfolipase A2/farmacologia , Venenos de Crotalídeos/antagonistas & inibidores , Abelhas , Fosfolipases A2 , Glicoproteínas/farmacologia , Fosfolipases A2 Secretórias/antagonistas & inibidores
7.
Langmuir ; 40(14): 7456-7462, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38546877

RESUMO

The primary constituents of honeybee venom, melittin and phospholipase A2 (PLA2), display toxin synergism in which the PLA2 activity is significantly enhanced by the presence of melittin. It has been shown previously that this is accomplished by the disruption in lipid packing, which allows PLA2 to become processive on the membrane surface. In this work, we show that melittin is capable of driving miscibility phase transition in giant unilamellar vesicles (GUVs) and that it raises the miscibility transition temperature (Tmisc) in a concentration-dependent manner. The induced phase separation enhances the processivity of PLA2, particularly at its boundaries, where a substantial difference in domain thickness creates a membrane discontinuity. The catalytic action of PLA2, in response, induces changes in the membrane, rendering it more conducive to melittin binding. This, in turn, facilitates further lipid phase separation and eventual vesicle lysis. Overall, our results show that melittin has powerful membrane-altering capabilities that activate PLA2 in various membrane contexts. More broadly, they exemplify how this biochemical system actively modulates and capitalizes on the spatial distribution of membrane lipids to efficiently achieve its objectives.


Assuntos
Venenos de Abelha , Meliteno , Meliteno/farmacologia , Lipossomas Unilamelares , Fosfolipases A2 , Lipídeos de Membrana
8.
Anticancer Agents Med Chem ; 24(10): 798-811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500290

RESUMO

INTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. RESULTS: Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. CONCLUSION: Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.


Assuntos
Antineoplásicos , Venenos de Abelha , Caenorhabditis elegans , Animais , Humanos , Venenos de Abelha/farmacologia , Venenos de Abelha/química , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Estrutura-Atividade , Feminino , Estrutura Molecular
9.
Dent Med Probl ; 61(1): 53-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38441304

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a critical chronic metabolic disease. Several treatment modalities are currently under investigation. Both bee venom (BV) and bone marrow mesenchymal stem cells (BMSCs) can possibly offer an approach for treating type I diabetes. OBJECTIVES: The aim of the present study was to investigate the mechanism underlying the anti-diabetic effect of BV as compared to BMSCs on the tongue mucosa of diabetic rats. MATERIAL AND METHODS: A total of 52 male albino rats were used in the current study. The rats were randomly assigned into 4 groups: group 1 (control); group 2 (streptozocin (STZ)); group 3 (BV-treated); and group 4 (BMSC-treated). Diabetes mellitus was induced via an intraperitoneal (IP) injection of STZ in the rats from groups 2, 3 and 4. Following the diagnosis of DM, the rats in group 3 were injected with a daily dose of 0.5 mg/kg of BV, while the rats in group 4 were treated with a single injection of BMSCs. All rats were euthanized after 4 weeks, and their tongues were dissected and divided into halves. The right halves of the tongues were utilized for the histological examination, followed by morphometric analysis. In contrast, the left halves were used to detect the local gene expression of transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF). RESULTS: Group 2 revealed marked disruption in the morphology of the fungiform and filiform papillae, and atrophic epithelial changes in both dorsal and ventral surface epithelium as compared to other groups. Group 4 showed a significantly larger number of taste buds, and a higher gene expression of TGF-ß1 and VEGF as compared to groups 2 and 3. Additionally, BV and BMSCs effectively increased the thickness of dorsal and ventral surface epithelium as compared to group 2. CONCLUSIONS: Treatment with BMSCs was associated with significant improvement in the morphology and number of lingual epithelial cells and taste buds in the tongues of diabetic rats as compared to BV-treated rats, which was due to the local upregulation of TGF-ß1 and VEGF gene expression.


Assuntos
Venenos de Abelha , Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Masculino , Animais , Ratos , Fator de Crescimento Transformador beta1 , Fator A de Crescimento do Endotélio Vascular , Diabetes Mellitus Experimental/terapia , Língua , Venenos de Abelha/farmacologia
10.
Toxicon ; 241: 107685, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503352

RESUMO

Determination of protein concentration in Hymenoptera venoms requires an accurate and reproducible assay as the results will be used to support subsequent proteomic techniques employed in their analyses. However, all protein assay techniques have inherent strengths and weaknesses, demanding their assessment before selecting the most suitable platform for sample analysis. In this study, protein profiles of ant, honeybee, and wasp venoms, and bovine serum albumin (BSA) and hyaluronidase standards were qualitatively assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Their amino acid and protein concentration were quantitatively determined via Amino Acid Analysis (AAA). Amino acid concentration was determined via hydrolysis, derivatization, and chromatographic quantification. Protein concentration was estimated using four different protein concentration assays. The ratios of protein concentration in venom samples to protein standards were calculated, and the accuracy of the protein concentration assays was analysed relative to the concentration determined from AAA. SDS-PAGE analysis showed that BSA contained several protein bands, while hyaluronidase contained a mixture of peptide and protein bands. Ant and honeybee venoms contained a higher proportion of peptide bands, while wasp venom contained more protein bands. As determined by AAA, the ratio of protein concentration in Hymenoptera venoms varied between 1.01 and 1.11 to BSA, and between 0.96 and 1.06 to hyaluronidase. Overall, the Bradford assay was found to be the least accurate and the BCA assay was the most accurate in estimating protein concentration in Hymenoptera venoms. There was no significant advantage in using hyaluronidase as a standard or increasing incubation temperature of BCA assay when analysing Hymenoptera venoms. Diluent solutions containing phenol and human serum albumin interfered with Lowry-based assays.


Assuntos
Venenos de Artrópodes , Venenos de Abelha , Himenópteros , Abelhas , Humanos , Animais , Proteoma , Hialuronoglucosaminidase/análise , Proteômica , Venenos de Vespas , Peçonhas , Aminoácidos , Soroalbumina Bovina , Peptídeos , Alérgenos
11.
Toxicology ; 503: 153768, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442839

RESUMO

The present work aims to clarify the genotype differences of a model organism Saccharomyces cerevisiae in response to bee venom. The study evaluated various endpoints including cell survival, induction of physiologically active superoxide anions, mitotic gene conversion, mitotic crossing-over, reverse mutations, DNA double-strand breaks, and Ty1 retrotransposition. The role of the intact mitochondria and the YAP1 transcription factor was also evaluated. Our results indicate a genotype-specific response. The first experimental evidence has been provided that bee venom induces physiologically active superoxide anions and DNA double-strand breaks in S. cerevisiae. The lack of oxidative phosphorylation due to disrupted or missing mitochondrial DNA reduces but not diminishes the cytotoxicity of bee venom. The possible modes of action could be considered direct damage to membranes (cytotoxic effect) and indirect damage to DNA through oxidative stress (genotoxic effect). YAP1 transcription factor was not found to be directly involved in cell defense against bee venom treatment.


Assuntos
Venenos de Abelha , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Venenos de Abelha/toxicidade , DNA/metabolismo , Dano ao DNA , Mitocôndrias/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Superóxidos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Humanos
12.
Toxins (Basel) ; 16(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38535786

RESUMO

Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and Apis mellifera venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A2 (PLA2), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.


Assuntos
Venenos de Abelha , Masculino , Animais , Abelhas , Meliteno , Membrana Celular , Apoptose , Morte Celular
13.
Arch Insect Biochem Physiol ; 115(3): e22104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506277

RESUMO

As a common defense mechanism in Hymenoptera, bee venom has complex components. Systematic and comprehensive analysis of bee venom components can aid in early evaluation, accurate diagnosis, and protection of organ function in humans in cases of bee stings. To determine the differences in bee venom composition and metabolic pathways between Apis cerana and Apis mellifera, proton nuclear magnetic resonance (1 H-NMR) technology was used to detect the metabolites in venom samples. A total of 74 metabolites were identified and structurally analyzed in the venom of A. cerana and A. mellifera. Differences in the composition and abundance of major components of bee venom from A. cerana and A. mellifera were mapped to four main metabolic pathways: valine, leucine and isoleucine biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and the tricarboxylic acid cycle. These findings indicated that the synthesis and metabolic activities of proteins or polypeptides in bee venom glands were different between A. cerana and A. mellifera. Pyruvate was highly activated in 3 selected metabolic pathways in A. mellifera, being much more dominant in A. mellifera venom than in A. cerana venom. These findings indicated that pyruvate in bee venom glands is involved in various life activities, such as biosynthesis and energy metabolism, by acting as a precursor substance or intermediate product.


Assuntos
Venenos de Abelha , Himenópteros , Mordeduras e Picadas de Insetos , Humanos , Abelhas , Animais , Ácido Pirúvico , Espectroscopia de Ressonância Magnética
14.
Toxins (Basel) ; 16(2)2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38393162

RESUMO

Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and whether BV-induced hair growth was facilitated by enhanced growth factor release by ASCs. The induction of the telogen-to-anagen phase was studied in mice. The underlying mechanism was investigated using organ cultures of mouse vibrissa hair follicles. When BV-treated ASCs were injected subcutaneously into mice, the telogen-to-anagen transition was accelerated and, by day 14, the hair weight increased. Quantitative polymerase chain reaction (qPCR) revealed that BV influenced the expression of several molecules, including growth factors, chemokines, channels, transcription factors, and enzymes. Western blot analysis was employed to verify the protein expression levels of extracellular-signal-regulated kinase (ERK) and phospho-ERK. Both the Boyden chamber experiment and scratch assay confirmed the upregulation of cell migration by BV. Additionally, ASCs secreted higher levels of growth factors after exposure to BV. Following BV therapy, the gene expression levels of alkaline phosphatase (ALP), fibroblast growth factor (FGF)-1 and 6, endothelial cell growth factor, and platelet-derived growth factor (PDGF)-C were upregulated. The findings of this study suggest that bee venom can potentially be utilized as an ASC-preconditioning agent for hair regeneration.


Assuntos
Venenos de Abelha , Animais , Camundongos , Venenos de Abelha/farmacologia , Venenos de Abelha/metabolismo , Proliferação de Células , Cabelo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco/metabolismo , Células Cultivadas
15.
J Anim Physiol Anim Nutr (Berl) ; 108(3): 792-805, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38311831

RESUMO

The objectives of the present study were to investigate the potential effects of purified bee venom (BV) on various aspects of growth, carcass, antioxidant, intestinal bacterial count and economic considerations in rabbits. A total of 240 male rabbits, comprising two distinct breeds (V-Line and New Zealand White [NZW]), 5 weeks old, with an average live body weight (BW) of 680 ± 20 g, were randomly divided into six groups, each containing 30 rabbits. Each group had five replicates, with six rabbits in each replicate. The allocation of animals to the groups followed a fully factorial design, incorporating two factors: breed (V-Line and NZW) and four levels of purified BV derived from Apis Mellifera. The control group (G1) received a basal diet without additives. The other three groups (G2, G3 and G4) received the basal diet with BV supplementation in their drinking water at 0.5, 1 and 2 mg/L respectively. The study results indicated that NZW rabbits significantly enhanced feed conversion ratio while maintaining consistent carcass attributes compared to the V-Line breed. Despite variations in growth parameters being less pronounced, the supplementation of BV at levels of 1-2 mg/L demonstrated significant improvements in various other parameters. Notably, the interaction between the BV supplement and the breed factor (p < 0.001) yielded notable distinctions in most production metrics, encompassing BW, weight gain, feed conversion, carcass attributes and blood parameters. Increasing levels of BV supplementation, particularly at 1 mg/L, led to substantial improvements in serum and tissue metabolites. Moreover, the levels of total bacterial count and Escherichia coli in the jejunum and colon were significantly diminished, while the population of Lactobacilli in the colon was augmented (p < 0.001) in rabbits from both breeds receiving BV supplementation (1-2 mg/L) compared to the control group. The results underscore the potential of the BV supplement to enhance final weights, bolster antioxidant status and mitigate the presence of pathogenic bacteria, thereby contributing to enhanced economic efficiency in rabbits. Further inquiries are warranted to comprehensively investigate BV supplementation's potential advantages and limitations across different breeds and dosage levels.


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Venenos de Abelha , Dieta , Suplementos Nutricionais , Animais , Masculino , Coelhos , Ração Animal/análise , Venenos de Abelha/farmacologia , Venenos de Abelha/administração & dosagem , Venenos de Abelha/química , Dieta/veterinária , Relação Dose-Resposta a Droga , Desmame
16.
Front Immunol ; 15: 1326033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318188

RESUMO

Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo. In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.


Assuntos
Venenos de Abelha , Meliteno , Meliteno/farmacologia , Meliteno/química , Meliteno/metabolismo , Peptídeos Antimicrobianos , Venenos de Abelha/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais
17.
Toxicon ; 241: 107666, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423220

RESUMO

Bee stings (BS) are a life-threatening issue and a growing concern for public health and animals in the Americas. We describe the clinical, pathological, and ultrastructural findings of a massive lethal bee attack in two non-human primates (NHPs). Both animals showed BS scattered throughout the skin, surrounded by a local reaction, diffuse pulmonary congestion, edema, hemorrhage, and remarkable degeneration and necrosis of renal epithelial cells from the proximal and distal tubules, characterizing a systemic bee envenomation reaction.


Assuntos
Venenos de Abelha , Cebinae , Mordeduras e Picadas de Insetos , Abelhas , Animais , Mordeduras e Picadas de Insetos/veterinária , Saimiri , Venenos de Abelha/toxicidade , Venenos de Abelha/química , Primatas
18.
Sci Rep ; 14(1): 1510, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233443

RESUMO

Breast cancer ranks as the second leading most significant of mortality for women. Studies have demonstrated the potential benefits of natural compounds in cancer treatment and prevention, either in isolation or in conjunction with chemotherapy. In order to improve Tamoxifen's therapeutic efficacy in in-vivo studies, our research sought to determine the effects of hesperidin, piperine, and bee venom as natural compounds, as well as their combination effect with or without Tamoxifen. First, 132 female albino rats were equally divided into six groups and five subgroups, and breast cancer was induced in the selected groups by xenografting of MCF7 cells. Second, the effect of single and best ratio combinations treatment from previous in vitro studies were selected. Next, tumorous mammary glands were collected for apoptotic and antiapoptotic biomarkers and cell cycle analysis. Single or combined natural products with or without Tamoxifen revealed a significant up-regulation in apoptotic genes Bax and Casp3 and a downregulation of antiapoptotic and angiogenesis genes Bcl-2 and VEGF genes. We found that cell cycle arrest in the G0/G1 phase was exclusively caused by Tamoxifen and/ or hesperidin. However, the cell cycle arrest in the G2/M phase is a result of the combination of piperine and bee venom, with or without Tamoxifen by using the flow cytometric technique. Our research concludes that bee venom, hesperidin, and piperine can synergistically enhance to increase Tamoxifen's efficiency in the management of breast cancer.


Assuntos
Alcaloides , Venenos de Abelha , Benzodioxóis , Neoplasias da Mama , Hesperidina , Piperidinas , Alcamidas Poli-Insaturadas , Humanos , Feminino , Ratos , Animais , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Células MCF-7 , Venenos de Abelha/farmacologia , Venenos de Abelha/uso terapêutico , Angiogênese , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Biomarcadores
19.
Vet Immunol Immunopathol ; 268: 110700, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38217942

RESUMO

Apitherapy is a form of alternative medicine that utilizes products from the western honeybee (Apis mellifera), including honey, propolis, and honeybee venom, to improve the health status of human patients by altering host immunity. An added benefit of these products is that they are nutraceuticals and relatively inexpensive to aquire. Currently, little is known about the use of honeybee products in veterinary species, as well as their impact on host immunity. In the present in vitro study, honey, propolis, and honeybee venom were co-cultured with enriched canine, equine, and chicken peripheral blood lymphocytes (PBLs) with cell proliferation, cell viability/apoptosis, and cellular morphology evaluated. Concanavalin A (Con A) and dexamethasone were used as stimulatory and suppressive controls, respectively. Honeybee products' effects on the three veterinary species varied by product and the species. Honey stimulated the PBLs proliferation in all three species but also displayed some increased cytotoxicity. Propolis stimulated proliferation in canine and equine PBLs, however, it suppressed proliferation in the chicken PBLs. Honeybee venom was the strongest PBL stimulant for all three species and in the equine, surpassed the stimulant response of Con A and yet, enhanced PBL cell viability post culture. In summary, the results of this preliminary in vitro study show that these three honeybee products do impact lymphocyte proliferation and viability in dogs, horses, and chickens, and that more research both in vitro and in vivo will be necessary to draw conclusions regarding their future use as immune stimulants or inhibitors.


Assuntos
Venenos de Abelha , Própole , Animais , Cães , Humanos , Cavalos , Abelhas , Apiterapia/veterinária , Galinhas , Própole/farmacologia , Linfócitos , Venenos de Abelha/farmacologia
20.
J Toxicol Environ Health B Crit Rev ; 27(2): 73-90, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38247328

RESUMO

Africanized bees have spread across the Americas since 1956 and consequently resulted in human and animal deaths attributed to massive attacks related to exposure from Argentina to the USA. In Brazil, more than 100,000 accidents were registered in the last 5 years with a total of 303 deaths. To treat such massive attacks, Brazilian researchers developed the first specific antivenom against Africanized honey bee sting exposure. This unique product, the first of its kind in the world, has been safely tested in 20 patients during a Phase 2 clinical trial. To develop the antivenom, a standardized process was undertaken to extract primary venom antigens from the Africanized bees for immunization of serum-producing horses. This process involved extracting, purifying, fractionating, characterizing, and identifying the venom (apitoxin) employing mass spectrometry to generate standardized antigen for hyperimmunization of horses using the major toxins (melittin and its isoforms and phospholipase A2). The current guide describes standardization of the entire production chain of venom antigens in compliance with good manufacturing practices (GMP) required by regulatory agencies. Emphasis is placed upon the welfare of bees and horses during this process, as well as the development of a new biopharmaceutical to ultimately save lives.


Assuntos
Venenos de Abelha , Mordeduras e Picadas de Insetos , Abelhas , Humanos , Animais , Antivenenos/uso terapêutico , Mordeduras e Picadas de Insetos/tratamento farmacológico , Venenos de Abelha/análise , Venenos de Abelha/química , Meliteno/análise , Meliteno/química , Fosfolipases A2 , Antígenos
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