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1.
Toxins (Basel) ; 14(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36287932

RESUMO

Streptococcus pyogenes (S. pyogenes) bacteria cause almost all primary skin infections in humans. Bee venom (BV) and melittin (Mel) have multiple effects, including antibacterial and anti-inflammatory activities. This study aims to demonstrate their effects on bacterial mouse skin infection using S. pyogenes. The dorsal skin was tape-stripped, then S. pyogenes was topically applied. BV or Mel were topically applied to the lesion. The tissues were stained with hematoxylin and eosin, while immunohistochemical staining was performed with anti-neutrophil. S. pyogenes-infected skin revealed increased epidermal and dermal layers, but it was reduced in the BV and Mel groups. Finding increased neutrophils in the mice infected with S. pyogenes, but the BV and Mel mice showed decreased expression. These results suggest that BV and Mel treatments could reduce the inflammatory reactions and help improve lesions induced by S. pyogenes skin infection. This study provides additional assessment of the potential therapeutic effects of BV and Mel in managing skin infection caused by S. pyogenes, further suggesting that it could be a candidate for developing novel treatment alternative for streptococcal skin infections.


Assuntos
Venenos de Abelha , Dermatopatias Bacterianas , Humanos , Camundongos , Animais , Meliteno/farmacologia , Meliteno/uso terapêutico , Venenos de Abelha/farmacologia , Venenos de Abelha/uso terapêutico , Streptococcus pyogenes , Amarelo de Eosina-(YS) , Hematoxilina , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Antibacterianos/uso terapêutico
2.
Toxins (Basel) ; 12(3)2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204567

RESUMO

Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%-3% dry weight of bee venom and is a peptide neurotoxin that contains 18 amino acid residues that are tightly crosslinked by two disulfide bonds. It is well known for its pharmacological functions, which irreversibly block Ca2+-activated K+ (SK) channels. Apamin regulates gene expression in various signal transduction pathways involved in cell development. The aim of this study was to review the current understanding of apamin in the treatment of apoptosis, fibrosis, and central nervous system diseases, which are the pathological processes of various diseases. Apamin's potential therapeutic and pharmacological applications are also discussed.


Assuntos
Apamina/uso terapêutico , Aterosclerose/tratamento farmacológico , Venenos de Abelha/química , Sistema Nervoso Central/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Canais de Potássio Cálcio-Ativados/antagonistas & inibidores , Apamina/isolamento & purificação , Apoptose/efeitos dos fármacos , Aterosclerose/metabolismo , Sistema Nervoso Central/patologia , Citocinas/antagonistas & inibidores , Fibrose , Humanos , Cirrose Hepática/patologia
3.
Am J Chin Med ; 47(8): 1869-1883, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786944

RESUMO

Bee venom of Apis mellifera is a traditional medicine in Asia. It has been used with promoting results for the treatment of pain, rheumatoid, and cancer disease. The purpose of this study was to investigate the effects of bee venom on epidermal growth factor (EGF)-induced epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) and determine possible signaling pathway affected in EGF-induced EMT in A549 cells. Bee venom inhibited EGF-induced F-actin reorganization and cell invasion, and suppressed EGF-induced EMT, processes associated with tumor metastasis in NSCLC. Bee venom enhanced the upregulation of E-cadherin and the downregulation of vimentin and inhibited EGF-induced ERK, JNK, FAK, and mTOR phosphorylation in A549 cells. However, the inhibition of JNK phosphorylation by bee venom was not related to the inhibitory effects of EMT. Furthermore, we found that bee venom suppressed the EMT-related transcription factors ZEB2 and Slug by blocking EGF-induced ERK, FAK and mTOR phosphorylation. Bee venom inhibits EGF-induced EMT by blocking the phosphorylation of ERK, FAK, and mTOR, resulting in the suppression of ZEB2 and Slug. These data suggest bee venom as a potential antimetastatic agent for NSCLC.


Assuntos
Venenos de Abelha/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/fisiopatologia , Células A549 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
4.
Br J Pharmacol ; 175(23): 4310-4324, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30187459

RESUMO

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is a multifactorial skin condition with complex interactions of innate and adaptive immune responses. There are several existing therapies for AD, including topical glucocorticosteroids, emollients, phototherapies, calcineurin inhibitors and immunosuppressants, such as cyclosporine A. Although these therapies reduce inflammation, they also cause serious side effects. Therefore, it is necessary to develop new therapeutic approaches for AD treatment without side effects. There are several studies on natural materials or toxins, such as herbs, ginseng extract and snake venom, for AD treatment. However, treatment of AD with bee venom and its major component, melittin has rarely been studied. EXPERIMENTAL APPROACH: Effects of bee venom and melittin were studied in a model of AD in vivo induced by 1-chloro-2,4-dinitrobenzene (DNCB) in female Balb/c mice and in cultures of human keratinocytes, stimulated by TNF-α/IFN-γ. The potential pharmacological effects of bee venom and melittin on these in vivo and in vitro AD-like skin disease models were studied. KEY RESULTS: Bee venom and melittin exhibited potent anti-atopic activities, shown by decreased AD-like skin lesions, induced by DNCB in mice. In vitro studies using TNF-α/IFN-γ-stimulated human keratinocytes showed that bee venom and melittin inhibited the increased expression of chemokines, such as CCL17 and CCL22, and pro-inflammatory cytokines, including IL-1ß, IL-6 and IFN-γ, through the blockade of the NF-κB and STAT signalling pathways. CONCLUSIONS AND IMPLICATIONS: Our results suggest that bee venom and melittin would be suitable for epicutaneous application, as topical administration is often appropriate for the treatment of AD.


Assuntos
Venenos de Abelha/farmacologia , Dermatite Atópica/tratamento farmacológico , Meliteno/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dermatite Atópica/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Relação Estrutura-Atividade
5.
Mol Med Rep ; 18(4): 3711-3718, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30132547

RESUMO

Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by recurrent eczema and itching. It is caused by a poorly controlled immune response and damage to the skin barrier. Purified bee venom (BV) is a natural toxin produced by honeybees (Apis mellifera L.), and is well known for its anti­inflammatory, analgesic and anti­cancer effects against various types of disease. However, treatment strategies based on anti­inflammatory properties have not been adequately studied in AD. Thus, the present study examined the progression of AD­like skin lesions induced by ovalbumin (OVA) and the mechanism of action of BV. BV, administered by intraperitoneal inoculation, was observed to reduce the symptoms of AD, in addition to the serum immunoglobulin E levels, according to dorsal skin thickness and histopathologic analysis. The treatment also inhibited the infiltration of eosinophils and mast cells. These results suggested that it is possible to develop novel AD alternative therapy using BV by effectively suppressing allergic skin inflammation in AD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Venenos de Abelha/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Abelhas , Dermatite Atópica/sangue , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/análise , Imunoglobulina E/sangue , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Camundongos Endogâmicos BALB C , Ovalbumina , Pele/patologia
6.
Mol Med Rep ; 17(5): 6632-6638, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29532888

RESUMO

Bee venom (BV) has long been used as anti-inflammatory agent in traditional oriental medicine; however, the effect of BV on chronic rhinosinusitis (CRS) is not commonly studied. The aim of the present study was to determine the anti-inflammatory effect of BV on an allergic CRS mouse model. An allergic CRS mouse model was established following the administration of ovalbumin with Staphylococcus aureus enterotoxin B (SEB) into the nose. A total of 0.5 or 5 ng/ml of BV were intranasally applied 3 times a week for 8 weeks. Histopathological alterations were observed using hematoxylin and eosin, and Periodic acid Schiff staining. The levels of inflammatory cell infiltration, interleukin (IL)­4, IL­10 and interferon (INF)­Î³ in nasal lavage fluid (NLF) were measured. Nuclear factor (NF)­κB and activator protein (AP)­1 expressions were also determined by immunohistochemical staining. The group treated with BV had significantly decreased inflammatory cell infiltration and PAS­positive cells. The levels of INF­Î³, and neutrophil and eosinophil counts in NLF were significantly decreased, and the SEB­induced NF­κB and AP­1 expressions in mouse nasal mucosa were significantly suppressed by 0.5 and 5 ng/ml BV. Thus, BV exerted significant anti­inflammatory effects in an allergic CRS mouse model and may have potential value for the treatment of CRS.


Assuntos
Anti-Inflamatórios/farmacologia , Venenos de Abelha/farmacologia , Rinite Alérgica/tratamento farmacológico , Sinusite/tratamento farmacológico , Animais , Doença Crônica , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Sinusite/induzido quimicamente , Sinusite/metabolismo , Sinusite/patologia , Fator de Transcrição AP-1/metabolismo
7.
Hip Pelvis ; 29(2): 81-90, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28611958

RESUMO

The volume of hip arthroplasty is stiffly increasing because of excellent clinical outcomes, however it has not been shown to decrease the incidence of transfusions due to bleeding related to this surgery. This is an important consideration since there are concerns about the side effects and social costs of transfusions. First, anemia should be assessed at least 30 days before elective hip arthroplasty, and if the subject is diagnosed as having anemia, an additional examination of the cause of the anemia should be carried and steps taken to address the anemia. Available iron treatments for anemia take 7 to 10 days to facilitate erythropoiesis, and preoperative iron supplementation, either oral or intravenous, is recommended. When using oral supplements for iron storage, administer elemental iron 100 mg daily for 2 to 6 weeks before surgery, and calculate the dose using intravenous supplement. Tranexamic acid (TXA) is a synthetic derivative of the lysine component, which reduces blood loss by inhibiting fibrinolysis and clot degradation. TXA is known to be an effective agent for reducing postoperative bleeding and reducing the need for transfusions in primary and revision total hip arthroplasties. Patient blood management has improved the clinical outcome after hip arthroplasty through the introduction and research of various agents, thereby reducing the need for allogeneic blood transfusions and reducing the risk of transfusion-related infections and the duration of hospitalizations.

8.
Toxins (Basel) ; 9(1)2016 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-28025545

RESUMO

Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%-60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD.


Assuntos
Toxinas Bacterianas/imunologia , Dermatite Atópica/imunologia , Alérgenos/imunologia , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/microbiologia , Fármacos Dermatológicos/farmacologia , Modelos Animais de Doenças , Humanos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Pele/imunologia , Pele/microbiologia , Staphylococcus aureus/imunologia
9.
Molecules ; 21(11)2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27834922

RESUMO

Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis (P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV against P. gingivalis LPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis.


Assuntos
Venenos de Abelha/farmacologia , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Polissacarídeos Bacterianos/farmacologia , Porphyromonas gingivalis/química , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor 4 Toll-Like/metabolismo
10.
Toxins (Basel) ; 7(11): 4758-72, 2015 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-26580653

RESUMO

Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient's skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. Studies have proven the effectiveness of bee venom in treating pathological conditions such as arthritis, pain and cancerous tumors. However, there has not been sufficient review to fully elucidate the cellular mechanisms of the anti-inflammatory effects of bee venom and its components. In this respect, the present study reviews current understanding of the mechanisms of the anti-inflammatory properties of bee venom and its components in the treatment of liver fibrosis, atherosclerosis and skin disease.


Assuntos
Anti-Inflamatórios/uso terapêutico , Venenos de Abelha/uso terapêutico , Fibrose/complicações , Fibrose/prevenção & controle , Inflamação/etiologia , Inflamação/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Venenos de Abelha/farmacologia , Humanos
11.
Toxins (Basel) ; 7(6): 1917-28, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26035488

RESUMO

Progressive renal fibrosis is the final common pathway for all kidney diseases leading to chronic renal failure. Bee venom (BV) has been widely used as a traditional medicine for various diseases. However, the precise mechanism of BV in ameliorating the renal fibrosis is not fully understood. To investigate the therapeutic effects of BV against unilateral ureteral obstruction (UUO)-induced renal fibrosis, BV was given intraperitoneally after ureteral ligation. At seven days after UUO surgery, the kidney tissues were collected for protein analysis and histologic examination. Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, BV treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of TNF-α and IL-1ß were significantly reduced in BV treated mice compared with UUO mice. In addition, treatment with BV significantly inhibited TGF-ß1 and fibronectin expression in UUO mice. Moreover, the expression of α-SMA was markedly withdrawn after treatment with BV. These findings suggest that BV attenuates renal fibrosis and reduces inflammatory responses by suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, BV may be a useful therapeutic agent for the prevention of fibrosis that characterizes progression of chronic kidney disease.


Assuntos
Anti-Inflamatórios/uso terapêutico , Venenos de Abelha/uso terapêutico , Obstrução Ureteral/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Venenos de Abelha/farmacologia , Modelos Animais de Doenças , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrose , Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Obstrução Ureteral/metabolismo
12.
Int Immunopharmacol ; 25(2): 400-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25708656

RESUMO

Bee venom is a natural ingredient produced by the honey bee (Apis mellifera), and has been widely used in China, Korea and Japan as a traditional medicine for various diseases such as arthritis, rheumatism, and skin diseases However, the regulation of the underlying molecular mechanisms of the anti-arthritis by bee venom and its major peptides is largely unknown. In this study, we investigated the potential molecular mechanisms underlying the anti-arthritis effect of bee venom and its major peptides, melittin and apamin, in tumor necrosis factor-α (TNF-α) responsive C57BL/6 mice chondrocyte cells. The bee venom and melittin significantly and selectively suppressed the TNF-α-mediated decrease of type II collagen expression, whereas the apamin had no effects on the type II collagen expression. We, furthermore, found that the bee venom and melittin inhibited the protein expression of matrix metalloproteinase (MMP)-1 and MMP-8, which suggests that the chondroprotective effect of bee venom may be caused by melittin. The inhibitory effects of melittin on the TNF-α-induced MMP-1 and MMP-8 protein expression were regulated by the inhibition of NF-kB and AP-1. In addition, melittin suppressed the TNF-α-induced phosphorylation of Akt, JNK and ERK1/2, but did not affect the phosphorylation of p38 kinase. These results suggest that melittin suppresses TNF-α-stimulated decrease of type II collagen expression by the inhibiting MMP-1 and MMP-8 through regulation of the NF-kB and AP-1 pathway and provision of a novel role for melittin in anti-arthritis action.


Assuntos
Venenos de Abelha/farmacologia , Condrócitos/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/farmacologia , Fator de Transcrição AP-1/antagonistas & inibidores , Animais , Células Cultivadas , Condrócitos/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
13.
Int J Mol Med ; 34(5): 1341-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25215662

RESUMO

Propionibacterium acnes (P. acnes) is a major contributing factor to the inflammatory component of acne. The many prescription medications for acne allow for a large number of potential combination treatments. However, several antibiotics, apart from their antibacterial effects, exert side­effects, such as the suppression of host inflammatory responses. Purified bee venom (BV) is a natural toxin produced by honeybees (Apis mellifera L.). BV has been widely used as a traditional medicine for various diseases. In the present study, to investigate the therapeutic effects of BV against P. acnes-induced inflammatory skin disease, P. acnes was intradermally injected into the ears of mice. After the injection, BV was applied to the skin surface of the right ear. Histological observation revealed that P. acnes induced a considerable increase in the number of infiltrated inflammatory cells. However, treatment with BV markedly reduced these reactions compared with the P. acnes-injected mice not treated with BV. Moreover, the expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß were significantly reduced in the BV-treated mice compared with the untreated P. acnes-injected mice. In addition, treatment with BV significantly inhibited Toll-like receptor (TLR)2 and CD14 expression in P. acnes-injected tissue. The binding activity of nuclear factor-κB (NF-κB) and activator protein (AP)-1 was markedly suppressed following treatment with BV. The results from our study, using an animal model, indicate that BV exerts an inhibitory effect on inflammatory skin diseases. In conclusion, our data indicate that BV has potential for use as an anti-acne agent and may be useful in the pharmaceutical and cosmetics industries.


Assuntos
Acne Vulgar/microbiologia , Venenos de Abelha/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Abelhas , Modelos Animais de Doenças , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
Am J Chin Med ; 42(5): 1139-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25178280

RESUMO

Renal fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) proteins such as type I collagen, fibronectin, and by the increased expression of PAI-1. This study evaluated the anti-fibrotic effect of bee venom and its major compounds (melittin and apamin) on TGF-ß-induced pro-fibrotic gene expression. Bee venom and melittin significantly suppressed type I collagen, fibronectin, and PAI-1 protein expression in the TGF-ß-treated kidney fibroblast. However, apamin only inhibited the expression of fibronectin and type I collagen. These results indicated that the inhibitory effects of bee venom on TGF-ß-induced pro-fibrotic gene expression are caused by melittin. Moreover, we attempted to elucidate mechanisms underlying the anti-fibrotic effect of melittin. Melittin dramatically inhibited the phosphorylation of TGFßRII and Smad2/3. Also, melittin inhibited the phosphorylation of ERK1/2 and JNK, but not the phosphorylation of PI3K, Akt, and p38. These results suggested that melittin inhibits TGF-ß-induced pro-fibrotic genes expression through the suppression of TGFßR-Smad2/3, ERK1/2, and JNK phosphorylation, and melittin can be used as a clinical drug for the treatment of fibrosis associated with renal diseases.


Assuntos
Venenos de Abelha/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibroblastos/patologia , Fibronectinas/genética , Fibronectinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Rim/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Meliteno/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Animais , Células Cultivadas , Depressão Química , Fibrose , Rim/citologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Meliteno/uso terapêutico , Fosforilação/efeitos dos fármacos , Ratos , Receptor do Fator de Crescimento Transformador beta Tipo II
15.
BMC Complement Altern Med ; 14: 286, 2014 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-25091565

RESUMO

BACKGROUND: Free radicals are involved in neuronal cell death in human neurodegenerative diseases. Since ancient times, honeybee venom has been used in a complementary medicine to treat various diseases and neurologic disorders. Melittin, the main component of honeybee venom, has various biologic effects, including anti-bacterial, anti-viral, and anti-inflammatory activities. METHODS: We investigated the neuroprotective effects of melittin against H2O2-induced apoptosis in the human neuroblastoma cell line SH-SY5Y. The neuroprotective effects of melittin on H2O2-induced apoptosis were investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide assay, caspase 3 activity, 4,6-diamidino-2-phenylindole staining, a lactate dehydrogenase release assay, Western blots, and reverse transcription-polymerase chain reaction. RESULTS: The H2O2-treated cells had decreased cell viability with apoptotic features and increased production of caspase-3. On the other hand, melittin treatment increased cell viability and decreased apoptotic DNA fragmentation. Melittin attenuated the H2O2-induced decrease in mRNA and protein production of the anti-apoptotic factor Bcl-2. In addition, melittin inhibited both the H2O2-induced mRNA and protein expression of Bax-associated pro-apoptotic factor and caspase-3. CONCLUSIONS: These findings suggest that melittin has potential therapeutic effects as an agent for the prevention of neurodegenerative diseases.


Assuntos
Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Meliteno/farmacologia , Neuroblastoma/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Neuroblastoma/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
Biol Pharm Bull ; 37(8): 1295-300, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25087951

RESUMO

Bee venom (BV) has been used as an anti-inflammatory and immune modulating agent in Oriental medicine. This study used a mouse model to investigate the anti-allergic effect of BV, which is used in the treatment of various inflammatory diseases in traditional medicine. BV was obtained from the National Institute of Agricultural Science and Technology of Korea. Female BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA). BV was administered nasally prior to the intranasal instillation of OVA. Allergic behavior, serum OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-10, and interferon-gamma (INF-γ) levels in nasal lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate histological change. BV attenuated nasal symptoms and inhibited the production of OVA-specific IgE and IL-4 in sensitized mice. The degree of inflammatory cell infiltration and goblet cell hyperplasia was attenuated by BV. Thus, BV effectively reduced allergic inflammation in a mouse model of allergic rhinitis, suggesting its potential as a useful therapeutic agent to treat allergic rhinitis.


Assuntos
Antialérgicos/uso terapêutico , Venenos de Abelha/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Alérgenos/imunologia , Animais , Antialérgicos/farmacologia , Venenos de Abelha/farmacologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Camundongos Endogâmicos BALB C , Mucinas/imunologia , NF-kappa B/imunologia , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Ovalbumina/imunologia , Rinite Alérgica/sangue , Rinite Alérgica/imunologia , Fator de Transcrição AP-1/imunologia
17.
Pharmacology ; 91(1-2): 39-47, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23154617

RESUMO

Bee venom (BV) has long been used as an oriental traditional medicine for the control of pain and inflammation. However, BV's anti-inflammatory mechanisms remain unclear. This study aimed to clarify the potential clinical efficacy of BV concerning the anti-inflammatory effect on nasal epithelial cell inflammation. Nasal polyp epithelial cells were obtained from patients. Cells were exposed to Alternaria alternata, Aspergillus nigra, Dermatophagoides pteronyssinus, Dermatophagoides farina and lipopolysaccharide with or without various concentrations of BV. Interleukin (IL)-6, IL-8, and granulocyte macrophage colony-stimulating factor were measured to determine the activation of epithelial cells. Nuclear factor-ĸB (NF-ĸB) and activator protein 1 expression and activity were determined with Western blot analysis and ELISA. Cytotoxicity of BV was measured using a CellTiter-96® aqueous cell proliferation assay kit. Cell survival was significantly decreased at BV concentrations exceeding 5 µg/ml. Fungi-induced cytokine production was more effectively inhibited by BV than house dust mite. Alternaria enhanced NF-ĸB expression, which was strongly inhibited by BV. BV appears to be relatively safe, and is of potential value for the treatment of airway inflammation and/or immunologic diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Venenos de Abelha/farmacologia , Poluentes Atmosféricos , Alérgenos , Alternaria , Animais , Aspergillus niger , Células Cultivadas , Citocinas/metabolismo , Dermatophagoides farinae , Dermatophagoides pteronyssinus , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , NF-kappa B/metabolismo , Pólipos Nasais , Fator de Transcrição AP-1/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-22645626

RESUMO

Apamin, a peptide component of bee venom (BV), has anti-inflammatory properties. However, the molecular mechanisms by which apamin prevents atherosclerosis are not fully understood. We examined the effect of apamin on atherosclerotic mice. Atherosclerotic mice received intraperitoneal (ip) injections of lipopolysaccharide (LPS, 2 mg/kg) to induce atherosclerotic change and were fed an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg) was administered by ip injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin reduced expression of tumor necrosis factor (TNF)-α, vascular cell adhesion molecule (VCAM)-1, and intracellular cell adhesion molecule (ICAM)-1, as well as the nuclear factor kappa B (NF-κB) signaling pathway. Apamin decreased the formation of atherosclerotic lesions as assessed by hematoxylin and elastic staining. Treatment with apamin reduced lipids, Ca(2+) levels, and TNF-α in the serum from atherosclerotic mice. Further, apamin significantly attenuated expression of VCAM-1, ICAM-1, TGF-ß1, and fibronectin in the descending aorta from atherosclerotic mice. These results indicate that apamin plays an important role in monocyte/macrophage inflammatory processing and may be of potential value for preventing atherosclerosis.

19.
J Arthroplasty ; 26(8): 1310-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21316911

RESUMO

The aim of this study was to assess the midterm results of primary cementless total hip arthroplasty using a tapered stem and alumina bearing couple in active patients. After a minimum of 5 years of follow-up, 78 arthroplasties in 72 patients were reviewed retrospectively. The mean Harris hip score was 94 points, and 2 hips had thigh pain. All components radiographically demonstrated stable fixation by bone ingrowth and mild stress shielding of the proximal femur were noted in 14% of hips. There was no significant osteolysis or aseptic loosening. There was a ceramic head fracture in 1 hip and audible sounds in 2 hips. The results of total hip arthroplasty with a straight, tapered, proximally porous-coated stem and alumina-on-alumina bearing were encouraging for active patients.


Assuntos
Óxido de Alumínio , Artroplastia de Quadril/instrumentação , Fêmur/cirurgia , Prótese de Quadril , Osteonecrose/cirurgia , Desenho de Prótese , Titânio , Adulto , Fatores Etários , Idoso , Artroplastia de Quadril/métodos , Feminino , Fêmur/diagnóstico por imagem , Seguimentos , Luxação Congênita de Quadril/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiologia , Articulação do Quadril/cirurgia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Radiografia , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos , Resultado do Tratamento
20.
Am J Chin Med ; 38(6): 1077-92, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21061462

RESUMO

The components of bee venom (BV) utilized in the current study were carefully scrutinized with chromatography. Despite its well documented anti-inflammatory property, there are no reports regarding the influence of BV on the expression of cellular adhesion molecules in the vascular endothelium. A great amount of information exists concerning the effects of an atherogenic diet on atherosclerotic changes in the aorta, but little is known about the molecular mechanisms and the levels of gene regulation involved in the anti-inflammatory process induced by BV. The experimental atherosclerosis was induced in mice by a lipopolysaccharide (LPS) injection and an atherogenic diet. The animals were divided into three groups, the NC groups of animals that were fed with a normal diet, the LPS/fat group was fed with the atherogenic diet and received intraperitoneal injections of LPS, and the LPS/fat + BV group was given LPS, an atherogenic diet and intraperitoneal BV injections. At the end of each treatment period, the LPS/fat + BV group had decreased levels of total cholesterol (TC) and triglyceride (TG) in their serum, compared to the LPS/fat group. The LPS/fat group had significant expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the serum, compared with the NC group (p < 0.05). The amount of cytokines reduced consistently in the BV treatment groups compared with those in LPS/fat group. BV significantly reduced the amount of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), transforming growth factor-ß1 (TGF-ß1) and fibronectin in the aorta, compared with the LPS/fat group (p < 0.05). A similar pattern was also observed in the heart. In conclusion, BV has anti-atherogenic properties via its lipid-lowering and anti-inflammatory mechanisms.


Assuntos
Anti-Inflamatórios/farmacologia , Aterosclerose/tratamento farmacológico , Venenos de Abelha/farmacologia , Gorduras na Dieta/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Apiterapia , Aterosclerose/sangue , Aterosclerose/patologia , Venenos de Abelha/uso terapêutico , Citocinas/sangue , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Fibronectinas/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-1beta/sangue , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1/sangue , Fator de Necrose Tumoral alfa/sangue , Molécula 1 de Adesão de Célula Vascular/sangue
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