RESUMO
BACKGROUND: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. OBJECTIVES: We aimed to investigate the efficacy of PA against B. abortus infection using a murine cell line and a murine model. METHODS: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O2â») analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. RESULTS: PA did not affect the growth of B. abortus. PA treatment in macrophages did not change B. abortus uptake but it did attenuate the intracellular survivability of B. abortus. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression. Compared to control cells, reduced nitrite accumulation, augmented O2â», and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus-infected cells. Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. CONCLUSIONS: Our results suggest that PA participates in the control of B. abortus within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus infection by fatty acids.
Assuntos
Antibacterianos/farmacologia , Brucella abortus/efeitos dos fármacos , Brucelose/prevenção & controle , Ácido Palmítico/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Substâncias Protetoras/farmacologia , Células RAW 264.7 , Organismos Livres de Patógenos EspecíficosRESUMO
The efficacy of a novel, live delivery vaccine was examined for protection against post-weaning diarrhea in pigs. An expression/secretion plasmid harboring genes encoding enterotoxigenic Escherichia coli K88ab, K88ac, FedA and FedF fimbriae was constructed and harbored in an attenuated Salmonella, which was used as the vaccine candidate. Groups A (n=3) and B (n=3) sows were orally immunized with the candidate vaccine and PBS as a control, respectively, at 8 and 11 weeks of pregnancy. All group piglets were challenged with two challenge strains at 5-week-old. All immunized sows had significantly increased IgG and IgA levels in both serum and colostrum to individual adhesins compared to the control (p ≤ 0.05). Immune response in Group A piglets were significantly increased (p ≤ 0.05). Furthermore, no clinical signs were observed in Group A piglets after the challenge and no challenge strains were detected in rectal swabs, while diarrhea was observed in 47.8% control piglets and challenge strains were isolated from all the diarrheic piglets. These results show that immune response of sucking piglets can maintain at higher levels through the milk of the immunized sows and vaccination of sows with the candidate may protect colibacillosis in weaned piglets.
Assuntos
Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Diarreia/veterinária , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/veterinária , Proteínas de Fímbrias/imunologia , Doenças dos Suínos/prevenção & controle , Animais , Animais Lactentes , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/genética , Colostro/imunologia , Diarreia/imunologia , Diarreia/microbiologia , Diarreia/prevenção & controle , Ensaio de Imunoadsorção Enzimática , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Feminino , Proteínas de Fímbrias/genética , Fímbrias Bacterianas/imunologia , Imunização/métodos , Imunização/veterinária , Leite/imunologia , Gravidez , Estatísticas não Paramétricas , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologiaRESUMO
Obesity and its associated metabolic disorders has become a major obstacle in improving the average life span. In this regard therapeutic approach using natural compounds are currently receiving much attention. Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism. Here, we have found that Ulmus pumila (UP) contained at least four different triterpenoids and inhibited adipogenesis of 3T3-L1 cells. The cell viability was dose dependently decreased by UP showing the increase of cell accumulation in G1 phase while reducing in S and G2/M phase of cell cycle. UP treatment also significantly decreased the GPDH activity and intracellular lipid accumulation. In addition, UP inhibited the mRNA levels of adipogenic transcription factors and lipogenic genes such as PPARγ, C/EBPα, SREBP1c and FAS while showing no effects on C/EBP-ß and C/EBP-δ. Importantly enough, treatment of cells with UP suppressed the TNF-α induced activation of NF-κB signaling. Collectively, our results indicate that UP extract effectively attenuated adipogenesis by controlling cell cycle progression and down regulating adipogenic gene expression.
Assuntos
Adipogenia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Ulmus/química , Células 3T3-L1 , Animais , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , DNA/biossíntese , DNA/genética , Cromatografia Gasosa-Espectrometria de Massas , Glicerol-3-Fosfato Desidrogenase (NAD+)/metabolismo , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Metanol , Camundongos , Extratos Vegetais/farmacologia , RNA/química , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Sincalida/metabolismo , SolventesRESUMO
The antibacterial activity of an herbal combination composed of Mume Fructus, Coptidis Rhizoma, and Schizandrae Fructus extracts on enterohemorrhagic Escherichia coli (EHEC) was evaluated in the present study. The combination demonstrated antibacterial activity against all EHEC strains tested in this study, including those resistant to multiple antibiotics; minimum inhibitory concentration values ranged from 0.49 to 31.25 mg/mL. In in vivo antibacterial activity assay, the herbal combination was administered to mice after initial E. coli O157 infection and had significant effects on mouse mortality. The effects of the herbal combination on Shiga toxin release from EHEC O26, EHEC O111, and EHEC O157 strains containing the stx1 and stx2 genes were assessed by the reversed passive latex agglutination method, and there was no increased Shiga toxin release in the strain cultures containing the herbal combination. These results suggested that the herbal combination may be a safe and effective remedy for EHEC inhibition.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Escherichia coli Êntero-Hemorrágica/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Prunus/química , Schisandra/química , Animais , Coptis chinensis , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Medicamentos de Ervas Chinesas/uso terapêutico , Escherichia coli Êntero-Hemorrágica/enzimologia , Escherichia coli Êntero-Hemorrágica/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/mortalidade , Proteínas de Escherichia coli/metabolismo , Feminino , Testes de Fixação do Látex , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Reação em Cadeia da Polimerase , Inibidores da Síntese de Proteínas/metabolismo , Toxinas Shiga/metabolismo , Resultado do TratamentoRESUMO
Luteolin (3',4',5,7-tetrahydroxylflavone) is a plant flavonoid and pharmacologically active agent that has been isolated from several plant species. In the present study, the effect of luteolin from the flowers of Lonicera japonica on phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell activation was examined. Luteolin significantly inhibited the induction of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by PMA plus A23187. Moreover, luteolin attenuated cyclooxygenase (COX)-2 expression and intracellular Ca2+ levels. In activated HMC-1 cells, the phosphorylation of extra-signal response kinase (ERK 1/2) and c-jun N-terminal Kinase (JNK 1/2), but not p38 mitogen-activated protein kinase (p38 MAPK) were decreased by treatment of the cells with luteolin. Luteolin inhibited PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB degradation, and luciferase activity. Furthermore, luteolin suppressed the expression of TNF-alpha, IL-8, IL-6, GM-CSF, and COX-2 through a decrease in the intracellular Ca2+ levels, and also showed a suppression of the ERK 1/2, JNK 1/2, and NF-kappaB activation. These results indicated that luteolin from the flowers of Lonicera japonica exerted a regulatory effect on mast cell-mediated inflammatory diseases, such as RA, allergy disease and IBD.
Assuntos
Flores/química , Mediadores da Inflamação/metabolismo , Lonicera/química , Luteolina/isolamento & purificação , Luteolina/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Calcimicina/farmacologia , Cálcio/metabolismo , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Macrophages play central roles in the innate immune system. The roots of Aralia cordata are widely used in Oriental medicine as a remedy for arthritis. During our program to screen medicinal plants for potential anti-inflammatory compounds, ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic acid; PA) was isolated from the roots of A. cordata. We examined the effect of PA on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. PA was found to significantly inhibit the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and interleukin-6 (IL-6), as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6. Furthermore, we examined whether mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are involved in LPS-induced RAW 264.7 cells. We found that a p38 inhibitor (SB203580) and an ERK 1/2 inhibitor (PD98059) significantly affected LPS-induced IL-6 production. In contrast, a JNK 1/2 inhibitor (SP600125) and PI3K inhibitor (wortmannin or LY294002) did not block the induction of IL-6 production by LPS. The LPS-induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK1/2) was inhibited by PA, but not the phosphorylation of JNK 1/2 and AKT (Ser473). Moreover, PA suppressed I kappaB alpha degradation, NF-kappaB activation and luciferase activity. These results suggest that PA isolated from A. cordata has a potential regulatory effect on inflammatory iNOS, COX-2 and IL-6 expression through blockade of the phosphorylation of MAPKs following I kappaB alpha degradation and NF-kappaB activation.
Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Aralia/química , Linhagem Celular , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Diterpenos/isolamento & purificação , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicina Tradicional do Leste Asiático , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
The antibacterial potential of a preparation of medicinal herbs for the treatment of salmonellosis was evaluated. The preparation contained a combination of methanolic extracts from Mume Fructus, Coptidis Rhizoma and Schizandrae Fructus, and is designated NP532. NP532 was tested against 26 different Salmonella stains. All these strains were affected by NP532 even though many of the salmonella strains were resistant to multiple antibiotics. The MIC values of this combination against the Salmonella strains varied from 0.49 to 7.8 mg/ml. The in vivo antibacterial activity of NP532 was examined using a S. Gallinarum infection chicken model. The chickens were initially infected with S. Gallinarum, and NP532 was then administered. This preparation was found to have major effects on mortality. The histopathological observations of the NP532 treated animals did not show any of the clinical signs and rarely showed histological damage associated with the disease. On the other hand, the untreated controls showed the clinical signs, e.g. congestion and necrotic changes in the liver, kidney, and spleen. This suggests that NP532 might be an effective treatment for salmonellosis.
Assuntos
Antibacterianos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Intoxicação Alimentar por Salmonella/tratamento farmacológico , Salmonella/efeitos dos fármacos , Animais , Bioensaio , Galinhas , Contagem de Colônia Microbiana , Coptis chinensis , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Salmonella/crescimento & desenvolvimento , Schisandra/química , Resultado do TratamentoRESUMO
Methanol extract and its fractions (hexane, EtOAc, n-BuOH, and H2O) of Dryopteris crassirhizoma were investigated for antibacterial activity against methicillin-resistant Staphylococcus aureus. The hexane fraction showed a good antibacterial activity against all tested strains.
Assuntos
Antibacterianos/farmacologia , Dryopteris , Fitoterapia , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Humanos , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêuticoRESUMO
Angelica dahurica (Umbelliferae) has been used to treat headache of common cold, supraorbital neuralgia, painful swelling on the body, nasal stuffiness, leukorrhea and arthralgia due to wind-dampness in Korean traditional medicine. It is also claimed to be effective in the treatment of acne, erythema, headache, toothache, sinusitis, colds and flu. The present study focused whether the ethyl acetate extract from Angelica Dahuricae Radix (EAAD) inhibits production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF)-alpha, as well as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated macrophages. EAAD inhibited LPS-induced NO, PGE(2) and TNF-alpha production as well as expression of iNOS and COX-2 in RAW 264.7 cells. EAAD inhibited LPS-induced TNF-alpha production in THP-1 cells. Furthermore, EAAD suppressed LPS-induced phosphorylation of p38 MAPK and extracellular-signal regulated kinases 1/2 (ERK1/2), I-kappaBalpha degradation, and NF-kappaB activation in RAW 264.7 cells. These results suggest that EAAD has the inhibitory effects on LPS-induced TNF-alpha, NO and PGE(2) production, and expression of iNOS and COX-2 in macrophage through blockade in the phosphorylation of MAPKs, following I-kappaBalpha degradation and NF-kappaB activation.
Assuntos
Angelica , Anti-Inflamatórios/farmacologia , Dinoprostona/metabolismo , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Acetatos/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Furocumarinas/análise , Humanos , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Extratos Vegetais/farmacologia , Raízes de Plantas , Solventes/química , Células Th1/efeitos dos fármacos , Células Th1/metabolismoRESUMO
The therapeutic potentials of twenty-two medicinal herb species traditionally used in Korea to treat gastrointestinal infections were evaluated for the treatment of salmonellosis. Candidates were primarily screened using the disk-agar method for antibacterial activity against three different Salmonella serotypes. Of the herbs tested, the aqueous and methanolic extracts of Schizandrae Fructus exhibited antibacterial activity against all three Salmonella. The extracts of this herb were further tested against 13 additional Salmonella strains of 6 different serotypes. All of these strains were also affected by these extracts, though the methanolic extract had slightly higher activity. The MIC values of this extract against the 16 Salmonella strains varied from 15.6 to 125 microg/ml. Nine of the 16 strains tested had MIC values of <31.3 microg/ml for the methanolic extract of Schizandrae Fructus. The in vivo antibacterial activity of Schizandrae Fructus extract was examined in a S. Typhimurium infection mouse model. Mice were initially infected with S. Typhimurium, and then administered with Schizandrae Fructus extract. The extract was found to have major effects on mortality and on the numbers of viable S. Typhimurium recovered from feces. Clinical signs and histological damages were rarely observed in the treated mice, whereas the untreated controls showed clinical signs, e.g., lethargy, and histological damage in the kidney, liver, intestine, and spleen. We conclude that Schizandrae Fructus has the potential to provide an effective treatment for salmonellosis.
Assuntos
Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Intoxicação Alimentar por Salmonella/tratamento farmacológico , Salmonella/efeitos dos fármacos , Animais , Bioensaio , Contagem de Colônia Microbiana , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Salmonella/crescimento & desenvolvimentoRESUMO
The anti-inflammatory and anti-nociceptive effects and sedative activities of the ethyl acetate fraction of Cynanchum paniculatum (EACP) were evaluated in mice and rats by acetic acid-induced vascular permeability, arachidonic acid-induced paw edema, cotton pellet-induced granuloma formation, formalin-induced licking time, acetic acid-induced writhing response, and pentobarbital-induced sleeping time. EACP at a dose of 40 mg/kg significantly exhibited anti-inflammatory activities on acetic acid-induced vascular permeability, arachidonic acid-induced paw edema, and the late phase of formalin-induced licking time. Moreover, it showed anti-nociceptive effects on acetic acid-induced writhing responses and significant sedative effects on pentobarbital-induced sleeping time. The results demonstrated that the anti-nociceptive effects are apparently related to the sedative effects of EACP. These results support the use of Cynanchum paniculatum in relieving inflammatory pain.