RESUMO
SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.
La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.
Assuntos
Animais , Feminino , Ratos , Medicamentos de Ervas Chinesas , Substâncias Protetoras/administração & dosagem , Íons Pesados/efeitos adversos , Scutellaria baicalensis/química , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Hormônio Liberador da Corticotropina , Ensaio de Imunoadsorção Enzimática , Ratos Wistar , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Hormônio Adrenocorticotrópico , Antígeno Nuclear de Célula em Proliferação , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/efeitos da radiação , Fatores Imunológicos/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/efeitos da radiaçãoRESUMO
The aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of Boswellia serrata against the experimental model of diabetic foot ulcer. α-Boswellic acid was isolated from the standardized extract of B. serrata and characterized (HPLC, 1H-NMR, 13C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i.âp.), and wounds were created on the dorsal surface of the hind paw. B. serrata (100, 200, and 400 mg/kg, p.âo.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na]+ = 455.37 as α-boswellic acid. Treatment with B. serrata (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-α, interleukin-1ß, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by B. serrata. It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by B. serrata. In conclusion, standardized extracts of B. serrata exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-α, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.
Assuntos
Apoptose/efeitos dos fármacos , Boswellia/química , Pé Diabético/tratamento farmacológico , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Animais , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental , Pé Diabético/induzido quimicamente , Fatores Imunológicos/antagonistas & inibidores , Fatores Imunológicos/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial and sporadic cases of IBD in a nationwide cohort study. METHODS: From national registries, covering a population of 8,295,773 individuals, we obtained information on date and year of diagnosis of IBD cases, gender, age, and family ties. Using Cox regression, we estimated hazard ratios for IBD-related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial and sporadic cases of IBD. However, patients with familial CD had significantly higher risk of major surgery than sporadic CD cases after 2 years of disease duration (hazard ratio, 1.62; 95% confidence interval, 1.26-2.07). Also, sensitivity analysis suggested a slightly reduced time from diagnosis to first tumor necrosis factor-α inhibitor treatment among familial CD and UC cases as compared with sporadic cases. CONCLUSION: We found only minor differences in surgery rates and tumor necrosis factor exposure, between familial and sporadic cases of IBD. These findings may represent purely social rather than functional effects, which is consoling for newly diagnosed CD or UC patients with a family history of IBD.
Assuntos
Terapia Biológica/estatística & dados numéricos , Colite Ulcerativa/patologia , Doença de Crohn/patologia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Estudos de Coortes , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Doença de Crohn/genética , Doença de Crohn/terapia , Dinamarca , Progressão da Doença , Família , Feminino , Fármacos Gastrointestinais/uso terapêutico , Predisposição Genética para Doença , Humanos , Fatores Imunológicos/antagonistas & inibidores , Fatores Imunológicos/uso terapêutico , Masculino , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Tempo para o Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/uso terapêuticoRESUMO
In this study we tested whether the isoquinoline alkaloid berberine can inhibit the growth of influenza A. Our experiments showed strong inhibition of the growth of H1N1 influenza A strains PR/8/34 or WS/33 in RAW 264.7 macrophage-like cells, A549 human lung epithelial-derived cells and murine bone marrow derived macrophages, but not MDCK canine kidney cells. Studies of the mechanism underlying this effect suggest that berberine acts post-translationally to inhibit virus protein trafficking/maturation which in turn inhibits virus growth. Berberine was also evaluated for its ability to inhibit production of TNF-α and PGE(2) from A/PR/8/34 infected-RAW 264.7 cells. Our studies revealed strong inhibition of production of both mediators and suggest that this effect is distinct from the anti-viral effect. Finally, we asked whether berberine-containing ethanol extracts of goldenseal also inhibit the growth of influenza A and production of inflammatory mediators. We found strong effectiveness at high concentrations, although upon dilution extracts were somewhat less effective than purified berberine. Taken together, our results suggest that berberine may indeed be useful for the treatment of infections with influenza A.
Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Hydrastis/química , Fatores Imunológicos/biossíntese , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Berberina/química , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Humanos , Immunoblotting , Fatores Imunológicos/antagonistas & inibidores , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H1N1/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteínas Virais/biossínteseAssuntos
Terapia Biológica , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos Monoclonais/uso terapêutico , Linfócitos B/efeitos dos fármacos , Terapia Biológica/métodos , Terapia Biológica/tendências , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase III como Assunto , Citocinas/antagonistas & inibidores , Medicina Baseada em Evidências , Humanos , Fatores Imunológicos/antagonistas & inibidores , Imunossupressores/uso terapêutico , Interferon-alfa/antagonistas & inibidores , Interferon gama/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/uso terapêutico , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
AIM OF THE STUDY: A herbal preparation using Scutellaria baicalensis (S. baicalensis) Georgi (Huang Qin, SB) was formulated to effectively protect cancer patients from inflammatory reactions. Although SB, is one of the most widely used herbs in oriental medicine for anti-inflammation, anti-cancer, anti-viral, anti-bacterial and tonifying the immune response, the underlying mechanism(s) by which these effects are induced remains unclear. RESULTS: Here, we report that SB displays anti-inflammatory effects in a zymosan-induced mouse air-pouch model by reducing the expression of nitric oxide (NO), inducible NOS (iNOS), Cyclooxygenase2 (COX-2), Prostaglandin E2 (PGE2), Nuclear Factor-kappaB (NF-kappaB) and IkappaBalpha as well as inflammatory cytokines, such as IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha. In a similar manner, SB also reduced the production of nitric oxide, PGE2, IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha, by decreasing the expression of iNOS, COX-2, IkappaB kinase alphabeta (IKKalphabeta) phosphorylation, IkappaBalpha and IkappaBalpha phosphorylation in LPS-treated Raw 264.7 cells. Additionally, SB interfered with the nuclear translocation of NF-kappaB p65 and p50, resulting in NF-kappaB-dependent transcriptional repression. We further demonstrate that SB attenuated the activity of c-Raf-1/MEK1/2, Erk1/2, p38 and JNK phosphorylation in LPS-treated Raw 264.7 cells. CONCLUSIONS: Taken together, these results confirm the strong anti-inflammatory properties of SB by inhibition of iNOS, COX-2, PGE2, IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha expression. This was achieved through the down-regulation of IKKalphabeta, IkappaBalpha, NF-kappaB activation via suppression of c-Raf-1/MEK1/2 (Mitogen-activated protein kinase/ERK kinase) and MAP kinase phosphorylation in the zymosan-induced mice air-pouch and Raw 264.7 cells. These results support the use of SB herbs for its potent anti-inflammatory activity.