RESUMO
BACKGROUND: The root of Angelica sinensis (AS), also known as "Dang-gui," was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time. This study aimed to determine the effects of ethyl acetate fraction from Angelica sinensis (EAAS) on the interleukin-1ß (IL-1ß)-induced proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) 2, and prostaglandin E2 (PGE2), involved in articular bone and cartilage destruction, by RASFs. RESULTS: RASF proliferation was evaluated with cholecystokinin octapeptide (CCK-8) reagent in the presence of IL-1ß with/without EAAS. Expression of MMPs, tissue inhibitor of metalloproteinases-1 (TIMP-1), COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signaling molecules, including p-ERK, p-p38, p-JNK, and NF-κB, were examined using immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. EAAS inhibited IL-1ß-induced RASF proliferation; MMP-1, MMP-3, and COX-2 mRNA and protein expressions; and PGE2 production. EAAS also inhibits the phosphorylation of ERK-1/2, p38, and JNK, and activation of NF-κB by IL-1ß. CONCLUSION: EAAS might be a new therapeutic modality for rheumatoid arthritis management.
Assuntos
Humanos , Artrite Reumatoide/metabolismo , Bolsa Sinovial/citologia , Mediadores da Inflamação/metabolismo , Angelica sinensis/química , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Artrite Reumatoide/patologia , Proteínas Recombinantes/farmacologia , Ensaio de Imunoadsorção Enzimática , Extratos Vegetais/farmacologia , Dinoprostona/metabolismo , Immunoblotting , NF-kappa B/efeitos dos fármacos , Raízes de Plantas/química , Metaloproteinases da Matriz/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Medicina Herbária , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Interleucina-1beta/farmacologia , Cultura Primária de Células , Reação em Cadeia da Polimerase em Tempo Real , Fibroblastos/citologia , Fibroblastos/metabolismo , Citometria de Fluxo , Articulação do Joelho/citologia , AcetatosRESUMO
BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.
Assuntos
Animais , Masculino , Ratos , Anti-Inflamatórios não Esteroides/efeitos adversos , Araquidonato 5-Lipoxigenase/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/efeitos dos fármacos , Ciclo-Oxigenase 1/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Modelos Animais de Doenças , Mucosa Gástrica/química , Fosfolipases A2 do Grupo IV/efeitos dos fármacos , Momordica/química , Peroxidase/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Sementes/química , Úlcera Gástrica/induzido quimicamente , Resultado do TratamentoRESUMO
Lung cancer is one of the leading causes of cancer related death in most developed and many developing countries of the world. Due to lack of validated screening methods and poor prognosis, treatment of lung cancer has not improved significantly over the last two decades. Therefore the risk of the disease needs to be minimized by preventive measures. One approach for lung cancer prevention envisages reversal or restriction of precancerous lesions by chemopreventive intervention. It demands a deeper understanding of the pathogenesis of the disease and identification of the ideal point of intervention. In the present investigation, tea components, epigallocatechin gallate (EGCG) and theaflavins (TF) were assessed for their chemopreventive potential when administered in the post initiation phase of lung carcinogenesis in an experimental mouse model. Histopathological changes in lungs of mice administered benzo(a)pyrene (BP) were followed serially and correlated with the expression of Cox-2, caspase-3 and caspase-7, which play key roles in histopathogenesis of neoplasia. The observations strongly indicate that both EGCG and TF can influence the expression of these genes to modulate the process of carcinogenesis, resulting in delayed onset and lowered incidence of pre-invasive lung lesions.