RESUMEN
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.
Asunto(s)
Animales , Masculino , Ratas , Antiinflamatorios no Esteroideos/efectos adversos , Araquidonato 5-Lipooxigenasa/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/efectos de los fármacos , Ciclooxigenasa 1/efectos de los fármacos , Ciclooxigenasa 2/efectos de los fármacos , Modelos Animales de Enfermedad , Mucosa Gástrica/química , Fosfolipasas A2 Grupo IV/efectos de los fármacos , Momordica/química , Peroxidasa/efectos de los fármacos , Extractos Vegetales/farmacología , Ratas Sprague-Dawley , Semillas/química , Úlcera Gástrica/inducido químicamente , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Humanos , Artritis Reumatoide/metabolismo , Bolsa Sinovial/citología , Mediadores de Inflamación/metabolismo , Angelica sinensis/química , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Artritis Reumatoide/patología , Proteínas Recombinantes/farmacología , Ensayo de Inmunoadsorción Enzimática , Extractos Vegetales/farmacología , Dinoprostona/metabolismo , Immunoblotting , FN-kappa B/efectos de los fármacos , Raíces de Plantas/química , Metaloproteinasas de la Matriz/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Medicina de Hierbas , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Interleucina-1beta/farmacología , Cultivo Primario de Células , Reacción en Cadena en Tiempo Real de la Polimerasa , Fibroblastos/citología , Fibroblastos/metabolismo , Citometría de Flujo , Articulación de la Rodilla/citología , AcetatosRESUMEN
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.