| Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint swelling, synovial membrane inflammation, and cartilage destruction. Up to date, the etiology of RA is not fully understood. Although there are a few anti-rheumatic drugs showing effectiveness on treating RA, their side effects and toxicity call for new and more effective natural drugs. Chaenomeles speciosa (sweet) Nakai is one of the valuable traditional herbs used in treatment for RA with a long history in traditional Chinese medicine. Glucosides of Chaenomeles speciosa (GCS), extracted from the fructus of Chaenomeles speciosa,, is an active compound. Previous studies from our laboratory showed that GCS possesses anti-inflammatory and analgesic properties. However, it is unknown whether or how GCS exerts its effect on the chronic autoimmune diseases such as RA. The present study was therefore designed to investigate the prophylactic and therapeutic effects of GCS on adjuvant arthritis (AA) of rat and its relative mechanisms by which GCS affected the synovial cells function of AA, especially on the signal transduction of G protein-adenylate cyclase (AC)-cyclic adenosine monophosphate (cAMP) of synoviocytes.AIM According to the changes of secondary paw swelling, pain response, polyarthritis, body weight, and histological morphological of rat AA, this study tends to clarify prophylactic and therapeutic effects of GCS on rat AA. We attempted to extend our understanding in the roles of GCS playing in hemorheology and immune functions. Meanwhile, Our study aimed to investigat effects of GCS on the ultrastructural changesof synoviocytes, the ultimate effectual cells of pathologic change, contributed to its secretory function which was related to the over-production of proimflammatory cytokines. To confirm the actions of GCS, this study sought to indentify relationships between the effects of GCS on rat AA and its relative mechanisms by which GCS affected the process of synoviocytes through G protein-AC-cAMP signal transduction pathway.METHODS Freund's Complete adjuvant(FCA) was used to induce AA in rats. Prophylactic treatment of intragastric administration with GCS (30, 60, 120 mg kg-1 d-1, d 7~d 14) and therapeutic treatment of intragastric administration with GCS (30, 60, 120 mg kg-1 d-1, d 17~d 24) were given after immunization. Actarit, TGP were given as positive control.Secondary paw swelling of AA rats was measured with volume meter. The pain response and polyarthritis index were scored. The blood viscosity was determined by hemorrheology instrument. Hematocrit of red blood cell was determined by the way of centrifugal deposit. The clotting time was determined by capillary. At the same time, the body weight and immune organs (thymus and spleen ) weight were assayed. ConA-induced T lymphocyte proliferation was assayed by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Interleukin-2 (IL-2) production was measured by using the activated mouse splenocytes proliferation assay. IL-1 activity of peritoneal macrophages (PM ) was measured by ConA-induced thymocyte proliferation of C57BL/6J mice assay. Tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) production of PM were determined by radioimmunoassay.Synovial cells from rat knees were excised and dispersed with sequential incubation of collagenase type II and trypsin. Fibroblast-like synovocytes were derivedfrom explant culture of tissue fragment of AA rats. Morphological changes of Synovial cells were observed by transmission electron microscope. The proliferation of fibroblast-like synoviocytes was assayed using the MTT assay. IL-1, TNFa, and PGE2 activity of supernants of cultured synoviocytes were examined by thymocyte proliferation assay and radioimmunoassay. cAMP level were examined by radioimmunoassay. mRNA expression of Gi, Gs, and TNFa were determined by reverse transcription polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay.RESULTS1. GCS had prophylactic and therapeutic effects on rat... |
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