RESUMEN
The present study explored the beneficial effect of Dendrobium huoshanense stem polysaccharide (cDHPS) after oral administration on rheumatoid arthritis (RA) using type â ¡ collagen-induced arthritis (CIA) mouse model. It was found that cDHPS effectively alleviated joint swelling, synovial hyperplasia, pannus formation, cartilage erosion and bone destruction in CIA mice. Concurrently, cDHPS remodeled the balance of Th17 and regulatory T cells, reduced the secretion of pro-inflammatory mediators related to fibroblast-like synoviocyte activation, angiogenesis, articular cartilage degradation and osteoclast differentiation, inhibited HIF-1α expression and promoted anti-inflammatory mediator release in the joint tissues and serum of CIA mice. Western blot of joint tissues showed that cDHPS significantly inhibited the phosphorylation of IκB, p65, JNK, p38, ERK1/2, AKT, PI3K, JAK1 and STAT3 in CIA mice. These results suggest that cDHPS possesses the potential of ameliorating RA and its anti-RA effect may be attributed to the inhibition of inflammatory signaling pathways.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Cartílago Articular/metabolismo , Dendrobium/metabolismo , Polisacáridos/química , Animales , Antiinflamatorios/farmacología , Artritis Experimental/metabolismo , Diferenciación Celular , Colágeno/química , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Inflamación , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos DBA , Fosforilación , Extractos Vegetales/farmacología , Polisacáridos/metabolismo , Transducción de Señal , Sinoviocitos/metabolismo , Linfocitos T Reguladores/citología , Células Th17/citología , Microtomografía por Rayos XRESUMEN
Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells is a pleiotropic hormone with beneficial potential related to islet function, diet control, glucose homeostasis, inflammation relief, and cardiovascular protection. The present study aimed at investigating the effect of Polygonatum cyrtonema polysaccharide (PCP) after structural identification on GLP-1 secretion and the possible mechanism involved in the PCP-stimulated secretion of GLP-1. It was found that GLP-1 secretion was effectively promoted (p < 0.01) by PCP both in rats with oral administration for 5 weeks (13.9 ± 0.3-35.8 ± 0.3 pmol/L) and ileal administration within 2 h (13.6 ± 0.4-34.1 ± 1.1 pmol/L) and in enteroendocrine NCI-H716 cells with direct stimulation within 24 h (2.05 ± 0.3-20.7 ± 0.2 pmol/L). The sweet taste receptor T1R2/T1R3 was identified to be essential for NCI-H716 cells to directly recognize PCP. The intervention experiments showed that PCP-stimulated GLP-1 secretion was significantly depressed (p < 0.01) not only by antibodies, siRNA, and the inhibitor of T1R2/T1R3 but also by an adenylate cyclase inhibitor. These results suggest that PCP stimulates GLP-1 secretion from enteroendocrine cells possibly through activation of the T1R2/T1R3-mediated cAMP signaling pathway.