ABSTRACT
Diabetic nephropathy (DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae (Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin (STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated withUmb (20, 40 mg·kg) orirbesartan (15 mg·kg) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides (TG) and total cholesterol (TC) were measured bycommercial assay kits, respectively. Histopathological changes andinflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine, and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β). These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.
ABSTRACT
Rheumatoid arthritis (RA) is the most common inflammatory arthritis and a major cause of disability. Presently, the clinical therapeutic medicines for inflammatory and arthritic diseases are unsatisfactory due to severe adverse effects or ineffectiveness. The Guge Fengtong formula (GGFT), containing the standardized extracts of Dioscoreae Nipponicae Rhizoma, Spatholobi Caulis, and Zingiberis Rhizoma, has long been used for RA treatment by Chinese doctorsin China. However, the detailed anti-inflammatory and anti-arthritic activity of GGFT has not been reported so far. In the present work, we aimed to evaluate the anti-inflammatory and anti-arthritic effects of GGFT using three in vivo animal models, and tried to uncover its preliminarythe underlying mechanism of action mechanism in RAW 264.7 macrophages. The obtained results indicated that GGFT significantly attenuated ear edema, decreased carrageenan-induced paw edema, reduced the arthritis score, and reversed the weight loss of the complete Freund's adjuvant (CFA)CFA-injected rats. Additionally, marked decrease of in synovial inflammatory infiltration and synovial lining hyperplasia in the joints and decline of inflammatory factors (TNF-α and IL-1β) in the serum were observed in the GGFT-treated rats. In lipopolysaccharide-activated RAW264.7 macrophages, GGFT reduced the production of NO, PGE2, and IL-6, and inhibited the expression of iNOS, COX-2, and NF-κB expression. Our results demonstrated that GGFT possessed considerable anti-inflammatory activity and have had potential therapeutic effects on adjuvant induced arthritis in rats, which provided providing experimental evidences for its traditional application in the treatment of RA and other inflammatory diseases.