ABSTRACT
Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.
ABSTRACT
Aim To observe the therapeutic effect of Pterocarya hupehensis Skan ethanol extract ( PHSEE ) on CIA model of SL) rats and to explore the mechanism of anti-inflammation and pro-apoptosis. Methods After the CIA model was established, the body weight, paw swelling rate, as well as arthritis index were recorded every 7 days. The rats were continuously fed with PI ISEE or TG for 28 days. The pathological changes of knee joint synovial membrane were observed in each group, while the apoptotic synoviocytes were evaluated by TUNEL assay. The changes of TNF-c∗, IL-lp, ALT, AST, BUN and SCr in the serum were tested by ELISA. And the expressions of NF-kB p65 phosphorylation ( p-p65 ) , cleaved caspase-3, Bcl-2 and Bax in the synovial tissue protein of the knee joint were detected by Western blot. Results Compared with model group, the paw swelling rate and arthritis index decreased in TG and PHSEE-lreated groups with statistical significance ( /' eulic efficacy on CIA rat. The mechanism may be related to down-regulating the expression of inflammatory cytokines and inducing apoptosis of synovial cells. At the same time, the extract can improve impaired liver and kidney function in CIA rats.
ABSTRACT
Rheumatoid arthritis (RA) is a multifactorial disease and requires interaction between genetic and environmental factors for predisposition. The presence of bacterial DNA of the gut residing commensals in synovium as well as dysbiosis of certain commensal bacteria in faecal samples of RA patients as compared to controls suggest a significant role of the gut flora in pathogenesis of RA. The gut commensals are involved in host immune development and function suggesting they might be critical epigenetic factors modifying autoimmune diseases like RA. This raises the question if gut-derived commensal can be exploited to generate a biomarker profile along with genetic factors to define individuals at risk. Genomic wide association studies have confirmed the HLA (human leukocyte antigen) class II genes as the strongest risk factor for predisposition to RA. HLA-DQ8 and DRB1*0401 molecules predispose to develop arthritis while DRB1*0402 provides protection. Interaction between host genetic factors like major histocompatibility complex (MHC) and gut microbiota and its impact on the development of RA is difficult to study in humans due to high variability in the genetic factors and diet. Animal models provide a means to study the molecular basis of pathogenesis thereby providing a basis for developing therapeutic strategies. Using transgenic mice expressing RA-associated and resistant HLA genes, we have developed a collagen-induced arthritis (CIA) model that shares similarities with human disease in sex-bias, autoantibody profile and phenotype. Studies in transgenic mice suggest that arthritis-susceptibility may be associated with dysbiosis in the gut microbiome. Studies in animal models underscore the impact of the gut flora in extra-intestinal diseases. Exploring the role of gut microbes will significantly advance our understanding of RA pathogenesis and may further help develop strategies for mucosal modulation of RA.