Anti-inflammatory effects of traditional mixed extract of medicinal herbs (MEMH) on monosodium urate crystal-induced gouty arthritis.

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs (MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate (MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mRNA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaOS-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators (IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mRNA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.

Nam JS ，Jagga S ，Sharma AR ，Lee JH ，Park JB ，Jung JS ，Lee SS ... -  《-》

Efficacy of Xixiancao (Herba Siegesbeckiae Orientalis) on interactions between nuclear factor kappa-B and inflammatory cytokines in inflammatory reactions of rat synovial cells induced by sodium urate.

Wang Z ，Fan X ，Xu Y ，Chen K ，Yu X ，Sun G ... -  《-》

Dolichos falcata Klein attenuated the inflammation induced by monosodium urate crystals in vivo and in vitro.

Dolichos falcata Klein (DF), a Chinese Dai ethnic medicine popularly known as "Tuoyeteng" in Yunnan province of China, has been widely used as a traditional herbal medicine for the treatment of fracture and beriberoid disease for a long time in China. The present study was carried out to investigate the anti-inflammatory activity and the bioactive chemical constituents of DF, and further to assess its possible mechanism on gouty arthritis in an animal model of the MSU crystals-induced gouty inflammation. The ethanol extract (EE) of DF at the doses of 10, 20 and 40 mg/kg was administered to the rats treated with MSU crystals to evaluate the anti-gouty arthritis effect. Subsequently, the components of EE were isolated and identified using classical methods. Phyto-chemical analysis of EE was further carried out by HPLC-DAD. Finally, the anti-inflammatory effect of EE and two isolated components were assessed using the MSU crystals-treated monocyte/macrophage cell line RAW 264.7 in vitro. EE (10, 20 and 40 mg/kg) significantly attenuated the pain threshold value, the joint swelling degree, the inflammatory cell infiltration of articular tissue and the increased levels of pro-inflammatory cytokines in MSU crystals-treated rats. Moreover, doliroside A (DA) and medicagenic acid-3-O-β-D-glucopyranoside (MG) were isolated and identified from EE. The major components of EE, including DA, MG and other triterpenoids, were well confirmed by HPLC. A further study revealed that EE, DA and MG (10, 20, 40μg/mL) exhibited stronger inhibitory effects on the production of pro-inflammatory cytokines (including interleukin-1β, interleukin-6 and tumor necrosis factor-α) in MSU crystals-treated RAW 264.7 cells. These findings indicate that the major triterpenoids present in DF have a remarkable effect on improving symptoms of acute gouty arthritis induced by MSU crystals through inhibiting the production of pro-inflammatory cytokines.

Chen L ，Mola M ，Deng X ，Mei Z ，Huang X ，Shu G ，Wei L ，Hou X ，Lan Z ，Lin Q ... -  《-》

Curcumin ameliorates monosodium urate-induced gouty arthritis through Nod-like receptor 3 inflammasome mediation via inhibiting nuclear factor-kappa B signaling.

Monosodium urate (MSU) crystals-induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti-inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive. We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals-stimulated cells were collected and subjected to enzyme-linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod-like receptor 3 (NLRP3) inflammasome/nuclear factor-kappa B (NF-κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU-induced gouty arthritis rat models. Curcumin could reduce MSU crystals-induced IL-1β and TNF-α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase-1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU-induced NF-κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU-induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL-1β, TNF-α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β were downregulated by curcumin in vivo. These results indicated that curcumin could effectively ameliorate MSU crystal-induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF-κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis.

Li X ，Xu DQ ，Sun DY ，Zhang T ，He X ，Xiao DM ... -  《-》

Doliroside A attenuates monosodium urate crystals-induced inflammation by targeting NLRP3 inflammasome.

Our previous study demonstrates that Dolichos falcata Klein (DF) ameliorates the gouty arthritis induced by monosodium urate (MSU) crystals, and one of the active components, doliroside A, contributed to the anti-gouty arthritis effect of DF according to the in vitro study. However, there is still little known about the potential beneficial effects and possible mechanism of action of doliroside A on gouty arthritis. Here, we investigated the underlying mechanism of action of doliroside A in vitro and the anti-inflammatory effects of doliroside A in vivo. Bone-marrow-derived macrophages were treated with doliroside A before or after lipopolysaccharide (LPS) and then stimulated with MSU crystals, nigericin and adenosine triphosphate (ATP). The expressions of proteins related to activation of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome were analyzed. The results manifested that doliroside A (15, 30, 45 and 60 μM) suppressed both LPS-induced priming and inflammasome activation in macrophages. Moreover, doliroside A was administered to the rats treated by MSU crystals. The results demonstrated that doliroside A (10, 20 and 40 mg/kg) ameliorated the symptoms of gouty arthritis, decreased the levels of pro-inflammatory cytokines, and inhibited the expressions of caspase-1 and pro-interleukin-1β (pro-IL-1β) proteins in MSU crystals-treated rats. These findings indicate that doliroside A exhibits a prominent effect on ameliorating gouty arthritis induced by MSU crystals. The action of doliroside A on gouty arthritis exerts via inhibiting the activation of caspase-1 and IL-1β secretion by affecting both LPS-induced priming and inflammasome activation.

Wei H ，Hu C ，Xie J ，Yang C ，Zhao Y ，Guo Y ，Mei Z ，Chen L ，Lan Z ... -  《-》