Protectin DX attenuates IL-1ß-induced inflammation via the AMPK/NF-κB pathway in chondrocytes and ameliorates osteoarthritis progression in a rat model.

Protectin DX (PDX) has been reported to have extensive anti-inflammatory effects. However, it is unknown whether PDX acts as an anti-inflammatory agent in the context of osteoarthritis (OA). This study aimed to evaluate the anti-inflammatory activity of PDX in vitro and in vivo in a model of OA. Primary rat chondrocytes were preincubated with PDX 1 h prior to IL-1ß treatment for 24 h. We found that PDX was nontoxic, and pretreatment with PDX increased cell viability in IL-1ß-induced chondrocytes. Preincubation with PDX also efficiently inhibited the degradation of type II collagen dose-dependently. Additionally, the expression of MMP-3, MMP-13, ADAMTS4, iNOS, COX-2, NO, and PGE2 decreased after IL-1ß stimulation when cells were preincubated with PDX. Moreover, PDX inhibited the increase in phosphorylated NF-κB p65 and IκBα upon IL-1ß stimulation, and the negative effects of IL-1ß on chondrocytes were partially blocked by treatment with pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor. In addition, we found that PDX increased AMPK phosphorylation in IL-1ß-mediated chondrocytes. The phosphorylation of AMPK could be inhibited by compound C, a classic AMPK inhibitor. Compound C also remarkably reversed the decrease in p65 phosphorylation and MMP-13 expression caused by PDX. Furthermore, nuclear translocation of NF-κB was visible by immunofluorescence after PDX-induced AMPK activation. Additionally, we verified that PDX ameliorated cartilage degradation in monosodium iodoacetate (MIA)-induced OA rats through histological evaluation and ELISA of TNF-α in the serum and intra-articular lavage fluid. In conclusion, we have shown that PDX suppresses inflammation in chondrocytes in vitro and in vivo, likely through the AMPK/NF-κB signaling pathway. Our results suggest that PDX could be a useful novel therapeutic agent for OA treatment.

Comparison of therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis.

OBJECTIVE: To compare the therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis to provide a basis for clinical practice. METHODS: Data from 83 patients with rheumatoid arthritis undergoing total knee arthroplasty were retrospectively analyzed. The 83 patients were divided into a drainage blood reinfusion group (DR group, n = 45) and a temporary clamping drainage group (CD group, n = 38). In the DR group, postoperative drainage blood was used for autotransfusion. In the CD group, closed drainage was adopted, and the drainage tube was clamped for 2 h postoperatively followed by patency. The postoperative drainage amount, hemoglobin level, rate and average volume of allogeneic blood transfusion, swelling and ecchymosis of the affected knee joint, time to straight-leg raising and range of active knee flexion were compared between the two groups. RESULTS: The total drainage volume was higher in the DR group than in the CD group (P = 0.000). The average volume of postoperative allogeneic blood transfusion (P = 0.000) and the decrease in the hemoglobin level 24 h after total knee arthroplasty (P = 0.012) were lower in the DR group than in the CD group. Swelling and ecchymosis of the affected knee joint, time to straight-leg raising and the range of active knee flexion were improved in the DR group compared with the CD group (all P<0.05). CONCLUSION: Compared with temporary clamping drainage, drainage blood reinfusion after total knee arthroplasty can reduce the allogeneic blood transfusion volume and is conducive to early rehabilitation in patients with rheumatoid arthritis.

Anti-inflammatory effects of Z-ligustilide nanoemulsion.

The Z-ligustilide (LIG) was studied for its anti-inflammatory activities with prepared LIG nanoemulsions (LIGNE). Healthy male adult Wistar rats were used in the study. Endotoxin-induced uveitis (EIU) was induced by a footpad injection of 200 µg lipopolysaccharide. EIU rats were administered orally with saline, LIG (20 mg/kg/day), and LIGNE (20 mg LIG /kg/day), respectively. Twenty-four hours later, rats were euthanized, and blood was collected from either right marginal ear vein to estimate inflammatory cells and inflammatory mediators. The drug dissolution profiles of LIGNE in both phosphate buffer pH 6.8 and 0.1 N HCl showed complete dissolution within 20 min. Pharmacokinetic studies suggested a significant increase (P < 0.0001) in the C pmax and AUC0→24 h were observed in the LIGNE group when compared with the LIG group. LIGNE significantly reduced the levels of tumor necrosis factor alpha, interleukin 1 beta, vascular endothelial growth factor alpha, and interleukin-17. The anti-inflammatory animal testing revealed that LIGNE led to an improvement in oral bioavailability.