peoniflorin and Lupus-Erythematosus--Systemic

The activation of macrophages and the release of inflammatory cytokines are the main reasons for the progress of systemic lupus erythematosus (SLE). MicroRNA (miRNA)-124 is involved in the regulation of macrophages and is a key regulator of inflammation and immunity.. To explore whether paeoniflorin (PF) regulates the biological functions of macrophages depends on miR-124.. RT-PCR, WB, ELISA, CCK-8 and flow cytometry were used to evaluate that PF regulated the biological functions of THP-1 cells through miR-124.. PF significantly inhibited the proliferation while promotes the apoptosis of THP-1 cells, and inhibited the release of IL-6, TNF-α and IL-1βin THP-1 cells. RT-PCR results shown that PF up-regulated the expression of miR-124 in THP-1 cells. Functional recovery experiments showed that compared with the LPS + mimic-NC group, LPS + miR-124 mimic significantly inhibited the proliferation and the release of IL-6, TNF-α and IL-1β, but promoted the apoptosis of THP-1 cells. In addition, compared with the LPS + PF + inhibitor-NC group, LPS + PF + miR-124 inhibitor significantly promoted the proliferation and the release of IL-6, TNF-α and IL-1β, but inhibited the apoptosis of THP-1 cells.. By down-regulating miR-124, PF inhibits the proliferation and inflammation of THP-1 cells, and promotes the apoptosis of THP-1 cells.

Topics: Apoptosis; Cell Proliferation; Flow Cytometry; Gene Expression Regulation, Neoplastic; Glucosides; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Lupus Erythematosus, Systemic; Macrophages; MicroRNAs; Monoterpenes; Signal Transduction; Transcriptional Activation; Tumor Necrosis Factor-alpha

The present study was to evaluate the effects of paeoniflorin (PA) on systemic lupus erythematosus induced depressive behaviors. 10 wild type mice and 20 MRL/lpr mice were applied for the research. The animals were randomly assigned to wild type, MRL/lpr group and MRL/lpr + PA group. PA restored depressive-like behaviors, such as sucrose consumption, immobile time in the tail suspension tests (TST) and forced swimming tests (FST). PA significantly decreased the levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) in serum and hippocampus of MRL/lpr mice. Western blot results demonstrated PA inhibited the levels of HMGB1/TLR4/NF-κB pathway. The findings showed that PA was beneficial for the prevention of systemic lupus erythematosus induced depressive behaviors, which possibly by suppressing HMGB1/TLR4/NF-κB pathway.

Topics: Animals; Behavior, Animal; Depression; Glucosides; Hindlimb Suspension; Hippocampus; HMGB1 Protein; Interleukin-1beta; Interleukin-6; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred MRL lpr; Monoterpenes; NF-kappa B; Sucrose; Swimming; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

To investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model.. Ten wild type mice and 40 MRL/lpr mice were used in this study. MRL/lpr mice were randomly assigned to MRL/lpr group,MRL/lpr + dexamethasone (1.5 mg/kg) group,MRL/lpr + paeoniflorin (20 mg/kg) group,and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde (MDA) , superoxide dismutase (SOD) ,catalase (CAT) ,glutathione peroxidase (GSH-Px) in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K),phospho-serine-threonine kinase B(P-Akt) ,phospho-nuclear factor kappa B (P-NF-κB),phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot.. Paeoniflorin decreased serum level of MDA and increased the levels of SOD,CAT,GSH-PX,and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K,P-Akt,P-NF-κBp65,and P-IκBα in the lung tissue of MRL/lpr mice.. Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.

Topics: Animals; Glucosides; Lung Injury; Lupus Erythematosus, Systemic; Mice; Mice, Inbred MRL lpr; Monoterpenes

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disease. Interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans and paeoniflorin has recently been reported to exhibit immunosuppressive properties. The aim of this study was to determine the effect of paeoniflorin on lipopolysaccharide (LPS)-triggered macrophage activation and and its role in LPS-induced IRAK1-nuclear factor κB (NF-κB) signaling pathways. Peritoneal macrophages from lupus-prone MRL/lpr mice and ICR mice were isolated, prepared and cultured. Cells were treated with LPS alone or LPS with paeoniflorin, and macrophage proliferation was analyzed using the CCK8 assay. The expression of IRAK1 in cells was analyzed by immunofluorescence staining. The level of gene expression of IRAK1, NF-κB, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by RT-PCR, and TNF-α, IL-6 levels in the cell supernatant were determined by ELISA. The protein expression of IRAK1 and downstream molecules tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase (IKK), NF-kappa-B inhibitor alpha (IKBα), and NF-κB was detected by Western-blot analysis. Paeoniflorin was found to decrease the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of TNF-α and IL-6. Taken together, the data obtained indicate that paeoniflorin inhibits LPS-induced cell activation by inhibiting the IRAK1-NF-κB pathway in MRL/lpr mouse macrophages. Therefore, paeoniflorin may be a potential therapy for SLE.

Topics: Animals; Drugs, Chinese Herbal; Female; Glucosides; Humans; Interleukin-1 Receptor-Associated Kinases; Lupus Erythematosus, Systemic; Macrophages, Peritoneal; Mice; Mice, Inbred MRL lpr; Monoterpenes; NF-kappa B; Paeonia; Plant Roots; Signal Transduction; TNF Receptor-Associated Factor 6; Tumor Necrosis Factor-alpha