scholarly journals Inhibition of Rheumatoid Arthritis Using Bark, Leaf, and Male Flower Extracts of Eucommia ulmoides

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yun-Yun Xing ◽  
Jian-Ying Wang ◽  
Kai Wang ◽  
Yan Zhang ◽  
Kun Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Male Flower ◽  
Joint Inflammation ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Eucommia Ulmoides

Eucommia ulmoides Oliv., a native Chinese plant species, has been used as a traditional Chinese medicine formulation to treat rheumatoid arthritis (RA), strengthen bones and muscles, and lower blood pressure. Various parts of this plant such as the bark, leaves, and flowers have been found to have anti-inflammatory properties. E. ulmoides has potential applications as a therapeutic agent against bone disorders, which were investigated in this study. In vitro, RA joint fibroblast-like synoviocytes (RA-FLS) were treated with different concentrations (0, 25, 50, 100, 200, 400, 800, and 1000 μg/mL) of E. ulmoides bark, leaf, and male flower alcoholic extracts (EB, EL, and EF, respectively) to determine their potential cytotoxicity. Tumor necrosis factor- (TNF-) α and nitric oxide (NO) levels in RA-FLS were quantified using enzyme-linked immunosorbent assay (ELISA). Furthermore, collagen-induced arthritis (CIA) rats were treated with EB, EL, EF, Tripterygium wilfordii polyglycoside (TG) or the normal control (Nor), and then ankle joint pathology, bone morphology, and serum and spleen inflammatory cytokine levels were evaluated. The results showed that, in RA-FLS, EB, EL, and EF were not cytotoxic; EB and EF reduced TNF-α supernatant levels; and EB, EL, and EF reduced NO levels. The results of in vivo experiments showed that EB, EL, and EF alleviated ankle swelling and joint inflammation, while all extracts diminished inflammatory cell infiltration, pannus and bone destruction, and bone erosion. All tested extracts inhibited interleukin- (IL-) 6, IL-17, and TNF-α mRNA in the spleen of CIA rats, while EB most effectively reduced osteoclasts and inhibited bone erosion. EF showed the most obvious inhibition of inflammatory factors and pannus. Thus, EB, EL, and EF may alleviate bone destruction by inhibiting inflammation.

scholarly journals Knockdown adiponectin receptor 1 expression in synovial tissue alleviate the progression of collagen-induced arthritis

2019 ◽  
Author(s):  
Yani Wang ◽  
Rui Liu ◽  
Pengfei Zhao ◽  
Qian Zhang ◽  
Yingheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Bone Erosion ◽  
Adiponectin Receptor ◽  
Inflammatory Factors ◽  
Nuclear Factor ◽  
Collagen Induced Arthritis ◽  
Adiponectin Receptor 1 ◽  
Receptor Activator

Abstract Background: Previous studies have shown that adiponectin (APN) is involved in the pathogenesis of rheumatoid arthritis (RA). The proinflammatory effect of APN is mainly mediated adiponectin receptor 1 (AdipoR1). The high expression of AdipoR1 have been suggested in RA synovial tissue. This study was aimed to investigate the effects of AdipoR1 in inflammation and bone erosion in collagen-induced arthritis (CIA) mice, and to further explore the underlying mechanisms. Methods: The expression of APN and AdipoR1 in synovial tissue of RA and osteoarthritis (OA) patient was tested by qPCR and western blot. RA synovial fibroblasts (RASFs) were stimulated with APN, IL-6 or TNF-α respectively. The expression of AdipoR1 on RASFs were tested by flow cytometry. To prove the pathogenic role, AdipoR1 was silenced in a human rheumatoid arthritis synovial fibroblast cell line (MH7A) and local joint of CIA mice by specific short hairpin RNAs (shRNAs) using a lentiviral delivery system. The levels of proliferation, apoptosis and inflammatory factors on MH7A were assessed in vitro. Local AdipoR1 knockdown on CIA mice were further estimated by arthritis clinical scores, inflammatory cytokine expression, micro-CT, H&E staining and receptor activator of nuclear factor к B ligand (RANKL) / osteoprotegerin (OPG) in vivo. Results: We found that the levels of APN and AdipoR1 expression were significantly higher in RASFs and the expression of AdipoR1 was upregulated by APN in RASFs. Silencing AdipoR1 could effectively reduce lipopolysaccharides (LPS) induced proliferation of MH7A cells, promote their apoptosis, and reduce the release of inflammatory factors. In CIA mice, local silencing AdipoR1 in arthritis markedly reduced joint inflammation and alleviated bone erosion and osteoporosis in vivo. Furthermore, local silencing AdipoR1 inhibited receptor activator of nuclear factor к B ligand (RANKL) expression and decreased RANKL / osteoprotegerin (OPG) ratio in knees and ankles of CIA mice. Conclusions: This study suggests that AdipoR1 plays a key role in the development of RA and silencing AdipoR1 might be a new target for the clinical treatment of RA.

scholarly journals Hordenine Protects Against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiyue Zhang ◽  
Li Du ◽  
Jinrong Zhang ◽  
Chunyan Li ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Protein Kinase ◽  
Lung Injury ◽  
Biological Activities ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Anti Inflammatory

Acute lung injury (ALI) is a respiratory disease that leads to death in severe cases. Hordenine (Hor), a barley-derived natural product, has various biological activities, including anti-inflammatory, and anti-oxidation activities. We investigated the effect of Hor on lipopolysaccharide-induced ALI and its potential mechanism. The anti-inflammatory effects of Hor were detected using in vivo and in vitro models by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blotting, and molecular docking simulations. Hor inhibited increases in the levels of inflammatory factors both in vivo and in vitro, and its anti-inflammatory effect inhibited activation of protein kinase B, nuclear factor-κB, and mitogen-activated protein kinase signaling. Hor alleviated lipopolysaccharide-induced ALI by inhibiting inflammatory cytokine increases in vivo and in vitro and shows potential for preventing inflammatory disease.

scholarly journals Pharmacological Effect ofCaulophyllum robustumon Collagen-Induced Arthritis and Regulation of Nitric Oxide, NF-κB, and Proinflammatory Cytokines In Vivo and In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Qiu-hong Wang ◽  
Shao-wa Lv ◽  
Yu-yan Guo ◽  
Ji-xin Duan ◽  
Shu-yu Dong ◽  
...  
Keyword(s):  
Membrane Damage ◽  
Clinical Score ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Collagen Induced Arthritis ◽  
Caulophyllum Robustum ◽  
Anti Inflammation ◽  
Gene Expression Levels

Caulophyllum robustumMaxim(C. robustum)has commonly been used as traditional Chinese medicine for the treatment of rheumatic pain and rheumatoid arthritis (RA) in China. This paper first investigated the anti-inflammation effect ofC. robustumextraction (CRME) on RAW264.7 cells stimulated by lipopolysaccharide (LPS) and gene expression levels of inflammatory factors. Moreover, we first evaluated the anti-RA effects of CRME using collagen-induced arthritis (CIA) in DBA/1J mice, and the incidence, clinical score, and joint histopathology were evaluated. The levels of IL-1, IL-6, TNF-α, and PGE2 inflammatory factors in sera of mice were detected by enzyme-linked immunosorbent assay. The expression of NF-κB p65 in the joint was tested by immune histochemical technique. The results showed that, compared with the model group, CRME significantly improved symptoms of the arthritis index, limb swelling, and histological findings by decreasing synovial membrane damage, the extent of inflammatory cell infiltration, and the expansion of capillaries in CIA mice. The results also showed that CRME can reduce the levels of IL-1, IL-6, TNF-α, and PGE2 and inhibit the expression of NF-κB p65. All these results indicated the anti-inflammatory efficacy of CRME as a novel botanical extraction for the treatment of RA.

scholarly journals ELMO1 Regulates RANKL-Stimulated Differentiation and Bone Resorption of Osteoclasts

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinyue Liang ◽  
Yafei Hou ◽  
Lijuan Han ◽  
Shuxiang Yu ◽  
Yunyun Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Small Gtpases ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Nucleotide Exchange

Bone homeostasis is a metabolic balance between the new bone formation by osteoblasts and old bone resorption by osteoclasts. Excessive osteoclastic bone resorption results in low bone mass, which is the major cause of bone diseases such as rheumatoid arthritis. Small GTPases Rac1 is a key regulator of osteoclast differentiation, but its exact mechanism is not fully understood. ELMO and DOCK proteins form complexes that function as guanine nucleotide exchange factors for Rac activation. Here, we report that ELMO1 plays an important role in differentiation and bone resorption of osteoclasts. Osteoclast precursors derived from bone marrow monocytes (BMMs) of Elmo1–/– mice display defective adhesion and migration during differentiation. The cells also have a reduced activation of Rac1, p38, JNK, and AKT in response to RANKL stimulation. Importantly, we show that bone erosion is alleviated in Elmo1–/– mice in a rheumatoid arthritis mouse model. Taken together, our results suggest that ELMO1, as a regulator of Rac1, regulates osteoclast differentiation and bone resorption both in vitro and in vivo.

scholarly journals Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis

Rheumatology ◽  
2020 ◽  
Author(s):  
Shixian Chen ◽  
Chunqing Guo ◽  
Ran Wang ◽  
Zhitao Feng ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Mouse Models ◽  
Th17 Cells ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Suppressor Cells ◽  
Th 17 ◽  
Autoimmune Conditions

Abstract Objectives While myeloid-derived suppressor cells (MDSCs) were previously shown to promote a proinflammatory T helper (Th) 17 response in autoimmune conditions, a potential impact of the MDSC-Th17 immune axis on abnormal bone destruction in RA remains largely unknown. Methods We investigated the correlation between the frequency of MDSCs or its subsets and joint destruction in RA patients. The reciprocal actions of patient-derived MDSCs and Th17 cells were studied using osteoclast (OC) differentiation and bone resorption assays in vitro, which were further validated using mouse models of RA. Contribution of MDSCs to osteoclastogenesis and bone erosion in vivo was determined by depletion or transfer of MDSCs. Results Human MDSCs, particularly monocytic MDSCs (M-MDSCs), exhibit inherent OC-differentiating capacity and positively correlate with clinical bone erosion in RA patients. Strikingly, patient-derived M-MDSCs can program Th17 cells towards a pro-osteoclastogenic phenotype, which in return potentiates OC differentiation via the receptor activator of nuclear factor κΒ ligand (RANK-L)-RANK signalling. This enhanced osteolysis driven by the reciprocal actions of M-MDSCs and Th17 cells is further confirmed using mouse models of RA. Selective depletion of M-MDSCs significantly ameliorates osteoclastogenesis and disease severity in arthritic mice, whereas transfer of M-MDSCs aggravates bone erosion associated with increased OCs in recipient mice. Conclusion Our findings highlight the functional plasticity of MDSCs and identify a novel pro-osteoclastogenic pathway governed by interplay between myeloid cells and T lymphocytes in autoimmune RA.

scholarly journals Inhibition of the IL-18 Receptor Signaling Pathway Ameliorates Disease in a Murine Model of Rheumatoid Arthritis

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 11 ◽  
Author(s):  
Yuji Nozaki ◽  
Jinhai Ri ◽  
Kenji Sakai ◽  
Kaoru Niki ◽  
Koji Kinoshita ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Bone Erosion ◽  
Quantitative Polymerase Chain Reaction ◽  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytokine Signaling ◽  
Pro Inflammatory Cytokines

Interleukin (IL)-18 expression in synovial tissue correlates with the severity of joint inflammation and the levels of pro-inflammatory cytokines. However, the role of the IL-18/IL-18 receptor-alpha (Rα) signaling pathway in autoimmune arthritis is unknown. Wild-type (WT) and IL-18Rα knockout (KO) mice were immunized with bovine type II collagen before the onset of arthritis induced by lipopolysaccharide injection. Disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum inflammatory cytokine and anticollagen antibody levels were quantified by an enzyme-linked immunosorbent assay. Joint cytokine and matrix metalloproteinases-3 levels were determined by a quantitative polymerase chain reaction. Splenic suppressors of cytokine signaling (SOCS) were determined by Western blot analysis as indices of systemic immunoresponse. IL-18Rα KO mice showed lower arthritis and histological scores in bone erosion and synovitis due to reductions in the infiltration of CD4+ T cells and F4/80+ cells and decreased serum IL-6, -18, TNF, and IFN-γ levels. The mRNA expression and protein levels of SOCS3 were significantly increased in the IL-18Rα KO mice. By an up-regulation of SOCS, pro-inflammatory cytokines were decreased through the IL-18/IL-18Rα signaling pathway. These results suggest that inhibitors of the IL-18/IL-18Rα signaling pathway could become new therapeutic agents for rheumatoid arthritis.

scholarly journals Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenghao Ren ◽  
Jie Jin ◽  
Wei Hu ◽  
Qi Chen ◽  
Jian Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Joint Disease ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Birch Bark ◽  
Necrosis Factor Alpha ◽  
Collagen Ii ◽  
Cox 2

Osteoarthritis (OA) is a common degenerative joint disease featuring the degeneration, destruction, and ossification of cartilage. Inflammation which may facilitate OA occurrence and development is considered as the main pathological factor. Betulin, a natural product extracted from birch bark, has been commonly used for inflammation treatment; however, its role in OA remains unclear. This study is aimed to explore whether betulin can suppress IL-1β–induced inflammation in chondrocytes and alleviate OA in vitro and in vivo. In in vitro studies, the generation of pro-inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), and nitric oxide (NO), was assessed using the enzyme-linked immunosorbent assay (ELISA) and Griess reaction. As revealed by results, betulin inhibited the expression of pro-inflammatory mediators. In addition, the protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP-13), thrombospondin motifs 5 (ADAMTS5), Collagen II, and Aggrecan were quantified using Western blot analysis. We found that betulin could inhibit the generation of COX-2 and iNOS induced by IL-1β, indicating that betulin has anti-inflammatory effects in chondrocytes. Furthermore, betulin downregulates the expression of MMP-13 and ADAMTS-5 and upregulates the expression of Collagen II and Aggrecan, indicating that it can inhibit the degradation of the extracellular matrix. In mechanism, betulin activated the AKT/Nrf2 pathway and inhibited the phosphorylation of p65. In in vivo studies, administration of betulin in vivo could inhibit cartilage destruction and inflammatory progression. Therefore, these findings suggest that betulin may alleviate IL-1β–induced OA via the AKT/Nrf2/HO-1/NF-κB signal axis, and betulin may be a potential drug for the treatment of OA.

scholarly journals Inhibitory Effect of Methotrexate on Rheumatoid Arthritis Inflammation and Comprehensive Metabolomics Analysis Using Ultra-Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry (UPLC-Q/TOF-MS)

2018 ◽  
Vol 19 (10) ◽  
pp. 2894 ◽  
Author(s):  
Zhiqiang Pang ◽  
Guoqiang Wang ◽  
Nan Ran ◽  
Hongqiang Lin ◽  
Ziyan Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inhibitory Effect ◽  
Sphingolipid Metabolism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Joint Tissue ◽  
Caspase 1 ◽  
Comprehensive Metabolomics ◽  
Metabolomics Analysis

Rheumatoid arthritis (RA) is a common autoimmune disease. The inflammation in joint tissue and system endanger the human health seriously. Methotrexate have exhibited a satisfactory therapeutic effect in clinical practice. The aim of this research was to establish the pharmacological mechanism of methotrexate on RA therapy. Collagen induced arthritic rats were used to identify how methotrexate alleviates inflammation in vivo. Lipopolysaccharide-induced inflammatory proliferation in macrophages was also be detected in vitro. The activation level of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nucleotide binding domain and leucine-rich repeat pyrin 3 domain (NLRP3)/Caspase-1 and related cytokines were examined by real-time PCR and western blotting or quantified with the enzyme-linked immunosorbent assay. Comprehensive metabolomics analysis was performed to identify the alteration of metabolites. Results showed that treating with methotrexate could alleviate the inflammatory condition, downregulate the activation of NF-κB and NLRP3/Caspase-1 inflammatory pathways and reduce the level of related cytokines. Docking interaction between methotrexate and caspase-1 was visualized as six H-bonds indicating a potential inhibitory effect. Metabolomics analysis reported three perturbed metabolic inflammation related pathways including arachidonic acid, linoleic acid and sphingolipid metabolism. These findings indicated that methotrexate could inhibit the onset of inflammation in joint tissue by suppressing the activation of NF-κB and NLRP3/Caspase-1 pathways and regulating the inflammation related metabolic networks.

scholarly journals Implication of the Association of Fibrinogen Citrullination and Osteoclastogenesis in Bone Destruction in Rheumatoid Arthritis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2720
Author(s):  
Ji Soo Kim ◽  
Mikyung Choi ◽  
Ji Yong Choi ◽  
Joo Yeon Kim ◽  
Jeong Yeon Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Peptidylarginine Deiminase ◽  
Inhibitory Function ◽  
Spectral Peaks ◽  
Polymerase Chain ◽  
Gene Expression Levels

Immune complexes containing citrullinated fibrinogen are present in the sera and synovium of rheumatoid arthritis patients and potentially contribute to synovitis. However, fibrinogen can inhibit the osteoclastogenesis of precursor cells. We investigated the direct effect of citrullinated fibrinogen on osteoclastogenesis to understand the role of citrullination on bone erosion of rheumatoid arthritis patients. We evaluated the fibrinogen citrullination sites using mass spectrometry and quantified osteoclast-related protein and gene expression levels by Western blotting, microarray, and real-time polymerase chain reaction. Differences in spectral peaks were noted between fibrinogen and citrullinated fibrinogen at five sites in α-chains, two sites in β-chains, and one site in a γ-chain. Transcriptome changes induced by fibrinogen and citrullinated fibrinogen were identified and differentially expressed genes grouped into three distinctive modules. Fibrinogen was then citrullinated in vitro using peptidylarginine deiminase. When increasing doses of soluble fibrinogen and citrullinated fibrinogen were applied to human CD14+ monocytes, citrullination restored osteoclastogenesis-associated changes, including NF-ATc1 and ß3-integrin. Finally, citrullination rescued the number of osteoclasts by restoring fibrinogen-induced suppression of osteoclastogenesis. Taken together, the results indicate that the inhibitory function of fibrinogen on osteoclastogenesis is reversed by citrullination and suggest that citrullinated fibrinogen may contribute to erosive bone destruction in rheumatoid arthritis.

scholarly journals The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study

2018 ◽  
Vol 48 (6) ◽  
pp. 2583-2595 ◽  
Author(s):  
Xiaobin Li ◽  
Dengying Wu ◽  
Zhichao Hu ◽  
Jiangwei Xuan ◽  
Xiaoxia Ding ◽  
...  
Keyword(s):  
Western Blotting ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Ecm Degradation ◽  
Collagen Ii ◽  
Cox 2 ◽  
Vitro Effect

Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

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