iridoids has been researched along with Arthritis--Rheumatoid* in 12 studies
1 review(s) available for iridoids and Arthritis--Rheumatoid
1 trial(s) available for iridoids and Arthritis--Rheumatoid
11 other study(ies) available for iridoids and Arthritis--Rheumatoid
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Geniposide alleviates VEGF-induced angiogenesis by inhibiting VEGFR2/PKC/ERK1/2-mediated SphK1 translocation.
Rheumatoid arthritis (RA) is an angiogenesis-dependent disease caused by the imbalance of pro- and anti-angiogenic factors. More effective strategies to block synovial angiogenesis in RA should be studied. Geniposide (GE), a natural product isolated from the fruit of Gardenia jasminoides Ellis (GJ), is reported to have anti-inflammatory, anti-angiogenic and other pharmacological effects. However, the underlying mechanism through which GE affects synovial angiogenesis in RA remains unclear.. In this research, we aimed to elucidate the effect and potential mechanisms of GE on angiogenesis in RA.. Synovial angiogenesis in patients with RA and a rat model of adjuvant arthritis (AA) was detected by hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), and western blottiing. The biological functions of vascular endothelial cells (VECs) and sphingosine kinase 1 (SphK1) translocation were checked by CCK-8, EdU, Transwell, tube formation, co-immunoprecipitation assays, and laser scanning confocal microscopy. The effect of the SphK1 gene on angiogenesis was assessed by transfection of SphK1-siRNA in cells and mices. The effect of GE on VEGF-induced angiogenesis was measured by Matrigel plug assay in a mouse model of AA.. GE effectively inhibited synovial angiogenesis and alleviated the disease process. SphK1, as a new regulatory molecule, has a potentially important relationship in regulating VEGF/VEGFR2 and S1P/S1PR1 signals. SphK1 translocation was activated via the VEGFR2/PKC/ERK1/2 pathway and was closely linked to the biological function of VECs. GE significantly reduced SphK1 translocation, thereby ameliorating the abnormal biological function of VECs. Furthermore, after transfection of SphK1 siRNA in VECs and C57BL/6 mice, silencing SphK1 caused effectively attenuation of VEGF-induced VEC biological functions and angiogenesis. In vivo, the Matrigel plug experiment indicated that GE significantly inhibited pericyte coverage, basement membrane formation, vascular permeability, and fibrinogen deposition.. Our findings suggest that GE inhibited VEGF-induced VEC biological functions and angiogenesis by reducing SphK1 translocation. Generally, studies have revealed that GE down-regulated VEGFR2/PKC/ERK1/2-mediated SphK1 translocation and inhibited S1P/S1PR1 signaling activation, thereby alleviating VEGF-stimulated angiogenesis. The above evidences indicated that angiogenesis inhibition may provide a new direction for RA treatment. Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Endothelial Cells; Humans; Iridoids; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Phosphotransferases (Alcohol Group Acceptor); Rats; RNA, Small Interfering; Vascular Endothelial Growth Factor A | 2022 |
The anti-angiogenesis mechanism of Geniposide on rheumatoid arthritis is related to the regulation of PTEN.
Rheumatoid arthritis (RA) is a systemic immune disease characterized by joint inflammation and pannus. The nascent pannus contributes to synovial hyperplasia, cartilage, and tissue damage in RA. This study aims to explore the therapeutic effect and potential mechanism of Geniposide (GE) on RA angiogenesis, involving the participation of phosphate and tension homology deleted on chromosome ten (PTEN) and downstream pathways. Clinical manifestations, synovial pathomorphology, microvessel density, and the level of angiogenesis-related factors were used to evaluate the therapeutic effect of GE on adjuvant-induced arthritis (AA) rats. The proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) indicate the degree of angiogenesis in vitro. Lentivirus over-expression of PTEN was employed to elucidate the potential mechanism. The results showed that GE improved the degree of arthritis and angiogenesis in AA rats. The expression of PTEN was decreased significantly in vivo and in vitro, and over-expression of PTEN improved the biological function of HUVECs to inhibit angiogenesis. GE inhibited the proliferation, migration, and tubule formation of HUVECs and plays an anti-angiogenesis role in vitro. Mechanism study showed that PTEN expression was increased and p-PI3K and p-Akt expression was decreased with GE treatment. It suggests that GE up-regulated the expression of PTEN and inhibited the activation of PI3K-Akt signal, which plays a role in inhibiting angiogenesis in RA in vivo and in vitro. Topics: Angiogenesis Inducing Agents; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Human Umbilical Vein Endothelial Cells; Humans; Iridoids; Neovascularization, Pathologic; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Rats; Signal Transduction | 2022 |
Geniposide restricts angiogenesis in experimentary arthritis via inhibiting Dnmt1-mediated PTEN hypermethylation.
Neovascularization in rheumatoid arthritis (RA) is a key bridge between malignant proliferative synovial tissue and pannus. In view of previous studies on the efficacy of Geniposide (GE) in experimentary arthritis, the purpose of this study was to investigate the possible mechanism of GE inhibiting angiogenesis by regulating the gene of phosphate and tension homology deleted on chromosome ten (PTEN). In this study, human umbilical vein endothelial cells (HUVEC) and adjuvant arthritis (AA) rat models were performed to research in vitro and in vivo. The results showed that GE treatment significantly reduced synovitis and angiogenesis in AA rats, which may be associated with the increased expression of PTEN with GE treatment. Meanwhile, the hypermethylation of PTEN accompanied by the over-expression of DNA methyltransferases (Dnmts) was demonstrated in TNF-α-induced HUVEC and AA rats. Knockdown of Dnmt1 by Dnmt1- siRNA significantly inhibited the tube formation of HUVEC in vitro. GE significantly restricted the angiogenesis of HUVEC by inhibiting DNA methylation, which was attributed to the down-regulation of Dnmt1 rather than Dnmt3a and Dnmt3b. The anti-angiogenesis effect of GE was further verified in AA model by the inhibition of Dnmt1. These results indicate that GE exhibited anti-angiogenesis effects in experimentary arthritis by inhibiting Dnmt1-mediated PTEN gene hypermethylation, which may brings new insights for the prevention and research of RA. Topics: Angiogenesis Inhibitors; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Human Umbilical Vein Endothelial Cells; Humans; Iridoids; Neovascularization, Pathologic; PTEN Phosphohydrolase; Rats | 2022 |
Geniposide inhibits SphK1 membrane targeting to restore macrophage polarization balance in collagen-induced arthritis mice.
Imbalance of macrophage polarization plays a critical role in the progression of rheumatoid arthritis (RA). Geniposide (GE) has been shown to exert anti-inflammatory effects. However, the effect of GE on macrophage polarization remains unclear. Here, we investigated the regulation of GE on the imbalance of macrophage polarization in RA and how it functions. We established a mouse model of collagen-induced arthritis (CIA) and isolated bone marrow-derived macrophages (BMDMs). The results confirmed that pro-inflammatory M1 macrophages were dominant in CIA mice, but the polarization imbalance of macrophages was restored to a certain extent after GE treatment. Furthermore, the membrane targeting of sphingosine kinase 1 (SphK1) was increased in BMDMs of CIA mice, as manifested by increased membrane and cytoplasmic expression of p-SphK1 and high secretion level of sphingosine-1-phosphate (S1P). RAW264.7 cells were stimulated with lipopolysaccharide (LPS)-interferon (IFN)-γ or interleukin (IL)-4 to induce M1 or M2 phenotype, respectively, to revalidate the results obtained in BMDMs. The results again observed SphK1 membrane targeting in LPS-IFN-γ-stimulated RAW264.7 cells. Selective inhibition of SphK1 by PF543 or inhibition of the S1P receptors by FTY720 both restored the proportion of M1 and M2 macrophages in LPS-IFN-γ-stimulated RAW264.7 cells, confirming that SphK1 membrane targeting mediated a proportional imbalance in M1 and M2 macrophage polarization. In addition, GE inhibited SphK1 membrane targeting and kinase activity. Taken together, results confirmed that the inhibition of SphK1 membrane targeting by GE was responsible for restoring the polarization balance of macrophages in CIA mice. Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Fingolimod Hydrochloride; Interferon-gamma; Iridoids; Lipopolysaccharides; Macrophages; Mice; Phosphotransferases (Alcohol Group Acceptor); Signal Transduction | 2022 |
[Effects of triterpenoid and iridoid of Eucommiae Cortex on collagen-induced arthritis in rats].
The ethyl acetate fraction of ethanol extract of Eucommiae Cortex can effectively inhibit joint inflammation and bone destruction in rats with collagen-induced arthritis(CIA) and has a potential therapeutic effect on rheumatoid arthritis. The triterpenoid(EU-Tid) and iridoid(EU-Idd) of Eucommiae Cortex are derivatives isolated from the ethyl acetate fraction of the ethanol extract of Eucommiae Cortex, and it is not clear whether they have inhibitory effects on joint inflammation and bone erosion in CIA rats. Therefore, based on the CIA model, the effects of EU-Tid, EU-Idd, and their combination(EU-TP) on arthritis in rats were observed, and the material basis of Eucommiae Cortex against arthritis was further clarified. The samples were collected two and four weeks after administration to observe the pathological changes in different stages of arthritis in CIA rats. For the rats in the model control group, with the prolongation of the disease course, the paw volume and arthritis score increased and histopathological lesions aggravated. Compared with the model control group, the drug administration groups showed reduced paw volumes and arthritis scores, and improved joint lesions and cartilage destruction. Additionally, the mRNA expression levels of tumor necrosis factor-α(TNF-α), interleukin-17(IL-17), and interleukin-23(IL-23) in the spleen were down-regulated in the drug administration groups. EU-TP and EU-Tid at concentrations of 160 and 320 μg·mL~(-1) could significantly inhibit the proliferation of human fibroblast-like synoviocytes-RA(HFLS-RA) and nitric oxide(NO) release in the supernatant of RAW264.7 cells induced by lipopolysaccharide(LPS) at the concentration range of 10-80 μg·mL~(-1) in vitro. EU-Idd had no effect on the proliferation of HFLS-RA but could reduce the NO release at concentrations of 40 and 80 μg·mL~(-1). The results indicated that the terpenoids of Eucommiae Cortex had great potential in the treatment of rheumatoid arthritis. Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cytokines; Ethanol; Humans; Inflammation; Iridoids; Plant Extracts; Rats; Triterpenes; Tumor Necrosis Factor-alpha | 2022 |
Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro.
The VEGF/SphK1/S1P pathway is closely related to angiogenesis in rheumatoid arthritis (RA), but the precise underlying mechanisms are unclear at present. Here, we explored the involvement of the VEGF/SphK1/S1P cascade in RA models and determined the effects of GE intervention. Our results showed abnormal expression of proteins related to this pathway in RA synovial tissue. Treatment with GE effectively regulated the signal axis, inhibited angiogenesis, and alleviated RA symptoms. In vitro, TNF-ɑ enhanced the VEGF/SphK1/S1P pathway in a co-culture model of fibroblast-like synoviocytes (FLS) and vascular endothelial cells (VEC). GE induced downregulation of VEGF in FLS, restored the dynamic balance of pro-/antiangiogenic factors, and suppressed SphK1/S1P signaling in VEC, resulting in lower proliferation activity, migration ability, tube formation ability, and S1P secretion ability of VEC cells. Additionally, SphK1-specific small interfering RNA (siRNA) blocked the VEGF/SphK1/S1P cascade, which can effectively alleviate the stimulatory effect of FLS on VEC and further enhanced the therapeutic effect of GE. Taken together, our results demonstrate that GE suppresses the VEGF/SphK1/S1P pathway and alleviates the stimulation of VEC by FLS, thereby preventing angiogenesis and promoting therapeutic effects against RA. Topics: Adaptor Proteins, Signal Transducing; Arthritis, Rheumatoid; Cell Proliferation; Cells, Cultured; Endothelial Cells; Fibroblasts; Humans; Iridoids; Neovascularization, Pathologic; Signal Transduction; Sphingosine-1-Phosphate Receptors; Synovial Membrane; Vascular Endothelial Growth Factor A | 2021 |
Novel anti-inflammatory target of geniposide: Inhibiting Itgβ1/Ras-Erk1/2 signal pathway via the miRNA-124a in rheumatoid arthritis synovial fibroblasts.
Geniposide (GE) is an active component isolated from the fruit of Gardenia jasminoides Ellis that has anti-inflammatory and other pharmacological effects; however, the underlying mechanism of GE action has not been elucidated in rheumatoid arthritis (RA). Previous studies have shown that GE plays a therapeutic role in RA via regulation of the integrin beta 1 (Itgβ1)-mediated Ras-Erk1/2 signalling pathway. However, the specific mechanism of GE action on Itgβ1 has not been clarified. Recent evidence indicates that microRNAs (miRNAs) are involved in the development of RA. In this study, we developed a miRNA-124a-based synoviocyte repair strategy. We demonstrated that miRNA-124a can directly inhibit the expression of the Itgβ1 gene and decrease TNF-α-stimulated cell proliferation in vitro. MH7A cells were obtained from the patient with RA and treated with GE in the presence of TNF-α (10 ng/mL). Additionally, we demonstrated that the expression of miRNA-124a can be regulated by GE. GE upregulated the expression of miRNA-124a and decreased the expression of Itgβ1 at the mRNA and protein levels. The results of the present study are the first to suggest that GE inhibits TNF-α-stimulated cell proliferation and blocks the activation of the Ras-Erk1/2 pathway via the upregulation of miRNA-124a expression. Our study elucidates the role of miRNA-124a as a protected miRNA in RA and may provide a novel strategy for the diagnosis and treatment of RA in the future. Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cell Line; Cell Proliferation; Fibroblasts; Gardenia; Gene Expression Regulation; Humans; Integrin beta1; Iridoids; MAP Kinase Signaling System; MicroRNAs; Oncogene Protein p21(ras); Synoviocytes; Tumor Necrosis Factor-alpha | 2018 |
Immune Tolerance Effect in Mesenteric Lymph Node Lymphocytes of Geniposide on Adjuvant Arthritis Rats.
Rheumatoid arthritis (RA) is a systemic, Th1 cytokine-predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague-Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Levels of interleukin-2 (IL-2), IL-4, and transforming growth factor-β1 were tested by ELISA. The expression of β2-AR, GRK2, and β-arrestin-1 and β-arrestin-2 was detected by western blot. Geniposide was found to relieve the secondary hind paw swelling and arthritis scores, along with attenuating histopathologic changes and decreasing IL-2 and increasing IL-4, transforming growth factor-β1 in mesenteric lymph node (MLN) lymphocytes of AA rats. In addition, GE in vivo increased the expression of β2-AR and decreased the expression of GRK2, β-arrestin-1 and β-arrestin-2, and level of cyclic adenosine monophosphate of MLN lymphocytes in AA rats. From these results, we can infer that GE on immune tolerance effects, β2-AR desensitization, and β2-AR-AC-cyclic adenosine monophosphate transmembrane signal transduction of MLN lymphocytes plays crucial roles in antiinflammatory and immunoregulatory pathogeneses of RA. Copyright © 2017 John Wiley & Sons, Ltd. Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; beta-Arrestin 1; beta-Arrestin 2; Cell Proliferation; Cyclic AMP; G-Protein-Coupled Receptor Kinase 2; Gardenia; Immune Tolerance; Interleukin-2; Interleukin-4; Iridoids; Lymph Nodes; Lymphocytes; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta1 | 2017 |
Apoptotic Effect of Geniposide on Fibroblast-Like Synoviocytes in Rats with Adjuvant-Induced Arthritis via Inhibiting ERK Signal Pathway In Vitro.
Stimulating fibroblast-like synoviocyte (FLS) apoptosis in rheumatoid arthritis (RA) is a promising strategy for clinical treatment. Previous studies have confirmed that geniposide shows a certain anti-arthritic effect in vivo. However, whether geniposide can induce RA FLS apoptosis and the underlying mechanisms has not been elucidated. Herein, adjuvant-induced arthritis (AIA) in rat was induced and FLS was isolated from synovial tissues by tissue explant cultivation method. MTT assay, Hoechst staining, and flow cytometric apoptosis assay were applied to evaluate apoptotic effect of geniposide on AIA FLS. Bcl-2, Bax, and caspase 3 messenger RNA (mRNA) levels, and extracellular-signal-regulated kinases (ERKs) and phosphorylated ERK protein levels were examined by real-time PCR and western blot, respectively. We found that geniposide dose-dependently inhibited AIA FLS proliferation in vitro. AIA FLS treated with geniposide displayed typical apoptotic morphological characteristics including nuclear shrinkage and chromatin condensation. Flow cytometric apoptosis assay indicated that geniposide significantly increased the apoptosis rate of AIA FLS. Additionally, geniposide treatment on AIA FLS decreased Bcl-2 mRNA level and increased Bax and caspase 3 mRNA levels, accompanied by reduced protein levels of phosphorylated-ERK1/2, without affecting total ERK1/2. In conclusion, geniposide effectively induces AIA FLS apoptosis through regulating the apoptosis-related gene expressions and inhibiting ERK signal pathway. Topics: Animals; Apoptosis; Arthritis, Experimental; Arthritis, Rheumatoid; bcl-2-Associated X Protein; Caspase 3; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Flow Cytometry; Iridoids; Male; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; RNA, Messenger; Synovial Membrane | 2016 |
Effects and mechanisms of Geniposide on rats with adjuvant arthritis.
Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis (GJ) fruit which has anti-inflammatory and other important therapeutic activities. The aim of this study was to investigate the effects of GE on adjuvant arthritis (AA) rats and its possible mechanisms. AA was induced by injecting with Freund's complete adjuvant (FCA). Male SD rats were subjected to treatment with GE at 30, 60 and 120mg/kg from days 18 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Interleukin (IL)-6, IL-17, IL-4 and transforming growth factor-beta 1 (TGF-β1) were determined by ELISA. c-Jun N-terminal kinase (JNK) and phospho-JNK (p-JNK) were detected by Western blot. GE (60, 120mg/kg) significantly relieved the secondary hind paw swelling and arthritis index, along with decreased Th17-cells cytokines and increased Treg-cell cytokines in mesenteric lymph node lymphocytes (MLNL) and peripheral blood lymphocytes (PBL) of AA rats. In addition, GE decreased the expression of p-JNK in MLNL and PBL of AA rats. In vivo study, it was also observed that GE attenuated histopathologic changes of MLN in AA rats. Collectively, GE might exert its anti-inflammatory and immunoregulatory effects through inducing Th17 cell immune tolerance and enhancing Treg cell-mediated activities by down-regulating the expression of p-JNK. The mechanisms of GE on JNK signaling in MLNL and PBL may play critical roles in the pathogenesis of rheumatoid arthritis. Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Cytokines; Foot Joints; Iridoids; JNK Mitogen-Activated Protein Kinases; Lymph Nodes; Lymphocytes; Male; Rats, Sprague-Dawley | 2014 |
[Effect of geniposide on serum IL-1beta and TNF-alpha of rheumatoid arthritis rats].
To study the effect of geniposide on serum IL-1beta and TNF-alpha levels of rheumatoid arthritis rats, as well as the mechanism of this drug.. To establish an experimental rat model of type II collagen-induced arthritic (CIA). The inhibitory effects on paw edema were observed, and serum IL-1beta and TNF-alpha levels were determined in experimental rats.. Compared with the model, geniposide delayed the starting time of right paw edema significantly, and the levels of serum IL-1beta and TNF-alpha were significantly decreased by geniposide at high dose or medium dose (P < 0.01).. Geniposide can lower serum IL-1beta and TNF-alpha levels in rheumatoid arthritis rats. The effect may be close related to inhibitory development of rheumatoid arthritis by the agent. Topics: Animals; Arthritis, Rheumatoid; Collagen Type II; Dose-Response Relationship, Drug; Edema; Gardenia; Hindlimb; Interleukin-1; Iridoids; Male; Plants, Medicinal; Pyrans; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha | 2005 |