Dextromethorphan Exhibits Anti-inflammatory and Immunomodulatory Effects in a Murine Model of Collagen-Induced Arthritis and in Human Rheumatoid Arthritis

The anti-inflammatory activity of licorice (LE) and roated licorice (rLE) extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA) model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE.

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SAT0057 INCREASED MICRORNA-155 IS ASSOCIATED WITH A SPECIFIC DEFECT OF ANTI-INFLAMMATORY M2 MACROPHAGES POLARIZATION BOTH IN HUMAN RHEUMATOID ARTHRITIS AND IN COLLAGEN-INDUCED-ARTHRITIS MICE

10.1136/annrheumdis-2019-eular.5415 ◽

2019 ◽

Author(s):

Audrey Paoletti ◽

Franceline Reynaud ◽

Julien Rohmer ◽

Juliette Pascaud ◽

Bineta Ly ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Human Rheumatoid Arthritis ◽

M2 Macrophages ◽

Collagen Induced Arthritis ◽

Macrophages Polarization ◽

Anti Inflammatory

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Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

Life ◽

10.3390/life11060587 ◽

2021 ◽

Vol 11 (6) ◽

pp. 587

Author(s):

Fu-Tzu Pai ◽

Cheng-You Lu ◽

Chia-Hsin Lin ◽

John Wang ◽

Ming-Cheng Huang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Suppressor Cells ◽

Clinical Severity ◽

Histopathological Analysis ◽

Human Rheumatoid Arthritis ◽

Psoralea Corylifolia ◽

Collagen Induced Arthritis ◽

Tnf Α ◽

Synovial Tissues ◽

Orthopedic Diseases

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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Diosmetin exhibits anti‐proliferative and anti‐inflammatory effects on TNF‐α‐stimulated human rheumatoid arthritis fibroblast‐like synoviocytes through regulating the Akt and NF‐κB signaling pathways

Phytotherapy Research ◽

10.1002/ptr.6596 ◽

2019 ◽

Vol 34 (6) ◽

pp. 1310-1319 ◽

Cited By ~ 2

Author(s):

You Chen ◽

Yongsheng Wang ◽

Min Liu ◽

Bingkang Zhou ◽

Guangjie Yang

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathways ◽

Human Rheumatoid Arthritis ◽

Tnf Α ◽

Anti Inflammatory ◽

Fibroblast Like Synoviocytes

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Anti-inflammatory effects of ursolic acid-3-acetate on human synovial fibroblasts and a murine model of rheumatoid arthritis

International Immunopharmacology ◽

10.1016/j.intimp.2017.05.028 ◽

2017 ◽

Vol 49 ◽

pp. 118-125 ◽

Cited By ~ 5

Author(s):

Jong Yeong Lee ◽

Jin Kyeong Choi ◽

Na-Hee Jeong ◽

Jeongsoo Yoo ◽

Yeong Su Ha ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Ursolic Acid ◽

Murine Model ◽

Synovial Fibroblasts ◽

Anti Inflammatory

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Comparative morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

10.21203/rs.3.rs-129415/v1 ◽

2020 ◽

Author(s):

Camilla Machado ◽

Adriana Kakehasi ◽

Felipe Dias ◽

Gustavo Resende ◽

Patrícia Oliveira ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Electron Microscopy ◽

Signaling Pathways ◽

Human Model ◽

Human Rheumatoid Arthritis ◽

Functional Responses ◽

Collagen Induced Arthritis ◽

Ultrastructural Characteristics ◽

Intracellular Pathways ◽

Fibroblast Like Synoviocytes

Abstract BackgroundFibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to compare ultrastructural characteristics and functional responses by human and mouse FLS. The objective of this study is to compare ultrastructural characteristics, IL-6 and MMP-3 production, and the activation of intracellular pathways in FLS from patients with RA (RA-FLS) and mice with collagen-induced arthritis (CIA-FLS). The objective of the study was to compare ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with Rheumatoid Arthritis (RA) and from mice with collagen-induced arthritis.MethodsFLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with collagen-induced arthritis (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor - alpha (TNF-α) and IL-1β.ResultsRA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs.ConclusionThere were differences between RA-FLSs and CIA-FLSs in their ultrastructural morphologies and functional responses. The differences shown in our study indicate that the adoption of an RA-FLS human model is a better alternative than the CIA-FLS animal model for in vitro studies of RA etiopathogenesis and new therapeutic targets.

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Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of human rheumatoid arthritis

International Journal of Rheumatic Diseases ◽

10.1111/1756-185x.12666 ◽

2015 ◽

Vol 20 (2) ◽

pp. 203-213 ◽

Cited By ~ 9

Author(s):

Gamal Ramadan ◽

Nadia M. El-Beih ◽

Roba M. Talaat ◽

Eman A. Abd El-Ghffar

Keyword(s):

Rheumatoid Arthritis ◽

Aqueous Extract ◽

Rat Model ◽

Black Tea ◽

Inflammatory Activity ◽

Human Rheumatoid Arthritis ◽

Anti Inflammatory

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Identification of small molecule inhibitors of RANKL and TNF signalling as anti-inflammatory and antiresorptive agents in mice

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-203700 ◽

2013 ◽

Vol 74 (1) ◽

pp. 220-226 ◽

Cited By ~ 9

Author(s):

Emmanuel Coste ◽

Iain R Greig ◽

Patrick Mollat ◽

Lorraine Rose ◽

Mohini Gray ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Loss ◽

Small Molecule ◽

Small Molecule Inhibitors ◽

Joint Destruction ◽

Luciferase Reporter ◽

Collagen Induced Arthritis ◽

Arthritis Model ◽

Anti Inflammatory ◽

Systemic Bone Loss

IntroductionInflammatory joint diseases such as rheumatoid arthritis are associated with local bone erosions and systemic bone loss, mediated by increased osteoclastic activity. The receptor activator of nuclear factor (NF) κB ligand (RANKL) plays a key role in mediating inflammation-induced bone loss, whereas tumour necrosis factor (TNF) plays a central role in the inflammatory process. Here we tested whether a recently identified class of small molecule inhibitors of RANKL signalling (ABD compounds) also affect TNF signalling and whether these compounds inhibit inflammation in an animal model of rheumatoid arthritis.MethodsThe inhibitory effects of the ABD compounds on TNF-induced signalling were tested in mouse macrophage cultures by western blotting and in an NFκB luciferase-reporter cell line. The anti-inflammatory effects of the compounds were tested in the mouse collagen-induced arthritis model of rheumatoid arthritis.ResultsThe ABD compounds ABD328 and ABD345 both inhibited TNF-induced activation of the NFκB pathway and the extracellular signal-regulated kinase (ERK) and Jun kinase (JNK) mitogen activated protein kinases (MAPKs). When tested in the mouse collagen-induced arthritis model of rheumatoid arthritis, the compounds suppressed inflammatory arthritis, inhibited joint destruction and prevented systemic bone loss. Furthermore, one of the compounds (ABD328) showed oral activity.ConclusionsHere we describe a novel class of small molecule compounds that inhibit both RANKL- and TNF-induced NFκB and MAPK signalling in osteoclasts and macrophages, and inflammation and bone destruction in a mouse model of rheumatoid arthritis. These novel compounds therefore represent a promising new class of treatments for inflammatory diseases, such as rheumatoid arthritis.

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