A Soft Coral-Derived Compound, 11-epi-Sinulariolide Acetate Suppresses Inflammatory Response and Bone Destruction in Adjuvant-Induced Arthritis

This study was performed to assess the efficacy of α-viniferin (Carex humilis Leyss) on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced by a single subcutaneous injection of 0.1 ml complete Freund's adjuvant (CFA) containing 7.5 mg Mycobacterium butyricum suspended in 1 ml sterile paraffin oil into the right hind paw. Forty female Sprague-Dawley rats were injected. Righting reflex was uniformly lost and considered to be the initial point of arthritis development on day 7 after CFA injection. Rats were divided into four groups, and upon development of arthritis, tested groups were orally administered 3 or 10 mg/kg α-viniferin or 10 mg/kg ketoprofen every day for 14 days. The control group was orally administered 2 ml of physiological saline solution. Bone mineral density (BMD), radiological changes and edematous volumes were measured for 35 days. α-viniferin suppressed the development of inflammatory edema, and inhibited the bone destruction, noted with a decrease in BMD ( p <0.05). Hind paw edema volume, BMD and radiological changes did not differ significantly in the ketoprofen and α-viniferin groups during the entire study period. In conclusion, α-viniferin suppressed arthritic inflammation and bony change in rats.

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Therapeutic Effect of Saponin Rich Fraction ofAchyranthes asperaLinn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats

Autoimmune Diseases ◽

10.1155/2015/943645 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Pankaj S. Kothavade ◽

Vipin D. Bulani ◽

Dnyaneshwar M. Nagmoti ◽

Padmini S. Deshpande ◽

Nitin B. Gawali ◽

...

Keyword(s):

Bone Destruction ◽

Therapeutic Benefit ◽

Stair Climbing ◽

Sprague Dawley ◽

Necrosis Factor Alpha ◽

Achyranthes Aspera ◽

Adjuvant Induced Arthritis ◽

Sprague Dawley Rats ◽

Antioxidant Parameters

Objective. Achyranthes asperaLinn. (AA) is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR) fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction ofAchyranthes asperain adjuvant-induced arthritic rats.Methods.Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine andin vivoantioxidant parameters were measured on the last day of the study.Results.SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints.Conclusion.These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats.

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Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats

Histochemistry and Cell Biology ◽

10.1007/s00418-005-0062-4 ◽

2005 ◽

Vol 125 (3) ◽

pp. 215-225 ◽

Cited By ~ 21

Author(s):

Quan Yong Tang ◽

Toshio Kukita ◽

Yuki Ushijima ◽

Akiko Kukita ◽

Kengo Nagata ◽

...

Keyword(s):

Caffeic Acid ◽

Bone Destruction ◽

Adjuvant Induced Arthritis ◽

Related Compounds

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Prophylactic or therapeutic administration of Holarrhena floribunda hydro ethanol extract suppresses Complete Freund’s Adjuvant-induced arthritis in Sprague-Dawley rats

10.21203/rs.3.rs-126064/v1 ◽

2020 ◽

Author(s):

Stephen Antwi ◽

Daniel Oduro-Mensah ◽

David Darko Obiri ◽

Clara Lewis ◽

Ebenezer Oduro-Mensah ◽

...

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Ethanol Extract ◽

Stem Bark ◽

Sprague Dawley ◽

Adjuvant Induced Arthritis ◽

Sprague Dawley Rats ◽

Freund’S Adjuvant ◽

Complete Freund's Adjuvant ◽

Freund's Adjuvant

Abstract Ethnopharmacological relevance In Ghanaian folk medicine, Holarrhena floribunda has anecdotal use for the treatment of inflammatory conditions. A hydro ethanol extract of the stem bark has previously been shown to be effective in the management of acute inflammation and anaphylaxis in rodents.Aim of the study This study was aimed at evaluating the usefulness of H. floribunda stem bark hydro ethanol extract (HFE) for the management of chronic inflammation in a murine model.Materials and Methods Anti-arthritic effect of the extract was evaluated using Complete Freund’s Adjuvant-induced arthritis in male Sprague-Dawley rats. Using both prophylactic and therapeutic treatment models, parameters assessed included oedema, serology of inflammatory response, radiology, bone tissue histology and haematology. Data were analysed by ANOVA followed by Tukey’s multiple comparisons post hoc test.Results HFE at 50–500 mg/kg dose-dependently [P ≥ 0.0354 (prophylactic) and P ≥ 0.0001 (therapeutic)] inhibited swelling of the injected paw upon prophylactic [≤ 81.26 % (P < 0.0001)] or therapeutic [≤ 67.92 % (P < 0.01)] administration — and prevented spread of arthritis to the contralateral paw. Inflammation alleviation activity of HFE was further demonstrated by decrease in arthritis score, radiologic score and erythrocyte sedimentation rate. HFE at all doses significantly reduced serum IL-1α (P < 0.0197), and 500 mg/kg HFE reduced serum IL-6 (P = 0.0032). In contrast, serum concentrations of IL-10, protein kinase A and cyclic adenosine monophosphate were enhanced (P ≤ 0.0436). HFE consistently showed better prophylactic activity than when administered therapeutically.Conclusions The data demonstrate that HFE suppresses CFA-induced arthritis and modulates regulators of inflammation; including IL-1α, -6 and -10 which also play mediatory roles in several immune response pathways. These make HFE a strong candidate for development as an agent for management and modulation of inflammation and the inflammatory response, including immune response-related adverse events such as seen in severe COVID-19.

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Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor.

Journal of Experimental Medicine ◽

10.1084/jem.182.2.449 ◽

1995 ◽

Vol 182 (2) ◽

pp. 449-457 ◽

Cited By ~ 73

Author(s):

J G Conway ◽

J A Wakefield ◽

R H Brown ◽

B E Marron ◽

L Sekut ◽

...

Keyword(s):

Bone Growth ◽

Distal Tibia ◽

Bone Destruction ◽

Cartilage Destruction ◽

Pannus Formation ◽

Direct Role ◽

Direct Evaluation ◽

Adjuvant Induced Arthritis ◽

And Cartilage

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4-hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant-induced arthritis.

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The NOD-scid IL2rγnullMouse Model Is Suitable for the Study of Osteoarticular Brucellosis and Vaccine Safety

Infection and Immunity ◽

10.1128/iai.00901-18 ◽

2019 ◽

Vol 87 (6) ◽

Cited By ~ 2

Author(s):

Omar H. Khalaf ◽

Sankar P. Chaki ◽

Daniel G. Garcia-Gonzalez ◽

Thomas A. Ficht ◽

Angela M. Arenas-Gamboa

Keyword(s):

Inflammatory Response ◽

Bone Destruction ◽

Vaccine Safety ◽

Confocal Imaging ◽

Live Attenuated Vaccine ◽

Content Type ◽

Multiple Organs ◽

Large Numbers ◽

Bone Changes ◽

Potential Use

ABSTRACTOsteoarticular brucellosis is the most common complication inBrucella-infected humans regardless of age, sex, or immune status. The mechanism of bone destruction caused byBrucellaspecies remained partially unknown due to the lack of a suitable animal model. Here, to study this complication, we explored the suitability of the use of the NOD-scid IL2rγnullmouse to study osteoarticular brucellosis and examined the potential use of this strain to evaluate the safety of live attenuated vaccine candidates. Mice were inoculated intraperitoneally with a single dose of 1 × 104, 1 × 105, or 1 × 106CFU ofB. abortusS19 or the vaccine candidateB. abortusS19ΔvjbRand monitored for the development of side effects, including osteoarticular disease, for 13 weeks. Decreased body temperature, weight loss, splenomegaly, and deformation of the tails were observed in mice inoculated withB. abortusS19 but not in those inoculated with S19ΔvjbR. Histologically, all S19-inoculated mice had a severe dose-dependent inflammatory response in multiple organs. The inflammatory response at the tail was characterized by the recruitment of large numbers of neutrophils, macrophages, and osteoclasts with marked bone destruction. These lesions histologically resembled what is typically observed inBrucella-infected patients. In contrast, mice inoculated withB. abortusS19ΔvjbRdid not show significant bone changes. Immunofluorescence,in situhybridization, and confocal imaging demonstrated the presence ofBrucellaat the sites of inflammation, both intra- and extracellularly, and large numbers of bacteria were observed within mature osteoclasts. These results demonstrate the potential use of the NOD-scid IL2rγnullmouse model to evaluate vaccine safety and further study osteoarticular brucellosis.

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Adenosine abolishes MTX-induced suppression of osteoclastogenesis and inflammatory bone destruction in adjuvant-induced arthritis

Laboratory Investigation ◽

10.1038/labinvest.2011.9 ◽

2011 ◽

Vol 91 (5) ◽

pp. 719-731 ◽

Cited By ~ 21

Author(s):

Junpei Teramachi ◽

Akiko Kukita ◽

Yin-Ji Li ◽

Yuki Ushijima ◽

Hiroshi Ohkuma ◽

...

Keyword(s):

Bone Destruction ◽

Adjuvant Induced Arthritis

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MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-206417 ◽

2015 ◽

Vol 75 (3) ◽

pp. 601-608 ◽

Cited By ~ 44

Author(s):

Yuji Nakamachi ◽

Kenichiro Ohnuma ◽

Kenichi Uto ◽

Yoriko Noguchi ◽

Jun Saegusa ◽

...

Keyword(s):

Morphological Changes ◽

Bone Destruction ◽

Luciferase Reporter ◽

Tartrate Resistant Acid Phosphatase ◽

Human Rheumatoid Arthritis ◽

Nuclear Factor ◽

Messenger Rnas ◽

Activated T Cells ◽

Adjuvant Induced Arthritis ◽

Human Osteoclasts

ObjectiveMicroRNAs (miRNAs) are small endogenous, non-coding RNAs that act as post-transcriptional regulators. We analysed the in vivo effect of miRNA-124 (miR-124, the rat analogue of human miR-124a) on adjuvant-induced arthritis (AIA) in rats.MethodsAIA was induced in Lewis rats by injecting incomplete Freund's adjuvant with heat-killed Mycobacterium tuberculosis. Precursor (pre)-miR-124 was injected into the right hind ankle on day 9. Morphological changes in the ankle joint were assessed by micro-CT and histopathology. Cytokine expression was examined by western blotting and real-time RT-PCR. The effect of miR-124 on predicted target messenger RNAs (mRNAs) was examined by luciferase reporter assays. The effect of pre-miR-124 or pre-miR-124a on the differentiation of human osteoclasts was examined by tartrate-resistant acid phosphatase staining.ResultsWe found that miR-124 suppressed AIA in rats, as demonstrated by decreased synoviocyte proliferation, leucocyte infiltration and cartilage or bone destruction. Osteoclast counts and expression level of receptor activator of the nuclear factor κB ligand (RANKL), integrin β1 (ITGB1) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) were reduced in AIA rats treated with pre-miR-124. Luciferase analysis showed that miR-124 directly targeted the 3′UTR of the rat NFATc1, ITGB1, specificity protein 1 and CCAAT/enhancer-binding protein α mRNAs. Pre-miR-124 also suppressed NFATc1 expression in RAW264.7 cells. Both miR-124 and miR-124a directly targeted the 3′-UTR of human NFATc1 mRNA, and both pre-miR-124 and pre-miR-124a suppressed the differentiation of human osteoclasts.ConclusionsWe found that miR-124 ameliorated AIA by suppressing critical prerequisites for arthritis development, such as RANKL and NFATc1. Thus, miR-124a is a candidate for therapeutic use for human rheumatoid arthritis.

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