Small Peptides Compound Isolated from Agkistrodon with Antiarthritic Effect in Collagen-Induced Arthritis Rats

Agkistrodon in Chinese medicine has long been used as an effective treatment against rheumatoid arthritis (RA). The present research further investigated the effects of peptides extracted from the crude Agkistrodon on the RA rat model. Extracted peptides were separated by parameter-optimized ion-exchange chromatography (IEC), peptide fractions were further analysed by MALDI-TOF/TOF MS, and nano-LC-MS/MS acquired mass spectra were further characterized using Mascot software, which ranks the best matches in the NCBI database. RT-PCR results in RAW264.7 cells indicated that Agkistrodon peptide components had inhibitory effects against inflammatory cytokines. The therapeutic efficacy of Agkistrodon peptides was evaluated on the Wistar rats with collagen-induced arthritis. Symptom relief and reduced cartilage destruction and bone erosion were observed, which can be explained by the direct suppression of inflammatory cytokines in the joints. Agkistrodon peptides downregulate the expression of TNF-α, IL-1β, and IL-6, which may alleviate cartilage destruction and bone erosion, thus relieving symptoms of RA.

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Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Arthritis & Rheumatism ◽

10.1002/art.20001 ◽

2004 ◽

Vol 50 (2) ◽

pp. 650-659 ◽

Cited By ~ 512

Author(s):

Erik Lubberts ◽

Marije I. Koenders ◽

Birgitte Oppers-Walgreen ◽

Liduine van den Bersselaar ◽

Christina J. J. Coenen-de Roo ◽

...

Keyword(s):

Bone Erosion ◽

Joint Inflammation ◽

Cartilage Destruction ◽

Interleukin 17 ◽

Collagen Induced Arthritis

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Effects of Portabella mushrooms on collagen-induced arthritis, inflammatory cytokines, and body composition in dilute brown non-agouti (DBA1) mice

Functional Foods in Health and Disease ◽

10.31989/ffhd.v1i9.123 ◽

2011 ◽

Vol 1 (9) ◽

pp. 279

Author(s):

Sandra Peterson ◽

Edralin A. Lucas ◽

Djibril Traore ◽

Lawrance Christopher ◽

Christine French ◽

...

Keyword(s):

Body Composition ◽

Mass Loss ◽

Inflammatory Cytokines ◽

Fat Mass ◽

Lean Mass ◽

Cell Function ◽

Bone Erosion ◽

Collagen Induced Arthritis ◽

Tnf Α

Background: Exotic mushrooms have long been used in Asia for treatment and/or prevention of chronic diseases due to their immunomodulatory properties. However, the health benefits of portabella mushrooms (PM) (brown Agaricus bisporous), on collagen-induced arthritis (CIA) and associated complications, (i.e. loss of lean mass, increased fat mass and inflammatory cytokines), have not been previously investigated.Methods: We investigated CIA pathogenesis, body composition and plasma levels of IL- 6, TNF-α and sICAM1 in DBA1 female mice fed either the AIN76 diet or the same diet fortified with 5% lyophilized PM (n=19-20/group). Ten mice/group were immunized with 100 µg bovine collagen type II on day 42 of the protocol, followed by 50 µg lipopolysaccharides on day 62, and euthanized on day 73-74. Cytokines were measured by ELISA.Results: Compared to baseline diet, PM had: no protective effect from CIA since all collagen-immunized mice developed severe edema, bone erosion, and mononuclear cell infiltration in paws. In mice with and those without CIA, feeding a PM-fortified diet resulted in higher percent of body fat than feeding the baseline diet (p<0.05). After CIA induction, PM provided the following beneficial effects: (a) a smaller reduction in lean mass and absolute thymus weight; (b) a higher fat mass loss; and (c) lower plasma TNF-α levels (p <0.05). PM-fortification did not alter plasma IL-6 and sICAM1 regardless of CIA status; but it increased in vitro IL-6 secretion by mitogen-treated spleen cells.Conclusion: Our data suggest that PM may reduce plasma TNF-α, attenuate lean mass loss and thymus atrophy associated with arthritis, and protect spleen cell function assessed by IL-6 secretion. However, PM-fortification did not attenuate overall CIA pathogenesis which may be due to lack of effect on plasma IL-6. Decreased TNF-α without alterations in IL-6 may reduce the risk of other conditions associated with chronic inflammation such as cardiovascular disease.Key words: portabella mushrooms, inflammatory cytokines, collagen-induced arthritis, body composition, TNF-α, IL-6, thymus, DBA1 mice.

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DMY protects the knee joints of rats with collagen-induced arthritis by inhibition of NF-κB signaling and osteoclastic bone resorption

Food & Function ◽

10.1039/d0fo00396d ◽

2020 ◽

Vol 11 (7) ◽

pp. 6251-6264

Author(s):

Jing Wu ◽

Kai-Jian Fan ◽

Qi-Shan Wang ◽

Bing-Xin Xu ◽

Qing Cai ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Animal Model ◽

Articular Cartilage ◽

Bone Resorption ◽

Bone Erosion ◽

Cartilage Destruction ◽

Osteoclastic Bone Resorption ◽

Knee Joints ◽

Collagen Induced Arthritis

Collagen-induced arthritis (CIA) is a widely used animal model for studying rheumatoid arthritis (RA), which manifests serious joint dysfunction, progressive bone erosion and articular cartilage destruction.

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Suppression of inflammation and cartilage destruction by steroid-rich methanolic extract of Withania Somnifera: A study on collagen induced arthritic rats

Journal of Experimental and Applied Animal Sciences ◽

10.20454/jeaas.2017.1281 ◽

2017 ◽

Vol 2 (2) ◽

pp. 172

Author(s):

Mahmood Ahmad Khan ◽

Mythily Subramaneyaan ◽

Vinod Kumar Arora ◽

Rafat Sultana Ahmed

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Withania Somnifera ◽

Methanolic Extract ◽

Bone Erosion ◽

Cartilage Destruction ◽

Normal Serum ◽

Inflammatory Disorder ◽

Tnf Α ◽

And Cartilage

Rheumatoid arthritis (RA) is an inflammatory disorder characterized by oxidative stress, inflammation and cartilage destruction. Withania somnifera (WS) is used in Indian folk medicine for the treatment of various musculoskeletal disorders. WS is considered to possess potent antioxidant and anti-inflammatory activities. The aim of the present study was to evaluate the possible mechanism of action of methanolic extract of Withania somnifera roots (WSMe) against collagen induced arthritic (CIA) rats. Arthritis in rats was induced by subcutaneous injection of bovine type II collagen and was treated with WSMe at the dose of 200 mg/kg BW for 20 days after arthritis was induced. Number of biochemical, molecular and histological changes was observed in CIA rats. In CIA rats we found an imbalance in antioxidant and oxidant status as level of MDA was increased while GST, GSH and FRAP was found to be decreased. Administration of WSMe200 significantly ameliorates the level of antioxidant and oxidant to near normal. Serum concentration of transcription factor NF-kB, inflammatory cytokines like TNF-α, IL-1β, IL-6 and IL-10 were altered in CIA rats. In consistent to this mRNA expression of NF-kB, TNF-α and MMP-8 were also found to be Up-regulated, which were significantly inhibited by WSMe200 treatment. These findings are positively correlated with the results of histological examinations of joints, which showed reduced inflammation and bone erosion in the treated group. The ability to inhibit the production of oxidative stress and subsequent modulation of the inflammatory cytokines shows the protective effect of WSMe and its potential use for the treatment of arthritis.

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The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms22052426 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2426

Author(s):

Askhat Myngbay ◽

Limara Manarbek ◽

Steve Ludbrook ◽

Jeannette Kunz

Keyword(s):

Rheumatoid Arthritis ◽

Drug Targets ◽

Triple Helix ◽

Cancer Metastasis ◽

Bone Erosion ◽

Cartilage Destruction ◽

Patient Treatment ◽

Collagen Triple Helix ◽

Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

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Anti-Salmonella Activity and Peptidomic Profiling of Peptide Fractions Produced from Sturgeon Fish Skin Collagen (Huso huso) Using Commercial Enzymes

Nutrients ◽

10.3390/nu13082657 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2657

Author(s):

Maryam Atef ◽

Yasmina Ait Chait ◽

Seyed Mahdi Ojagh ◽

Ali Mohammad Latifi ◽

Mina Esmaeili ◽

...

Keyword(s):

Antibacterial Activity ◽

Degree Of Hydrolysis ◽

Fish Skin ◽

Small Peptides ◽

Skin Collagen ◽

Dependent Inhibition ◽

Acetone Fractionation ◽

Chain Lengths ◽

Peptide Fractions ◽

Fish Skin Collagen

This study investigated peptide fractions from fish skin collagen for antibacterial activity against Escherichia coli and Salmonella strains. The collagen was hydrolyzed with six commercial proteases, including trypsin, Alcalase, Neutrase, Flavourzyme, pepsin and papain. Hydrolyzed samples obtained with trypsin and Alcalase had the largest number of small peptides (molecular weight < 10 kDa), while the hydrolysate produced with papain showed the lowest degree of hydrolysis and highest number of large peptides. Four hydrolysates were found to inhibit the growth of the Gram-negative bacteria, with papain hydrolysate showing the best activity against E. coli, and Neutrase and papain hydrolysates showing the best activity against S. abony; hydrolysates produced with trypsin and pepsin did not show detectable antibacterial activity. After acetone fractionation of the latter hydrolysates, the peptide fractions demonstrated enhanced dose-dependent inhibition of the growth (colony-forming units) of four Salmonella strains, including S. abony (NCTC 6017), S. typhimurium (ATCC 13311), S. typhimurium (ATCC 14028) and S. chol (ATCC 10708). Shotgun peptidomics analysis of the acetone fractions of Neutrase and papain hydrolysates resulted in the identification of 71 and 103 peptides, respectively, with chain lengths of 6–22 and 6–24, respectively. This work provided an array of peptide sequences from fish skin collagen for pharmacophore identification, structure–activity relationship studies, and further investigation as food-based antibacterial agents against pathogenic microorganisms.

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Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation

Chinese Medicine ◽

10.1186/s13020-021-00448-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Di Hua ◽

Jie Yang ◽

Qinghai Meng ◽

Yuanyuan Ling ◽

Qin Wei ◽

...

Keyword(s):

Cell Differentiation ◽

Lymph Nodes ◽

Inflammatory Cytokines ◽

Th17 Cell ◽

Collagen Induced Arthritis ◽

Expression Levels ◽

Th17 Cell Differentiation ◽

Spleen And Lymph Nodes ◽

Seed Coats

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. Methods For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. Results SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. Conclusions Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

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