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Mixed effects of caffeic acid phenethyl ester (CAPE) on joint inflammation, bone loss and gastrointestinal inflammation in a murine model of collagen antibody-induced arthritis

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Abstract

Objective

To investigate the effect of caffeic acid phenethyl ester (CAPE) on local and systemic inflammation and bone loss in collagen antibody-induced arthritis (CAIA) mice.

Methods

Four groups of mice (n = 8 per group) were allocated; control, CAPE (1 mg/kg), CAIA and CAIA + CAPE (1 mg/kg). Local inflammation and bone loss were evaluated using clinical paw scores, in vivo micro-computed tomography (micro-CT), histological assessment and tartrate-resistant acid phosphatase (TRAP) staining. Serum levels of C-reactive protein (CRP) and C-terminal telopeptide (CTX-1) were measured by ELISA. Jejunum and colon sections were evaluated histopathologically for damage and toxicity.

Results

Greater paw scores and percentage change in paw volume were observed in CAIA + CAPE compared to the control groups (p < 0.05). Bone volume over time remained unchanged (p = 0.94) and the number of multinucleated TRAP-positive cells was greatest in CAIA + CAPE mice (p < 0.05). CRP and CTX-1 levels did not differ between groups. CAIA + CAPE mice exhibited lower colon toxicity scores and a reduced percentage of cavitated goblet cells in the colon crypts compared with CAIA mice (p = 0.026 and p = 0.003, respectively). Histopathology in the jejunum was not altered.

Conclusion

CAPE did not reduce paw inflammation or bone loss in CAIA mice. CAPE reduced histopathological changes in the colon of CAIA mice.

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Abbreviations

CAPE:

Caffeic acid phenethyl ester

CAIA:

Collagen antibody-induced arthritis

CTX-1:

C-terminal telopeptide

RA:

Rheumatoid arthritis

NF-κB:

Nuclear factor-kappa B

TRAP:

Tartrate-resistant acid phosphatase

BV:

Bone volume

PV:

Paw volume

TNF-α:

Tumour necrosis factor alpha

DMARDs:

Disease-modifying anti-rheumatic drugs

PE:

Polyethylene

micro-CT:

Micro-computed tomography

CRP:

C-reactive protein

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Authors’ contributions

BW, VM and ET carried out the animal model. ET, TC, RS, RG and BW carried out the immunoassays and immunohistochemical staining and analysis. MC, TC and AD conceived the study and participated in the experimental design and data interpretation. EP and BW carried out micro-CT scans and analysis. BW, EP and RS performed the statistical analysis. All authors contributed to the manuscript and read and approved the final manuscript.

Acknowledgements

This project was kindly funded by The Estate of the Late Marion Alice Simpson, Arthritis Australia. The professional assistance received throughout this study: Mr. Victor Marino, Mr. Richard Bright and Dr. Jiake Xu for assistance with the animal model. Dr. Egon Perilli for his ongoing help with micro-CT analysis and Adelaide Microscopy, specifically Ruth Williams for her guidance with the SkyScan 1076. The University of Adelaide Animal Laboratory Services for animal handling training and assistance with the animal model. The University of Adelaide, School of Medicine, Histology Services for their assistance with processing and cutting tissues.

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Authors and Affiliations

  1. Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia

    Bonnie Williams, Eleni Tsangari, Romany Stansborough, Melissa Cantley, Anak Dharmapatni, Rachel Gibson & Tania Crotti

  2. School of Dentistry, The University of Adelaide, Adelaide, SA, Australia

    Victor Marino

  3. Division of Health Sciences, University of South Australia, Adelaide, SA, Australia

    Rachel Gibson

  4. School of Computer Science, Engineering and Mathematics, Flinders University, Adelaide, SA, Australia

    Egon Perilli

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  1. Bonnie Williams
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  2. Eleni Tsangari
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  4. Victor Marino
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  7. Rachel Gibson
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Corresponding author

Correspondence to Bonnie Williams.

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Conflict of interest

Not applicable.

Ethics approval

The study was approved by the Animal Ethics Committee of the University of Adelaide (M-2014-175) and complied with National Health and Research Council (Australia) Code of Practice for Animal Care in Research and Training (2014). All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Funding

This project was kindly funded by The Estate of the Late Marion Alice Simpson, Arthritis Australia. The funding body was not involved in the design of the study or collection, analysis and interpretation of the data.

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Williams, B., Tsangari, E., Stansborough, R. et al. Mixed effects of caffeic acid phenethyl ester (CAPE) on joint inflammation, bone loss and gastrointestinal inflammation in a murine model of collagen antibody-induced arthritis. Inflammopharmacol 25, 55–68 (2017). https://doi.org/10.1007/s10787-016-0306-z

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