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Mar. Drugs 2014, 12(1), 36-53; doi:10.3390/md12010036
Article

Solomonsterol A, a Marine Pregnane-X-Receptor Agonist, Attenuates Inflammation and Immune Dysfunction in a Mouse Model of Arthritis

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1 Department of Experimental and Clinical Medicine, University of Perugia, Gambuli Street, S. Andrea delle Fratte, Perugia 06132, Italy 2 Department of Pharmacy, University of Naples "Federico II", D. Montesano Street, 49, Naples 80131, Italy 3 University and City Hospital of Perugia, Perugia 06100, Italy
* Authors to whom correspondence should be addressed.
Received: 21 October 2013 / Revised: 6 December 2013 / Accepted: 9 December 2013 / Published: 24 December 2013
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Abstract

In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol A was effective in protecting against the development of arthritis induced by injecting transgenic mice harboring a humanized PXR, with anti-collagen antibodies (CAIA) with beneficial effects on joint histopathology and local inflammatory response reducing the expression of inflammatory markers (TNFα, IFNγ and IL-17 and chemokines MIP1α and RANTES) in draining lymph nodes. Solomonsterol A rescued mice from systemic inflammation were assessed by measuring arthritis score, CRP and cytokines in the blood. In summary, the present study provides a molecular basis for the regulation of systemic local and systemic immunity by PXR agonists.
Keywords: marine sponge; Theonella swinhoei; rheumatoid arthritis; inflammation; pregnane X receptor (PXR); solomonsterol A marine sponge; Theonella swinhoei; rheumatoid arthritis; inflammation; pregnane X receptor (PXR); solomonsterol A
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mencarelli, A.; D'Amore, C.; Renga, B.; Cipriani, S.; Carino, A.; Sepe, V.; Perissutti, E.; D'Auria, M.V.; Zampella, A.; Distrutti, E.; Fiorucci, S. Solomonsterol A, a Marine Pregnane-X-Receptor Agonist, Attenuates Inflammation and Immune Dysfunction in a Mouse Model of Arthritis. Mar. Drugs 2014, 12, 36-53.

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