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Honokiol, a Natural Plant Product, Inhibits Inflammatory Signals and Alleviates Inflammatory Arthritis¹

Melissa E. Munroe^*, Jack L. Arbiser and Gail A. Bishop^2,*,,

^* Department of Microbiology and Department of Internal Medicine, University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242; and Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322

Honokiol (HNK), a phenolic compound isolated and purified from magnolia, has been found to have a number of pharmacologic benefits, including anti-angiogenic and anti-inflammatory properties. HNK has long been used in traditional Asian medicine without toxic side effects. We and others have extensively studied signaling to B cells by CD40 and its Epstein Barr viral mimic, latent membrane protein 1 (LMP1), which has been implicated in exacerbation of chronic autoimmune disease. We asked whether HNK could inhibit CD40 and LMP1 inflammatory signaling mechanisms. In vivo, HNK stabilized the severity of symptomatic collagen-induced arthritis in both CD40-LMP1 transgenic mice and their congenic C57BL/6 counterparts. Ex vivo studies, including collagen-specific serum Ab and Ag recall responses, as well as CD40 or LMP1-mediated activation of splenic B cells, supported the anti-inflammatory effects of HNK. In mouse B cell lines expressing the human CD40-LMP1 chimeric receptor, CD40- and LMP1-mediated NF-B and AP-1 activation were abrogated in a dose-dependent manner, with a concomitant decrease in TNF- and IL-6. These promising findings suggest that the nontoxic anti-inflammatory properties of HNK could be valuable for blocking the autoimmune response.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health and the Veterans’ Administration (to G.A.B.) and postdoctoral fellowship support provided by the American Heart Association and the American Cancer Society (to M.E.M.).

² Address correspondence and reprint requests to Dr. Gail A. Bishop, 2193B Medical Education and Research Facility, Department of Microbiology, University of Iowa, Iowa City, IA 52242. E-mail address: gail-bishop{at}uiowa.edu

³ Abbreviations used in this paper: RA, rheumatoid arthritis; LMP, latent membrane protein; Tg, transgenic; m, mouse; CIA, collagen-induced arthritis; HNK, honokiol; h, human; WT, wild type; CII, type II chicken collagen.