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

Abstract

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-κB and AP-1 activation were abrogated in a dose-dependent manner, with a concomitant decrease in TNF-α and IL-6. These promising findings suggest that the nontoxic anti-inflammatory properties of HNK could be valuable for blocking the autoimmune response.

Honokiol Inhibits the Progression of Collagen-Induced Arthritis by Reducing Levels of Pro-inflammatory Cytokines and Matrix Metalloproteinases and Blocking Oxidative Tissue Damage

“…The results of recent studies have shown that honokiol inhibits NO synthesis and TNF-α expression in lipopolysaccharide-activated macrophages (30) and RANKL-induced osteoclastogenesis in RAW264.7 cells (31). Intraperitoneal injection of honokiol at a dosage of 3 mg/ mouse per day ameliorated murine CIA by suppressing the production of anti-CII-specific antibodies and CD40-mediated signaling in activated B cells (32). In the present study, in order to further characterize the anti-arthritic effects and mechanisms underlying the activity of orally administered honokiol, we focused on CIA-induced pro- NO in the articular chondrocytes (34,35).…”

Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents

“…An impressive series of studies has shown that all of these major indicators are positively impacted by Magnolia lignans, even if the full anti-inflammatory mechanisms have not yet been elucidated (Choi et al, 2007;Lin et al, 2007;Munroe et al, 2007;Kang et al, 2008;Lee et al, 2011). Upregulating signaling cascades composed of Ras, Raf, and MAPK, downregulating the activation of NF-κB, and blocking NF-κB activation mediated by CD40 and latent membrane protein 1 are speculated to be the action mechanism of Magnolia lignans (Lin et al, 2007;Kim and Cho, 2008;Lee et al, 2011).…”

A Naturally Occurring Rexinoid, Honokiol, Can Serve as a Regulator of Various Retinoid X Receptor Heterodimers

“…To date, honokiol has been shown to exert many pharmacological effects, including anti-inflammatory, 36) anti-arrhythmic, 37) anxiolytic, 35) antitumor, 33) antithrombotic, 38) antiarthritic, 34) and anti-allergic 39) effects. However, the molecular targets underlying the numerous activities of honokiol have been poorly understood.…”

“…Specifically, the therapeutic effects of the PPARγ agonists thiazolidinediones and VDR agonist 1α,25(OH) 2 D 3 are hampered by their severe side effects. 31,32) On the other hand, honokiol has been well tolerated in models of arthritis, heart disease, and cancer, 33,34) and has been used without noticeable side effects for many years in traditional Japanese or Chinese medicines. 35) Therefore, combination therapies using honokiol and low doses of the respective agonists may overcome such problems.…”