Honokiol stimulates osteoblastogenesis by suppressing NF-κB activation

Abstract

Abstract. Magnolia officinalis, a component of Asian herbal teas, has long been employed in traditional Japanese and Chinese medicine to treat numerous maladies. Honokiol, a biphenolic compound, is now considered to be one of the major active ingredients of Magnolia extract, and is under intense investigation for its anti-angiogenic, anti-inflammatory, antitumor and neuroprotective properties. Biochemically, honokiol has been recognized to modulate the nuclear factor κ B (NF-κB) signal transduction pathway suggesting that it possesses antiinflammatory properties. Inflammation is intimately associated with bone turnover and skeletal deterioration and consequently, anti-inflammatory drugs may hold significant promise as bone protective agents to stem bone loss in osteoporotic conditions. We and others have demonstrated that suppression of NF-κB blunts osteoclastic bone resorption, but promotes osteoblastic bone formation. Indeed previous studies have demonstrated the anti-osteoclastogenic effects of honokiol, however, activities on osteoblast differentiation and activity have yet to be investigated. In this study, we show that honokiol is a potent inducer of in vitro osteoblast differentiation by virtue of its capacity to suppress basal and tumor necrosis factor alpha (TNFα)-induced NF-κB activation and to alleviate the suppressive action of TNFα on bone morphogenetic protein (BMP)-2-induced Smad activation. Our data confirm that honokiol may have considerable promise as a dual anabolic/anti-catabolic agent for the amelioration of multiple osteoporotic diseases.

Suppression of NF-κB Activation By Gentian Violet Promotes Osteoblastogenesis and Suppresses Osteoclastogenesis

“…TNFα further antagonizes BMP signaling by upregulating Smad ubiquitination regulatory factor 1 (Smurf1), promoting proteasomal degradation of bone morphogenetic signaling proteins [42]. Consistent with this data we have reported that multiple suppressors of NF-κB activation including the carotenoid beta-cryptoxanthin [43], the biphenol honokiol [19], vitamin K 2 [9], quercetin [20], zinc [24] and a pharmacological NF-κB inhibitor based on the NEMO binding domain [1] are all capable of rescuing the inhibitory effect of TNFα on BMP2 and/or TGFβ-induced Smad activation.…”

“…Interestingly, we have recently reported that several natural compounds, long believed to possess anabolic and/or anti-catabolic properties, may protect bone by antagonizing NF-κB activation. Among these agents are vitamin K 2 [9], 17beta-estradiol [17], the carotene, p-hydroxycinnamic acid, the xanthophyll, beta-cryptoxanthin [18], honokiol, a component of Asian herbal teas used extensively in traditional Japanese and Chinese medicine [19], and the plant-derived flavonoid quercetin [20]. …”

Honokiol inhibits EMT-mediated motility and migration of human non-small cell lung cancer cells in vitro by targeting c-FLIP

“…It was reported that HNK induces osteoblast differentiation in vitro because of its capacity to inhibit basal and TNF-α-induced NF-κB activation and to reduce the suppressive action of TNF-α on BMP-2-induced Smad activation [20,21] . Based on this, we examined whether Smad and NF-κB signaling were linked with c-FLIP after NSCLC cells were exposed to HNK.…”

The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis

“…We have shown that vitamin K2 [114], Honokiol [115], Zinc [116], and the carotenoid p -hydroxycinnamic [117, 118] are all capable of modulating NF- κ B activation in osteoblast and osteoclast precursors in vitro by antagonizing RANKL- and TNF α -induced NF- κ B activation in osteoblasts and osteoclasts, respectively.…”