Anti-Inflammatory Bioactivities of Honokiol through Inhibition of Protein Kinase C, Mitogen-Activated Protein Kinase, and the NF-κB Pathway To Reduce LPS-Induced TNFα and NO Expression

Abstract

Much recent research has demonstrated that honokiol, a phenolic compound originally isolated from Magnolia officinalis, has potent anticancer activities; however, the detailed molecular mechanism of its anti-inflammatory activity has not yet been fully addressed. In this study we demonstrated that honokiol inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha secretion in macrophages, without affecting the activity of the tumor necrosis factor-alpha converting enzyme. At the same time, honokiol not only inhibited nitric oxide expression in LPS-stimulated murine macrophages but also inhibited the LPS-induced phosphorylation of ERK1/2, JNK1/2, and p38. By means of confocal microscope analysis we demonstrated that phosphorylation and membrane translocation of protein kinase C-alpha, as well as NF-kappaB activation, were inhibited by honokiol in LPS-stimulated macrophages. Furthermore, it was found that honokiol neither antagonizes the binding of LPS to cells nor alters the cell surface expression of toll-like receptor 4 and CD14. Our current results have exhaustively described the anti-inflammatory properties of honokiol, which could lead to the possibility of its future pharmaceutical application in the realm of immunomodulation.

Honokiol rescues sepsis-associated acute lung injury and lethality via the inhibition of oxidative stress and inflammation

“…Lee et al [39] have shown that magnolol and honokiol could inhibit the NF-jB element, which exists in cyclooxygenase-2, IL-8, and TNF-a promoters in monocytic cells to exert their anti-inflammatory effects. A recent study also demonstrated that honokiol inhibits protein kinase C-a, mitogen-activated protein kinase, and NF-jB activation to reduce TNF-a and NO expression in LPS-stimulated macrophages [40]. In the present study, honokiol shows promise as a therapeutic agent after induction of endotoxemia and sepsis in the mouse models.…”

Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O-methylhonokiol in zymosan-induced animal models

“…Structural analogs, such as magnolol, ovobatol, and honokiol, showed similar selectivity and potency as MH in cellular assays. These analogs are reported to inhibit gene expression and protein production of inflammatory mediators, such as TNF-a, IL-1b, IL-6, iNOS, and COX, and the synthesis of NO and PGs, generally by blocking NF-jB, MAPK, or Akt/PI3 K pathways in immune cells at lM concentrations (Son et al 2000;Seo et al 2013;Fu et al 2013;Choi et al 2007;Chao et al 2010). However, in our hand, MH analogs at non-toxic concentrations may inhibit strongly COX-2, but might affect slightly other inflammatory responses.…”

Size-Dependent Attenuation of TLR9 Signaling by Gold Nanoparticles in Macrophages

“…Murine Raw264.7 cells were cultured in DMEM supplemented with 10% FBS, L-glutamine at 37˚C in a humidified atmosphere under 5% CO 2 . RAW-Blue cells that stably express an NF-kB and AP-1-inducible SEAP were provided by Dr. Kuo-Feng Hua, originally purchased from InvivoGen (26). The SEAP activities were measured using QUANTI-Blue (InvivoGen) SEAP detection medium.…”