Honokiol inhibits the progression of collagen-induced arthritis by reducing levels of pro-inflammatory cytokines and matrix metalloproteinases and blocking oxidative tissue damage.
Plant-derived compounds with potent anti-inflammatory activity have attracted a great deal of attention as a source for novel anti-arthritic agents with minimal side effects. We attempted to determine the anti-arthritic effects of orally administered honokiol isolated from Magnolia species. The oral administration of honokiol inhibited the progression and severity of type II collagen (CII)-induced arthritis (CIA) by reducing clinical arthritis scores and paw swelling. The histological analysis demonstrated preserved joint space; and the immunohistochemical data showed that the levels of interleukin (IL)-17, matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, and receptor activator for nuclear factor-κB ligand, as well as nitrotyrosine formation, were substantially suppressed in the honokiol-treated CIA mice. The elevated serum levels of tumor necrosis factor-α and IL-1β in the CIA mice were also restored to control levels via honokiol treatment. In the CIA mice, honokiol inhibited CII- or lipopolysaccharide-stimulated cytokine secretion in spleen cells, as well as CII-stimulated spleen cell proliferation. Furthermore, honokiol treatment reduced CIA-induced oxidative damage in the liver and kidney tissues of CIA mice. Collectively, the oral administration of honokiol inhibited CIA development by reducing the production of pro-inflammatory cytokines, MMP expressions, and oxidative stress. Thus, honokiol is an attractive candidate for an anti-arthritic agent.
Kim
Ki Rim
KR
Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, and Brain Korea 21 Project, Yonsei University College of Dentistry, Korea.
Park
Kwang-Kyun
KK
Chun
Kyung-Soo
KS
Chung
Won-Yoon
WY
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002417:Cattle; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018450:Disease Progression; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D017705:Lignans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols