title: Sesamin inhibits lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc.
abstract: Intervertebral disc (IVD) degeneration contributes to most spinal degenerative diseases, while treatment inhibiting IVD degeneration is still in the experimental stage. Sesamin, a bioactive component extracted from sesame, has been reported to exert chondroprotective and anti-inflammatory effects. Here, we analyzed the anti-inflammatory and anti-catabolic effects of sesamin on rat IVD in vitro and ex vivo. Results show that sesamin significantly inhibits the lipopolysaccharide (LPS)-induced expression of catabolic enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5) and inflammation factors (IL-1β, TNF-α, iNOS, NO, COX-2, PGE2) in a dose-dependent manner in vitro. It is also proven that migration of macrophages induced by LPS can be inhibited by treatment with sesamin. Organ culture experiments demonstrate that sesamin protects the IVD from LPS-induced depletion of the extracellular matrix ex vivo. Moreover, sesamin suppresses LPS-induced activation of the mitogen-activated protein kinase (MAPK) pathway through inhibiting phosphorylation of JNK, the common downstream signaling pathway of LPS and IL-1β, which may be the potential mechanism of the effects of sesamin. In light of our results, sesamin protects the IVD from inflammation and extracellular matrix catabolism, presenting positive prospects in the treatment of IVD degenerative diseases.
authors.affiliation: a Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery , Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: a Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery , Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery , Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: a Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery , Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Lu
authors.initials: L
authors.lastname: Mao
authors.affiliation: a Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery , Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000070614:Nucleus Pulposus / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004149:Dioxoles; D053583:Interleukin-1beta; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C054125:sesamin
keywords: extracellular matrix; inflammation; intervertebral disc; lipopolysaccharide; organ culture; sesamin