Piperine mediates LPS induced inflammatory and catabolic effects in rat intervertebral disc.
Piperine is an exact of the active phenolic component from Black pepper. It has been reported to have many biological activities including anti-oxidant, anti-inflammatory and anti-tumor effects. Intervertebral disc degeneration (IDD) is a degenerative disease closely relate to inflammation of nucleus pulposus (NP) cells. This study aimed to assess the anti-inflammatory and anti-catabolic effects of piperine in rat intervertebral disc using in vitro and ex vivo analyzes. We demonstrated that piperine could inhibit LPS induced expression and production of inflammatory factors and catabolic proteases in NP cells culture model. It significantly inhibited multiple inflammatory factors and oxidative stress-associated genes (IL-1β, TNF-α, IL-6, iNOS), MMPs (MMP-3, MMP-13), ADAMTS (ADAMTS-4, ADAMTS-5) mRNA expression and NO production in a concentration-dependent manner. Moreover, piperine could reverse the LPS-induced inhibition of gene expression of aggrecan and collagen-II. Histologic and dimethylmethylene blue analysis indicated piperine could also against LPS induced proteoglycan (PG) depletion in a rat intervertebral disc culture model. Western blot results showed that piperine inhibited the LPS-mediated phosphorylation of JNK and activation of NF-κB. Finally, our results demonstrated the ability of piperine to antagonize LPS-mediated inflammation of NP cells and suppression of PG in rat intervertebral disc, suggesting a potential agent for treatment of IDD in future.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road, Shanghai 200011, China.
Yan
Y
Li
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road, Shanghai 200011, China.
Kang
K
Li
Zhejiang Chinese Medical University 548 Binwen Road, Hangzhou 310053, Zhejiang, China.
Yiqin
Y
Hu
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road, Shanghai 200011, China.
Bo
B
Xu
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road, Shanghai 200011, China.
Jie
J
Zhao
D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009924:Organ Culture Techniques; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D053674:Aggrecans; D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D052117:Benzodioxoles; D024043:Collagen Type II; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D008666:Metalloendopeptidases; C008922:piperine
Piperine; inflammation; intervertebral disc degeneration; nucleus pulposus cells