A Polyphenol-rich Pomegranate Fruit Extract Suppresses NF-kappaB and IL-6 Expression by Blocking the Activation of IKKbeta and NIK in Primary Human Chondrocytes.

A Polyphenol-rich Pomegranate Fruit Extract Suppresses NF-kappaB and IL-6 Expression by Blocking the Activation of IKKbeta and NIK in Primary Human Chondrocytes.

Haseeb Abdul; Khan Nazir M; Ashruf Omer S; Haqqi Tariq M

Phytotherapy research : PTR

2017

2017-05

Pomegranate fruit extract (PE) rich in polyphenols has been shown to exert chondroprotective effects, but the mechanism is not established. Here, we used an in vitro model of inflammation in osteoarthritis (OA) to investigate the potential of PE to suppress interleukin 1 beta (IL-1beta)-stimulated expression of inflammatory cytokine IL-6, generation of reactive oxygen species (ROS) levels, and investigated the mechanism of NF-kappaB inhibition by analyzing the activation of the kinases upstream of IkappaBalpha in primary human chondrocytes. Total and phosphorylated forms of kinases and expression of IL-6 were determined at protein and mRNA levels by western immunoblotting and Taqman assay, respectively. Dihydrorhodamine 123 staining estimated ROS generation. Pomegranate fruit extract inhibited the mRNA and protein expression of IL-6, generation of ROS, and inhibited the IL-1beta-mediated phosphorylation of inhibitor of nuclear factor kappa-B kinase subunit beta (IKKbeta), expression of IKKbeta mRNA, degradation of IkappaBalpha, and activation and nuclear translocation of

chondrocytes; Chondrocytes – Drug Effects; Chondrocytes/drug effects; Fruit; Fruit/chemistry; Gene Expression Regulation/drug effects; Genes – Drug Effects; Humans; I-kappa B Kinase/genetics/*metabolism; IkappaB; IKKbeta; IL-1beta; Interleukin 1 – Metabolism; Interleukin-1beta/metabolism; Interleukin-6/genetics/*metabolism; Interleukins; Interleukins – Metabolism; NF-kappa B; NF-kappa B – Metabolism; NF-kappa B/genetics/*metabolism; NF-kappaB; NIK; osteoarthritis; Phosphorylation – Drug Effects; Phosphorylation/drug effects; Plant Extracts; Plant Extracts – Pharmacodynamics; Plant Extracts/chemistry/*pharmacology; Polyphenols – Pharmacodynamics; Polyphenols/pharmacology; pomegranate; Pomegranate; Protein-Serine-Threonine Kinases/genetics/*metabolism; Proteins – Metabolism; Punicaceae/*chemistry; Signal Transduction – Drug Effects; Signal Transduction/drug effects; Transcription Factor RelA/metabolism; Transferases; Transferases – Metabolism

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