title: Pycnogenol attenuates the inflammatory and nitrosative stress on joint inflammation induced by urate crystals.
abstract: Acute gouty arthritis results from monosodium urate (MSU) crystal deposition in joint tissues. Deposited MSU crystals induce an acute inflammatory response which leads to damage of joint tissue. Pycnogenol (PYC), an extract from the bark of Pinus maritime, has documented antiinflammatory and antioxidant properties. The present study aimed to investigate whether PYC had protective effects on MSU-induced inflammatory and nitrosative stress in joint tissues both in vitro and in vivo. MSU crystals upregulated cyclooxygenase 2 (COX-2), interleukin 8 (IL-8) and inducible nitric oxide synthase (iNOS) gene expression in human articular chondrocytes, but only COX-2 and IL-8 in synovial fibroblasts. PYC inhibited the up-regulation of COX-2, and IL-8 in both articular chondrocytes and synovial fibroblasts. PYC attenuated MSU crystal induced iNOS gene expression and NO production in chondrocytes. Activation of NF-κB and SAPK/JNK, ERK1/2 and p38 MAP kinases by MSU crystals in articular chondrocytes and synovial fibroblasts in vitro was attenuated by treatment with PYC. The acute inflammatory cell infiltration and increased expression of COX-2 and iNOS in synovial tissue and articular cartilage following intra-articular injection of MSU crystals in a rat model was inhibited by coadministration of PYC. Collectively, this study demonstrates that PYC may be of value in treatment of MSU crystal-induced arthritis through its anti-inflammatory and anti-nitrosative activities.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, No.161, Minchun E. Rd, Neihu114, Taipei, Taiwan. yijen0426@gmail.com
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.forename: Chian-Her
authors.initials: CH
authors.lastname: Lee
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Wang
authors.forename: Donald M
authors.initials: DM
authors.lastname: Salter
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015210:Arthritis, Gouty / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D017746:Joint Capsule / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D014527:Uric Acid
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D016209:Interleukin-8; D010936:Plant Extracts; D014527:Uric Acid; C024070:pycnogenols; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2