کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5501787 | 1534937 | 2017 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes
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کلمات کلیدی
Nrf2ADAMTSHeme oxygenase-1cyclo-oxygenase-2NQO1IL-1βGCLCPGE2ECMiNOSERKCOX-2HO-1Col2a1AggrecanIL-6ACANSOD-2MMPNAD(P)H: quinone oxidoreductaseERK1/2 - ERK1 / 2MAPK - MAPKROS - ROSOsteoarthritis - استئوآرتریت(آرتروز)interleukin-6 - اینترلوکین ۶Interleukin-1β - اینترلوکین-1βa disintegrin and metalloproteinase with thrombospondin motifs - تخریب و متالوپروتئیناز با ترومبوسپوندین موتیفRedox - ردوکس(اکسایش و کاهش)inducible nitric oxide synthase - سنتاز اکسید نیتریک القاییextracellular signal regulated kinase - سیگنال خارج سلولی kinase را تنظیم می کندTumor Necrosis Factor- α - عامل ناکروز تومور- αTNF-α - فاکتور نکروز توموری آلفاnuclear factor (erythroid-derived 2)-like 2 - فاکتور هسته ای (erythroid-derived 2) -like 2Extracellular matrix - ماتریکس خارج سلولیmatrix metalloproteinase - ماتریکس متالوپروتئینازNitric oxide - نیتریک اکسیدWogonin - وگوونینmitogen activated protein kinase - پروتئین کیناز فعال Mitogen فعال استProstaglandin E2 - پروستاگلاندین E2glutamate-cysteine ligase catalytic subunit - کلوتامین کاتالیزوری لیگاز گلوتامات-سیستئینReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Here, we evaluated the potential chondroprotective and anti-inflammatory effects of Wogonin, a naturally occurring flavonoid, in IL-1β-stimulated human OA chondrocytes and cartilage explants. Wogonin completely suppressed the expression and production of inflammatory mediators including IL-6, COX-2, PGE2, iNOS and NO in IL-1β-stimulated OA chondrocytes. Further, Wogonin exhibits potent chondroprotective potential by switching the signaling axis of matrix degradation from catabolic towards anabolic ends and inhibited the expression, production and activities of matrix degrading proteases including MMP-13, MMP-3, MMP-9, and ADAMTS-4 in OA chondrocytes, and blocked the release of s-GAG and COL2A1 in IL-1β-stimulated OA cartilage explants. Wogonin also elevated the expression of cartilage anabolic factors COL2A1 and ACAN in chondrocytes and inhibited the IL-1β-mediated depletion of COL2A1 and proteoglycan content in the matrix of cartilage explants. The suppressive effect of Wogonin was not mediated through the inhibition of MAPKs or NF-κB activation. Instead, Wogonin induced mild oxidative stress through the generation of ROS and depletion of cellular GSH, thereby modulating the cellular redox leading to the induction of Nrf2/ARE pathways through activation of ROS/ERK/Nrf2/HO-1-SOD2-NQO1-GCLC signaling axis in OA chondrocytes. Molecular docking studies revealed that Wogonin can disrupt KEAP-1/Nrf-2 interaction by directly blocking the binding site of Nrf-2 in the KEAP-1 protein. Genetic ablation of Nrf2 using specific siRNA, significantly abrogated the anti-inflammatory and chondroprotective potential of Wogonin in IL-1β-stimulated OA chondrocytes. Our data indicates that Wogonin exerts chondroprotective effects through the suppression of molecular events involved in oxidative stress, inflammation and matrix degradation in OA chondrocytes and cartilage explants. The study provides novel insights into the development of Nrf2 as a promising candidate and Wogonin as a therapeutic agent for the management of OA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 106, May 2017, Pages 288-301
Journal: Free Radical Biology and Medicine - Volume 106, May 2017, Pages 288-301
نویسندگان
Nazir M. Khan, Abdul Haseeb, Mohammad Y. Ansari, Pratap Devarapalli, Sara Haynie, Tariq M. Haqqi,