Baicalein Inhibits MMPs Expression via a MAPK-Dependent Mechanism in Chondrocytes

Background: Baicalein is a flavonoid isolated from Scutellaria baicalensis Georgi. Here, we investigated the anti-osteoarthritic effect of baicalein in vitro and in vivo. Methods: Interleukin-1 beta (IL-1β)-induced chondrocytes were treated with different concentrations of baicalein, real-time PCR and ELISA were performed to detect the matrix metalloproteinases (MMPs) expression. Western blot was used to evaluate the mitogen-activated protein kinase (MAPK) expression. In experimental osteoarthritis (OA), rabbits were treated with baicalein, gross morphological and histological assessment was performed to evaluate the cartilage damage. Results: Baicalein significantly reduced the expression of MMPs in vitro and in vivo. Moreover, baicalein significantly reduced the phosphorylation of p38 and extracellular signal regulated kinase (ERK), but not of c-Jun N-terminal kinase (JNK). In addition, intra-articular injection of baicalein ameliorated the cartilage damage in a rabbit model of OA induced by anterior cruciate ligament transection (ACLT). Conclusions: The results indicate that baicalein may be considered as a potential agent for OA treatment.

[1]  Qiyu Zhang,et al.  Anticancer Effects of Baicalein on Hepatocellular Carcinoma Cells , 2014, Phytotherapy research : PTR.

[2]  Lianbo Xiao,et al.  Baicalein ameliorates inflammatory-related apoptotic and catabolic phenotypes in human chondrocytes. , 2014, International immunopharmacology.

[3]  Li-Dong Wu,et al.  Astaxanthin reduces matrix metalloproteinase expression in human chondrocytes. , 2014, International Immunopharmacology.

[4]  Zong-fang Li,et al.  Baicalein Reduces the Invasion of Glioma Cells via Reducing the Activity of p38 Signaling Pathway , 2014, PloS one.

[5]  Zong-fang Li,et al.  Baicalein Inhibits the Invasion and Metastatic Capabilities of Hepatocellular Carcinoma Cells via Down-Regulation of the ERK Pathway , 2013, PloS one.

[6]  Yang Yang,et al.  Baicalein Inhibits Interleukin-1β-Induced Proliferation of Human Rheumatoid Arthritis Fibroblast-like Synoviocytes , 2013, Inflammation.

[7]  Yuan Zhang,et al.  Anti-inflammatory Activity of Baicalein in LPS-Stimulated RAW264.7 Macrophages via Estrogen Receptor and NF-κB-Dependent Pathways , 2013, Inflammation.

[8]  L. Luo,et al.  Baicalein reduces lipopolysaccharide-induced inflammation via suppressing JAK/STATs activation and ROS production , 2013, Inflammation Research.

[9]  K. Kang,et al.  Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system , 2012, Cell Biology and Toxicology.

[10]  Xiuli Yi,et al.  Baicalein protects human melanocytes from H₂O₂-induced apoptosis via inhibiting mitochondria-dependent caspase activation and the p38 MAPK pathway. , 2012, Free radical biology & medicine.

[11]  Li-Dong Wu,et al.  Morin inhibits interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes. , 2012, International immunopharmacology.

[12]  J. Hyun,et al.  Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human Keratinocytes , 2012, Biomolecules & therapeutics.

[13]  Chih-Yang Huang,et al.  Baicalein inhibits the migration and invasive properties of human hepatoma cells. , 2011, Toxicology and applied pharmacology.

[14]  Li-Dong Wu,et al.  Anti-arthritic effects of chlorogenic acid in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model. , 2011, International immunopharmacology.

[15]  Li-Dong Wu,et al.  Alleviation of osteoarthritis by Trichostatin A, a histone deacetylase inhibitor, in experimental osteoarthritis , 2010, Molecular Biology Reports.

[16]  Li-Dong Wu,et al.  Variation patterns of two degradation enzyme systems in articular cartilage in different stages of osteoarthritis: regulation by dehydroepiandrosterone. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[17]  Y. Iwamoto,et al.  Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation. , 2009, Osteoarthritis and cartilage.

[18]  H. Afif,et al.  Histone deacetylase inhibitors suppress interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. , 2008, Osteoarthritis and cartilage.

[19]  D. Boyd,et al.  Regulation of matrix metalloproteinase gene expression , 2007, Journal of cellular physiology.

[20]  C. Brinckerhoff,et al.  Matrix metalloproteinases: role in arthritis. , 2006, Frontiers in bioscience : a journal and virtual library.

[21]  D. D’Lima,et al.  Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis , 2004, Annals of the rheumatic diseases.

[22]  P. Anract,et al.  Effect of inhibition of matrix metalloproteinases on cartilage loss in vitro and in a guinea pig model of osteoarthritis. , 2005, Arthritis and rheumatism.

[23]  D. Zukor,et al.  Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. , 2005, Arthritis and rheumatism.

[24]  J. Riancho,et al.  [Risk factors and stroke among patients of different ages]. , 2003, Revista clinica espanola.

[25]  A. Poole,et al.  Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. , 2001, The Journal of clinical investigation.

[26]  H. Scharf,et al.  Interleukin-1β Induces Different Gene Expression of Stromelysin, Aggrecan and Tumor-Necrosis-Factor-Stimulated Gene 6 in Human Osteoarthritic Chondrocytes in vitro , 2000, Pathobiology.

[27]  C. Brinckerhoff,et al.  Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. , 2000, Arthritis and rheumatism.

[28]  R. Moskowitz,et al.  Temporal pattern of cysteine endopeptidase (cathepsin B) expression in cartilage and synovium from rabbit knees with experimental osteoarthritis: gene expression in chondrocytes in response to interleukin-1 and matrix depletion , 1997, Annals of the rheumatic diseases.

[29]  H. Dorfman,et al.  Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. , 1971, The Journal of bone and joint surgery. American volume.