Icariin protects murine chondrocytes from lipopolysaccharide-induced inflammatory responses and extracellular matrix degradation

• Published in: Nutrition research (New York, N.Y.) Vol. 30; no. 1; pp. 57 - 65
• Main Authors: Liu, Man-Hai, Sun, Jui-Sheng, Tsai, Shaio-Wen, Sheu, Shiow-Yunn, Chen, Ming-Hong
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2010; Tarrytown, N.Y.: Elsevier Science Inc; Elsevier
• Subjects: Animals; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; arthritis; Arthritis, Infectious - drug therapy; Biological and medical sciences; Cell Survival - drug effects; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; collagen; Collagen - metabolism; COX-2; dose response; Epimedium; Epimedium - chemistry; Epimedium pubescens; extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Feeding. Feeding behavior; flavonoids; Flavonoids - pharmacology; Flavonoids - therapeutic use; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Gene expression; gene expression regulation; glucosides; glycosaminoglycans; Glycosaminoglycans - metabolism; human diseases; Icariin; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; iNOS; Lipopolysaccharides; matrix metalloproteinase; Matrix Metalloproteinases, Secreted - metabolism; medicinal plants; metalloproteinases; Mice; MMPs; nitric oxide; Nitric Oxide - biosynthesis; nitric oxide synthase; Oriental traditional medicine; phytochemicals; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; protective effect; Vertebrates: anatomy and physiology, studies on body, several organs or systems; viability; Icariin; COX-2; 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide; MMPs; PGE 2; Inflammation; GAG; MTT; Gene expression; ECM; LPS; reverse transcriptase-polymerase chain reaction; RT-PCR; Chondrocytes; iNOS; prostaglandin E 2; Mice; lipopolysaccharide; matrix metalloproteinases; glycosaminoglycan; extracellular matrix; Chondrocyte; Rodentia; Degradation; Vertebrata; Mammalia; Mouse; Animal; Lipopolysaccharide; Extracellular matrix
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2009.10.020

Abstract Septic arthritis is an inflammatory arthropathy characterized by degeneration of articular cartilage. Icariin, the main active flavonoid glucoside isolated from Epimedium pubescens , is used as antirheumatics (or antiinflammatory), tonics, and aphrodisiacs in traditional Chinese medicine. In this study, we used lipopolysaccharide (LPS) to simulate the in vitro inflammatory response of chondrocytes during septic arthritis. Our hypothesis is that the icariin can protect chondrocytes from LPS-induced inflammation and extracellular matrix degradation. The inflammation of neonatal mice chondrocytes was induced by LPS and the antiinflammatory effects were examined. The synthesis of nitric oxide was analyzed, whereas the titer of glycosaminoglycan and total collagen were measured and the gene expressions (including inducible nitric oxide synthase [iNOS], matrix metalloproteinase [MMP]–1, MMP-3, and MMP-13) were evaluated. The results showed that the viability of chondrocytes, extracellular matrix synthesis, was significantly decreased, whereas nitric oxide synthesis was significantly increased in the presence of 10−5 g/mL LPS. Icariin pretreatment can partially reverse these effects. The up-regulated expressions of MMP-1, 3, 13, cyclooxygenase-2 (COX-2), and iNOS genes by LPS treatment were also significantly down-regulated by the pretreatment of icariin to 1.8%, 0.056%, 7.7%, 3.1%, and 5.3% of the LPS-positive control sample, respectively. Our results demonstrate that icariin is a safe anabolic agent of chondrocytes. Icariin may exert its protective effects through inhibition of nitric oxide and MMP synthesis, and may then reduce the extracellular matrix destruction.