title: Ginsenosides from Korean red ginseng inhibit matrix metalloproteinase-13 expression in articular chondrocytes and prevent cartilage degradation.
abstract: Among the mammalian matrix metalloproteinases (MMPs), MMP-1, -3 and -13 are collagenases. Particularly, MMP-13 is important for the degradation of major collagens in cartilage under certain pathological conditions such as osteoarthritis. To establish a potential therapeutic strategy for cartilage degradation disorders, the effects of 11 ginseng saponins (ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rg5, Rk1 and F4) on MMP-13 induction were examined in a human chondrocyte cell line, SW1353. Among these, several saponins including ginsenoside Rc, Rd, Rf, Rg3 and F4 were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at non-cytotoxic concentrations (1-50 μM). The most prominent inhibitors were ginsenosides F4 and Rg3. Ginsenoside F4 inhibited MMP-13 expression 33.5% (P<0.05), 57.9% (P<0.01) and 90.0% (P<0.01) at 10, 30 and 50 μM, respectively. Significantly, ginsenoside F4 was found to strongly inhibit activation of p38 mitogen-activated protein kinase in signal transduction pathways (86.6 and 100.0% inhibition at 30 and 50 μM, P<0.01). The MMP-13 inhibitory effect was also supported by the finding that ginsenosides F4 and Rg3 reduced glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. Taken together, these results indicate that several ginsenosides inhibit MMP-13 expression in IL-1β-treated chondrocytes. Ginsenoside F4 and Rg3 blocked cartilage breakdown in rabbit cartilage tissue culture. Thus, it is suggested that certain ginsenosides have therapeutic potential for preventing cartilage collagen matrix breakdown in diseased tissues such as those found in patients with arthritic disorders.
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lim
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Omer
authors.initials: O
authors.lastname: Shehzad
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea. Electronic address: hpkim@kangwon.ac.kr.
authors.forename: Hyun Pyo
authors.initials: HP
authors.lastname: Kim
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D005894:Panax; D011817:Rabbits
chemical_list: D036145:Ginsenosides; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: Cartilage; Chondrocyte; Ginsenoside; Matrix metalloproteinase-13