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KMID : 0043320150380061108
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Archives of Pharmacal Research
2015 Volume.38 No. 6 p.1108 ~ p.1116
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Inhibition of matrix metalloproteinase-13 expression in IL-1β-treated articular chondrocytes by a steroidal saponin, spicatoside A, and its cellular mechanisms of action
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Lim Hyun
Min Dong-Suk
Kang Yu-Na
Kim Hyeong-Won
Son Kun-Ho
Kim Hyun-Pyo
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Abstract
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Matrix metalloproteinase-13 (MMP-13) plays a critical role in degrading major collagens in human cartilage under some pathological conditions such as osteoarthritis. To establish the therapeutic potential against cartilage degradation, the effects of 12 naturally-occurring triterpenoids and steroids on MMP-13 induction were examined in the human chondrocyte cell line, SW1353. They included coreanoside F1, suavissimoside R1, spicatoside A, 25(S)-ruscogenin, methyl protogracillin, hederagenin, loniceroside A, loniceroside B, loniceroside C, smilaxin A, smilaxin C, and ursolic acid. Among these, only spicatoside A and 25(S)-ruscogenin were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at a pharmacologically-relevant concentration of 10 μM. These effects were also supported by the finding that spicatoside A (20 μM) reduced glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. When the cellular mechanisms of action of spicatoside A in MMP-13 inhibition were investigated, the blocking point was not found among the MMP-13 signaling molecules examined such as mitogen-activated protein kinases, activator protein-1, and nuclear transcription factor-κB. Instead, spicatoside A was found to reduce MMP-13 mRNA stability. All of these findings suggest that spicatoside A and 25(S)-ruscogenin have a therapeutic potential for protecting against cartilage breakdown in arthritic disorders.
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KEYWORD
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Spicatoside A, Triterpenoid, Steroid, Matrix metalloproteinase-13, Chondrocyte
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