Impressic acid from Acanthopanax koreanum, possesses matrix metalloproteinase-13 down-regulating capacity and protects cartilage destruction

Publication date: 14 September 2017
Source:Journal of Ethnopharmacology, Volume 209
Author(s): Hyun Lim, Dong Suk Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Le Duc Dat, Young Ho Kim, Hyun Pyo Kim
Ethnopharmacological relevanceAcanthopanax koreanum (Araliaceae) has been used in traditional medicine for enhancing vitality, rheumatism, and bone-related pains. But its activity on cartilage protection has not been known yet.Aim of the studyMatrix metalloproteinase (MMP)−13 has an important role in degrading cartilage materials under pathologic conditions such as arthritis. The present study was designed to find the inhibitory activity of impressic acid on MMP-13 expression and cartilage protective action.Materials and methods70% ethanol extract of Acanthopanax koreanum leaves and impressic acid, a major constituent isolated from the same plant materials, were examined on MMP-13 down-regulating capacity in IL-1β-treated human chondrocyte cell line (SW1353) and rabbit cartilage explants.ResultsIn IL-1β-treated SW1353 cells, impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 0.5–10μM. Impressic acid was found to be able to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/−2 (STAT-1/−2) and activation of c-Jun and c-Fos among the cellular signaling pathways involved. Further, impressic acid was found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10μM), glycosaminoglycan release (42.2% reduction at 10μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. In addition, a total of 21 lupane-type triterpenoids structurally-related to impressic acid were isolated from the same plant materials and their suppressive activities against MMP-13 expression were also examined. Among these derivatives, compounds 2, 3, 16, and 18 clearly down-regulated MMP-13 expression. However, impressic acid was more potent than these derivatives in down-regulating MMP-13 expression.ConclusionsImpressic acid, its related triterpenoids, and A. koreanum extract have potential as therapeutic agents to prevent cartilage degradation by inhibiting matrix protein degradation.

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