Impressic acid from Acanthopanax koreanum, possesses matrix metalloproteinase-13 down-regulating capacity and protects cartilage destruction. (14th September 2017)

• Record Type: Journal Article
• Authors: Lim, Hyun; Min, Dong Suk; Yun, Han Eul; Kim, Kil Tae; Sun, Ya Nan; Dat, Le Duc; Kim, Young Ho; Kim, Hyun Pyo
• Is Part Of: Journal of ethnopharmacology. Volume 209(2017)
• Page Start: 73
• Page End: 81
• Publication Date: 2017-09-14
• Subjects: MMP matrix metalloproteinase -- MAPK mitogen-activated protein kinase -- JAK/STAT Janus kinase/signal transducer and activator of transcription, NF-κB, nuclear transcription factor-κB -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- PMSF phenylmethylsulfonyl fluoride -- DTT dithiothreitol -- ECL enhanced chemiluminescence -- DMMB dimethylmethylene blue -- GAG glycosaminoglycan -- PG proteoglycan, AP-1, activator protein-1 -- NEAT nuclear factor of activated T-cells -- ERK extracellular signal-regulated kinase, JNK, c-Jun N-terminal kinase -- MyD88 myeloid differentiation primary response gene 88, IRAK1, interleukin-1 receptor-associated kinase 1, TRAF6, TNF receptor-associated factor 6 -- TBST Tris-buffered saline with Tween 20; Acanthopanax koreanum -- Impressic acid -- Matrix metalloproteinase -- Cartilage; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2017.07.034
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Acanthopanax 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 study: Matrix 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 methods: 70% 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. Results: In IL-1β-treated SW1353 cells, impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 0.5–10 μM. 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 10 μM), glycosaminoglycan release (42.2% reduction at 10 μM) 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, compounds2, 3, 16, and18 clearly down-regulated MMP-13 expression. However, impressic acid was more potent than these derivatives in down-regulating MMP-13 expression. Conclusions: Impressic acid, its related triterpenoids, and A. koreanum extract have potential as therapeutic agents to prevent cartilage degradation by inhibiting matrix protein degradation. Graphical abstract: