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

Hyun Lim; Dong Suk Min; Han Eul Yun; Kil Tae Kim; Ya Nan Sun; Le Duc Dat; Young Ho Kim; Hyun Pyo Kim

doi:10.1016/j.jep.2017.07.034

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

J Ethnopharmacol. 2017 Sep 14:209:73-81. doi: 10.1016/j.jep.2017.07.034. Epub 2017 Jul 21.

Authors

Hyun Lim¹, Dong Suk Min¹, Han Eul Yun¹, Kil Tae Kim¹, Ya Nan Sun², Le Duc Dat³, Young Ho Kim⁴, Hyun Pyo Kim⁵

Affiliations

¹ College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
² College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
³ College of Pharmacy, Catholic University of Deagu, Gyeongsan 712-702, South Korea.
⁴ College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea. Electronic address: yhk@cnu.ac.kr.
⁵ College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea. Electronic address: hpkim@kangwon.ac.kr.

PMID: 28735730
DOI: 10.1016/j.jep.2017.07.034

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 0.5-10μM. 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.

Conclusions: Impressic acid, its related triterpenoids, and A. koreanum extract have potential as therapeutic agents to prevent cartilage degradation by inhibiting matrix protein degradation.

Keywords: Acanthopanax koreanum; Cartilage; Impressic acid; Matrix metalloproteinase.

MeSH terms

Animals
Cartilage / drug effects*
Chondrocytes / drug effects*
Eleutherococcus / chemistry*
Gene Expression Regulation, Enzymologic / drug effects
Humans
Male
Matrix Metalloproteinase 13 / metabolism*
Molecular Structure
Plant Leaves / chemistry
Rabbits
Tissue Culture Techniques
Triterpenes / chemistry
Triterpenes / pharmacology*

Substances

3,11-dihydroxylup-20(29)-en-28-oic acid
Triterpenes
Matrix Metalloproteinase 13