Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
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Viscum album and its Constituents Downregulate MMP-13 Expression in Chondrocytes and Protect Cartilage Degradation

  • Lee, Ju Hee (College of Pharmacy, Kangwon National University) ;
  • Kwon, Yong Soo (College of Pharmacy, Kangwon National University) ;
  • Jung, Da Young (College of Pharmacy, Kangwon National University) ;
  • Kim, Na Young (College of Pharmacy, Kangwon National University) ;
  • Lim, Hyun (College of Pharmacy, Kangwon National University) ;
  • Kim, Hyun Pyo (College of Pharmacy, Kangwon National University)
  • Received : 2021.05.25
  • Accepted : 2021.08.16
  • Published : 2021.09.30
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Abstract

Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs) including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanol extract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yielded five constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2), syringin (3), homoflavoyadorinin B (4), and 4,4'-dihydroxy-3,6'-dimethoxychalcone-2'-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 - 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

Keywords

Acknowledgement

This study was financially supported by BK21-plus project from the Ministry of Education (Korea). Bioassay facility of New Drug Development Inst. (KNU) was used and greatly acknowledged.

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