Nat Prod Sci.  2021 Sep;27(3):151-160. 10.20307/nps.2021.27.3.151.

Viscum album and its Constituents Downregulate MMP-13 Expression in Chondrocytes and Protect Cartilage Degradation

• Lee JH
• Kwon YS
• Jung DY
• Kim NY
• Lim H
• Kim HP

• KMID: 2521083
• DOI: http://doi.org/10.20307/nps.2021.27.3.151

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 ethanolextract 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.

Keyword

Viscum album; chalcone; matrix metalloproteinase; cartilage