The inhibitory effect of pseudoshikonin I from Lithospermi radix on matrix-metalloproteinase (MMPs) production and expression in interleukin-1β induced SW1353 chondrosarcoma cells

A new compound, named as pseudoshikonin I, was isolated from the 70% ethanol extract of Lithospermi radix. The structure was identified as 1-(1,7-dihydroxynaphthalen-3-yl)-4-methylpent-3-enyl-3-methylbut-2-enoate, by means of spectroscopic methods, including HR-FAB/MS, 1D NMR (¹H, ¹³C, DEPT), and 2D NMR (gCOSY, gHSQC, gHMBC, NOESY) spectroscopic analysis. We evaluated the inhibitory effect of pseudoshikonin I (PS) on matrix-metalloproteinase (MMPs) [1] production and expression in interleukin-1β induced SW1353 chondrosarcoma cells. Following treatment with PS (50, 100 µM), active MMP-1, -2, -3, -9, and 13 were quantified in the SW1353 cell culture supernatants using a commercially available ELISA kit. PS treatment effectively inhibited the production of MMPs. The gene expression of MMP-1, -2, -3, 9 and 13, TIMP-2, iNOS and COX-2 in SW1353 cells was investigated by RT-PCR [2]. The MMP-9 (74.2 ± 1.4-fold), MMP-13 (70.2 ± 3.9-fold), iNOS (74.7 ± 2.6-fold) and COX-2 (85.9 ± 3.2-fold) were suppressed by PS treatment in a dose dependent manner. The TIMP-2 mRNA expression was significantly up-regulated by PS (100 µM) treatment compared to the control groups (100-fold). Therefore, pseudoshikonin I from Lithospermi radix might be used to protect cartilage by the inhibitory effect on the production of MMPs as a potential natural ant-inflammatory or anti-osteoarthritis agent.

References:

[1] Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: Role in arthritis. Front in Biosc. 2006; 11: 529 – 543

[2] Piecha D, Weik J, Kheil H, Becher G, Timmermann A, Jaworski A, Burger M, Hofmann MW. Novel selective MMP-13 inhibitors reduce collagen degradation in bovine articular and human osteoarthritis cartilage explants. Inflamm Res 2010; 59:379 – 389