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Two matrix metalloproteinases inhibitors from Ferula persica var. persica
A R Shahverdi1, F Saadat, M R Khorramizadeh
1Department of Pharmaceutical Biotechnology and Medicinal Plant Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. shahverd@sina.tums.ac.ir
Abstract:
Matrix metalloproteinases (MMPs) play a role in several physiologic and pathologic events. There is some evidence indicating the involvement of MMPs in tumor invasion and inflammatory diseases. Here we studied the chloroform extract of Ferula persica var. persica. The influence of these extracts vs. a reference drug, diclofenac sodium, on MMP production by the fibrosarcoma cell line was investigated using an in vitro cytotoxicity assay, sodium dodecyl sulfate-polyacrylamide, and gelatin zymography. The total extract of the roots was found to exhibit a selective inhibitory effect on tumor cell invasion. The bioactivity-guided fractionation of this extract led to the isolation of two compounds. These compounds showed highest MMP inhibitory effect at minimal toxic dose levels. Using conventional spectroscopy methods, the active fractions were identified as t-butyl 3-[(1-methylthiopropyl)dithio]-2-propenyl malonate (persicasulphide B) and umbelliprenin, previously isolated from F. persica var. latisecta. Since inhibition of MMP activity has been employed in modality therapy in diseases such as cancer, this compound might be promising in the preparation of anti-MMP therapeutic derivatives.
Insights
Ferula persica root extract selectively inhibits tumor cell invasion by reducing matrix metalloproteinases (MMPs). Two isolated compounds, persicasulphide B and umbelliprenin, show potent MMP inhibitory effects, suggesting potential anti-cancer applications.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Cancer Biology
Background:
- Matrix metalloproteinases (MMPs) are implicated in tumor invasion and inflammatory diseases.
- Targeting MMPs is a therapeutic strategy for various pathologies, including cancer.
Purpose of the Study:
- To investigate the anti-MMP activity of Ferula persica var. persica root extract.
- To identify bioactive compounds from the extract with MMP inhibitory potential.
Main Methods:
- In vitro cytotoxicity assay using a fibrosarcoma cell line.
- Sodium dodecyl sulfate-polyacrylamide and gelatin zymography to assess MMP production.
- Bioactivity-guided fractionation and spectroscopic methods for compound identification.
Main Results:
- The Ferula persica root extract demonstrated selective inhibition of tumor cell invasion.
- Two compounds, persicasulphide B and umbelliprenin, were isolated and exhibited significant MMP inhibitory effects.
- These active compounds showed maximum efficacy at low, non-toxic concentrations.
Conclusions:
- Ferula persica var. persica exhibits anti-MMP activity, with potential for developing anti-cancer therapeutics.
- Persicasulphide B and umbelliprenin are promising candidates for anti-MMP drug development.
- Further research into these compounds could lead to novel therapeutic derivatives.
