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. 2021 Apr 26;26(9):2537.
doi: 10.3390/molecules26092537.

Constituents of Aquilaria sinensis Leaves Upregulate the Expression of Matrix Metalloproteases 2 and 9

Sui-Wen Hsiao  1 , Yu-Chin Wu  2 , Hui-Ching Mei  3 , Yu-Hsin Chen  4 , George Hsiao  5 , Ching-Kuo Lee  1   2   6   7
Affiliations

Constituents of Aquilaria sinensis Leaves Upregulate the Expression of Matrix Metalloproteases 2 and 9

Sui-Wen Hsiao et al. Molecules. .

Abstract

In this novel study, we isolated 28 compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on a bioassay-guided procedure and also discovered the possible matrix metalloprotease 2 (MMP-2) and 9 (MMP-9) modulatory effect of pheophorbide A (PA). To evaluate the regulatory activity on MMP-2 and MMP-9, the HT-1080 human fibrosarcoma cells were treated with various concentrations of extracted materials and isolated compounds. PA was extracted by methanol from the leaves of A. sinensis and separated from the fraction of the partitioned ethyl acetate layer. PA is believed to be an active component for MMP expression since it exhibited significant stimulation on MMP-2 and proMMP-9 activity. When treating with 50 μM of PA, the expression of MMP-2 and MMP-9 were increased 1.9-fold and 2.3-fold, respectively. PA also exhibited no cytotoxicity against HT-1080 cells when the cell viability was monitored. Furthermore, no significant MMP activity was observed when five PA analogues were evaluated. This study is the first to demonstrate that C-17 of PA is the deciding factor in determining the bioactivity of the compound. The MMP-2 and proMMP-9 modulatory activity of PA indicate its potential applications for reducing scar formation and comparative medical purposes.

Keywords: Aquilaria sinensis; HT-1080; MMP-2; MMP-9; pheophorbide A.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Effects of crude extracts and partitioned parts of A. sinensis leaves on MMP-2 and MMP-9 activity. Results of gelatin zymography. CR, crude extracts; EA, ethyl acetate layer; BuOH, butanol layer; water, water layer.
Figure 2
Figure 2
Flow diagram of bioassay-guided procedure. Bioassay-guided fractionation and isolation of the MeOH extract of the leaves of A. sinensis resulted in the isolation of 28 compounds.
Figure 3
Figure 3
Representative HPLC trace of compound AQ20. (a) Eluent from RT 15-18 min was collected in one bottle and subjected to semi-preparative HPLC for further separation. (b) Peak at RT 12.9 min was collected and identified as AQ20. MP, mobile phase condition.
Figure 4
Figure 4
Effects of the isolated compounds AQ—AQ20 on MMP-2 and MMP-9 activity and cytotoxicity. (a) Results of gelatin zymography. (b) Activity of the compounds on MMPs expression. (c) Cell viability test. Data represent the mean ± SD (n = 3). PMA (5 μΜ); AQ1—AQ20 (50 μΜ); * p < 0.05, ** p < 0.001.
Figure 5
Figure 5
Effects of PA at various concentration.
Figure 6
Figure 6
Structures of PA and its analogues. PA (AQ20), PA analogues (AQ9, 20A–E).
See this image and copyright information in PMC

References

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