Saussurea costus root extract contains 28 tentatively identified compounds, including flavonoids, phenolics, and sesquiterpenes, as detailed in an LC–ESI–MS/MS investigation published in Nature.
The major constituents by peak area are apigenin at 12.99%, medioresinol at 8.32%, luteolin at 8.32%, rhoifolin at 7.34%, luteolin-7-O-glucoside at 7.13%, and cirsimaritin at 6.75%. Previously undetected compounds in the root extract include brevifolin carboxylic acid, tricin, salvigenin, cirsimaritin, ergosta-5,7-dienol, and ergosta-5,7,24(28)-trienol.
Experimental evaluations show that the extract, designated as COS, and doxorubicin, known as DOX, exhibit dose-dependent cytotoxicity against human breast cancer cell lines. COS recorded an IC50 value of 106.8 µg/mL against MCF7 cells and 116.8 µg/mL against MDA-MB-231 cells. Subsequent functional assays utilized half-IC50 concentrations of 53 µg/mL for MCF7 cells and 58 µg/mL for MDA-MB-231 cells.
Predicted binding affinities for MMP2 and MMP9
Active ingredients in COS show varying predicted binding affinities for MMP2 and MMP9 proteins, according to molecular docking results. Luteolin showed the most favorable calculated binding energy for MMP2 at -8.90 kcal/mol and MMP9 at -9.50 kcal/mol.
Apigenin-7-O-glucoside registered -9.10 kcal/mol for MMP2. Docking analysis using NLDock_v1.0 demonstrated strong predicted binding of apigenin, medioresinol, and luteolin to both MMP2 and MMP9 mRNAs, with free energies ranging from -51.072 to -80.999 kcal/mol, as outlined in additional docking data.
Molecular dynamics simulations over 100 ns revealed that luteolin induces MMP2 compaction while flexibly binding MMP9. The MMP2-luteolin complex stabilized at an RMSD of 0.45 to 0.55 nm with a progressive decrease in solvent-accessible surface area from ~90.1 nm² to ~86.9 nm². For MDA-MB-231 cells treated with the combination of DOX and COS, MMP2 mRNA relative fold change decreased to 0.65, while MMP9 mRNA relative fold change dropped to 0.19 compared to untreated controls.
Combined treatment reduces wound-healing closure
Combined treatment of DOX and COS significantly reduced wound-healing closure in MCF7 cells and MDA-MB-231 cells. Transwell migration assays demonstrated that the combination treatment reduced migrated MCF7 cells and MDA-MB-231 cells.
In MDA-MB-231 cells, simultaneous treatment with DOX and COS caused apoptosis. Cell cycle analysis of MDA-MB-231 cells treated with the combination exhibited a G2/M phase increase compared to the control group.
Compounds identified in Saussurea costus root extract
What were the primary compounds identified in Saussurea costus root extract?
The major compounds identified by peak area percentage are apigenin at 12.99%, medioresinol at 8.32%, luteolin at 8.32%, rhoifolin at 7.34%, luteolin-7-O-glucoside at 7.13%, and cirsimaritin at 6.75%.
What half-IC50 concentrations were used for the functional assays?
The half-IC50 concentrations applied in subsequent functional assays were 53 µg/mL for COS and 53 µg/mL for DOX against MCF7 cells.
How did the combination treatment affect cell migration?
Transwell migration assays showed that the combination treatment reduced migrated cells in MCF7 cells and MDA-MB-231 cells.
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