## 2 Materials and Methods
### Solid-Phase Extraction (SPE) of Total Extract from S. repens Leaves and Roots  
The samples of total extracts of _S. repens_ leaves and roots (50 mg) were ultrasonically dissolved in tridistilled water (10 mL), centrifuged (6000\(\times\)_g_, 15 min), and the final solutions passed through SPE polyamide cartridges (10 g) preconditioned with methanol (100 mL) and water (150 mL). Elution was performed with water (300 mL; SPE-1 fraction) and 60% methanol (300 mL; SPE-2 fraction). The eluates were concentrated in vacuo until dryness and stored at 4 \({}^{\circ}\)C before HPLC-PDA-ESI-tQ-MS analysis. The yields of SPE fractions were 25.8-29.4% for SPE-1 and 16.3-20.9% for SPE-2 (Table S1).  
High-Performance Liquid Chromatography with Photodiode Array Detection and Electrospray Ionization Triple Quadrupole Mass Spectrometric Detection (HPLC-PDA-ESI-tQ-MS): Metabolite Profiling and Quantification  
Metabolite profiling of _S. repens_ SPE fractions (Section 2.5) was realized using high-performance liquid chromatography with photodiode array detection and electrospray ionization triple quadrupole mass spectrometric detection (HPLC-PDA-ESI-tQ-MS) performed on a liquid chromatograph LC-20 Prominence coupled photodiode array detector SPD-M30A (wavelength range 200-600 nm), triple-quadrupole mass spectrometer LCMS 8050 (all Shimadzu, Columbia, MD, USA), and C18 column (GLC Mastro; 150 \(\times\) 2.1 mm, 3 \(\upmu\)m; Shimadzu, Kyoto, Japan) at the column temperature 35 \({}^{\circ}\)C. Eluent A was water and eluent B was acetonitrile. The injection volume was 1 \(\upmu\)L, and elution flow was 180 \(\upmu\)L/min. Gradient program for SPE-1 eluate (mode 1, analysis of ecydsteroids): 0.0-5.0 min 7.0-20.0%B, 5.0-15.0 min 20-100%B, 15.0-20.0 min 100-7%B. Gradient program for SPE-2 eluate (mode 2, analysis of glycosylflavones): 0.0-5.0 min 7-15%B, 5.0-10.0 min 15-60 %B, 10.0-15.0 min 60-70%B, 15.0-20.0 min 70-5%B. MS detection was performed in positive and negative ESI modes using the parameters as follows: temperature levels of ESI interface, desolvation line, and heat block were 300 \({}^{\circ}\)C, 250 \({}^{\circ}\)C, and 400 \({}^{\circ}\)C, respectively. The flow levels of nebulizing gas (N\({}_{2}\)), heating gas (air) and collision-induced dissociation gas (Ar) were 3 L/min, 10 L/min and 0.3 mL/min, respectively. The MS spectra were recorded in negative (\(-\)3--5 kV source voltage) and positive mode (+3-4 kV source voltage) by scanning in the range of \(m/z\) 100-1900 at the collision energy of 5-40 eV. The system was operated under LabSolutions workstation software with the internal LC-MS library. The identification of compounds was done by the analysis of their retention time, ultraviolet, and mass-spectrometric data, comparing the same parameters with the reference samples and/or literature data (Table S2).  
To quantify compounds **6**, **7**, **13-18** in _S. repens_ SPE fractions, the reference standards (5 compounds) were accurately weighed (10 mg) and individually dissolved in DMSO-50% methanol mixture (1:10) in a volumetric flask (10 mL). The stock solutions were used to build external standard calibration curves generated using six data points, 100, 50, 25, 10, 5, and 1 \(\upmu\)g/mL followed by plotting the MS peak area vs. the concentration levels. The validation criteria (correlation coefficients, \(r^{2}\); standard deviation, S\({}_{YX}\); limits of detection, LOD; limits of quantification, LOQ; and linear ranges) were calculated using the previous recommendations [32] (Table S3). All analyses were carried out in triplicate, and the data were expressed as mean value \(\pm\) standard deviation (S.D.). Before analysis, a sample of the fraction (SPE-1 or SPE-2; 1 mg) was dissolved in 1 mL of 70% acetonitrile, then centrifuged (6000\(\times\)\(g\), 15 min), filtered through a membrane filter (0.45 \(\upmu\)m), and used for analysis (1 \(\upmu\)L).