Software v 5

All the ¹H-NMR spectra were manually phased and baseline corrected using Chenomx software (v. 5.1, Alberta, Canada). The ¹H-NMR spectrum of each sample was processed and binned (0.04 ppm bin width) over the spectral region of δ 0.50 to δ 10.00 ppm. All spectra were then automatically converted to ASCII files and transferred into a Microsoft Excel (version 1997–2003) worksheet. Residual water (δ 4.70–4.90 ppm) and methanol (δ 3.27–3.31 ppm) regions were excluded from the spectral data to retain only signals from endogenous metabolites. The resulting dataset was saved as an Excel file and further subjected to multivariate analysis using SIMCA-P+ version 13.0 (Umetrics, Umea°, Sweden).

Chenomx software (v. 5.1, Alberta, Canada) was used to correct the phasing and baseline of all the NMR spectra. The spectral region (δ 0.5–10.0) was binned with a width of δ 0.04, resulting in 237 integral regions per NMR spectrum. The residual signal of DMSO at δ 2.50 was removed from the spectra. The multivariate data analysis (MVDA) was performed using SIMCA-P software (Version 13.0, Umetrics, Umeå, Sweden). Principal component (PCA) and partial least-squares analyses (PLS) were conducted to evaluate the correlation between the activities tested and the metabolites identified. The Pareto scaling was applied in all analysis.