Combining the\nStrengths of MS and NMR in Biochemometrics:\nA Case Study on <i>Buddleja officinalis</i>

Biochemometrics has emerged as promising\nstrategy for\nthe targeted\nidentification of bioactive constituents from natural sources. It\nis based on the correlation of bioactivity data with chemical data\nto reveal constituents contributing to activity. Providing complementary\ndata and structural information, MS- and NMR-based biochemometric\napproaches have both been separately applied in the past. The herein\npresented study is dedicated to the evaluation of a combined MS- and\nNMR-based biochemometric workflow for the unambiguous identification\nof bioactives. As an example, a flower extract of <i>Buddleja\nofficinalis</i> Maxim. was selected to unravel bioactive constituents\nin the context of dry eye disease pathology. While NMR-based biochemometrics\nrelies on heterocovariance analysis (HetCA) of <sup>1</sup>H NMR spectra\nusing the previously established ELINA approach, a biochemometric\nmolecular network was generated for the MS-based approach. Both analyses\nwere performed in parallel and were ultimately combined to increase\ntheir power to identify the bioactive constituents from the complex\nmixture. As a result, phenylethanoid glycosides and triterpene saponins\nwere discovered as main contributors for the antioxidant and cytotoxic\neffects of the extract. This article illustrates the advantages, opportunities,\nand limitations of MS and NMR in the context of biochemometrics.