UHPLC-QTOF-MS based metabolite profiling analysis and the correlation with biological properties of wild and...

To date, the agarwood has been over exploited worldwide in the wild due to high demand. As an alternative, the agarwood obtained through artificial methods has greatly resolved the shortage of agarwood supply in the global market. However, little information about the difference in chemical constituents and bioactivities of the wild agarwood and the artificial agarwood is available. This study aims to systematically compare the chemical composition and the bioactivities between wild and artificial agarwood on the basis of the integrated method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF-MS) and multivariate statistical analysis. The invitro antioxidant activity was determined using the 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical scavenging activity assays. The cytotoxic activity of agarwood from different origin against three human cancer cell lines (i.e., A375, U251, and Skov3) were compared using the MTT assay. Fifty metabolites from UPLC-QTOF-MS spectra were identified and included in the multivariate analysis. Among these metabolites, 2-(2-phenylethyl) chromone derivatives (PECs), bi-2-(2-phenylethyl) chromone derivatives (BPECs) and sesquiterpene-2-(2-phenylethyl) chromone conjugates (SPECs) were found to be the major metabolites and acted as discriminant compounds in agarwood from different origin. The antioxidant activity study showed that the wild agarwood displayed significant antioxidant capacity compared with the artificial agarwood. Particularly, the content of secondary metabolites of SPEC analogs shown a positive effect on the radical scavenging activities, whereas the PECs were negatively correlated. Interestingly, no significant difference was observed between wild and artificial agarwood in terms of cytotoxic activity against three human cancer cell lines (i.e., A375, U251, and Skov3). To the best of our knowledge, this research is the first to study the metabolite profiles and bioactivities of the wild and the artificial agarwood in a holistic approach, and is expected to provide a rational basis for the quality assessment of artificial agarwood as a substitute for wild agarwood.