Metabolomics of the secondary metabolites of Ammi visnaga L. roots (family Apiaceae) and evaluation of their biological potential

Abstract

Recent scientific advancements in biotechnological, nanobiotechnological, and omics approaches have blossomed into a plethora of applications that hold the potential to revolutionize natural product-based drug discovery. In this context, the present work was undertaken to unveil the secondary metabolites of the under-explored roots of Ammi visnaga L. (family Apiaceae) using HPLC‒HESI‒HRMS-based metabolomics, along with evaluating their anti-proliferative potential against a number of tumor cells in comparison with their green synthesized silver nanoparticles (SNPs), for the first time. Overall, the total ethanol extract of A. visnaga roots (TEEAVR) revealed potent inhibitory actions against colon cancer (Caco-2), breast cancer (Mcf-7), and hepatocellular carcinoma (HepG-2) cell lines, with IC50 values of 3.19 ± 0.07, 12.36 ± 0.13, and 18.38 ± 0.09 µg/mL, respectively. More interestingly, the prepared biogenic SNPs of TEEAVR exhibited more prominent inhibitory potential, particularly against Caco-2 tumor cells (IC50= 0.24 ± 0.05 µg/mL), which was even higher than that of doxorubicin (IC50= 2.12 ± 0.04 µg/mL). Moreover, HPLC‒HESI‒HRMS metabolic profiling of TEEAVR resulted in the characterization of a group of chemically varied metabolites, including phenylpropanoids, flavonoids, isobenzofuranones, coumarins, and chromones. Among them, junipediol A 4-O-glucoside (1a), junipediol A 8-O-glucoside (1b), acacetin (2), and apiumetin-O-glucoside (7) exhibited greater binding affinities to the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase compared to the reference drug, erlotinib; suggesting their possible contribution as EGFR inhibitors to the promising anti-proliferative properties of TEEAVR. These findings cast a new light on the metabolic diversity of A. visnaga roots as an overlooked underground treasure of pharmaceutically relevant phytochemicals that could be incorporated into future anticancer drug research.