Comprehensive Metabolomic Profiling and Biological Activity Analysis of Eschscholzia californica Extracts Using LC‐ESI‐QTOF‐MS

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ABSTRACT The current investigation was designed to explore the chemical composition, antioxidant capacity, enzyme inhibitory activity, and cytotoxic potential of four different extracts (Ethyl Acetate, Ethanol, Ethanol/Water (70%) and Water) derived from the aerial parts of Eschscholzia californica . In vitro, assessments were performed utilizing diverse antioxidant assays, along with evaluations of neuroprotective enzyme inhibition targeting acetylcholine and butyl choline enzymes, as well as antidiabetic activities against α‐amylase and α‐glucosidase and a potential candidate for a tyrosinase inhibitor. LC‐ESI‐QTOF‐MS identification provided a total of 70 compounds in the extracted samples of E. californica , including kaempferol 3‐(deoxyhexosyl‐hexoside)‐7‐hexoside, rutin, quercetin dideoxyhexoside, caffeic acid hexoside, quinoline alkaloids, morphine derivatives, and scoulerine. Moreover, the ethanol extract exhibited the highest anti‐AChE (2.39 mg GALAE/g), while ethyl acetate exhibited anti‐BChE (3.31 mg GALAE/g), Ethanol/Water (70%) anti‐tyrosinase (53.09 mg KAE/g) and anti‐glucosidase (1.09 mmol ACAE/g) activities. Additionally, the ethyl acetate extract effectively inhibited carbonic anhydrase I and II isoenzymes. Furthermore, the ethanol and ethanol/water extracts demonstrated significant cytotoxicity against A549 lung cancer cells. However, E. californica partially/weakly triggers the apoptosis of cancer cells. Furthermore, the investigation identified 885 target genes for E. californica 's phytochemicals, 31 of which were familiar to insomnia. In silico studies demonstrated that protopine, rutin, eschscholtzidine, boldine, and (S)‐scoulerine exhibited notable inhibitory effects on insomnia‐related DRD5, DRD4, and SERT proteins. These findings highlight the potential pharmacological applications of the aerial parts of E. californica as a source for developing novel phytopharmaceuticals targeting various oxidative stress‐related conditions, including diabetes, cancer, Alzheimer's disease, and insomnia.