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

. 2025 Sep ; 13 (9) : e70885. [epub] 20250902

Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40909255

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.

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Acquaviva, A. , Nilofar, Bouyahya A., et al. 2023. “Chemical Characterization of Different Extracts From Artemisia Annua and Their Antioxidant, Enzyme Inhibitory and Anti‐Inflammatory Properties.” Chemistry & Biodiversity 20, no. 8: e202300547. PubMed

Akpulat, U. , Cetiz M. V., Baloglu M. C., Altunoglu Y. C., and Zengin G.. 2025. “Anti‐Atrophic Role of

Al‐Snafi, A. E. 2017a. “A Review on

Al‐Snafi, A. E. 2017b. “

Apostolova, N. , and Victor V. M.. 2015. “Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications.” Antioxidants & Redox Signaling 22, no. 8: 686–729. PubMed PMC

Asal, D. , Çimen A. Ö., and Güner A.. 2022. “Türkiye'den İstilâcı Bir Bitki Kaydı:

Aslan, M. , Orhan N., Orhan D. D., and Ergun F.. 2010. “Hypoglycemic Activity and Antioxidant Potential of Some Medicinal Plants Traditionally Used in Turkey for Diabetes.” Journal of Ethnopharmacology 128, no. 2: 384–389. PubMed

Bahsi, M. , Di Simone S. C., Zheleva‐Dimitrova D., et al. 2025. “Unlocking New Pharma/Nutraceutical Frontiers With Neuroprotective Properties of Three Hypericum Species: A Study Combination With In Vitro and In Silico Methodologies.” Food Science & Nutrition 13, no. 4: e70069. PubMed PMC

Barreiro, E. , and Hussain S. N.. 2010. “Protein Carbonylation in Skeletal Muscles: Impact on Function.” Antioxidants & Redox Signaling 12, no. 3: 417–429. PubMed

Beck, M.‐A. , and Häberlein H.. 1999. “Flavonol Glycosides From Eschscholtzia Californica.” Phytochemistry 50, no. 2: 329–332. PubMed

Becker, A. , Yamada Y., and Sato F.. 2023. “California Poppy ( PubMed PMC

Bonomo, M. G. , Russo D., Faraone I., et al. 2023. “Antimicrobial and Antioxidant Properties and Quantitative Screening of Phytochemicals of PubMed

Builders PF . 2018. “Introductory Chapter: Introduction to Herbal Medicine.” In Herbal Medicine. IntechOpen.

Büyükbalci, A. , and El S. N.. 2008. “Determination of In Vitro Antidiabetic Effects, Antioxidant Activities and Phenol Contents of Some Herbal Teas.” Plant Foods for Human Nutrition 63: 27–33. PubMed

Cahlíková, L. , Macáková K., Kuneš J., et al. 2010. “Acetylcholinesterase and Butyrylcholinesterase Inhibitory Compounds From PubMed

Cetiz, M. V. , Ahmed S., Zengin G., et al. 2025. “Bioinformatic and Experimental Approaches to Uncover the Bio‐Potential of

Cetiz, M. V. , Yagi S., Kurt U., et al. 2024. “Bridging HPLC‐ESI‐MS/MS Analysis and In Vitro Biological Activity Assay Through Molecular Docking and Network Pharmacology: The Example of European Nettle Tree (

Cetiz, M. V. , Yagi S., Sinan K. I., et al. 2025. “The Biopotential of PubMed PMC

Chandra, J. , Samali A., and Orrenius S.. 2000. “Triggering and Modulation of Apoptosis by Oxidative Stress.” Free Radical Biology & Medicine 29, no. 3–4: 323–333. PubMed

Choi, H. , Ryu I. Y., Choi I., et al. 2022. “Identification of (Z)‐2‐Benzylidene‐Dihydroimidazothiazolone Derivatives as Tyrosinase Inhibitors: Anti‐Melanogenic Effects and In Silico Studies.” Computational and Structural Biotechnology Journal 20: 899–912. PubMed PMC

Clark, C. 1997. Eschscholzia. In: Flora of North America Editorial Committee (Eds.), Flora of North America. Vol. 3, 308–312. Oxford University Press.

Creagh, E. M. , Conroy H., and Martin S. J.. 2003. “Caspase‐Activation Pathways in Apoptosis and Immunity.” Immunological Reviews 193, no. 1: 10–21. PubMed

Datkhile, K. D. , Patil S. R., Patil M. N., Durgawale P. P., Jagdale N. J., and Deshmukh V. N.. 2020. “Studies on Phytoconstituents, In Vitro Antioxidant, Antibacterial and Cytotoxicity Potential of

De Luca, V. , Salim V., Atsumi S. M., and Yu F.. 2012. “Mining the Biodiversity of Plants: A Revolution in the Making.” Science 336, no. 6089: 1658–1661. PubMed

Du, A.‐L. , Du A.‐L., Ren H.‐M., et al. 2009. “Carbonic Anhydrase III Is Insufficient in Muscles of Myasthenia Gravis Patients.” Autoimmunity 42, no. 3: 209–215. PubMed

Duran, T. , and Tuncer Z.. 2023. “Investigation of Cytotoxic and Apoptotic Effects of Styrax Liquidus Obtained From PubMed PMC

Dwivedi, M. , and Pandey A. R.. 2020. “Diabetes Mellitus and Its Treatment: An Overview.” Journal of Advancement in Pharmacology 1, no. 1: 48–58.

Elhawary, E. A. , Nilofar N., Zengin G., and Eldahshan O. A.. 2024. “Variation of the Essential Oil Components of PubMed PMC

Er, A. 2023. “Various Carbonic Anhydrases in Physiopathological Events, Carbonic Anhydrase Inhibitors, and Hybrid Compounds.” Letters in Drug Design & Discovery 20, no. 10: 1427–1436.

Ferreira, A. , Proença C., Serralheiro M., and Araujo M.. 2006. “The In Vitro Screening for Acetylcholinesterase Inhibition and Antioxidant Activity of Medicinal Plants From Portugal.” Journal of Ethnopharmacology 108, no. 1: 31–37. PubMed

Fulda, S. , Gorman A. M., Hori O., and Samali A.. 2010. “Cellular Stress Responses: Cell Survival and Cell Death.” International Journal of Cell Biology 2010, no. 1: 214074. PubMed PMC

Gao, B.‐B. , Clermont A., Rook S., et al. 2007. “Extracellular Carbonic Anhydrase Mediates Hemorrhagic Retinal and Cerebral Vascular Permeability Through Prekallikrein Activation.” Nature Medicine 13, no. 2: 181–188. PubMed

Godman, B. , Basu D., Pillay Y., et al. 2020. “Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future.” Frontiers in Pharmacology 11: 108. PubMed PMC

Gogoi, P. , Kumar A., Das A., and Baishya G.. 2023. “Tyrosinase Inhibitory Kinetics, LC‐QTOF‐MS Based Chemical Profiling and Molecular Docking of Phytochemicals From

Gonçalves, S. , and Romano A.. 2017. “Inhibitory Properties of Phenolic Compounds Against Enzymes Linked With Human Diseases.” Phenolic Compounds‐Biological Activity 40, no. 5: 100–120.

Grochowski, D. M. , Uysal S., Aktumsek A., et al. 2017. “In Vitro Enzyme Inhibitory Properties, Antioxidant Activities, and Phytochemical Profile of

Gusev, E. Y. , and Zotova N. V.. 2019. “Cellular Stress and General Pathological Processes.” Current Pharmaceutical Design 25, no. 3: 251–297. PubMed

Hanus, M. , Lafon J., and Mathieu M.. 2004. “Double‐Blind, Randomised, Placebo‐Controlled Study to Evaluate the Efficacy and Safety of a Fixed Combination Containing Two Plant Extracts (Crataegus Oxyacantha and Eschscholtzia Californica) and Magnesium in Mild‐To‐Moderate Anxiety Disorders.” Current Medical Research and Opinion 20, no. 1: 63–71. PubMed

Harvey, A. L. , Edrada‐Ebel R., and Quinn R. J.. 2015. “The Re‐Emergence of Natural Products for Drug Discovery in the Genomics Era.” Nature Reviews. Drug Discovery 14, no. 2: 111–129. PubMed

Hetmann, M. , Langner C., Durmaz V., et al. 2023. “Identification and Validation of Fusidic Acid and Flufenamic Acid as Inhibitors of SARS‐CoV‐2 Replication Using DrugSolver CavitomiX.” Scientific Reports 13, no. 1: 11783. PubMed PMC

Hosseini, A. , Mobasheri L., Rakhshandeh H., Rahimi V. B., Najafi Z., and Askari V. R.. 2024. “Edible Herbal Medicines as an Alternative to Common Medication for Sleep Disorders: A Review Article.” Current Neuropharmacology 22, no. 7: 1205–1232. PubMed PMC

Hryć, B. , Kljakić A. C., Cetiz M. V., et al. 2025. “Network Pharmacology of PubMed

Jan, R. 2019. “Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics.” Advanced Pharmaceutical Bulletin 9, no. 2: 205–218. PubMed PMC

Kannan, K. , and Jain S. K.. 2000. “Oxidative Stress and Apoptosis.” Pathophysiology 7, no. 3: 153–163. PubMed

Karch, S. , Broichhagen J., Schneider J., et al. 2018. “A New Fluorogenic Small‐Molecule Labeling Tool for Surface Diffusion Analysis and Advanced Fluorescence Imaging of β‐Site Amyloid Precursor Protein‐Cleaving Enzyme 1 Based on Silicone Rhodamine: SiR‐BACE1.” Journal of Medicinal Chemistry 61, no. 14: 6121–6139. PubMed

Kashyap, D. , Garg V. K., and Goel N.. 2021. “Intrinsic and Extrinsic Pathways of Apoptosis: Role in Cancer Development and Prognosis.” Advances in Protein Chemistry and Structural Biology 125: 73–120. PubMed

Kilbride, S. , and Prehn J.. 2013. “Central Roles of Apoptotic Proteins in Mitochondrial Function.” Oncogene 32, no. 22: 2703–2711. PubMed

Kobus‐Cisowska, J. , Szczepaniak O., Szymanowska‐Powałowska D., Piechocka J., Szulc P., and Dziedziński M.. 2019. “Antioxidant Potential of Various Solvent Extract From

Kucukoglu, K. , Gul H. I., Taslimi P., Gulcin I., and Supuran C. T.. 2019. “Investigation of Inhibitory Properties of Some Hydrazone Compounds on hCA I, hCA II and AChE Enzymes.” Bioorganic Chemistry 86: 316–321. 10.1016/j.bioorg.2019.02.008. PubMed DOI

Livak, K. J. , and Schmittgen T. D.. 2001. “Analysis of Relative Gene Expression Data Using Real‐Time Quantitative PCR and the 2− ΔΔCT Method.” Methods 25, no. 4: 402–408. PubMed

Llorent‐Martínez, E. J. , Yagi S., Zengin G., et al. 2025. “Characterization of the Chemical Profiles and Biological Activities of Thesium Bertramii Azn. Extracts Using a Combination of In Vitro, In Silico, and Network Pharmacology Methods.” Fitoterapia 180: 106329. PubMed

Marucci, G. , Buccioni M., Dal Ben D., Lambertucci C., Volpini R., and Amenta F.. 2021. “Efficacy of Acetylcholinesterase Inhibitors in Alzheimer's Disease.” Neuropharmacology 190: 108352. PubMed

Mopuri, R. , Ganjayi M., Meriga B., Koorbanally N. A., and Islam M. S.. 2018. “The Effects of PubMed PMC

Mustarichie, R. , Saptarini N. M., and Megantara S.. 2022. “Molecule Attachment and Prediction of ADMET Compounds in

Nilofar, D. T. , Uba A. I., Cvetanović Kljakić A., et al. 2024. “Extractions of Aerial Parts of Hippomarathrum Scabrum With Conventional and Green Methodologies: Chemical Profiling, Antioxidant, Enzyme Inhibition, and Anti‐Cancer Effects.” Journal of Separation Science 47, no. 1: 2300678. PubMed

Nilofar, N. , Dall'Acqua S., Sut S., et al. 2024. “Exploring the Effects of Post‐Distillation and Post‐Supercritical CO2 Extraction on Chemical Profile and Biological Activities of Two Salvia Species (

O'Brien, M. A. , and Kirby R.. 2008. “Apoptosis: A Review of Pro‐Apoptotic and Anti‐Apoptotic Pathways and Dysregulation in Disease.” Journal of Veterinary Emergency and Critical Care 18, no. 6: 572–585.

Özbey, F. , Taslimi P., Gülçin İ., Maraş A., Göksu S., and Supuran C. T.. 2016. “Synthesis of Diaryl Ethers With Acetylcholinesterase, Butyrylcholinesterase and Carbonic Anhydrase Inhibitory Actions.” Journal of Enzyme Inhibition and Medicinal Chemistry 31, no. sup2: 79–85. 10.1080/14756366.2016.1189422. PubMed DOI

Papoutsis, K. , Zhang J., Bowyer M. C., Brunton N., Gibney E. R., and Lyng J.. 2021. “Fruit, Vegetables, and Mushrooms for the Preparation of Extracts With α‐Amylase and α‐Glucosidase Inhibition Properties: A Review.” Food Chemistry 338: 128119. PubMed

Pires, D. E. , Blundell T. L., and Ascher D. B.. 2015. “pkCSM: Predicting Small‐Molecule Pharmacokinetic and Toxicity Properties Using Graph‐Based Signatures.” Journal of Medicinal Chemistry 58, no. 9: 4066–4072. PubMed PMC

Poh Loh, K. , Hong Huang S., De Silva R., BK H. T., and Zhun Zhu Y.. 2006. “Oxidative Stress: Apoptosis in Neuronal Injury.” Current Alzheimer Research 3, no. 4: 327–337. PubMed

Prince, M. , Guerchet M., and Prina M.. 2015. “The Epidemiology and Impact of Dementia‐Current State and Future Trends.” WHO Thematic Briefing.

Pulido, R. , Bravo L., and Saura‐Calixto F.. 2000. “Antioxidant Activity of Dietary Polyphenols as Determined by a Modified Ferric Reducing/Antioxidant Power Assay.” Journal of Agricultural and Food Chemistry 48, no. 8: 3396–3402. PubMed

Rolland, A. , Fleurentin J., Lanhers M., Misslin R., and Mortier F.. 2001. “Neurophysiological Effects of an Extract of PubMed

Royal Botanic Gardens K . 2016. “State of the World's Plants 2016”.

Schäfer, H. , Schäfer H., Schneider W., and Elstner E.. 1995. “Sedative Action of Extract Combinations of Eschscholtzia Californica and Corydalis Cava.” Arzneimittel‐Forschung 45, no. 2: 124–126. PubMed

Scozzafava, A. , Mastrolorenzo A., and Supuran C. T.. 2004. “Modulation of Carbonic Anhydrase Activity and Its Applications in Therapy.” Expert Opinion on Therapeutic Patents 14, no. 5: 667–702.

Shahidi, F. , and Zhong Y.. 2015. “Measurement of Antioxidant Activity.” Journal of Functional Foods 18: 757–781.

Sleep, H. C. 2021. The Elixir of Life: How to Restore Sleep With Herbs and Natural Healing. Aeon Books.

Slinkard, K. , and Singleton V. L.. 1977. “Total Phenol Analysis: Automation and Comparison With Manual Methods.” American Journal of Enology and Viticulture 28, no. 1: 49–55.

Soane, L. , Kahraman S., Kristian T., and Fiskum G.. 2007. “Mechanisms of Impaired Mitochondrial Energy Metabolism in Acute and Chronic Neurodegenerative Disorders.” Journal of Neuroscience Research 85, no. 15: 3407–3415. PubMed PMC

Soobrattee, M. A. , Neergheen V. S., Luximon‐Ramma A., Aruoma O. I., and Bahorun T.. 2005. “Phenolics as Potential Antioxidant Therapeutic Agents: Mechanism and Actions.” Mutation Research, Fundamental and Molecular Mechanisms of Mutagenesis 579, no. 1–2: 200–213. PubMed

Supuran, C. T. 2021. “Emerging Role of Carbonic Anhydrase Inhibitors.” Clinical Science 135, no. 10: 1233–1249. PubMed

Temperini, C. , and Scozzafava A.. 2009. Drug Design of Zinc‐Enzyme Inhibitors: Functional, Structural, and Disease Applications, edited by Supuran C. T. and Winum J.‐Y.. Wiley.

Tkachenko, A. 2024. “Apoptosis and Eryptosis: Similarities and Differences.” Apoptosis 29, no. 3: 482–502. PubMed

Tlili, N. , and Sarikurkcu C.. 2020. “Bioactive Compounds Profile, Enzyme Inhibitory and Antioxidant Activities of Water Extracts From Five Selected Medicinal Plants.” Industrial Crops and Products 151: 112448.

Torres, T. M. S. , Álvarez‐Rivera G., Mazzutti S., et al. 2022. “Neuroprotective Potential of Extracts From Leaves of Ora‐Pro‐Nobis (

Trott, O. , and Olson A. J.. 2010. “AutoDock Vina: Improving the Speed and Accuracy of Docking With a New Scoring Function, Efficient Optimization, and Multithreading.” Journal of Computational Chemistry 31, no. 2: 455–461. PubMed PMC

Twig, G. , Zucker I., Afek A., et al. 2020. “Adolescent Obesity and Early‐Onset Type 2 Diabetes.” Diabetes Care 43, no. 7: 1487–1495. PubMed

Vaezi, M. 2022. “In Silico and In Vitro Studies of Naturally Occurring Tyrosinase Inhibitors: Structure–Activity Relationship.” Chemistry Africa 5, no. 6: 1873–1887.

Viscusi, E. R. , and Viscusi A. R.. 2020. “Blood–Brain Barrier: Mechanisms Governing Permeability and Interaction With Peripherally Acting μ‐Opioid Receptor Antagonists.” Regional Anesthesia and Pain Medicine 45, no. 9: 688–695. PubMed PMC

Winum, J.‐Y. , Scozzafava A., Montero J.‐L., and Supuran C. T.. 2006. “New Zinc Binding Motifs in the Design of Selective Carbonic Anhydrase Inhibitors.” Mini Reviews in Medicinal Chemistry 6, no. 8: 921–936. PubMed

Yagi, S. , Zengin G., Eldahshan O. A., et al. 2024. “Functional Constituents of Colchicum Lingulatum Boiss. & Spruner Subsp. Rigescens K. Perss. Extracts and Their Biological Activities With Different Perspectives.” Food Bioscience 60: 104496.

Zengin, G. , Fernández‐Ochoa Á., MdlL C.‐G., et al. 2023. “Phytochemical Profile and Biological Activities of Different Extracts of Three Parts of PubMed PMC

Zheleva‐Dimitrova, D. , Gevrenova R., Yagi S., et al. 2025. “Exploring Hidden Natural Resources for Bioactive Compounds: Focused Chemical and Biological Studies on Some Anthemis Species.” Food and Chemical Toxicology 202: 115467. PubMed

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