{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T19:12:32Z","timestamp":1784315552211,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","award":["2025\/2026"],"award-info":[{"award-number":["2025\/2026"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SAMRC RCDI-Nested PhD Scholarship Programme","award":["2024\/2026"],"award-info":[{"award-number":["2024\/2026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Despite growing interest in South African medicinal plants, advanced metabolomic workflows that integrate positive (ESI+) and negative (ESI\u2212) ionization modes in UPLC-MS\/MS remain sparsely applied to South African flora, and especially to Acorus calamus and Lippia javanica species. Herein, application of a dual-polarity (positive (ESI+) and negative (ESI\u2212) ionization modes) using an untargeted UPLC\u2013MS\/MS workflow, integrated with HEK293T cytotoxicity screening, to map their metabolomes, and rank potential signature metabolites for targeted antiviral follow-up. SwissADME supported in silico drug-likeness. Neither plant extract was cytotoxic across the concentration range, with absorbance-based cell viability of 73.82% for L. javanica and 77.23% for A. calamus at 250 \u00b5g\/mL, and fluorescence-based cell viability \u226559.87% and \u226555.89%, respectively. Dual-polarity expanded coverage with ESI\u2212 yielded 312 features, compared with 225 with ESI+, consistent with the predominance of acidic phenolics in plant species. Unsupervised and supervised models segregated the plant species (PCA PC1\/PC2 variance: ESI+ 89.4%\/3.0%; ESI\u2212 93.5%\/1.8%; R2X(cum) = 0.799). Differential analysis identified 118 significant features in ESI+ with 80 up-regulated, 38 down-regulated, and 139 in ESI\u2212 with 96 up-regulated, 43 down-regulated. The ESI\u2212 showed the wider dynamic range. Chemotypes enriched among significant metabolites include flavonols of 3-O-methylkaempferol, apigenin, and conjugates of Pollenin A, iridoid glycosides of oleoside, forsythoside B, and jasmonate-pathway oxylipins of 7-epi-12-hydroxyjasmonic acid and its glucoside. These also include caryoptosidic acid and catechin-7-glucoside, which are ionized in both modes, pinning the increase in biomarker robustness. In conclusion, a dual-mode UPLC\u2013MS\/MS approach, integrated with cytotoxicity exploration, delivers a complementary metabolome coverage and a safety awareness for shortlisting of potential signature metabolites from L. javanica and A. calamus. Moreover, in vitro inhibition of SARS-CoV-2 papain-like protease (PLpro) by these plants links chemical signatures to antiviral relevance. Shortlisted significant metabolites that demonstrated favorable drug-likeness include flavonol scaffolds of 3-O-methylkaempferol, Pollenin A, and jasmonate-pathway derivatives of 7-epi-12-hydroxyjasmonic acid. Moreover, the dual ionization mode may eliminate ionization bias, broaden metabolome coverage, and yield a mechanism-ready shortlist of metabolites from South African medicinal plants for downstream antiviral investigation.<\/jats:p>","DOI":"10.3390\/plants15020232","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identifying Key Metabolites in South African Medicinal Plants Using Dual Electrospray Ionization Metabolomics"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6080-1848","authenticated-orcid":false,"given":"Mmamudi Anna","family":"Makhafola","sequence":"first","affiliation":[{"name":"Department of Biology and Environmental Sciences, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9164-8213","authenticated-orcid":false,"given":"Clarissa Marcelle","family":"Naidoo","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Sciences, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikwelu Lawrence","family":"Obi","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Sciences, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benson Chuks","family":"Iweriedor","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Sciences, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8004-3187","authenticated-orcid":false,"given":"Oyinlola Oluwunmi","family":"Olaokun","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Sciences, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3048-4304","authenticated-orcid":false,"given":"Earl","family":"Prinsloo","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Sulaiman","family":"Zubair","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Tadulako, Palu 94118, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-4522","authenticated-orcid":false,"given":"Nqobile Monate","family":"Mkolo","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Sciences, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gao, P., Liu, J., and Liu, M. (2022). Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph191912422"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.sajb.2011.08.011","article-title":"The Potential of South African Plants in the Development of New Medicinal Products","volume":"77","year":"2011","journal-title":"S. Afr. J. Bot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6746071","DOI":"10.1155\/2017\/6746071","article-title":"Lippia javanica (Burm.f.) Spreng.: Traditional and Commercial Uses and Phytochemical and Pharmacological Significance in the African and Indian Subcontinent","volume":"2017","author":"Maroyi","year":"2017","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_5","unstructured":"D\u00f6ring, M. (2022). Acorus calamus L., 1753. English Wikipedia\u2014Species Pages, Wikimedia Foundation. Available online: https:\/\/doi.org\/10.15468\/c3kkgh."},{"key":"ref_6","unstructured":"South African National Biodiversity Institute (SANBI) (2007). African Plant Database: Acorus Calamus, SANBI. Available online: http:\/\/www.ville-ge.ch\/musinfo\/bd\/cjb\/africa\/details.php?langue=an&id=30524."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Almeida, M.C., Pina, E.S., Hernandes, C., Zingaretti, S.M., Taleb-Contini, S.H., Salimena, F.R.G., Slavov, S.N., Haddad, S.K., Fran\u00e7a, S.C., and Pereira, A.M.S. (2018). Genetic diversity and chemical variability of Lippia spp. (Verbenaceae). BMC Res. Notes, 11.","DOI":"10.1186\/s13104-018-3839-y"},{"key":"ref_8","first-page":"238","article-title":"Molecular and chemical profiling of \u2018sweet flag\u2019 (Acorus calamus L.) germplasm from India","volume":"11","author":"Rana","year":"2013","journal-title":"Plant Genet. Resour. Charact. Util."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/13880200701538724","article-title":"Acorus calamus: Scientific Validation of Ayurvedic Tradition from Natural Resources","volume":"45","author":"Mukherjee","year":"2007","journal-title":"Pharm. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.sajb.2019.02.012","article-title":"Zulu Medicinal Ethnobotany: New Records from the Amandawe Area of KwaZulu-Natal","volume":"122","author":"Mhlongo","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.sajb.2019.06.037","article-title":"Advancement of Analytical Techniques in Some South African Commercialized Medicinal Plants: Current and Future Perspectives","volume":"126","author":"Masondo","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1039\/C9NP00004F","article-title":"Innovative omics-based approaches for prioritisation and targeted isolation of natural products\u2014New strategies for drug discovery","volume":"36","author":"Wolfender","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Qi, J., Li, K., Shi, Y., Li, Y., Dong, L., Liu, L., Li, M., Ren, H., Liu, X., and Fang, C. (2021). Cross-Species Comparison of Metabolomics to Decipher the Metabolic Diversity in Ten Fruits. Metabolites, 11.","DOI":"10.3390\/metabo11030164"},{"key":"ref_14","first-page":"36","article-title":"Comparative metabolite fingerprinting of legumes using LC-MS-based untargeted metabolomics","volume":"79","author":"Marinangeli","year":"2019","journal-title":"J. Food Compos. Anal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6487","DOI":"10.1007\/s00018-021-03918-3","article-title":"Metabolomics and health: From nutritional crops and plant-based medicines to profiling of bioactive compounds","volume":"78","author":"Marchev","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_16","unstructured":"Salem, M.A., J\u00fcppner, J., Bajdzienko, K., and Giavalisco, P. (2020). Protocols for metabolite profiling in plant systems using LC\u2013MS and GC\u2013MS. Metabolites, 10."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e201301007","DOI":"10.5936\/csbj.201301007","article-title":"Untargeted Metabolomics: An Emerging Approach to Determine the Composition of Herbal Products","volume":"4","author":"Commisso","year":"2013","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jpha.2017.06.005","article-title":"Application of HPLC and ESI-MS Techniques in the Analysis of Phenolic Acids and Flavonoids from Green Leafy Vegetables (GLVs)","volume":"7","author":"Kumar","year":"2017","journal-title":"J. Pharm. Anal."},{"key":"ref_19","first-page":"3","article-title":"Electrospray Ionisation Mass Spectrometry: Principles and Clinical Applications","volume":"24","author":"Ho","year":"2003","journal-title":"Clin. Biochem. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1046\/j.1432-1327.2000.01606.x","article-title":"Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity","volume":"267","author":"Wilson","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12347","DOI":"10.3390\/s120912347","article-title":"Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays","volume":"12","author":"Rampersad","year":"2012","journal-title":"Sensors"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jep.2006.04.003","article-title":"Anti-infective potential of natural products: How to develop a stronger in vitro \u201cproof-of-concept\u201d","volume":"106","author":"Cos","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Te\u00f3filo, M.N.G., Costa, L.G., Rocha, J.D., Barbosa, F.G., Melo, A.M., de Matos, G.G., Morgado, C.M.A., Fernandes, A.S., de Carvalho, L.B.R., and Gomes, C.M. (2025). Bioactive Compounds, Antioxidant, Cytotoxic, and Genotoxic Investigation of the Standardized Liquid Extract from Eugenia involucrata DC. Leaves. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050764"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s11306-006-0037-z","article-title":"Statistical strategies for avoiding false discoveries in metabolomics and related experiments","volume":"2","author":"Broadhurst","year":"2006","journal-title":"Metabolomics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nprot.2010.50","article-title":"Global metabolic profiling procedures for urine using UPLC\u2013MS","volume":"5","author":"Want","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1007\/s11306-012-0434-4","article-title":"Mass appeal: Metabolite identification in mass spectrometry-focused untargeted metabolomics","volume":"9","author":"Dunn","year":"2013","journal-title":"Metabolomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/mas.10008","article-title":"Practical Implications of Some Recent Studies in Electrospray Ionization Fundamentals","volume":"20","author":"Cech","year":"2001","journal-title":"Mass Spectrom. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cole, R.B. (2010). Electrospray and MALDI Mass Spectrometry: Fundamentals, Instrumentation, Practicalities, and Biological Applications, John Wiley & Sons.","DOI":"10.1002\/9780470588901"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1021\/acs.analchem.9b03481","article-title":"Strategies for Drawing Quantitative Conclusions from Nontargeted Liquid Chromatography\u2014High-Resolution Mass Spectrometry Analysis","volume":"92","author":"Kruve","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1007\/s13361-018-2023-x","article-title":"Charging and Charge Switching of Unsaturated Lipids and Apolar Compounds Using Patern\u00f2-B\u00fcchi Reactions","volume":"29","author":"Esch","year":"2018","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kasote, D.M., Lei, Z., Kranawetter, C.D., Conway-Anderson, A., Sumner, B.W., and Sumner, L.W. (2024). A Novel UHPLC-MS\/MS Based Method for Isomeric Separation and Quantitative Determination of Cyanogenic Glycosides in American Elderberry. Metabolites, 14.","DOI":"10.3390\/metabo14070360"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/FTD.0000000000000471","article-title":"Enhancement and Suppression of Ionization in Drug Analysis Using HPLC-MS\/MS in Support of Therapeutic Drug Monitoring: A Review of Current Knowledge of Its Minimization and Assessment","volume":"40","author":"George","year":"2018","journal-title":"Ther. Drug Monit."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1186\/1477-5956-10-S1-S8","article-title":"Ion annotation-assisted analysis of LC-MS based metabolomic experiment","volume":"10","author":"Varghese","year":"2012","journal-title":"Proteome Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/ac0351670","article-title":"Favorable Effects of Weak Acids on Negative-Ion Electrospray Ionization Mass Spectrometry","volume":"76","author":"Wu","year":"2004","journal-title":"Anal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, C., Gong, X., Bo, A., Zhang, L., Zhang, M., Zang, E., Zhang, C., and Li, M. (2020). Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics. Molecules, 25.","DOI":"10.3390\/molecules25020287"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102491","DOI":"10.1016\/j.fochx.2025.102491","article-title":"Plant Iridoids: Chemistry, Dietary Sources and Potential Health Benefits","volume":"27","author":"Guo","year":"2025","journal-title":"Food Chem. X"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kachlicki, P., Piasecka, A., Stobiecki, M., and Marczak, \u0141. (2016). Structural Characterization of Floweroid Glycoconjugates and Their Derivatives with Mass Spectrometric Techniques. Molecules, 21.","DOI":"10.3390\/molecules21111494"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104970","DOI":"10.1016\/j.chemphyslip.2020.104970","article-title":"Enhancing Detection and Characterization of Lipids Using Charge Manipulation in Electrospray Ionization-Tandem Mass Spectrometry","volume":"232","author":"Randolph","year":"2020","journal-title":"Chem. Phys. Lipids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1039\/B711844A","article-title":"Understanding Organofluorine Chemistry. An Introduction to the C\u2013F Bond","volume":"37","year":"2008","journal-title":"Chem. Soc. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1021\/cr500209t","article-title":"Enzymatic Fluorination and Biotechnological Developments of the Fluorinase","volume":"115","author":"Deng","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_42","first-page":"92","article-title":"Multivariate Analysis in Metabolomics","volume":"1","author":"Worley","year":"2013","journal-title":"Curr. Metabolomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1469-8137.2007.02252.x","article-title":"Hydroxylated jasmonates are commonly occurring metabolites of jasmonic acid and contribute to a partial switch-off in jasmonate signaling","volume":"177","author":"Miersch","year":"2008","journal-title":"New Phytol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jarocka-Karpowicz, I., and Markowska, A. (2021). Therapeutic Potential of Jasmonic Acid and Its Derivatives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168437"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1016\/j.bbagen.2017.06.006","article-title":"A Jasmonic Acid Derivative Improves Skin Healing and Induces Changes in Proteoglycan Expression and Glycosaminoglycan Structure","volume":"1861","author":"Henriet","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_46","first-page":"202","article-title":"Anti-inflammatory and membrane stabilizing properties of methyl jasmonate in rats","volume":"5","author":"Umukoro","year":"2017","journal-title":"Chin. J. Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/BF02910407","article-title":"Pollen as food and medicine\u2014A review","volume":"51","author":"Llnskens","year":"1997","journal-title":"Econ. Bot."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kond\u017ea, M., Brizi\u0107, I., and Joki\u0107, S. (2024). Flavonoids as CYP3A4 Inhibitors In Vitro. Biomedicines, 12.","DOI":"10.20944\/preprints202401.0803.v1"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109211","DOI":"10.1016\/j.cbi.2020.109211","article-title":"Roles of Flavonoids against Coronavirus Infection","volume":"328","author":"Russo","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6306","DOI":"10.1080\/07391102.2020.1796811","article-title":"Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An In Silico Study for Drug Development","volume":"39","author":"Pandey","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Periferakis, A., Periferakis, A.T., Troumpata, L., Periferakis, K., Scheau, A.E., Savulescu-Fiedler, I., Caruntu, A., Badarau, I.A., Caruntu, C., and Scheau, C. (2023). Kaempferol: A Review of Current Evidence of Its Antiviral Potential. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216299"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Arabyan, E., Hakobyan, A., Hakobyan, T., Grigoryan, R., Izmailyan, R., Avetisyan, A., Karalyan, Z., Jackman, J.A., Ferreira, F., and Elrod, C.C. (2021). Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.736780"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41586-020-2601-5","article-title":"Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity","volume":"587","author":"Shin","year":"2020","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/14756366.2019.1690480","article-title":"Inhibition of SARS-CoV 3CL protease by flavonoids","volume":"35","author":"Jo","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1007\/s00705-017-3417-y","article-title":"Flavonoids: Promising natural compounds against viral infections","volume":"162","author":"Zakaryan","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2174\/138955708783955926","article-title":"Biological and pharmacological activities of iridoids: Recent developments","volume":"8","author":"Tundis","year":"2008","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev-arplant-042817-040440","article-title":"The oxylipin pathways: Biochemistry and function","volume":"69","author":"Wasternack","year":"2018","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0163-7827(01)00003-0","article-title":"Plasmalogens: Biosynthesis and Functions","volume":"40","author":"Nagan","year":"2001","journal-title":"Prog. Lipid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.bbadis.2012.05.008","article-title":"Functions of Plasmalogen Lipids in Health and Disease","volume":"1822","author":"Braverman","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An Overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/jmv.1890150110","article-title":"Antiviral Effect of Flavonoids on Human Viruses","volume":"15","author":"Kaul","year":"1985","journal-title":"J. Med. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1126\/science.1128294","article-title":"Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis","volume":"313","author":"Ozcan","year":"2006","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biocel.2015.01.015","article-title":"The Therapeutic Effects of 4-Phenylbutyric Acid in Maintaining Proteostasis","volume":"61","author":"Kolb","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40199-023-00461-3","article-title":"Flavonoid as Possible Therapeutic Targets against COVID-19: A Scoping Review of In Silico Studies","volume":"31","author":"Toigo","year":"2023","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yang, H.X., Liu, Q.P., Zhou, Y.X., Chen, Y.Y., An, P., Xing, Y.Z., Zhang, L., Jia, M., and Zhang, H. (2022). Forsythiasides: A Review of the Pharmacological Effects. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.971491"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sadowska-Bartosz, I., and Bartosz, G. (2021). Biological Properties and Applications of Betalains. Molecules, 26.","DOI":"10.3390\/molecules26092520"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1002\/fsn3.3308","article-title":"Phytobioactive Compounds as Therapeutic Agents for Human Diseases: A Review","volume":"11","author":"Riaz","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Maury, G.L., Rodr\u00edguez, D.M., Hendrix, S., Arranz, J.C.E., Boix, Y.F., Pacheco, A.O., D\u00edaz, J.G., Morris-Quevedo, H.J., Dubois, A.F., and Aleman, E.I. (2020). Antioxidants in Plants: A Valorization Potential Emphasizing the Need for the Conservation of Plant Biodiversity in Cuba. Antioxidants, 9.","DOI":"10.3390\/antiox9111048"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"736837","DOI":"10.1155\/2012\/736837","article-title":"Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions","volume":"2012","author":"Lushchak","year":"2012","journal-title":"J. Amino Acids"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tinte, M.M., Chele, K.H., van der Hooft, J.J.J., and Tugizimana, F. (2021). Metabolomics-Guided Elucidation of Plant Abiotic Stress Responses in the 4IR Era: An Overview. Metabolites, 11.","DOI":"10.3390\/metabo11070445"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10545-017-0130-7","article-title":"Promises and Pitfalls of Untargeted Metabolomics","volume":"41","author":"Gertsman","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2419683","DOI":"10.1080\/15592324.2024.2419683","article-title":"Climate Change and Its Impact on the Bioactive Compound Profile of Medicinal Plants: Implications for Global Health","volume":"19","author":"Alum","year":"2024","journal-title":"Plant Signal. Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated Data and New Features for Efficient Prediction of Protein Targets of Small Molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/2\/232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:18:11Z","timestamp":1768367891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/2\/232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":74,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["plants15020232"],"URL":"https:\/\/doi.org\/10.3390\/plants15020232","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}