{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:08:04Z","timestamp":1791209284880,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ruta chalepensis L. var. angustifolia (Pers.) Willk. (Rutaceae) has been traditionally associated with hypocholesterolemic effects, although the bioactive metabolites responsible for this activity remain largely unknown. This study aimed to fractionate the methanolic extract of R. chalepensis var. angustifolia, identify its major phenolic constituents, and evaluate their inhibitory activity against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The methanolic extract was fractionated by open column chromatography, and selected fractions were analyzed by thin layer chromatography and HPLC-DAD. Rutin was identified as one of the major flavonoids, while three chromatographically pure fractions corresponded to unidentified phenolic compounds. Their inhibitory activity was assessed using a commercial HMG-CoA reductase assay. Pravastatin showed 87.5% inhibition and served as the positive control. Among the isolated fractions, one unidentified phenolic fraction exhibited the highest inhibitory activity (66.0%), exceeding that of rutin (45.8%), whereas another fraction showed negligible activity (8.3%). These findings indicate that the HMG-CoA reductase inhibitory potential of R. chalepensis var. angustifolia cannot be attributed solely to rutin and suggest the presence of additional bioactive phenolic metabolites. Further structural characterization and mechanistic studies are required to identify the active compound and confirm its hypocholesterolemic potential in biological systems.<\/jats:p>","DOI":"10.3390\/molecules31193552","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:47:07Z","timestamp":1791208027000},"page":"3552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenolic Compounds from Ruta chalepensis Var. angustifolia as Potential HMG-CoA Reductase Inhibitors: Bioactivity-Guided Fractionation and Preliminary Identification of Active Metabolites"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8275-6076","authenticated-orcid":false,"given":"Giselle","family":"Teresa-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Epigmenio Gonz\u00e1lez 500, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Patricia","family":"Rodr\u00edguez-Castillo","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Epigmenio Gonz\u00e1lez 500, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Anayantzin","family":"Torres-Morales","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Epigmenio Gonz\u00e1lez 500, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Goretti","family":"Arvizu-Espinoza","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Epigmenio Gonz\u00e1lez 500, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8802-8897","authenticated-orcid":false,"given":"Carmen","family":"T\u00e9llez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Eco-Intensification of Agro-Industrial Eco-Processes, Laboratory of Engineering Science for Environment LaSIE-UMR-CNRS 7356, Institute Littoral Urbain Durable Intelligent, La Rochelle University, 17042 La Rochelle, France"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-1186","authenticated-orcid":false,"given":"Anaberta","family":"Cardador-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Epigmenio Gonz\u00e1lez 500, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Maritza","family":"Alonzo-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Epigmenio Gonz\u00e1lez 500, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brown, A.J., Coates, H.W., and Sharpe, L.J. (2021). Cholesterol synthesis. Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier.","DOI":"10.1016\/B978-0-12-824048-9.00005-5"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Martinez-Hervas, S., and Ascaso, J. (2018). Hypercholesterolemia. Encyclopedia of Endocrine Diseases, Elsevier.","DOI":"10.1016\/B978-0-12-801238-3.65340-0"},{"key":"ref_3","first-page":"1","article-title":"Cardiovascular disease as a leading cause of death: How are pharmacists getting involved?","volume":"8","author":"Alzubaidi","year":"2019","journal-title":"Integr. Pharm. Res. Pract."},{"key":"ref_4","unstructured":"Ibrahim, M., Asuka, E., Jialal, I., and Corcione, J. (2023). Hypercholesterolemia (Nursing), StatPearls."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1146\/annurev-biochem-081820-101010","article-title":"Posttranslational Regulation of HMG CoA Reductase, the Rate-Limiting Enzyme in Synthesis of Cholesterol","volume":"90","author":"Schumacher","year":"2021","journal-title":"Annu. Rev. Biochem."},{"key":"ref_6","unstructured":"Bansal, A.B., and Cassagnol, M. (2026). HMG-CoA Reductase Inhibitors, StatPearls."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1126\/science.1059344","article-title":"Structural Mechanism for Statin Inhibition of HMG-CoA Reductase","volume":"292","author":"Istvan","year":"2001","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1161\/CIRCRESAHA.116.308537","article-title":"Pleiotropic Effects of Statins on the Cardiovascular System","volume":"120","author":"Oesterle","year":"2017","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.sajb.2018.04.011","article-title":"Antioxidant and anticholinesterase effects of the ethanol extract, ethanol extract fractions and total alkaloids from the cultivated Ruta chalepensis","volume":"120","author":"Gali","year":"2019","journal-title":"South Afr. J. Bot."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6459","DOI":"10.2147\/DDDT.S494417","article-title":"Traditional Uses, Phytochemistry, Pharmacology and Toxicology of Ruta graveolens L.: A Critical Review and Future Perspectives","volume":"18","author":"Luo","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_11","first-page":"1","article-title":"A brief review of phenolic compounds identified from plants: Their extraction, analysis, and biological activity","volume":"17","author":"Zhang","year":"2022","journal-title":"Nat. Prod. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6326","DOI":"10.1111\/ijfs.15936","article-title":"Role of phenolic acid, tannins, stilbenes, lignans and flavonoids in human health\u2014A review","volume":"57","author":"Oluwole","year":"2022","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8254","DOI":"10.21037\/apm-21-1343","article-title":"The role of flavonoids in the prevention and management of cardiovascular complications: A narrative review","volume":"10","author":"Chen","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Grosso, G., Godos, J., Currenti, W., Micek, A., Falzone, L., Libra, M., Giampieri, F., Forbes-Hern\u00e1ndez, T.Y., Quiles, J.L., and Battino, M. (2022). The Effect of Dietary Polyphenols on Vascular Health and Hypertension: Current Evidence and Mechanisms of Action. Nutrients, 14.","DOI":"10.3390\/nu14030545"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113076","DOI":"10.1016\/j.jep.2020.113076","article-title":"Genus Ruta: A natural source of high value products with biological and pharmacological properties","volume":"260","author":"Coimbra","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Szewczyk, A., Marino, A., Molinari, J., Ekiert, H., and Miceli, N. (2022). Phytochemical Characterization, and Antioxidant and Antimicrobial Properties of Agitated Cultures of Three Rue Species: Ruta chalepensis, Ruta corsica, and Ruta graveolens. Antioxidants, 11.","DOI":"10.3390\/antiox11030592"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/13880209.2020.1762669","article-title":"Ruta graveolens and rutin, as its major compound: Investigating their effect on spatial memory and passive avoidance memory in rats","volume":"58","author":"Asgharian","year":"2020","journal-title":"Pharm. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nahar, L., El-Seedi, H.R., Khalifa, S.A.M., Mohammadhosseini, M., and Sarker, S.D. (2021). Ruta Essential Oils: Composition and Bioactivities. Molecules, 26.","DOI":"10.3390\/molecules26164766"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9921218","DOI":"10.1155\/jfbc\/9921218","article-title":"Phytochemical Investigation and Biological Activities of Ruta chalepensis Methanolic Extract: Antioxidant, Anti-Inflammatory, Anticollagenase, and Antielastase Properties","volume":"2024","author":"Althaher","year":"2024","journal-title":"J. Food Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bailly, C. (2023). Ruta angustifolia Pers. (Narrow-Leaved Fringed Rue): Pharmacological Properties and Phytochemical Profile. Plants, 12.","DOI":"10.3390\/plants12040827"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1177\/117863370700200005","article-title":"Platelet aggregation inhibitors from aerial parts of Ruta chalepensis grown in Jordan","volume":"2","author":"Shehadeh","year":"2007","journal-title":"Integr. Med. Insights"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1871530320666200628025430","article-title":"Ruta Montana Evokes Antihypertensive Activity Through an Increase of Prostaglandins Release in L-NAME-Induced Hypertensive Rats","volume":"21","author":"Fadwa","year":"2021","journal-title":"Endocr. Metab. Immune Disord.-Drug Targets"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Al-Majmaie, S., Nahar, L., Rahman, M.M., Nath, S., Saha, P., Talukdar, A.D., Sharples, G.P., and Sarker, S.D. (2021). Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3\u2032,7-Dimethyl ether. Molecules, 26.","DOI":"10.3390\/molecules26041114"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Elizondo-Lu\u00e9vano, J.H., Rodr\u00edguez-Garza, N.E., Bazald\u00faa-Rodr\u00edguez, A.F., Romo-S\u00e1enz, C.I., Tamez-Guerra, P., Verde-Star, M.J., Gomez-Flores, R., and Quintanilla-Licea, R. (2023). Cytotoxic, Anti-Hemolytic, and Antioxidant Activities of Ruta chalepensis L. (Rutaceae) Extract, Fractions, and Isolated Compounds. Plants, 12.","DOI":"10.3390\/plants12112203"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pavi\u0107, V., Fla\u010der, D., Jakovljevi\u0107, M., Molnar, M., and Joki\u0107, S. (2019). Assessment of Total Phenolic Content, In Vitro Antioxidant and Antibacterial Activity of Ruta graveolens L. Extracts Obtained by Choline Chloride Based Natural Deep Eutectic Solvents. Plants, 8.","DOI":"10.3390\/plants8030069"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3166\/phyto-2019-0153","article-title":"Composition chimique, activit\u00e9 antioxydante et anticanc\u00e9reuse des extraits de Ruta chalepensis sur des lign\u00e9es de cellules leuc\u00e9miques humaines","volume":"16","author":"Terkmane","year":"2018","journal-title":"Phytoth\u00e9rapie"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chunmei, Z., and Shuai, W. (2025). Molecular mechanisms of neuroprotective effect of rutin. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1599167"},{"key":"ref_28","first-page":"110","article-title":"Antioxidant and \u03b1-amylase inhibition activity of Ruta chalepensis L. extracts","volume":"14","author":"Ajo","year":"2022","journal-title":"Carpathian J. Food Sci. Technol."},{"key":"ref_29","first-page":"26","article-title":"Phenolic compound profiles and antioxidant activity of Ruta chalepensis L. leaves, a spontaneous medicinal herb: Influence of harvest zone (Western Algeria)","volume":"7","author":"Zohra","year":"2021","journal-title":"Int. J. Minor Fruits Med. Aromat. Plants"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yeshi, K., Crayn, D., Ritmejeryt\u0117, E., and Wangchuk, P. (2022). Plant Secondary Metabolites Produced in Response to Abiotic Stresses Has Potential Application in Pharmaceutical Product Development. Molecules, 27.","DOI":"10.3390\/molecules27010313"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1021\/acs.jnatprod.2c00720","article-title":"Digital Database of Absorption Spectra of Diverse Flavonoids Enables Structural Comparisons and Quantitative Evaluations","volume":"86","author":"Taniguchi","year":"2023","journal-title":"J. Nat. Prod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e202200545","DOI":"10.1002\/cbdv.202200545","article-title":"Phenolic Content and In Vitro Antioxidant, Anti-Inflammatory and antimicrobial Evaluation of Algerian Ruta graveolens L.","volume":"19","author":"Mokhtar","year":"2022","journal-title":"Chem. Biodivers."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"606","DOI":"10.5530\/pj.2023.15.127","article-title":"HPLC isolation of rutin, hesperidin and quercetin from Ruta chalepensis extract growing in Iraq","volume":"15","year":"2023","journal-title":"Pharmacogn. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/14786419.2017.1326491","article-title":"Ruta chalepensis L. (Rutaceae) leaf extract: Chemical composition, antioxidant and hypoglicaemic activities","volume":"32","author":"Loizzo","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kaczorov\u00e1, D., Karalija, E., Dahija, S., Be\u0161ta-Gajevi\u0107, R., Pari\u0107, A., and \u0106avar Zeljkovi\u0107, S. (2021). Influence of Extraction Solvent on the Phenolic Profile and Bioactivity of Two Achillea Species. Molecules, 26.","DOI":"10.3390\/molecules26061601"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"162750","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and biological activities of flavonoids: An overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. World J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mabry, T.J., Markham, K., and Thomas, M. (1970). The Systematic Identification of Flavonoids, Springer. [1st ed.].","DOI":"10.1007\/978-3-642-88458-0"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jbiotec.2020.11.020","article-title":"Genome-wide transcriptome variation landscape in Ruta chalepensis organs revealed potential genes responsible for rutin biosynthesis","volume":"325","author":"Faisal","year":"2021","journal-title":"J. Biotechnol."},{"key":"ref_39","first-page":"61","article-title":"Dose-dependent Additive And Antagonistic Effects on Phenolics, Tannins, Flavonoids, And Antioxidant Activity Of Platycladus orientalis (L.) Franco In Binary Mixtures With Selected East Asian Medicinal Plants","volume":"21","author":"Lim","year":"2026","journal-title":"Jordan J. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1475-2875-10-S1-S4","article-title":"Whole plant extracts versus single compounds for the treatment of malaria: Synergy and positive interactions","volume":"10","author":"Rasoanaivo","year":"2011","journal-title":"Malar. J."},{"key":"ref_41","first-page":"1","article-title":"Antioxidant Activity and its Interaction Effect on Polyherbal Formulations of Nephrodium inophyllum, Polygonum minus Annona squamosal L. and Stevia rebaudiana","volume":"61","author":"Rahim","year":"2019","journal-title":"J. Adv. Res. Fluid Mech. Therm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6198","DOI":"10.1021\/acs.jpcb.8b03500","article-title":"Comprehensive Investigation of the Antioxidant and Pro-oxidant Effects of Phenolic Compounds: A Double-Edged Sword in the Context of Oxidative Stress?","volume":"122","author":"Reina","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.polymdegradstab.2018.05.003","article-title":"Assessment of pro-oxidant activity of natural phenolic compounds in bio-polyesters","volume":"152","author":"Dintcheva","year":"2018","journal-title":"Polym. Degrad. Stab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1039\/D4EM00191E","article-title":"Effects of copper on chemical kinetics and brown carbon formation in the aqueous \u02d9OH oxidation of phenolic compounds","volume":"26","author":"Yang","year":"2024","journal-title":"Environ. Sci. Processes Impacts"},{"key":"ref_45","unstructured":"Fedenko, V.S., Shemet, S.A., Guidi, L., and Landi, M. (2020). Metal\/metalloid-induced accumulation of phenolic compounds in plants. Metal Toxicity in Higher Plants, Nova Science Publishers Inc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/bs.afnr.2021.02.010","article-title":"Antioxidant\/pro-oxidant and antiproliferative activities of phenolic-rich foods and extracts: A cell-based point of view","volume":"Volume 98","author":"Granato","year":"2021","journal-title":"Advances in Food and Nutrition Research"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2602559123","DOI":"10.1073\/pnas.2602559123","article-title":"The ERAD pathway mediates cross talk between two control points in cholesterol synthesis: HMG CoA reductase and squalene monooxygenase","volume":"123","author":"Faulkner","year":"2026","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gesto, D.S., Pereira, C.M.S., Cerqueira, N.M.F.S., and Sousa, S.F. (2020). An atomic-level perspective of HMG-CoA-reductase: The target enzyme to treat hypercholesterolemia. Molecules, 25.","DOI":"10.3390\/molecules25173891"},{"key":"ref_49","first-page":"263","article-title":"Statin-Induced Mitochondrial Damage","volume":"Volume 32","author":"Langsjoen","year":"2024","journal-title":"Advances in Biochemistry in Health and Disease"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ikushiro, S. (2026). Metabolism and Absorption: Enzyme-Assisted Synthesis and Potential Role of Polyphenol Metabolites. Functional Food Factors, Springer.","DOI":"10.1007\/978-981-95-7068-3_38"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"402995","DOI":"10.1016\/j.mrgentox.2018.12.003","article-title":"Use of human derived liver cells for the detection of genotoxins in comet assays","volume":"845","author":"Nersesyan","year":"2019","journal-title":"Mutat. Res.-Genet. Toxicol. Environ. Mutagen."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5324","DOI":"10.1080\/10408398.2024.2410874","article-title":"A critical examination of human data for the biological activity of phenolic acids and their phase-2 conjugates derived from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines","volume":"65","author":"Williamson","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jab.2016.09.001","article-title":"Modulation of HMG-CoA reductase and glutathione-linked enzymes and protection against pro-oxidant induced oxidative damage in colon (Caco-2) cells and rat colon homogenates by phenolic extracts from Shaddock (Citrus maxima) peels","volume":"15","author":"Ademosun","year":"2017","journal-title":"J. Appl. Biomed."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"151833","DOI":"10.1016\/j.bbrc.2025.151833","article-title":"Rutin isolated from Acalypha indica L.: A comprehensive analysis of its antibacterial and anticancer activities","volume":"765","author":"Chekuri","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4103\/2221-1691.267659","article-title":"Nrf2-inducing and HMG-CoA reductase inhibitory activities of a polyphenol-rich fraction of Guazuma ulmifolia leaves","volume":"9","author":"Sulistiyani","year":"2019","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s10787-009-8044-0","article-title":"Methanolic extract of Ruta graveolens L. inhibits inflammation and oxidative stress in adjuvant induced model of arthritis in rats","volume":"17","author":"Ratheesh","year":"2009","journal-title":"Inflammopharmacology"},{"key":"ref_57","first-page":"136","article-title":"The Effect of Methanolic and Ethanolic Extracts of Ruta graveolens L. Leaves on Formalin-Induced Inflammation in Rats","volume":"1","author":"Alireza","year":"2016","journal-title":"Tradit. Integr. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/acs.jnatprod.8b00677","article-title":"Bioactive Dimeric Acylphloroglucinols from the Mexican Fern Elaphoglossum paleaceum","volume":"82","author":"Henriques","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gerlach, M., Stoschek, T., Leonhardt, H., Hackenberger, C.P., Schumacher, D., and Helma, J. (2019). Tubulin tyrosine ligase-mediated modification of proteins. Enzyme-Mediated Ligation Methods, Springer.","DOI":"10.1007\/978-1-4939-9546-2_17"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/19\/3552\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:47:25Z","timestamp":1791208045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/19\/3552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":59,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["molecules31193552"],"URL":"https:\/\/doi.org\/10.3390\/molecules31193552","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]}}}