{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:17:27Z","timestamp":1783595847493,"version":"3.55.0"},"reference-count":104,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of extracts derived from its aerial (AgP) and underground (UgP) parts. The phytochemical constituents of various P. autumnale extracts were analyzed using LC-MS\/MS, and their phenolic content was quantified. The biological activities were evaluated through in vitro assays\u2014including antioxidant, anti-inflammatory, acetylcholinesterase-inhibitory, and photoprotection assessments\u2014and in vivo experiments, including evaluations of acute oral toxicity, anti-inflammatory, and analgesic effects. UgP extracts demonstrated significant antioxidant activity, with the methanolic extract exhibiting the highest reducing and superoxide scavenging capacities. Dichloromethane and ethyl acetate extracts performed exceptionally well in ABTS and DPPH assays. The aqueous extract from AgP exhibited noteworthy anti-inflammatory and analgesic effects, surpassing diclofenac in vitro and demonstrating efficacy in vivo. It also showed considerable acetylcholinesterase inhibition, while the ethyl acetate extract displayed high photoprotective potential. The acute toxicity was moderate (LD50: 300\u2013400 mg\/kg), indicating dose-dependent risks. LC-MS\/MS analysis revealed diverse phenolics potentially contributing to both therapeutic and adverse effects. This research enhances the medicinal prospects of P. autumnale, provides new perspectives on plant utilization, and suggests its potential as a natural anti-inflammatory agent. However, due to moderate toxicity and dose-dependent effects, cautious application is advised. These findings underscore the importance of toxicological evaluation alongside bioactivity screening in ethnopharmacology to ensure safety.<\/jats:p>","DOI":"10.3390\/toxins18070285","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:56:55Z","timestamp":1782838615000},"page":"285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comprehensive Chemical\u2013Biological Investigation of the Moderately Toxic Plant Prospero autumnale: Insights into Its Bioactive Potential Using In Vitro and In Vivo Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7111-7985","authenticated-orcid":false,"given":"Maroua","family":"Korichi","sequence":"first","affiliation":[{"name":"Laboratory of Valorization and Promotion of Saharan Resources (VPRS), Faculty of Mathematics and Matter Sciences, University of Ouargla, Ouargla 30000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouanissa","family":"Smara","sequence":"additional","affiliation":[{"name":"Laboratory of Valorization and Promotion of Saharan Resources (VPRS), Faculty of Mathematics and Matter Sciences, University of Ouargla, Ouargla 30000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1264-2344","authenticated-orcid":false,"given":"Lilya","family":"Harchaoui","sequence":"additional","affiliation":[{"name":"Research Laboratory on Arid Zones (LRZA), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), BP 32 El-Alia, Bab Ezzouar, Algiers 16111, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4407-2781","authenticated-orcid":false,"given":"Gilda","family":"D\u2019Urso","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8154-2693","authenticated-orcid":false,"given":"Latifa","family":"Khattabi","sequence":"additional","affiliation":[{"name":"Biotechnology Research Centre, Constantine (CRBT), Ali Mendjli Nouvelle Ville UV 03, BP E73, Constantine 25016, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2310-9426","authenticated-orcid":false,"given":"Agostino","family":"Casapullo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5065-9717","authenticated-orcid":false,"given":"Gianluigi","family":"Lauro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Chini","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, 86090 Isernia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Bifulco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1551-4237","authenticated-orcid":false,"given":"Alessio","family":"Cimmino","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hocine","family":"Dendougui","sequence":"additional","affiliation":[{"name":"Laboratory of Valorization and Promotion of Saharan Resources (VPRS), Faculty of Mathematics and Matter Sciences, University of Ouargla, Ouargla 30000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-5984","authenticated-orcid":false,"given":"Wafa","family":"Zahnit","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie, Ing\u00e9nierie Mol\u00e9culaire et Nanostructures, Department of Chemistry, Faculty of Sciences, University of Ferhat ABBAS Setif 1, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0609-8902","authenticated-orcid":false,"given":"Marco","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5584-5607","authenticated-orcid":false,"given":"Mahdi","family":"Belguidoum","sequence":"additional","affiliation":[{"name":"Laboratory of Valorization and Promotion of Saharan Resources (VPRS), Faculty of Mathematics and Matter Sciences, University of Ouargla, Ouargla 30000, Algeria"},{"name":"Applied Sciences Faculty, University of Ouargla, Ouargla 30000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Izah, S.C., Ogwu, M.C., and Akram, M. (2023). Historical perspectives and overview of the value of herbal medicine. Herbal Medicine Phytochemistry: Applications and Trends, Springer International Publishing.","DOI":"10.1007\/978-3-031-21973-3"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107572","DOI":"10.1016\/j.phrs.2024.107572","article-title":"A comprehensive review on the plant sources, pharmacological activities and pharmacokinetic characteristics of Syringaresinol","volume":"212","author":"Zhang","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S178","DOI":"10.1016\/S2221-1691(12)60154-3","article-title":"Evaluation of in vitro anti-inflammatory activity of coffee against the denaturation of protein","volume":"2","author":"Chandra","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s11101-019-09629-9","article-title":"Importance of ethnopharmacological studies in drug discovery: Role of medicinal plants","volume":"19","year":"2020","journal-title":"Phytochem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_6","unstructured":"Hannoodee, S., and Nasuruddin, D.N. (2024). Acute inflammatory response. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106820","DOI":"10.1016\/j.phrs.2023.106820","article-title":"Structure-activity relationship, bioactivities, molecular mechanisms, and clinical application of nuciferine on inflammation-related diseases","volume":"193","author":"Zhao","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_8","unstructured":"Pahwa, R., Goyal, A., and Jialal, I. (2022). Chronic Inflammation. StatPearls, StatPearls Publishing."},{"key":"ref_9","first-page":"1","article-title":"Significant role of free radicals in inflammation","volume":"11","author":"Eiz","year":"2022","journal-title":"Oxid. Antioxid. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106812","DOI":"10.1016\/j.phrs.2023.106812","article-title":"Phenolic metabolites as therapeutic in inflammation and neoplasms: Molecular pathways explaining their efficacy","volume":"193","author":"Liu","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_11","first-page":"129","article-title":"Photoprotection of natural flavonoids","volume":"3","author":"Saewan","year":"2013","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_12","first-page":"84","article-title":"Pharmacological evaluation of different extracts of Asparagus officinalis (Asparagaceae) as an analgesic, anti-inflammatory and anti-arthritic agent in rats","volume":"15","author":"Kumar","year":"2023","journal-title":"Phcog. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"585","DOI":"10.4172\/pharmaceutical-sciences.1000266","article-title":"Phenolic Composition, Antioxidant and Cytotoxic Activities of Prospero autumnale","volume":"79","author":"Mammadov","year":"2017","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205048","DOI":"10.1155\/2013\/205048","article-title":"Commercially important medicinal plants of South Africa: A review","volume":"2013","author":"Street","year":"2013","journal-title":"J. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jep.2012.10.053","article-title":"The cytotoxic effects of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) aqueous extract on cultured HepG2 cells","volume":"145","author":"Pillay","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s00606-022-01835-x","article-title":"Phylogeny, biogeography, and character evolution in the genus Scilla s.l. and its close relatives Chionodoxa, Gemicia, Puschkinia, and Prospero (Asparagaceae)","volume":"308","year":"2022","journal-title":"Plant Syst. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34343","DOI":"10.1039\/D1RA06091K","article-title":"Inhibitory mechanism of two homoisoflavonoids from Ophiopogon japonicus on tyrosinase activity: Insight from spectroscopic analysis and molecular docking","volume":"11","author":"Wang","year":"2021","journal-title":"RSC Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1021\/acs.jnatprod.4c01263","article-title":"Cytotoxic Stilbenoids, Hetero- and Homodimers of Homoisoflavonoids from Prospero autumnale","volume":"88","author":"Aru","year":"2025","journal-title":"J. Nat. Prod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S2221-1691(12)60019-7","article-title":"Antioxidant activities of Indigofera cassioides Rottl. Ex. DC. using various in vitro assay models","volume":"2","author":"Kumar","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chaves, N., Santiago, A., and Al\u00edas, J.C. (2020). Quantification of the Antioxidant Activity of Plant Extracts: Analysis of Sensitivity and Hierarchization Based on the Method Used. Antioxidants, 9.","DOI":"10.3390\/antiox9010076"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Parimelazhagan, T. (2015). Pharmacological Assays of Plant-Based Natural Products, Springer.","DOI":"10.1007\/978-3-319-26811-8"},{"key":"ref_22","first-page":"84","article-title":"Evaluation of in vitro antioxidant, anti-inflammatory and thrombolytic activities of Scilla hyacinthina, an endangered medicinal plant","volume":"7","author":"Alluri","year":"2015","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1021\/acs.jafc.3c04022","article-title":"The Chemistry Behind the Folin\u2013Ciocalteu Method for the Estimation of (Poly)phenol Content in Food: Total Phenolic Intake in a Mediterranean Dietary Pattern","volume":"71","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e15980","DOI":"10.1111\/jfpp.15980","article-title":"Biochemical components, enzyme inhibitory, antioxidant and antimicrobial activities in endemic plant Scilla mesopotamica speta","volume":"45","author":"Aktepe","year":"2021","journal-title":"J. Food Process. Preserv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2515260","DOI":"10.1155\/2022\/2515260","article-title":"Evaluation of Antioxidant, Cytotoxic, Anti-Inflammatory, Antiarthritic, Thrombolytic, and Anthelmintic Activity of Methanol Extract of Lepidagathis hyalina Nees Root","volume":"2022","author":"Islam","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1002\/ptr.7100","article-title":"Plant species used in Brazil and Asia regions with toxic properties","volume":"35","author":"Marmitt","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35506","DOI":"10.1021\/acsomega.2c01309","article-title":"Preclinical Safety Assessment of Chemically Cross-Linked Modified Mandua Starch: Acute and Sub-Acute Oral Toxicity Studies in Swiss Albino Mice","volume":"7","author":"Malik","year":"2022","journal-title":"ACS Omega"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0378-8741(02)00184-8","article-title":"Medicinal bulbous plants of South Africa and their traditional relevance in the control of infectious diseases","volume":"82","author":"Louw","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2478\/intox-2018-0001","article-title":"Advances in acute toxicity testing: Strengths, weaknesses and regulatory acceptance","volume":"11","author":"Erhirhie","year":"2018","journal-title":"Interdiscip. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mpofana, N., Chipangura, J.K., Paulse, M., Yalo, M., Gqaleni, N., Nxumalo, C.T., Dlova, N.C., Hussein, A.A., and Crouch, N.R. (2023). An Investigation into the Acute and Subacute Toxicity of Extracts of Cassipourea flanaganii Stem Bark In Vivo. Plants, 12.","DOI":"10.20944\/preprints202304.0395.v1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125992","DOI":"10.1016\/j.ijbiomac.2023.125992","article-title":"Recent advances in lignin antioxidant: Antioxidant mechanism, evaluation methods, influence factors and various applications","volume":"251","author":"Li","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ji, M., Gong, X., Li, X., Wang, C., and Li, M. (2020). Advanced Research on the Antioxidant Activity and Mechanism of Polyphenols from Hippophae Species-A Review. Molecules, 25.","DOI":"10.3390\/molecules25040917"},{"key":"ref_33","first-page":"9","article-title":"Scilla bifolia L. (Orman S\u00fcmb\u00fcl\u00fc) Bitki K\u0131s\u0131mlar\u0131n\u0131n Antioksidan Aktivitesinin Belirlenmesi","volume":"7","year":"2022","journal-title":"J. Anatol. Environ. Anim. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Munteanu, I.G., and Apetrei, C. (2021). Analytical Methods Used in Determining Antioxidant Activity: A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073380"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1152\/physrev.00040.2012","article-title":"Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases","volume":"94","author":"Bhattacharyya","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1104\/pp.106.077073","article-title":"Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life","volume":"141","author":"Halliwell","year":"2006","journal-title":"Plant Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"827","DOI":"10.2174\/092986707780090954","article-title":"SAR and QSAR of the antioxidant activity of flavonoids","volume":"14","author":"Beslo","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.sajb.2020.10.022","article-title":"Investigation of the anti-inflammatory and antioxidant activities of luteolin, kaempferol, apigenin and quercetin","volume":"137","author":"Tian","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.bmcl.2006.12.008","article-title":"Synthesis, structural revision, and antioxidant activities of antimutagenic homoisoflavonoids from Hoffmanosseggia intricata","volume":"17","author":"Siddaiah","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.tet.2005.10.059","article-title":"A concise synthesis of polyhydroxydihydrochalcones and homoisoflavonoids","volume":"62","author":"Siddaiah","year":"2006","journal-title":"Tetrahedron"},{"key":"ref_41","first-page":"475","article-title":"Naturally occurring homoisoflavonoids: Phytochemistry, biological activities and synthesis","volume":"2","author":"Abegaz","year":"2007","journal-title":"Nat. Prod. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"119921","DOI":"10.1016\/j.lfs.2021.119921","article-title":"Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives","volume":"284","author":"Li","year":"2021","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40816-019-0137-8","article-title":"Evaluation of anti-inflammatory activity of Justicia secunda Vahl leaf extract using in vitro and in vivo inflammation models","volume":"5","author":"Anyasor","year":"2019","journal-title":"Clin. Phytoscience"},{"key":"ref_44","first-page":"31","article-title":"In vitro anti-inflammatory activity of different parts of Pedalium murex (L.)","volume":"4","author":"Sangeetha","year":"2016","journal-title":"Inflammation"},{"key":"ref_45","first-page":"327","article-title":"The in vitro anti-denaturation effects induced by natural products and non-steroidal compounds in heat treated (immunogenic) bovine serum albumin is proposed as a screening assay for the detection of anti-inflammatory compounds, without the use of animals, in the early stages of the drug discovery process","volume":"57","author":"Williams","year":"2008","journal-title":"West Indian Med. J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ullah, H.M., Zaman, S., Juhara, F., Akter, L., Tareq, S.M., Masum, E.H., and Bhattacharjee, R. (2014). Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-346"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kuete, V. (2017). Chapter 9\u2014Anti-inflammatory and Anti-nociceptive Activities of African Medicinal Spices and Vegetables. Medicinal Spices and Vegetables from Africa, Academic Press.","DOI":"10.1016\/B978-0-12-809286-6.00010-8"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5651390","DOI":"10.1155\/2020\/5651390","article-title":"Acute Oral Toxicity and Anti-inflammatory and Analgesic Effects of Aqueous and Methanolic Stem Bark Extracts of Piliostigma thonningii (Schumach.)","volume":"2020","author":"Olela","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.intimp.2011.03.012","article-title":"Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin","volume":"11","author":"Nakamura","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7432797","DOI":"10.1155\/2016\/7432797","article-title":"Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?","volume":"2016","author":"Hussain","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shamsudin, N.F., Ahmed, Q.U., Mahmood, S., Shah, S.A.A., Sarian, M.N., Khattak, M., Khatib, A., Sabere, A.S.M., Yusoff, Y.M., and Latip, J. (2022). Flavonoids as Antidiabetic and Anti-Inflammatory Agents: A Review on Structural Activity Relationship-Based Studies and Meta-Analysis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012605"},{"key":"ref_52","first-page":"189","article-title":"In vitro anti-inflammatory activity of methanol extract of Enicostemma axillare","volume":"3","author":"Leelaprakash","year":"2011","journal-title":"Int. J. Drug Dev. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/0006-2952(70)90234-0","article-title":"Stabilization of serum albumin by anti-inflammatory drugs","volume":"19","author":"Grant","year":"1970","journal-title":"Biochem. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.24198\/ijpst.v1i1.36323","article-title":"Anti inflammatory Activity of the Ethanol Extract of Cinnamon (Cinnamomum burmannii) Bark using Membrane Stabilization Method and Protein Denaturation","volume":"1","author":"Shalihah","year":"2021","journal-title":"Indones. J. Pharm. Sci. Technol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.sajb.2019.06.034","article-title":"African plants with in vitro anti-inflammatory activities: A review","volume":"126","author":"Elgorashi","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jep.2014.02.034","article-title":"Antimycobacterial, anti-inflammatory and genotoxicity evaluation of plants used for the treatment of tuberculosis and related symptoms in South Africa","volume":"153","author":"Madikizela","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jep.2004.10.021","article-title":"Effect of storage on the chemical composition and biological activity of several popular South African medicinal plants","volume":"97","author":"Stafford","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0378-8741(96)01395-5","article-title":"Screening of Zulu medicinal plants for prostaglandin-synthesis inhibitors","volume":"52","author":"Hutchings","year":"1996","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.apjtb.2017.05.013","article-title":"Phytochemical analysis and anti-oxidant activities of Albuca bracteata Jacq. and Albuca setosa Jacq bulb extracts used for the management of diabetes in the Eastern Cape, South Africa","volume":"7","author":"Odeyemi","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Di Meo, F., Valentino, A., Petillo, O., Peluso, G., Filosa, S., and Crispi, S. (2020). Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072564"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3945\/an.114.007500","article-title":"Flavonoid-Based Therapies in the Early Management of Neurodegenerative Diseases","volume":"6","author":"Solanki","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.sajb.2018.09.011","article-title":"Acetylcholinesterase inhibitors from southern African plants: An overview of ethnobotanical, pharmacological potential and phytochemical research including and beyond Alzheimer\u2019s disease treatment","volume":"120","author":"Masondo","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.bmc.2016.11.048","article-title":"Multitarget drug design strategy against Alzheimer\u2019s disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties","volume":"25","author":"Li","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/14740338.2020.1721456","article-title":"An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer\u2019s disease","volume":"19","author":"Haake","year":"2020","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.toxrep.2015.05.003","article-title":"In-vitro anti-cholinesterase activity of essential oil from four tropical medicinal plants","volume":"2","author":"Owokotomo","year":"2015","journal-title":"Toxicol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1039\/C4FO00287C","article-title":"Inhibition of flavonoids on acetylcholine esterase: Binding and structure\u2013activity relationship","volume":"5","author":"Xie","year":"2014","journal-title":"Food Funct."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.biopha.2018.03.007","article-title":"Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects","volume":"101","author":"Khan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10957","DOI":"10.1080\/07391102.2023.2190825","article-title":"Sappanin-type homoisoflavonoids from Scilla nervosa inhibits acetylcholinesterase enzyme: A combined in silico and in vitro approach","volume":"41","author":"Famuyiwa","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Santos, T.C.d., Gomes, T.M., Pinto, B.A.S., Camara, A.L., and Paes, A.M.d.A. (2018). Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer\u2019s Disease Therapy. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01192"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Braidy, N., Poljak, A., Jayasena, T., and Sachdev, P. (2017). Natural Plant-Derived Acetylcholinesterase Inhibitors: Relevance for Alzheimer\u2019s Disease. Natural Products Targeting Clinically Relevant Enzymes, Wiley-VCH.","DOI":"10.1002\/9783527805921.ch12"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1515\/revneuro-2017-0054","article-title":"Medicinal plants with acetylcholinesterase inhibitory activity","volume":"29","author":"Patel","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Campanella, C., Pace, A., Caruso Bavisotto, C., Marzullo, P., Marino Gammazza, A., Buscemi, S., and Palumbo Piccionello, A. (2018). Heat Shock Proteins in Alzheimer\u2019s Disease: Role and Targeting. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092603"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Teleanu, D.M., Niculescu, A.-G., Lungu, I.I., Radu, C.I., Vlad\u00e2cenco, O., Roza, E., Cost\u0103chescu, B., Grumezescu, A.M., and Teleanu, R.I. (2022). An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115938"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1080\/00207454.2016.1212854","article-title":"Neuroinflammation pathways: A general review","volume":"127","author":"Shabab","year":"2017","journal-title":"Int. J. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.gendis.2020.11.008","article-title":"Sulfuretin exerts diversified functions in the processing of amyloid precursor protein","volume":"8","author":"Chen","year":"2021","journal-title":"Genes Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/sj.bjp.0704047","article-title":"Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid","volume":"133","author":"Yan","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejphar.2014.12.013","article-title":"Deoxysappanone B, a homoisoflavone from the Chinese medicinal plant Caesalpinia sappan L., protects neurons from microglia-mediated inflammatory injuries via inhibition of I\u03baB kinase (IKK)-NF-\u03baB and p38\/ERK MAPK pathways","volume":"748","author":"Zeng","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_78","first-page":"963520","article-title":"ROS and Brain Diseases: The Good, the Bad, and the Ugly","volume":"2013","author":"Mitran","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7406","DOI":"10.1016\/j.bmc.2013.09.050","article-title":"Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine\u2013Homoisoflavonoid hybrids","volume":"21","author":"Sun","year":"2013","journal-title":"Bioorganic Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1039\/C7MD00199A","article-title":"Synthesis and pharmacological evaluation of multi-functional homoisoflavonoid derivatives as potent inhibitors of monoamine oxidase B and cholinesterase for the treatment of Alzheimer\u2019s disease","volume":"8","author":"Liu","year":"2017","journal-title":"Medchemcomm"},{"key":"ref_81","first-page":"389","article-title":"Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer\u2019s disease: Synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives","volume":"31","author":"Wang","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1021\/jm1013709","article-title":"Homoisoflavonoids: Natural Scaffolds with Potent and Selective Monoamine Oxidase-B Inhibition Properties","volume":"54","author":"Desideri","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/ics.12165","article-title":"Photoprotection in changing times\u2014UV filter efficacy and safety, sensitization processes and regulatory aspects","volume":"37","author":"Stiefel","year":"2015","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00403-009-1001-3","article-title":"Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms","volume":"302","author":"Nichols","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/jocd.13609","article-title":"In vivo SPF from multifunctional sunscreen systems developed with natural compounds\u2014A review","volume":"20","author":"Freire","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jphotobiol.2019.03.003","article-title":"Photoprotection assessment of olive (Olea europaea L.) leaves extract standardized to oleuropein: In vitro and in silico approach for improved sunscreens","volume":"193","author":"Paiva","year":"2019","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_87","unstructured":"The Commission of the European Communities (2006). Recommendation of 22 September. On Sun Screen Products and Manufacturers Claims Made Relating Thereto (notified under document number C(2006) 4089). Off. J. Eur. Union, L 265, 39\u201343."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"9352","DOI":"10.1021\/acs.jpca.5b05129","article-title":"Application of time-dependent density functional and natural bond orbital theories to the UV\u2013vis absorption spectra of some phenolic compounds","volume":"119","author":"Markovic","year":"2015","journal-title":"J. Phys. Chem. A"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.foodchem.2011.08.034","article-title":"UV\/Visible spectra of natural polyphenols: A time-dependent density functional theory study","volume":"131","author":"Anouar","year":"2012","journal-title":"Food Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1139\/b84-389","article-title":"Interactions of light with phytochemicals in some natural and novel systems","volume":"62","author":"Towers","year":"1984","journal-title":"Can. J. Bot."},{"key":"ref_91","unstructured":"Goncalo, C.J. (2017). Homoisoflavonoids from Caesalpinia spp.: A Closer Look at Chemical and Biological Aspects. Flavonoids, IntechOpen. Chapter 5."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.lwt.2010.02.004","article-title":"Antioxidant capacity and related parameters of different fruit formulations","volume":"43","author":"Gnoyke","year":"2010","journal-title":"LWT Food Sci. Technol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.foodchem.2006.09.028","article-title":"A new flavone from antioxidant extracts of Pistacia terebinthus","volume":"103","author":"Ay","year":"2007","journal-title":"Food Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant Determinations by the Use of a Stable Free Radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0378-5173(90)90201-E","article-title":"Oxygen radical scavenging activity of curcumin","volume":"58","author":"Kunchandy","year":"1990","journal-title":"Int. J. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"307","DOI":"10.5264\/eiyogakuzashi.44.307","article-title":"Studies on Products of Browning Reaction Antioxidative Activities of Products of Browning Reaction Prepared from Glucosamine","volume":"44","author":"Oyaizu","year":"1986","journal-title":"Jpn. J. Nutr. Diet."},{"key":"ref_98","first-page":"729","article-title":"Evaluation of anti-inflammatory activity of Canthium parviflorum by in-vitro method","volume":"1","author":"Kumar","year":"2013","journal-title":"Indian J. Res. Pharm. Biotechnol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_100","first-page":"150","article-title":"Determination of Sun Protection Factor (SPF) number of some aqueous herbal extracts","volume":"3","author":"Nath","year":"2013","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_101","first-page":"121","article-title":"Determina\u00e7\u00e4o do fator de prote\u00e7\u00e4o solar por espectrofotometria","volume":"61","author":"Mansur","year":"1986","journal-title":"An. Bras. Dermatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1751-1097.1979.tb07090.x","article-title":"A comparison of in vivo and in vitro testing of sunscreening formulas","volume":"29","author":"Sayre","year":"1979","journal-title":"Photochem. Photobiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11094-025-03365-5","article-title":"Effect of Solvents Polarity on Phytochemical Composition and Pharmacological Properties of Zygophyllum cornutum Coss","volume":"59","author":"Harchaoui","year":"2025","journal-title":"Pharm. Chem. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1007\/s11696-023-03221-4","article-title":"Teucrium pseudochamaepitys L.: Chemical composition, acute toxicity, antioxidant, anti-inflammatory, and analgesic properties","volume":"78","author":"Belguidoum","year":"2024","journal-title":"Chem. Pap."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/7\/285\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:25:23Z","timestamp":1783592723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/7\/285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":104,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["toxins18070285"],"URL":"https:\/\/doi.org\/10.3390\/toxins18070285","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}