{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:54:42Z","timestamp":1783115682134,"version":"3.54.6"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["118262"],"award-info":[{"award-number":["118262"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of the Western Cape (UWC)","award":["118262"],"award-info":[{"award-number":["118262"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Protea cynaroides (king protea) is a flowering plant that belongs to the Proteaceae family. This multi-stemmed shrub is the national flower of South Africa and has important economic and medicinal values. Traditionally, the main therapeutic benefits of this plant species include the treatment of cancer, bladder, and kidney ailments. There are very limited reports on the isolation of phytochemicals and their biological evaluation from P. cynaroides. In this study, the leaves of P. cynaroides were air-dried at room temperature, powdered, and extracted with 80% methanol followed by solvent fractionation (hexane, dichloromethane, ethyl acetate, and butanol). The ethyl acetate and butanol extracts were chromatographed and afforded four new (1\u20134) and four known (5\u20138) compounds, whose structures were characterized accordingly as 3,4-bis(4-hydroxybenzoyl)-1,5-anhydro-D-glucitol (1), 4-hydroxybenzoyl-1,5-anhydro-D-glucitol (2), 2-(hydroxymethyl)-4-oxo-4H-pyran-3-yl-6-O-benzoate-\u03b2-D-glucopyranoside (3), 3-hydroxy-7,8-dihydro-\u03b2-ionone 3-O-\u03b2-D-glucopyranoside (4), 4-hydroxybenzoic acid (5), 1,5-anhydro-D-glucitol (6), 3,4-dihydroxybenzoic acid (7), and 3-hydroxykojic acid (8). The structural elucidation of the isolated compounds was determined based on 1D and 2D NMR, FTIR, and HRMS spectroscopy, as well as compared with the available literature data. The tyrosinase inhibitory activities of the extracts and isolated compounds were also determined. According to the results, compounds 7 and 8 exhibited potent competitive tyrosinase inhibitory activity against L-tyrosine substrates with IC50 values of 0.8776 \u00b1 0.012 and 0.7215 \u00b1 0.090 \u00b5g\/mL compared to the control (kojic acid, IC50 = 0.8347 \u00b1 0.093), respectively. This study is the first chemical investigation of compounds 1\u20134 from a natural source and the first report of the biological evaluation of compounds 1\u20135 against the tyrosinase enzyme. The potent anti-tyrosinase activity exhibited by P. cynaroides constituents will support future exploration of the plant in the cosmetic field upon further biological and clinical investigations.<\/jats:p>","DOI":"10.3390\/plants11131751","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T01:40:36Z","timestamp":1656639636000},"page":"1751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of Four New Compounds from Protea cynaroides Leaves and Their Tyrosinase Inhibitory Potential"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9860-1629","authenticated-orcid":false,"given":"Masande","family":"Yalo","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-8345","authenticated-orcid":false,"given":"Masixole","family":"Makhaba","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-9959","authenticated-orcid":false,"given":"Ahmed A.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Chemistry Department, Cape Peninsula University of Technology, Symphony Rd., Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8823-2401","authenticated-orcid":false,"given":"Rajan","family":"Sharma","sequence":"additional","affiliation":[{"name":"Chemistry Department, Cape Peninsula University of Technology, Symphony Rd., Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mkhuseli","family":"Koki","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-8863","authenticated-orcid":false,"given":"Ndikho","family":"Nako","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred T.","family":"Mabusela","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/14756366.2018.1545767","article-title":"A comprehensive review on tyrosinase inhibitors","volume":"34","author":"Zolghadri","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1007\/s00018-005-5054-y","article-title":"Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition mechanism and perspective for the future","volume":"62","author":"Kim","year":"2005","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.1467-2494.2000.00019.x","article-title":"Resveratrol: An original mechanism on tyrosinase inhibition","volume":"22","author":"Bernard","year":"2000","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.phymed.2004.09.001","article-title":"Tyrosinase inhibitory lignans from the methanol extract of the roots of Vitex negundo Linn. and their structure\u2013activity relationship","volume":"13","author":"Malik","year":"2006","journal-title":"Phytomedicine"},{"key":"ref_5","first-page":"299","article-title":"Developing a long-lasting tyrosinase inhibitor from Morus alba L.","volume":"121","author":"Kim","year":"2007","journal-title":"Nat. Org. Cosmet. RD Marketpl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.phytochem.2006.05.008","article-title":"Bioactive constituents of Spatholobus suberectus in regulating tyrosinase-related proteins and mRNA in HEMn cells","volume":"67","author":"Lee","year":"2006","journal-title":"Phytochemistry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.3390\/ijms10062440","article-title":"An updated review of tyrosinase inhibitors","volume":"10","author":"Chang","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.2174\/1568026614666140523121427","article-title":"Tyrosinase enzyme: 1. An overview on a pharmacological target","volume":"14","author":"Torrens","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_9","first-page":"1963","article-title":"Common hyperpigmentation disorders in adults: Part II. Melanoma, seborrheic keratoses, acanthosis nigricans, melasma, diabetic dermopathy, tinea versicolor, and postinflammatory hyperpigmentation","volume":"68","author":"Stulberg","year":"2003","journal-title":"Am. Fam. Physician"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.molstruc.2014.12.073","article-title":"Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship","volume":"1085","author":"Akhtar","year":"2015","journal-title":"J. Mol. Struct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.foodchem.2014.04.106","article-title":"Inhibitory effect of morin on tyrosinase: Insights from spectroscopic and molecular docking studies","volume":"163","author":"Wang","year":"2014","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10068-013-0236-0","article-title":"Flaniostatin, a new isoflavonoid glycoside isolated from the leaves of Cudrania tricuspidata as a tyrosinase inhibitor","volume":"22","author":"Kang","year":"2013","journal-title":"Food Sci. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1080\/14756366.2016.1235568","article-title":"Tyrosinase inhibitory components from Aloe vera and their antiviral activity","volume":"32","author":"Kim","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1271\/bbb.69.1999","article-title":"Identifying 6, 7, 4\u2032-trihydroxyisoflavone as a potent tyrosinase inhibitor","volume":"69","author":"Chang","year":"2005","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.11646\/phytotaxa.261.3.1","article-title":"The number of known plants species in the world and its annual increase","volume":"261","author":"Christenhusz","year":"2016","journal-title":"Phytotaxa"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1095-8339.1975.tb01644.x","article-title":"On the Proteaceae\u2014The evolution and classification of a southern family","volume":"70","author":"Johnson","year":"1975","journal-title":"Bot. J. Linn. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1021\/np9902237","article-title":"Polyphenolic glycosides from african proteaceae","volume":"62","author":"Verotta","year":"1999","journal-title":"J. Nat.Prod."},{"key":"ref_18","unstructured":"Bremer, K., Bremer, B., and Thulin, M. (2003). Introduction to Phylogeny and Systematics of Flowering Plants, Department of Systematic Botany, University of Uppsala."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1017\/S0953756299008461","article-title":"Systematics of selected foliicolous fungi associated with leaf spots of Proteaceae","volume":"103","author":"Crous","year":"1999","journal-title":"Mycol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sajb.2013.02.171","article-title":"Antimicrobial activities of Dilobeia thouarsii Roemer and Schulte, a traditional medicinal plant from Madagascar","volume":"87","author":"Razafintsalama","year":"2013","journal-title":"South Afr. J. Bot."},{"key":"ref_21","unstructured":"Rebelo, T. (2000). Field guide to the Proteas of the Cape Peninsula, Protea Atlas Project, National Botanical Institute."},{"key":"ref_22","unstructured":"Paterson-Jones, C. (2000). Protea family in Southern Africa, Struik."},{"key":"ref_23","unstructured":"Arendse, M.L. (2013). Medicinal Plant Use in the Dwarsrivier Valley, Stellenbosch. [Ph.D. Thesis, University of the Western Cape]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1039\/p19890001215","article-title":"Neriifolin, an ester glucoside of benzene-1, 2, 4-triol","volume":"1","author":"Perold","year":"1989","journal-title":"J. Chem.Soc. Perkin Trans."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.indcrop.2014.02.024","article-title":"Phenolic compounds, antioxidant activity and ultrastructural study from Protea hybrid \u2018Susara\u2019","volume":"55","author":"Alfayate","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1071\/BT04098","article-title":"Taxonomic patterns in the distribution of polyols within the Proteaceae","volume":"53","author":"Bieleski","year":"2005","journal-title":"Aust. J. Bot."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Perold, G.W., Rosenberg, M.E., Howard, A.S., and Huddle, P.A. (1979). Metabolites of proteaceae. Part 9. Eximin (6-O-benzoylarbutin) and the synthesis of aryl glycoside esters. J. Chem. Soc. Perkin Trans. 1, 239\u2013243.","DOI":"10.1039\/p19790000239"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10725-007-9191-1","article-title":"The phenolic, 3, 4-dihydroxybenzoic acid, is an endogenous regulator of rooting in Protea cynaroides","volume":"52","author":"Wu","year":"2007","journal-title":"Plant Growth Regul."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1021\/acs.jafc.9b06361","article-title":"Detailed Phenolic Characterization of Protea Pure and Hybrid Cultivars by Liquid Chromatography\u2013Ion Mobility\u2013High Resolution Mass Spectrometry (LC-IM-HR-MS)","volume":"68","author":"Masike","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jep.2013.09.031","article-title":"An ethnobotanical survey of medicinal plants used in Rwanda for voluntary depigmentation","volume":"150","author":"Kamagaju","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.tetasy.2016.09.006","article-title":"Dual action of acertannins as potential regulators of intracellular ceramide levels","volume":"27","author":"Kamori","year":"2016","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Machida, S., Mukai, S., Kono, R., Funato, M., Saito, H., and Uchiyama, T. (2019). Synthesis and comparative structure\u2013activity study of carbohydrate-based phenolic compounds as \u03b1-glucosidase inhibitors and antioxidants. Molecules, 24.","DOI":"10.3390\/molecules24234340"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1016\/0031-9422(89)80369-3","article-title":"Ionone and lignan glycosides from Epimedium diphyllum","volume":"28","author":"Miyase","year":"1989","journal-title":"Phytochemistry"},{"key":"ref_34","first-page":"1705","article-title":"Oxidative degradation of antibacterial drug, methylparaben, by Mn-VII in perchloric acid medium: A kinetic and mechanistic approach","volume":"92","author":"Ariga","year":"2015","journal-title":"J. Indian Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"273","DOI":"10.22146\/ijc.21342","article-title":"3, 4-dihydroxybenzoic acid and 3, 4-dihydroxybenzaldehyde from the fern Trichomanes chinense L.; isolation, antimicrobial and antioxidant properties","volume":"12","author":"Syafni","year":"2012","journal-title":"Indones. J. Chem."},{"key":"ref_36","first-page":"802","article-title":"3-Oxykojic Acid, a New \u03b3-Pyrone formed by Gluconobacter","volume":"25","author":"Terada","year":"1961","journal-title":"Agric. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12071","DOI":"10.3390\/molecules181012071","article-title":"Gaultheria: Phytochemical and pharmacological characteristics","volume":"18","author":"Liu","year":"2013","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"812","DOI":"10.3109\/14756366.2010.482529","article-title":"Tyrosinase inhibitory effect of benzoic acid derivatives and their structure-activity relationships","volume":"25","author":"Khan","year":"2010","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S0006-2952(98)00340-2","article-title":"Inhibitors of mammalian melanocyte tyrosinase: In vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors","volume":"57","author":"Curto","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1021\/jf020935u","article-title":"Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots","volume":"51","author":"Nerya","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1467-2494.1997.tb00194.x","article-title":"Biological screening of 100 plant extracts for cosmetic use (II): Anti-oxidative activity and free radical scavenging activity","volume":"19","author":"Kim","year":"1997","journal-title":"Int. J. Cosmet. Sci."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/13\/1751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:29Z","timestamp":1760139689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/13\/1751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":41,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["plants11131751"],"URL":"https:\/\/doi.org\/10.3390\/plants11131751","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}