{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:01:58Z","timestamp":1785826918452,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Agriculture of South Africa","award":["VIM012403000094"],"award-info":[{"award-number":["VIM012403000094"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of medicinal plants in primary healthcare and livelihoods around the world is both ancient and well-documented. Agathosma betulina (P.J. Bergius) Pillans, commonly known as \u2018buchu\u2019, has long been utilised in traditional medicine as a household remedy for various ailments and is also valued for its essential oils in the cosmetics and pharmaceutical industries. This study aimed to profile and quantify the secondary metabolites in buchu using ultra-performance liquid chromatography quadrupole time-of-flight combined with mass spectrometry (UPLC-QTOF-MS) techniques, whereby plant material from three distinct locations in the Western Cape Province, Groot Winterhoek, Citrusdal, and Cederberg, was collected. A total of 32 maker compounds were identified from buchu leaves. The results revealed a significant location-dependent variation in the accumulation of multiple classes of phytochemicals, including phenolic acids, flavonoids, saponins, terpenoids, oligosaccharides, vitamins, and steroids. Citrusdal samples had the most bioactive compounds compared to the Cederberg and Groot Winterhoek. Citrusdal had the highest flavonoid levels, while Cederberg samples were the richest in phenolic acids and Groot Winterhoek was dominant in iridoid glycoside levels. Principal component analysis (PCA) revealed distinct clusters corresponding to the three different regions, confirming chemical differences. Elucidating the distribution of secondary metabolites in this species may provide new information for possible medicinal and pharmacological uses, such as the creation of novel and enhanced organic medications and food products. These results will aid in selecting a buchu chemotype with optimal attributes for the intended therapeutic application, helping to protect wild populations from over-exploitation through cultivation.<\/jats:p>","DOI":"10.3390\/ijms27104486","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Geographic Influence on Secondary Metabolite Profiles in Leaves of the Endemic Agathosma betulina (P.J. Bergius) Pillans. in the Western Cape Province, South Africa"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9027-3971","authenticated-orcid":false,"given":"Nompumelelo H.","family":"Mnisi","sequence":"first","affiliation":[{"name":"Department of Crop Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"},{"name":"Agricultural Research Council Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-969X","authenticated-orcid":false,"given":"Rotondwa P.","family":"Gunununu","sequence":"additional","affiliation":[{"name":"Department of Crop Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luvolwethu","family":"Dukashe","sequence":"additional","affiliation":[{"name":"Department of Crop Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa"},{"name":"Agricultural Research Council Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manaka J.","family":"Makgato","sequence":"additional","affiliation":[{"name":"Agricultural Research Council Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2059-7532","authenticated-orcid":false,"given":"Azwimbavhi R.","family":"Mulidzi","sequence":"additional","affiliation":[{"name":"Agricultural Research Council Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9031-1117","authenticated-orcid":false,"given":"Callistus","family":"Bvenura","sequence":"additional","affiliation":[{"name":"Department of Horticulture, Faculty of Applied Sciences, Cape Peninsula University of Technology, Bellville 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngwatshipane M.","family":"Mashabela","sequence":"additional","affiliation":[{"name":"Agricultural Research Council Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"ref_1","first-page":"658","article-title":"The importance of non-timber forest products in rural livelihood security and as safety nets: A review of evidence from South Africa","volume":"100","author":"Shackleton","year":"2004","journal-title":"S. Afr. J. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Viljoen, A., Sandasi, M., Fouche, G., Combrinck, S., and Vermaak, I. (2023). Agathosma\u00a0betulina. The South African Herbal Pharmacopoeia: Monographs of Medicinal and Aromatic Plants, Elsevier.","DOI":"10.1016\/B978-0-323-99794-2.00019-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jep.2008.05.029","article-title":"A broad review of commercially important Southern African medicinal plants","volume":"119","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.sajb.2017.03.015","article-title":"Micropropagation and secondary metabolites in Agathosma betulina (Berg.)","volume":"111","author":"Witbooi","year":"2017","journal-title":"S. Afr. J. Bot."},{"key":"ref_6","unstructured":"Viljoen, A., Chen, W., Mulaudzi, N., Kamatou, G., and Sandasi, M. (2021). Phytochemical Profiling of Commercially Important South African Plants, Academic Press."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Brendler, T., and Abdel-Tawab, M. (2022). Buchu (Agathosma betulina and A. crenulata): Rightfully forgotten or underutilized. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.813142"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Oguntibeju, O. (2014). Buchu\u2014The multi-purpose ethnomedicinally important specie and its benefits in the reproductive system. Antioxidant-Antidiabetic Agents and Human Health, InTech.","DOI":"10.5772\/57029"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1016\/j.phytochem.2007.09.017","article-title":"From waste products to ecochemicals: Fifty years research of plant secondary metabolism","volume":"68","author":"Hartmann","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1071\/FP02076","article-title":"Understanding plant responses to drought from genes to the whole plant","volume":"30","author":"Chaves","year":"2003","journal-title":"Funct. Plant Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.indcrop.2012.06.020","article-title":"Influencing the product quality by deliberately applying drought stress during the cultivation of medicinal plants","volume":"42","author":"Selmar","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104905","DOI":"10.1016\/j.bse.2024.104905","article-title":"Geographic based phenolic compound variations in South African Schinus molle L. peppercorns","volume":"117","author":"Bvenura","year":"2024","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/10412905.2006.12067112","article-title":"The biological activity and essential oil composition of 17 Agathosma (Rutaceae) species","volume":"18","author":"Viljoen","year":"2006","journal-title":"J. Essent. Oil Res."},{"key":"ref_14","first-page":"177","article-title":"An inventory of medicinal plants traded on the Western Cape\u2019s informal markets","volume":"67","author":"Botha","year":"2001","journal-title":"S. Afr. J. Bot."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s12355-025-01647-6","article-title":"A Metabolomic Study Reveals Substantial Genetic Variation in Volatile and Non-Volatile Compounds in Sugarcane Juice","volume":"28","author":"Li","year":"2025","journal-title":"Sugar Tech"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1016\/j.jchromb.2010.09.027","article-title":"Comprehensive separation and identification of chemical constituents from Apocynum venetum leaves by high-performance counter-current chromatography and high performance liquid chromatography coupled with mass spectrometry","volume":"878","author":"Zhang","year":"2010","journal-title":"J. Chromatogr. B"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kucharska, A.Z., and Fecka, I. (2016). Identification of iridoids in edible honeysuckle berries (Lonicera caerulea L. var. kamtschatica Sevast.) by UPLC-ESI-qTOF-MS\/MS. Molecules, 21.","DOI":"10.3390\/molecules21091157"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104740","DOI":"10.1016\/j.fitote.2020.104740","article-title":"Chemotypic variation of non-volatile constituents of Artemisia afra (African wormwood) from South Africa","volume":"147","author":"Sotenjwa","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116192","DOI":"10.1016\/j.ijms.2019.116192","article-title":"HPLC-DAD-MS\/MS profiling of phenolics from different varieties of peach leaves and evaluation of their antioxidant activity: A comparative study","volume":"445","author":"Mokrani","year":"2019","journal-title":"Int. J. Mass Spectrom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10337-013-2404-z","article-title":"Identification and determination of related substances in diosmin bulk drug and pharmaceutical formulations by HPLC and HPLC\u2013MS","volume":"76","author":"Adouani","year":"2013","journal-title":"Chromatographia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1002\/pca.3262","article-title":"Identification of in vivo metabolites of Citri Sarcodactylis Fructus by UHPLC\u2013Q\/Orbitrap HRMS","volume":"34","author":"Deng","year":"2023","journal-title":"Phytochem. Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jpba.2017.12.051","article-title":"Chemical profiling of Euphorbia fischeriana Steud. by UHPLC-Q\/TOF-MS","volume":"151","author":"Wang","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chavez Carvajal, P., Coppo, E., Di Lorenzo, A., Gozzini, D., Bracco, F., Zanoni, G., Nabavi, S.M., Marchese, A., Arciola, C.R., and Daglia, M. (2016). Chemical characterization and in vitro antibacterial activity of Myrcianthes hallii (O. Berg) McVaugh (Myrtaceae), a traditional plant growing in Ecuador. Materials, 9.","DOI":"10.3390\/ma9060454"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/bmc.3057","article-title":"HPLC-Q-TOF-MS\/MS for analysis of major chemical constituents of Yinchen\u2013Zhizi herb pair extract","volume":"28","author":"Fu","year":"2014","journal-title":"Biomed. Chromatogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/pca.2866","article-title":"UHPLC-DAD-ESI-MS\/MS and HPTLC profiling of ash leaf samples from different commercial and natural sources and their in vitro effects on mediators of inflammation","volume":"31","author":"Kiss","year":"2020","journal-title":"Phytochem. Anal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40659-019-0246-3","article-title":"Stress and defense responses in plant secondary metabolites production","volume":"52","author":"Isah","year":"2019","journal-title":"Biol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.plantsci.2012.07.014","article-title":"Flavonoids as antioxidants in plants: Location and functional significance","volume":"196","author":"Agati","year":"2012","journal-title":"Plant Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"709","DOI":"10.4161\/psb.6.5.15069","article-title":"Stress-induced flavonoid biosynthesis and the antioxidant machinery of plants","volume":"6","author":"Fini","year":"2011","journal-title":"Plant Signal. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, L., Pan, X., Jiang, L., Chu, Y., Gao, S., Jiang, X., Zhang, Y., Chen, Y., Luo, S., and Peng, C. (2022). The biological activity mechanism of chlorogenic acid and its applications in food industry: A review. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.943911"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.sajb.2015.05.012","article-title":"Adulteration in commercial buchu dietary supplements: Analyses of commercial and authentic buchu samples and comparative studies of Agathosma betulina and Agathosma crenulata by microscopy and HPTLC","volume":"100","author":"Raman","year":"2015","journal-title":"S. Afr. J. Bot."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biopha.2017.10.064","article-title":"Chlorogenic acid (CGA): A pharmacological review and call for further research","volume":"97","author":"Naveed","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cortez, N., Villegas, C., Burgos, V., Ortiz, L., Cabrera-Pardo, J.R., and Paz, C. (2024). Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105189"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e14254","DOI":"10.1111\/jfbc.14254","article-title":"A review of the protective effects of chlorogenic acid against different chemicals","volume":"46","author":"Rashidi","year":"2022","journal-title":"J. Food Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100122","DOI":"10.1016\/j.crphar.2022.100122","article-title":"Plant metabolite diosmin as the therapeutic agent in human diseases","volume":"3","author":"Mustafa","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_35","first-page":"51","article-title":"One-year diosmin therapy (600 mg) in patients with chronic venous insufficiency\u2014Results and analysis","volume":"3","author":"Batchvarov","year":"2010","journal-title":"J. Biomed. Clin. Res."},{"key":"ref_36","first-page":"25","article-title":"Hesperidin and diosmin\u2014A novel drugs","volume":"10","author":"Roy","year":"2020","journal-title":"Int. J. Pharm. Res. Technol. (IJPRT)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jsps.2016.04.025","article-title":"The pharmacological potential of rutin","volume":"25","author":"Ganeshpurkar","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jff.2017.10.047","article-title":"Antioxidant and anti-inflammatory activities of quercetin and its derivatives","volume":"40","author":"Lesjak","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1080\/14786419.2023.2238113","article-title":"\u03b1-Glucosidase inhibitory activities of constituents from Psidium guajava leaves","volume":"38","author":"Zheng","year":"2023","journal-title":"Nat. Prod. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22606\/jamb.2019.31001","article-title":"Quercetin 3-galactoside from Azadirachta indica","volume":"3","author":"Rao","year":"2019","journal-title":"J. Adv. Mol. Biol."},{"key":"ref_41","first-page":"187","article-title":"Bio-flavonoids with promising antidiabetic potentials: A critical survey","volume":"661","author":"Brahmachari","year":"2011","journal-title":"Res. Signpost"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e42682","DOI":"10.1016\/j.heliyon.2025.e42682","article-title":"Phytochemical Insights into Flavonoids in Cancer: Mechanisms, Therapeutic Potential, and the Case of Quercetin","volume":"11","author":"Canales","year":"2025","journal-title":"Heliyon"},{"key":"ref_43","unstructured":"Wink, M. (2010). Introduction: Biochemistry, physiology and ecological functions of secondary metabolites. Annual Plant Reviews Volume 40: Biochemistry of Plant Secondary Metabolism, Blackwell Publishing Ltd."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","unstructured":"Zhang, S., Feng, Z., Gao, W., Duan, Y., Fan, G., Geng, X., Wu, B., Li, K., Liu, K., and Peng, C. (2020). Aucubin attenuates liver ischemia-reperfusion injury by inhibiting the HMGB1\/TLR-4\/NF-\u03baB signaling pathway, oxidative stress, and apoptosis. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.544124"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1021\/np0704248","article-title":"Cytochrome P3A4 inhibitors and other constituents of Fibraurea tinctoria","volume":"70","author":"Su","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Allsopp, N., Colville, J.F., and Verboom, G.A. (2014). Drivers, ecology, and management of fire in fynbos. Fynbos: Ecology, Evolution, and Conservation of a Megadiverse Region, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780199679584.001.0001"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Santacruz-Garc\u00eda, A.C., Bravo, S., del Corro, F., Garc\u00eda, E.M., Molina-Terr\u00e9n, D.M., and Nazareno, M.A. (2021). How do plants respond biochemically to fire? The role of photosynthetic pigments and secondary metabolites in the post-fire resprouting response. Forests, 12.","DOI":"10.3390\/f12010056"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nchembio.2007.5","article-title":"The function of terpene natural products in the natural world","volume":"3","author":"Gershenzon","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_50","first-page":"191","article-title":"Riboflavin (vitamin B2)","volume":"Volume 5","author":"Pinto","year":"2013","journal-title":"Handbook of Vitamins"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1210\/er.2015-1036","article-title":"The regulation of steroid action by sulfation and desulfation","volume":"36","author":"Mueller","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15031","DOI":"10.1038\/s41598-018-33390-2","article-title":"Structural rearrangements maintain the glycan shield of an HIV-1 envelope trimer after the loss of a glycan","volume":"8","author":"Ferreira","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12275","DOI":"10.1038\/s41598-020-69080-1","article-title":"Exogenous abscisic acid induces the lipid and flavonoid metabolism of tea plants under drought stress","volume":"10","author":"Gai","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, F., Li, X., Wang, F., Zhang, D., Xia, Y., and He, F. (2020). A novel P300 classification algorithm based on a principal component analysis-convolutional neural network. Appl. Sci., 10.","DOI":"10.3390\/app10041546"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/00010694-194501000-00006","article-title":"Determination of total, organic, and available forms of phosphorus in soils","volume":"59","author":"Bray","year":"1945","journal-title":"Soil Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6859","DOI":"10.1021\/acs.analchem.8b01041","article-title":"Vertical ultrafiltration-facilitated DNA digestion for rapid and sensitive UHPLC-MS\/MS detection of DNA modifications","volume":"90","author":"Lai","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: Data-independent MS\/MS deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nmeth.4512","article-title":"Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics","volume":"15","author":"Lai","year":"2018","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:51:47Z","timestamp":1779115907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,16]]},"references-count":58,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104486"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104486","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,16]]}}}