{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:41:33Z","timestamp":1783608093519,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan International Cooperation Agency (JICA)\u2013Japan Science and Technology Research Partnership for Sustainable Development (SATREPS) project"},{"name":"Ministry of Higher Education, Scientific Research and Executive Training (MHESRET) of Kingdom of Morocco"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Plant saponins are abundant and diverse natural products with a great potential for use in drug-discovery research. Here, we evaluated extracts of saponins-rich fractions of argan leaves and argan oil extraction byproducts (shell, pulp, press cake) for their effect on melanogenesis. Results show that from among the samples tested, only the saponins-rich fraction from leaves (ALS) inhibited melanin production in B16 murine melanoma (B16) cells. The mechanism of the melanogenesis inhibition was elucidated by determining the protein and mRNA expression of melanogenesis-associated enzymes tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT), and microphthalmia-associated transcription factor (MITF), and performing DNA microarray analysis. Results showed that 10 \u00b5g\/mL ALS significantly inhibited melanogenesis in B16 cells and human epidermal melanocytes by 59% and 48%, respectively, without cytotoxicity. The effect of ALS on melanogenesis can be attributed to the decrease in TYR, TRP1, and MITF expression at the protein and mRNA levels. MITF inhibition naturally led to the downregulation of the expression of Tyr and Trp1 genes. Results of the DNA microarray analysis revealed the effect on melanogenesis-associated cAMP and Wnt signaling pathways\u2019 genes. The results of this study suggest that ALS may be used in cosmeceuticals preparations for hyperpigmentation treatment.<\/jats:p>","DOI":"10.3390\/molecules27196762","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:50:01Z","timestamp":1665449401000},"page":"6762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular Analysis of the Melanogenesis Inhibitory Effect of Saponins-Rich Fraction of Argania spinosa Leaves Extract"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-3323","authenticated-orcid":false,"given":"Myra O.","family":"Villareal","sequence":"first","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8572, Ibaraki, Japan"},{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8572, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanyanan","family":"Chaochaiphat","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8572, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachida","family":"Makbal","sequence":"additional","affiliation":[{"name":"Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4524-5362","authenticated-orcid":false,"given":"Chemseddoha","family":"Gadhi","sequence":"additional","affiliation":[{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8572, Ibaraki, Japan"},{"name":"Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco"},{"name":"Agrobiotechnology and Bioengineering Center, CNRST-labeled Research Unit (AgroBiotech-URL-CNRST-05 Center), Cadi Ayyad University, Marrakesh 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-9541","authenticated-orcid":false,"given":"Hiroko","family":"Isoda","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8572, Ibaraki, Japan"},{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tennodai 1-1-1, Tsukuba City 305-8572, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","article-title":"The protective role of melanin against UV damage in human skin","volume":"84","author":"Brenner","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jdermsci.2004.08.014","article-title":"Biogenesis of pigment granules: A sensitive way to regulate melanocyte function","volume":"37","author":"Hearing","year":"2005","journal-title":"J. Dermatol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1042\/bj3540131","article-title":"The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase","volume":"354","author":"Olivares","year":"2001","journal-title":"Biochem. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.biocel.2006.10.003","article-title":"Melanocytes: The new black","volume":"39","author":"Goding","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1473-2165.2007.00321.x","article-title":"Hyperpigmentation and melasma","volume":"6","author":"Rigopoulos","year":"2007","journal-title":"J. Cosmetic Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2165\/00128071-200001050-00001","article-title":"Management of facial hyperpigmentation","volume":"1","author":"Camacho","year":"2000","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1468-3083.2005.01218.x","article-title":"Toxicology and health risks of hydroquinone in skin lightening formulations","volume":"20","author":"Kooyers","year":"2006","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_8","unstructured":"(2022, January 25). Available online: https:\/\/edition.cnn.com\/2022\/01\/25\/world\/as-equals-skin-whitening-global-market-explainer-intl-cmd\/index.html."},{"key":"ref_9","first-page":"1","article-title":"Melasma and post inflammatory hyperpigmentation: Management update and expert opinion","volume":"21","author":"Sofen","year":"2016","journal-title":"Skin Ther. Lett."},{"key":"ref_10","first-page":"1435","article-title":"Clinical evaluation of a 4% hydroquinone + 1% retinol treatment regimen for improving melasma and photodamage in Fitzpatrick skin types III-VI","volume":"15","author":"Rendon","year":"2016","journal-title":"J. Drugs Dermatol."},{"key":"ref_11","first-page":"665","article-title":"Safety of skin care products during pregnancy","volume":"57","author":"Bozzo","year":"2011","journal-title":"Can. Fam. Physician"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/GRF.0000000000000077","article-title":"Physiological skin changes during pregnancy","volume":"58","author":"Tyler","year":"2015","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_13","first-page":"18","article-title":"Psychosocial impact of postinflammatory hyperpigmentation in patients with acne vulgaris","volume":"10","author":"Darji","year":"2017","journal-title":"J. Clin. Aesthetic Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2147\/CCID.S158129","article-title":"The impact of acne and facial post-inflammatory hyperpigmentation on quality of life and self-esteem of newly admitted Nigerian undergraduates","volume":"11","author":"Akinboro","year":"2018","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/j.1600-0625.2009.00964.x","article-title":"Hirseins inhibit melanogenesis by regulating the gene expressions of Mitf and melanogenesis enzymes","volume":"19","author":"Villareal","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_16","first-page":"28","article-title":"Melanin synthesis inhibiting function of \u03b2-carotene","volume":"29","author":"Kamei","year":"2001","journal-title":"Fragr. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"340107","DOI":"10.1155\/2013\/340107","article-title":"Activation of MITF by argan oil leads to the inhibition of the tyrosinase and dopachrome tautomerase expressions in B16 murine melanoma cells","volume":"2013","author":"Villareal","year":"2013","journal-title":"Evid.-Based Complementary Altern Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Makbal, R., Villareal, M.O., Gadhi, C., Hafidi, A., and Isoda, H. (2020). Argania spinosa fruit shell extract-induced melanogenesis via cAMP signaling pathway activation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072539"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bourhim, T., Villareal, M.O., Couderc, F., Hafidi, A., Isoda, H., and Gadhi, C. (2021). Melanogenesis promoting effect, antioxidant activity, and UPLC-ESI-HRMS characterization of phenolic compounds of Argan leaves extract. Molecules, 26.","DOI":"10.3390\/molecules26020371"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1007\/s10616-018-0232-6","article-title":"Depigmenting effect of argan press-cake extract through the down-regulation of Mitf and melanogenic enzymes expression in B16 murine melanoma cells","volume":"70","author":"Bourhim","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1023\/A:1026030100167","article-title":"Secondary metabolites from Argania spinosa (L.) Skeels","volume":"1","author":"Charrouf","year":"2002","journal-title":"Phytochem. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mugford, S.T., and Osbourn, A. (2012). Saponin synthesis and function. Isoprenoid synthesis in plants and microorganisms: New Concepts Experimental Approaches, Springer.","DOI":"10.1007\/978-1-4614-4063-5_28"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.lwt.2018.10.033","article-title":"Induction of superoxide anion radical-scavenging capacity in an argan press cake-suspension by fermentation using Lactobacillus plantarum Argan-L1","volume":"100","author":"Goto","year":"2019","journal-title":"LWT"},{"key":"ref_24","first-page":"2534","article-title":"Triterpenoid saponins of Sapotaceae plants and their bioactivities","volume":"45","author":"Akihisa","year":"2018","journal-title":"Chiang Mai J. Sci."},{"key":"ref_25","first-page":"381","article-title":"Secondary metabolites of the argan tree (Morocco) may have disease prevention properties","volume":"4","author":"Khallouki","year":"2005","journal-title":"African J. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kamal, R., Kharbach, M., Heyden, Y.V., Yu, H., Bouklouze, A., Cherrah, Y., and Alaoui, K. (2021). In vitro & in vivo anti-hyperglycemic potential of saponins cake and argan oil from Argania spinosa. Foods, 10.","DOI":"10.3390\/foods10051078"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cannell, R.J.P. (1998). Special Problems with the Extraction of Plants. Natural Products Isolation. Methods in Biotechnology, Humana Press.","DOI":"10.1007\/978-1-59259-256-2"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Makkar, H.P.S., Siddhuraju, P., and Becker, K. (2007). Plant Secondary Metabolites, Humana Press.","DOI":"10.1007\/978-1-59745-425-4"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12485","DOI":"10.1073\/pnas.171460498","article-title":"Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor","volume":"98","author":"Lane","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36351","DOI":"10.1074\/jbc.M113.520528","article-title":"IQGAP1 protein regulates nuclear localization of -catenin via importin-5 protein in Wnt signaling","volume":"288","author":"Goto","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e63093","DOI":"10.7554\/eLife.63093","article-title":"MITF reprograms the extracellular matrix and focal adhesion in melanoma","volume":"10","author":"Dilshat","year":"2021","journal-title":"eLife"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1473-2165.2008.00384.x","article-title":"Prevalence of pigmentary disorders and their impact on quality of life: A prospective cohort study","volume":"7","author":"Taylor","year":"2008","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2147\/CCID.S233185","article-title":"Effects of skin lightening cream agents\u2014hydroquinone and kojic acid, on the skin of adult female experimental rats","volume":"13","author":"Owolabi","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"628","DOI":"10.3109\/15376516.2015.1053650","article-title":"The molecular mechanisms of liver and islets of Langerhans toxicity by benzene and its metabolite hydroquinone in vivo and in vitro","volume":"25","author":"Bahadar","year":"2015","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_35","first-page":"28","article-title":"Are natural ingredients effective in the management of hyperpigmentation? A systematic review","volume":"11","author":"Hollinger","year":"2018","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_36","first-page":"6","article-title":"A review on saponins from medicinal plants: Chemistry, isolation, and determination","volume":"8","author":"Ashour","year":"2019","journal-title":"J. Nanomed. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1248\/bpb.19.153","article-title":"Studies of cuticle drugs from natural sources. IV. Inhibitory effects of some Arctostaphylos plants on melanin biosynthesis","volume":"19","author":"Matsuda","year":"1996","journal-title":"Biol. Pharm. Bull."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2000037","DOI":"10.1002\/cbdv.202000037","article-title":"Antimelanogenic Activity of Ocotillol-Type Saponins from Panax vietnamensis","volume":"17","author":"Nguyen","year":"2020","journal-title":"Chem. Biodivers."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1007\/s11418-017-1082-9","article-title":"Triterpenoid saponins from Polaskia chichipe Backbg. and their inhibitory or promotional effects on the melanogenesis of B16 melanoma cells","volume":"71","author":"Fujihara","year":"2017","journal-title":"J. Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.bmc.2012.11.038","article-title":"Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells","volume":"21","author":"Nakamura","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1055\/s-0030-1250477","article-title":"Anti-inflammatory and anti-melanogenic steroidal saponin glycosides from Fenugreek (Trigonella foenum-graecum L.) seeds","volume":"77","author":"Kawabata","year":"2011","journal-title":"Planta Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1755-148X.2009.00653.x","article-title":"Fifteen-year quest for microphthalmia-associated transcription factor target genes","volume":"23","author":"Cheli","year":"2010","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1600-0625.2009.01053.x","article-title":"\u201cTranscription physiology\u201d of pigment formation in melanocytes: Central role of MITF","volume":"19","author":"Vachtenheim","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nature05660","article-title":"Melanocyte biology and skin pigmentation","volume":"445","author":"Lin","year":"2007","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1093\/emboj\/21.11.2703","article-title":"Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling","volume":"21","author":"Yasumoto","year":"2002","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1128\/MCB.18.2.694","article-title":"Different cis-acting elements are involved in the regulation of TRP1 and TRP2 promoter activities by cyclic AMP: Pivotal role of M boxes (GTCATGTGCT) and of microphthalmia","volume":"18","author":"Bertolotto","year":"1998","journal-title":"Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.1182\/blood-2010-01-265561","article-title":"Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP\/protein kinase A signaling cascade","volume":"116","author":"Roberts","year":"2010","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1101\/gad.14.14.1712","article-title":"Mitf from neural crest to melanoma: Signal transduction and transcription in the melanocyte lineage","volume":"14","author":"Goding","year":"2000","journal-title":"Genes Dev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1242\/jcs.112.8.1237","article-title":"E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin\/LEF-1-mediated transactivation","volume":"112","author":"Orsulic","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/exd.12641","article-title":"Polymorphism of the E-cadherin gene CDH 1 is associated with susceptibility to vitiligo","volume":"24","author":"Mira","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_51","first-page":"17","article-title":"Phenolic compounds of argan tree, Argania spinosa (endemic species of south western Morocco)","volume":"1","author":"Tahrouch","year":"2011","journal-title":"TOJSAT"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s10600-013-0467-6","article-title":"Characterization and quantification of phenolic compounds of Argania spinosa leaves by HPLC-PDA-ESI-MS analyses and their antioxidant activity","volume":"48","author":"Joguet","year":"2013","journal-title":"Chem. Nat. Compd."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/pca.2585","article-title":"Analytical profiling of bioactive phenolic compounds in argan (Argania spinosa) leaves by combined microextraction by packed sorbent (MEPS) and LC-DAD-MS\/MS","volume":"27","author":"Mercolini","year":"2015","journal-title":"Phytochem. Anal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"167","DOI":"10.51227\/ojafr.2020.23","article-title":"Study of the flavonoids and secondary metabolites of the argan tree (Argania spinosa L.)","volume":"10","author":"Hilali","year":"2020","journal-title":"Online J. Animal Feed Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/ejlt.201000342","article-title":"Pentacyclic triterpenic acids from Argania spinosa","volume":"113","author":"Guinda","year":"2011","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/10412905.2002.9699801","article-title":"Chemical composition and antimicrobial activity of the leaf essential oil of Argania spinosa L. Skeels","volume":"14","author":"Charrouf","year":"2002","journal-title":"J. Essential Oil Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/12538078.1998.10516305","article-title":"Les substances volatiles de Argania spinosa (Sapotaceae)","volume":"145","author":"Tahrouch","year":"1998","journal-title":"Acta Bot. Gall."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0367-326X(03)00031-5","article-title":"Triterpenoid saponins from the roots of Silene cucubalus","volume":"74","author":"Larhsini","year":"2003","journal-title":"Fitoterapia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1055\/a-1141-0151","article-title":"Tara tannin regulates pigmentation by modulating melanogenesis enzymes and melanosome transport proteins expression","volume":"7","author":"Villareal","year":"2020","journal-title":"Planta Med. Intl. Open"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid calorimetric assay for cellular growth and survival: Application to proliferation and cytotoxic assays","volume":"65","author":"Mossman","year":"1983","journal-title":"J. Immunol. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:49:20Z","timestamp":1760143760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,10]]},"references-count":60,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196762"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196762","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,10]]}}}