{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:49:36Z","timestamp":1792183776761,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>With the aging global population, interest in skin aging and skin health products is increasing. Nelumbo nucifera Gaertn. (lotus) has been widely used for its pharmacological benefits, including antioxidant, anti-inflammatory, skin-whitening, and anti-aging properties. In this study, we aimed to develop a safe and biologically active extract by extracting lotus flowers with hot water, followed by sequential fractionation using porous resin chromatography with stepwise ethanol elution (100% water and 30%, 70%, and 100% ethanol). The 30% and 70% ethanol fractions showed the highest total polyphenol and flavonoid contents. Liquid chromatography\u2013electrospray ionization\u2013mass spectrometry analysis identified major flavonoids, including myricetin and quercetin derivatives, in these fractions. These fractions were combined to formulate a novel Nelumbo nucifera flower extract (NFE), which exhibited potent antioxidant activity confirmed by 2,2-diphenyl-1-picrylhydrazyl, 2,2\u2032-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and ferric reducing antioxidant power assays. NFE significantly inhibited nitric oxide and prostaglandin E2 secretion in lipopolysaccharide-activated murine RAW264.7 macrophages. In human keratinocytes HaCaT cells, NFE reduced tumor necrosis factor-\u03b1-induced expression and secretion of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 without cytotoxicity. These findings demonstrate that NFE has strong in vitro antioxidant and anti-inflammatory activities, supporting its potential as a bioactive ingredient for application in improving skin health preparations.<\/jats:p>","DOI":"10.3390\/cimb47121065","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:45:07Z","timestamp":1766065507000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chemical Composition and Bioactivity of Nelumbo nucifera Gaertn. Flower Extract Fractions: In Vitro Antioxidant and Anti-Inflammatory Properties"],"prefix":"10.3390","volume":"47","author":[{"given":"Jung Ha","family":"Choo","sequence":"first","affiliation":[{"name":"Science Research Park, LG Household and Healthcare Ltd., Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Science Research Park, LG Household and Healthcare Ltd., Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungin","family":"Min","sequence":"additional","affiliation":[{"name":"Science Research Park, LG Household and Healthcare Ltd., Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nae Gyu","family":"Kang","sequence":"additional","affiliation":[{"name":"Science Research Park, LG Household and Healthcare Ltd., Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","unstructured":"(2025, November 12). Ageing and Health. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/ageing-and-health."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s43546-021-00180-4","article-title":"Active ageing of elderly consumers: Insights and opportunities for future business strategies","volume":"2","author":"Guido","year":"2022","journal-title":"SN Bus. Econ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"308","DOI":"10.4161\/derm.22804","article-title":"Skin anti-aging strategies","volume":"4","author":"Ganceviciene","year":"2012","journal-title":"Derm.-Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3390\/biom5020545","article-title":"Oxidative stress in aging human skin","volume":"5","author":"Rinnerthaler","year":"2015","journal-title":"Biomolecules"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shin, S.H., Lee, Y.H., Rho, N.-K., and Park, K.Y. (2023). Skin aging from mechanisms to interventions: Focusing on dermal aging. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1195272"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Agrawal, R., Hu, A., and Bollag, W.B. (2023). The skin and Inflamm-aging. Biology, 12.","DOI":"10.3390\/biology12111396"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00011-022-01598-8","article-title":"Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin","volume":"71","author":"Salminen","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Michalak, M. (2023). Plant extracts as skin care and therapeutic agents. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015444"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Michalak, M. (2022). Plant-derived antioxidants: Significance in skin health and the ageing process. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020585"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.chroma.2011.12.098","article-title":"Analysis of flavonoids from lotus (Nelumbo nucifera) leaves using high performance liquid chromatography\/photodiode array detector tandem electrospray ionization mass spectrometry and an extraction method optimized by orthogonal design","volume":"1227","author":"Chen","year":"2012","journal-title":"J. Chromatogr. A"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tungmunnithum, D., Pinthong, D., and Hano, C. (2018). Flavonoids from Nelumbo nucifera Gaertn., a medicinal plant: Uses in traditional medicine, phytochemistry and pharmacological activities. Medicines, 5.","DOI":"10.3390\/medicines5040127"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/j.1365-2621.2005.00990.x","article-title":"Antioxidant effect of Korean traditional lotus liquor (Yunyupju)","volume":"40","author":"Lee","year":"2005","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_13","first-page":"42","article-title":"Ethno-medicinal uses and pharmacological activities of lotus (Nelumbo nucifera)","volume":"2","author":"Sheikh","year":"2014","journal-title":"J. Med. Plants Stud."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"789124","DOI":"10.1155\/2015\/789124","article-title":"Phytochemical Profile and Biological Activity of Nelumbo nucifera","volume":"2015","author":"Paudel","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tungmunnithum, D., Drouet, S., and Hano, C. (2022). Validation of a high-performance liquid chromatography with photodiode array detection method for the separation and quantification of antioxidant and skin anti-aging flavonoids from Nelumbo nucifera Gaertn. Stamen extract. Molecules, 27.","DOI":"10.3390\/molecules27031102"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10616-022-00521-7","article-title":"Lotus root extract inhibits skin damage through suppression of collagenase production in vitro","volume":"74","author":"Iwamoto","year":"2022","journal-title":"Cytotechnology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s11814-010-0357-6","article-title":"Nelumbo nucifera extracts as whitening and anti-wrinkle cosmetic agent","volume":"28","author":"Kim","year":"2011","journal-title":"Korean J. Chem. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Moon, S.H., Kim, E., Kim, H.-I., Kim, S.-Y., Seo, H.-H., Lee, J.H., Lee, M.-S., Lee, S.-K., Moh, S.H., and Bae, S. (2023). Skin-whitening effect of a callus extract of Nelumbo nucifera isolate Haman. Plants, 12.","DOI":"10.3390\/plants12233923"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zheng, W., Chen, R., Xu, K., Wang, R., Wang, Z., Li, H., Go, Y., Chan, X., Huang, Q., and Wu, J. (2025). Flavonoids in lotus stamen extract inhibit high glucose-induced intracellular glycation in fibroblasts by upregulating the expression of glyoxalase 1 and alleviating oxidative stress. Antioxidants, 14.","DOI":"10.3390\/antiox14040392"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6623","DOI":"10.1021\/jf900950z","article-title":"Antioxidative effect and active components from leaves of lotus (Nelumbo nucifera)","volume":"57","author":"Lin","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","first-page":"3078","article-title":"Antimicrobial activity of Nelumbo nucifera leaves","volume":"12","author":"Niranjan","year":"2023","journal-title":"Int. J. Biol. Pharm. Allied Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e407025","DOI":"10.1590\/acb407025","article-title":"Hepatoprotective effect of lotus leaf against non-alcoholic fatty liver disease in rats via alteration of AMPK\/SIRT1 and Nrf2\/HO-1 signaling pathway","volume":"40","author":"Shen","year":"2025","journal-title":"Acta Cir. Bras."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105331","DOI":"10.1016\/j.jff.2022.105331","article-title":"Water extract of lotus leaves has hepatoprotective activity by enhancing Nrf2- and epigenetics-mediated cellular antioxidant capacity in mouse hepatocytes","volume":"99","author":"Su","year":"2022","journal-title":"J. Funct. Foods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1186\/1423-0127-17-S1-S42","article-title":"Antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in rats fed a high fat diet","volume":"17","author":"Du","year":"2010","journal-title":"J. Biomed. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13765-020-00541-x","article-title":"The anti-obesity effect of lotus leaves on high-fat-diet-induced obesity by modulating lipid metabolism in C57BL\/6J mice","volume":"63","author":"Wu","year":"2020","journal-title":"Appl. Biol. Chem."},{"key":"ref_26","first-page":"72","article-title":"Hypoglycemic effect of lotus (Nelumbo nucifera Gaertn.) flower ethanolic extract on alloxan induced diabetes rat model","volume":"6","author":"Thu","year":"2016","journal-title":"Ho Chi Minh City Open Univ. J. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101282","DOI":"10.1016\/j.fochx.2024.101282","article-title":"Hypoglycemic activity in vivo and in vitro of the lotus (Nelumbo nucifera Gaertn.) seed skin (Testa) phenolic-rich extracts","volume":"22","author":"Xu","year":"2024","journal-title":"Food Chem. X"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e202402788","DOI":"10.1002\/cbdv.202402788","article-title":"Assessment of the properties and mechanism of three lotus (Nelumbo nucifera Gaertn.) parts for sleep improvement","volume":"22","author":"He","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10553","DOI":"10.3390\/molecules200610553","article-title":"Analysis of flavonoids in lotus (Nelumbo nucifera) leaves and their antioxidant activity using macroporous resin chromatography coupled with LC-MS\/MS and antioxidant biochemical assays","volume":"20","author":"Zhu","year":"2015","journal-title":"Molecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13765-020-00568-0","article-title":"Validation of an optimized HPLC\/UV method for the quantification of flavonoids in lotus","volume":"63","author":"Lee","year":"2020","journal-title":"Appl. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.aca.2012.02.051","article-title":"Simultaneous qualitative assessment and quantitative analysis of flavonoids in various tissues of lotus (Nelumbo nucifera) using high performance liquid chromatography coupled with triple quad mass spectrometry","volume":"724","author":"Chen","year":"2012","journal-title":"Anal. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e202301493","DOI":"10.1002\/cbdv.202301493","article-title":"An updated review on Nelumbo nucifera Gaertn: Chemical composition, nutritional value and pharmacological activities","volume":"21","author":"Sahu","year":"2024","journal-title":"Chem. Biodivers."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Park, C.H., Yeo, H.J., Baskar, T.B., Park, Y.E., Park, J.S., Lee, S.Y., and Park, S.U. (2019). In vitro antioxidant and antimicrobial properties of flower, leaf, and stem extracts of Korean mint. Antioxidants, 8.","DOI":"10.3390\/antiox8030075"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.foodchem.2007.01.047","article-title":"Bioactive compounds and antioxidant capacities in different edible tissues of citrus fruit of four species","volume":"104","author":"Abeysinghe","year":"2007","journal-title":"Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jing, L., Ma, H., Fan, P., Gao, R., and Jia, Z. (2015). Antioxidant potential, total phenolic and total flavonoid contents of Rhododendron anthopogonoides and its protective effect on hypoxia-induced injury in PC12 cells. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0820-3"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dhanaraj, F.I., Kalimuthu, J.K., Balamurugan, P.S., Subramani, P., Katerere, D.R., and Gurusamy, M. (2025). Investigating the phytochemical profile and antioxidant activity of different solvent extracts of Sesamum prostratum Retz. Plants, 14.","DOI":"10.3390\/plants14040519"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jfca.2006.01.003","article-title":"Comparison of ABTS, DPPH, FRAP, and ORAC assays for estimating antioxidant activity from guava fruit extracts","volume":"19","author":"Thaipong","year":"2006","journal-title":"J. Food Compos. Anal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e14264","DOI":"10.1111\/jfbc.14264","article-title":"Health benefits of polyphenols: A concise review","volume":"46","author":"Rana","year":"2022","journal-title":"J. Food Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0024-3205(01)01482-5","article-title":"Antioxidant activity of anti-inflammatory plant extracts","volume":"70","author":"Schinella","year":"2002","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Parham, S., Kharazi, A.Z., Bakhsheshi-Rad, H.R., Nur, H., Ismail, A.F., Sharif, S., RamaKrishna, S., and Berto, F. (2020). Antioxidant, antimicrobial and antiviral properties of herbal materials. Antioxidants, 9.","DOI":"10.3390\/antiox9121309"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Yoldi, M.J. (2021). Anti-inflammatory and antioxidant properties of plant extracts. Antioxidants, 10.","DOI":"10.3390\/antiox10060921"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.20307\/nps.2019.25.1.44","article-title":"Antioxidant activity and phenolic content of different parts of lotus and optimization of extraction condition using response surface methodology","volume":"25","author":"Jang","year":"2019","journal-title":"Nat. Prod. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3390\/oxygen3030018","article-title":"Successive solvent extraction of polyphenols and flavonoids from Cistus creticus L. Leaves","volume":"3","author":"Palaiogiannis","year":"2023","journal-title":"Oxygen"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dias, M.C., Pinto, D.G.C.A., and Silva, A.M.S. (2021). Plant flavonoids: Chemical characteristics and biological activity. Molecules, 26.","DOI":"10.3390\/molecules26175377"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Xue, F., and Yang, Y. (2023). Hot water extraction of antioxidants from tea leaves\u2014Optimization of brewing conditions for preparing antioxidant-rich tea drinks. Molecules, 28.","DOI":"10.3390\/molecules28073030"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nutho, B., and Tungmunnithum, D. (2023). Exploring major flavonoid phytochemicals from Nelumbo nucifera Gaertn. as potential skin anti-aging agents: In silico and in vitro evaluations. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316571"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.bcp.2010.01.004","article-title":"Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf","volume":"79","author":"Jung","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.tiv.2009.09.015","article-title":"Protective effects of myricetin against ultraviolet-B-induced damage in human keratinocytes","volume":"24","author":"Huang","year":"2010","journal-title":"Toxicol. In Vitro"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ejphar.2016.05.025","article-title":"Flavonoid myricetin inhibits TNF-\u03b1-stimulated production of inflammatory mediators by suppressing the Akt, mTOR and NF-\u03baB pathways in human keratinocytes","volume":"784","author":"Lee","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/jocd.12399","article-title":"Myricetin protects keratinocyte damage induced by UV through I\u03baB\/NF\u03bab signaling pathway","volume":"16","author":"Xie","year":"2017","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/toxsci\/kfac138","article-title":"Myricetin treatment has ameliorative effects in DNFB-induced atopic dermatitis mice under high-fat conditions","volume":"191","author":"Gao","year":"2023","journal-title":"Toxicol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"115212","DOI":"10.1016\/j.intimp.2025.115212","article-title":"Myricetin alleviates DNCB-induced atopic dermatitis by modulating macrophage M1\/M2 polarization","volume":"163","author":"Zhang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ha, A.T., Rahmawati, L., You, L., Hossain, M.A., Kim, J.-H., and Cho, J.Y. (2021). Anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis effects of quercetin 3-O-\u03b2-D-glucuronide in human keratinocytes and melanoma cells via activation of NF-\u03baB and AP-1 pathways. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010433"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.redox.2018.05.002","article-title":"Antioxidant response elements: Discovery, classes, regulation and potential applications","volume":"17","author":"Raghunath","year":"2018","journal-title":"Redox Biol."},{"key":"ref_55","first-page":"243","article-title":"Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-\u03baB activation","volume":"480\u2013481","author":"Surh","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.crfs.2022.07.007","article-title":"Anti-inflammatory activity of flavonols via inhibiting MAPK and NF-\u03baB signaling pathways in RAW264.7 macrophages","volume":"5","author":"Zhong","year":"2022","journal-title":"Curr. Res. Food Sci."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/12\/1065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:12:21Z","timestamp":1766067141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/12\/1065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cimb47121065"],"URL":"https:\/\/doi.org\/10.3390\/cimb47121065","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}