{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:24:18Z","timestamp":1787736258134,"version":"build-2784847793"},"reference-count":49,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Despite known antioxidant activity, the effects of plant-derived compounds on aging-related physiological functions and mechanisms remain unclear, which necessitates investigation at cellular and organismal levels. To examine whether these compounds can mitigate age-related physiological decline, Nelumbo nucifera Gaertn. (sacred lotus) embryo extract\u2013water-soluble fraction (NEW), stilbene glycoside from Pleuropterus multiflorus (Thunb.) Turcz. ex Nakai (PM-SG), and pterostilbene were investigated through chemical profiling, antioxidant activity, HepG2 liver cells, and Caenorhabditis elegans longevity assays, while principal component analysis (PCA) elaborated on the results. Quantitative LC-MS revealed that NEW extract was rich in alkaloids (neferine and liensinine), while PM-SG mainly contained 2,3,5,4\u2032-tetrahydroxystilbene-2-O-\u03b2-D-glucoside. PM-SG showed the strongest radical-scavenging activity (DPPH, TEAC, and ORAC), followed by pterostilbene. However, pterostilbene exhibited the strongest cellular antioxidant activity among the three test materials (NEW, PM-SG, and pterostilbene), an effect attributed to its superior cellular uptake, although it was less potent than the reference standards EGCG and quercetin. All samples extended the lifespan of C. elegans dose-dependently, with the strongest effect from pterostilbene (40\u201350%), then PM-SG (25\u201335%) and NEW (18\u201322%). Pterostilbene and PM-SG improved health measures, including enhanced resistance to heat and oxidative stress, and maintained feeding function. Discrepancies between in vitro antioxidant rankings and observed cellular effects indicate that radical-scavenging activity alone cannot fully predict in vivo anti-aging efficacy, which depends on cellular uptake, activation of endogenous defense mechanisms, and modulation of longevity pathways. Further clinical studies are needed to determine the potential relevance of these findings to human health.<\/jats:p>","DOI":"10.3390\/molecules31172981","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:05:46Z","timestamp":1787735146000},"page":"2981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Level Evaluation of Antioxidant Activity, Aging-Related Physiological Functions, and Longevity Effects of Nelumbo nucifera Gaertn. Embryo Extract, Pleuropterus multiflorus (Thunb.) Turcz. ex Nakai Stilbene Glycoside, and Pterostilbene"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5774-0567","authenticated-orcid":false,"given":"Kuo-Ching","family":"Jan","sequence":"first","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Neipu, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9616-489X","authenticated-orcid":false,"given":"Jung-Chun","family":"Tai","sequence":"additional","affiliation":[{"name":"Chiayi Industry Innovation and Research Center, Chiayi 60002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1849-0906","authenticated-orcid":false,"given":"Xiao-Zhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Chiayi Industry Innovation and Research Center, Chiayi 60002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5854-7439","authenticated-orcid":false,"given":"Yu-Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Chiayi Industry Innovation and Research Center, Chiayi 60002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4904-0519","authenticated-orcid":false,"given":"Mohsen","family":"Gavahian","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Neipu, Pingtung 91201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wei, Y., Jia, S., Ding, Y., Xia, S., and Giunta, S. (2023). Balanced basal-levels of ROS (redox-biology), and very-low-levels of pro-inflammatory cytokines (cold-inflammaging), as signaling molecules can prevent or slow-down overt-inflammaging, and the aging-associated decline of adaptive-homeostasis. Exp. Gerontol., 172.","DOI":"10.1016\/j.exger.2022.112067"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rogina, B., and Tissenbaum, H.A. (2024). SIRT1, resveratrol and aging. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1393181"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wei, P., Zhang, X., Yan, C., Sun, S., Chen, Z., and Lin, F. (2025). Mitochondrial dysfunction and aging: Multidimensional mechanisms and therapeutic strategies. Biogerontology, 26.","DOI":"10.1007\/s10522-025-10273-4"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zheng, Q., Chen, J., Yuan, Y., Zhang, X., Zhai, Y., Zhang, Y., Li, L., and Li, B. (2023). Structural characterization of a low-molecular-weight polysaccharide from Plumula Nelumbinis and evaluation of its antioxidant and anti-inflammatory activity. Food Biosci., 56.","DOI":"10.1016\/j.fbio.2023.103235"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Huang, J., He, G., Wu, L., Ma, P., Xu, L., Sun, L., and Xiao, P. (2025). The edible lotus (Nelumbo nucifera Gaertn.) and its byproducts as valuable source of natural antioxidants: A review of phytochemicals, health benefits, safety and food applications. Future Foods, 11.","DOI":"10.1016\/j.fufo.2025.100603"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhu, C., Li, J., Tang, W., Li, Y., Lin, C., Peng, D., and Yang, C. (2025). 2,3,5,4\u2032-Tetrahydroxystilbene-2-O-\u03b2-D-glucoside (TSG) from Polygonum multiflorum Thunb.: A systematic review on anti-aging. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073381"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00280-010-1525-4","article-title":"Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, Pterostilbene, in rats","volume":"68","author":"Kapetanovic","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Salla, M., Karaki, N., El Kaderi, B., Ayoub, A.J., Younes, S., Abou Chahla, M.N., Baksh, S., and El Khatib, S. (2024). Enhancing the bioavailability of resveratrol: Combine it, derivatize it, or encapsulate it?. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16040569"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Beghelli, D., Zallocco, L., Barbalace, M.C., Paglia, S., Strocchi, S., Cirilli, I., Marzano, V., Putignani, L., Lupidi, G., and Hrelia, S. (2022). Pterostilbene promotes mean lifespan in both male and female Drosophila melanogaster modulating different proteins in the two sexes. Oxidative Med. Cell. Longev., 2022.","DOI":"10.1155\/2022\/1744408"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Du, N., Song, L., Yang, R., Liu, K., Niu, Z., Zhang, Z., and Sun, Q. (2025). Early-stage administration of hydroxytyrosol extends lifespan and delays aging in C. elegans. Biol. Direct, 20.","DOI":"10.1186\/s13062-025-00634-x"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jan, K.C., and Gavahian, M. (2025). Ultrasound-assisted extraction combined with enzyme hydrolysis enhanced the anti-aging effects and bioactivity of longan flower, mulberry, and roselle: Phytochemical profiling and in vivo C. elegans validation. Food Biosci., 68.","DOI":"10.1016\/j.fbio.2025.106686"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Della Vedova, L., Baron, G., Morazzoni, P., Aldini, G., and Gado, F. (2025). The potential of polyphenols in modulating the cellular senescence process: Implications and mechanism of action. Pharmaceuticals, 18.","DOI":"10.3390\/ph18020138"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/s43587-024-00663-7","article-title":"Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice","volume":"4","author":"Zumerle","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tifs.2022.12.013","article-title":"Autophagy and polyphenol intervention strategy in aging","volume":"132","author":"Gu","year":"2023","journal-title":"Trends Food Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wei, X., Zhang, M., Yang, M., Ogutu, C., Li, J., and Deng, X. (2024). Lotus (Nelumbo nucifera) benzylisoquinoline alkaloids: Advances in chemical profiling, extraction methods, pharmacological activities, and biosynthetic elucidation. Veg. Res., 4.","DOI":"10.48130\/vegres-0024-0004"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhao, D., Ma, L., Brownlie, J., Tonissen, K., Pan, Y., and Feng, Y. (2025). Neuroprotective potential of major alkaloids from Nelumbo nucifera (Lotus): Mechanisms and therapeutic implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178280"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Platzer, M., Kiese, S., Tybussek, T., Herfellner, T., Schneider, F., Schweiggert-Weisz, U., and Eisner, P. (2022). Radical scavenging mechanisms of phenolic compounds: A quantitative structure-property relationship (QSPR) study. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.882458"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Baliyan, S., Mukherjee, R., Priyadarshini, A., Vibhuti, A., Gupta, A., and Pandey, R.P. (2022). Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules, 27.","DOI":"10.3390\/molecules27041326"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yamauchi, M., Kitamura, Y., Nagano, H., Kawatsu, J., and Gotoh, H. (2024). DPPH measurements and structure-activity relationship studies on the antioxidant capacity of phenols. Antioxidants, 13.","DOI":"10.3390\/antiox13030309"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, L., and Chen, J. (2018). Biological effects of tetrahydroxystilbene glucoside: An active component of a rhizome extracted from Polygonum multiflorum. Oxidative Med. Cell. Longev., 2018.","DOI":"10.1155\/2018\/3641960"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16895","DOI":"10.1021\/acs.est.3c05377","article-title":"Unraveling multiple pathways of electron donation from phenolic moieties in natural organic matter","volume":"57","author":"Yang","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1021\/acs.jafc.3c04022","article-title":"The chemistry behind the Folin-Ciocalteu 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_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.7324\/JAPS.2019.90717","article-title":"Resveratrol and Pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties","volume":"9","author":"Chan","year":"2019","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Reiniers, M.J., de Haan, L.R., Reeskamp, L.F., Broekgaarden, M., Hoekstra, R., van Golen, R.F., and Heger, M. (2022). Optimal use of 2\u2032,7\u2032-dichlorofluorescein diacetate in cultured hepatocytes. Mitochondrial Medicine: Volume 1, Probing Mitochondrial Function, Humana.","DOI":"10.1007\/978-1-0716-2099-1_39"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1080\/10408398.2021.2009436","article-title":"Alkaloids from lotus (Nelumbo nucifera): Recent advances in biosynthesis, pharmacokinetics, bioactivity, safety, and industrial applications","volume":"63","author":"Wang","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wang, C., Dai, S., Gong, L., Fu, K., Ma, C., Liu, Y., Zhou, H., and Li, Y. (2022). A review of pharmacology, toxicity and pharmacokinetics of 2,3,5,4\u2032-tetrahydroxystilbene-2-O-\u03b2-D-glucoside. Front. Pharmacol., 1.","DOI":"10.3389\/fphar.2021.791214"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nagarajan, S., Mohandas, S., Ganesan, K., Xu, B., and Ramkumar, K.M. (2022). New insights into dietary Pterostilbene: Sources, metabolism, and health promotion effects. Molecules, 27.","DOI":"10.3390\/molecules27196316"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1039\/D3NP00021D","article-title":"The role of Caenorhabditis elegans in the discovery of natural products for healthy aging","volume":"40","author":"Kirchweger","year":"2023","journal-title":"Nat. Prod. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sun, M., Wei, C., Gao, Y., Chen, X., Zhong, K., Li, Y., Yang, Z., Gao, Y., and Wang, H. (2024). TSG extends the longevity of Caenorhabditis elegans by targeting the DAF-16\/SKN-1\/SIR-2.1-mediated mitochondrial quality control process. Antioxidants, 13.","DOI":"10.3390\/antiox13091086"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bei, Y., Wang, T., and Guan, S. (2025). Berberine extends lifespan in C. elegans through multi-target synergistic antioxidant effects. Antioxidants, 14.","DOI":"10.3390\/antiox14040450"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8774","DOI":"10.1039\/D1FO01908B","article-title":"Polygonum multiflorum Thunb extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16\/SIR-2.1\/SKN-1","volume":"12","author":"Sun","year":"2021","journal-title":"Food Funct."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Agostini, F., Bisaglia, M., and Plotegher, N. (2023). Linking ROS levels to autophagy: The key role of AMPK. Antioxidants, 12.","DOI":"10.3390\/antiox12071406"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Vakkayil, K.L., and Hoppe, T. (2022). Temperature-dependent regulation of proteostasis and longevity. Front. Aging, 3.","DOI":"10.3389\/fragi.2022.853588"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, S., Youn, E., Tran, S.H., Bae, W.Y., Nguyen, U.T.T., Ho, P.L., Kim, J.H., Park, K., Kim, C.Y., and Kang, K. (2026). Kukoamine A from the root bark of Lycium chinense Miller enhances mobility in an aged Caenorhabditis elegans model by regulating mitochondrial function through HSF-1-mediated upregulation of heat shock proteins. J. Ethnopharmacol., 354.","DOI":"10.1016\/j.jep.2025.120469"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Xu, W., Chen, S., Wang, X., Wu, H., Yamada, H., and Hirano, T. (2020). Bisbenzylisoquinoline alkaloids and P-glycoprotein function: A structure activity relationship study. Bioorganic Med. Chem., 28.","DOI":"10.1016\/j.bmc.2020.115553"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, C., Zhou, Y., Gong, X., Zheng, L., and Li, Y. (2020). In vitro and in situ study on characterization and mechanism of the intestinal absorption of 2,3,5,4\u2032-tetrahydroxy-stilbene-2-O-\u03b2-D-glucoside. BMC Pharmacol. Toxicol., 21.","DOI":"10.1186\/s40360-020-0384-9"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1007\/s11030-025-11144-3","article-title":"Pterostilbene as a potent ESR-1 in breast cancer therapy: Insights from network pharmacology, molecular docking, dynamics simulations, ADMET, and in vitro analysis","volume":"29","author":"Marwah","year":"2025","journal-title":"Mol. Divers."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14261","DOI":"10.1021\/acs.jmedchem.2c01147","article-title":"Hydrogen-bond donors in drug design","volume":"65","author":"Kenny","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/biof.1405","article-title":"Oral delivery system enhanced the bioavailability of stilbenes: Resveratrol and Pterostilbene","volume":"44","author":"Peng","year":"2018","journal-title":"BioFactors"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/09637480903292601","article-title":"ORAC and DPPH assay comparison to assess antioxidant capacity of tea infusions: Relationship between total polyphenol and individual catechin content","volume":"61","author":"Roy","year":"2010","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_41","unstructured":"(2026, August 07). POWO. Plants of the World Online. Facilitated by the Royal Botanic Gardens, Kew. Published on the Internet. Available online: https:\/\/powo.science.kew.org\/."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kumar, A., Kaundal, R., and Kumar, D. (2025). Development and validation of a rapid and accurate ultra performance liquid chromatography-photodiode array method for concurrent quantification of thirty-two polyphenols in edible fruit of Cordia myxa Linn. J. Chromatogr. A, 1743.","DOI":"10.1016\/j.chroma.2024.465609"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1080\/14786419.2024.2354850","article-title":"A new flavonostilbene glycoside and four new stilbene derivatives from the roots of Polygonum multiflorum","volume":"39","author":"Li","year":"2025","journal-title":"Nat. Prod. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/j.foohum.2023.11.016","article-title":"Exploring bioactive compounds and antioxidant properties of twenty-six Indian medicinal plant extracts: A correlative analysis for potential therapeutic insights","volume":"1","author":"Kumar","year":"2023","journal-title":"Food Humanit."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Arancibia-D\u00edaz, A., Astudillo-Castro, C., Altamirano, C., Vergara-Castro, M., Soto-Maldonado, C., C\u00f3rdova, A., Fuentes, P., Z\u00fa\u00f1iga-Hansen, M.E., and Bravo, J. (2025). Enhanced antioxidant capacity and yield of release of chlorogenic acids and derivates by solid-state fermentation of spent coffee ground under controlled conditions of aeration and moisturizing. Food Chem., 479.","DOI":"10.1016\/j.foodchem.2025.143744"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bhat, A., Cox, R.L., Hendrickson, B.G., Das, N.K., Schaller, M.L., Tuckowski, A.M., Wang, E., Shah, Y.M., and Leiser, S.F. (2024). A diet of oxidative stress\u2013adapted bacteria improves stress resistance and extends lifespan through mitogen-activated protein kinase pathway activation. Sci. Adv., 10.","DOI":"10.1126\/sciadv.adk8823"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kuznetsov, M., Klein, E., Velina, D., Mutallibzoda, S., Orlovtseva, O., Tefikova, S., Klyuchnikova, D., and Nikitin, I. (2025). Using machine learning for the discovery and development of multitarget flavonoid-based functional products in MASLD. Molecules, 30.","DOI":"10.3390\/molecules30214159"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19800","DOI":"10.1021\/acs.jmedchem.5c00920","article-title":"Drug and clinical candidate drug data in ChEMBL","volume":"68","author":"Hunter","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jan, K.-C., and Gavahian, M. (2024). Cold plasma at various voltage, gas flow rate, and time assisted extraction of blue pea flower: Quantitative UPLC-ESI\/MS\/MS analysis of bioactive compounds, phenolics, and anthocyanin content. Innov. Food Sci. Emerg. Technol., 98.","DOI":"10.1016\/j.ifset.2024.103837"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/17\/2981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:06:07Z","timestamp":1787735167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/17\/2981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":49,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["molecules31172981"],"URL":"https:\/\/doi.org\/10.3390\/molecules31172981","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}