{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:00:44Z","timestamp":1781319644633,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skin dullness, characterized by pigmentation disorders and yellowing, is a major cosmetic concern in Asian populations. Lipofuscin exhibits ultraviolet (UV)\/visible light spectral absorption, reduces skin reflectance, and contributes to dullness, whereas existing therapies targeting melanogenesis and glycation lack comprehensive efficacy. This study aimed to evaluate the multimodal anti\u2010dullness effects of a novel formulation (HNHT: hyaluronic acid, niacinamide, hydrolyzed red algae, and tranexamic acid).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro models (melanocytes, keratinocytes, fibroblasts, ex\u00a0vivo skin model, and three\u2010dimensional (3D) skin models) were used to assess melanin regulation, glycation inhibition, and lipofuscin clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In ultraviolet B (UVB)\u2010exposed 3D skin models, 12.5% HNHT significantly improved skin color, appearance, and brightness (8.44% increase in\n                      <jats:italic>L<\/jats:italic>\n                      * value) and reduced melanin content (12.5% inhibition). Then, 12.5% HNHT downregulated the expression of key melanogenic genes (\n                      <jats:italic>TYR<\/jats:italic>\n                      and\n                      <jats:italic>MITF<\/jats:italic>\n                      ;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) in melanocytes and decreased UVB\u2010induced \u03b1\u2010melanocyte\u2010stimulating hormone secretion in keratinocytes (2867.78 versus 3444.72\u2009pg\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The formulation enhanced melanosome clearance through autophagy activation (174% LC3\u2010II increase, 80% GP100 reduction;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and boosted antioxidant capacity via Nrf2 activation and reactive oxygen species reduction (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In glycation, 50% HNHT upregulated anti\u2010glycation enzymes (\n                      <jats:italic>GLO1<\/jats:italic>\n                      ,\n                      <jats:italic>GLO2<\/jats:italic>\n                      , and\n                      <jats:italic>GPX1<\/jats:italic>\n                      ) and reduced carboxymethyllysine (CML) by 23.16% in fibroblasts (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), while 100% HNHT decreased CML by 34.93% in ex\u00a0vivo skin model. Furthermore, 50% HNHT suppressed hydrogen peroxide\u2010induced lipofuscin accumulation by 52.20% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight HNHT as a multitargeted therapeutic agent that alleviates skin dullness through melanogenesis inhibition, enhances melanosome degradation, suppresses glycation, mitigates oxidative stress, and promotes lipofuscin clearance, thereby establishing a novel therapeutic paradigm against solar radiation\u2010induced hyperpigmentation and skin yellowing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.70789","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:41:08Z","timestamp":1779169268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multitargeted Modulation of Skin Dullness by\n                    <scp>HNHT<\/scp>\n                    Formulation: Synergistic Inhibition of Melanogenesis, Glycation, and Lipofuscin Deposition"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2991-1509","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"first","affiliation":[{"name":"Meyer Bio\u2010Medicine Co., Ltd.  Jinan China"},{"name":"Shandong Meimao Pharmaceutical Co., Ltd.  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5238-1106","authenticated-orcid":false,"given":"Yumei","family":"Fan","sequence":"additional","affiliation":[{"name":"Meyer Bio\u2010Medicine Co., Ltd.  Jinan China"},{"name":"Shandong Meimao Pharmaceutical Co., Ltd.  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixue","family":"Ling","sequence":"additional","affiliation":[{"name":"Meyer Bio\u2010Medicine Co., Ltd.  Jinan China"},{"name":"Shandong Meimao Pharmaceutical Co., Ltd.  Jinan China"},{"name":"National Glycoengineering Research Center Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13407"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2011.06.015"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0846.2009.00416.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0846.2009.00396.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13831"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17071144"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8687"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpap.2021.100044"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2004.00131.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S72244"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12555"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S226331"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.12338"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209787185823"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12994"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2002.5665"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2002.04834.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0906-6705.2005.00309.x"},{"issue":"6","key":"e_1_2_11_20_1","first-page":"1214","article-title":"Skin Whitening Capability of Shikimic Acid Pathway Compound","volume":"20","author":"Chen Y. 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