{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T20:46:33Z","timestamp":1766436393841,"version":"3.48.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Excessive ultraviolet exposure triggers skin pigment deposition, potentially leading to conditions such as melasma, freckles, and post\u2010inflammatory hyperpigmentation. The skin of individuals with these dermatological conditions exhibits reduced levels of nicotinamide nucleotide transhydrogenase (NNT). While many seek skin\u2010whitening products to address pigmentation, existing options often fail to achieve optimal efficacy. To accomplish a synergistic whitening effect, we developed PPV, a composite formulation incorporating three depigmenting agents:\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Pterocarpus marsupium<\/jats:italic>\n                      <\/jats:styled-content>\n                      bark extract (PMBE),\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Pinus strobus<\/jats:italic>\n                      <\/jats:styled-content>\n                      bark extract (PSBE), and ascorbyl tetraisopalmitate (VC\u2010IP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to investigate the effects of PPV on skin whitening and elucidate its mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      After administering PPV to B16F10 melanoma cells, we measured melanin content and gene expression of\n                      <jats:italic>TYR<\/jats:italic>\n                      ,\n                      <jats:italic>TRP\u20101<\/jats:italic>\n                      , and\n                      <jats:italic>TRP\u20102<\/jats:italic>\n                      using a microplate reader and qPCR. Western blotting was used to assess p\u2010CREB, CREB, MITF, and NNT expression. The Jin's formula was used to evaluate the combined effect of the three components of PPV on\n                      <jats:italic>NNT<\/jats:italic>\n                      at the genetic level. Oxidative stress levels were evaluated with ROS, GSH\/GSSG, and NADP\n                      <jats:sup>+<\/jats:sup>\n                      \/NADPH assay kits, along with confocal microscopy. Transmission electron microscopy and ELISA were employed to quantify the eumelanin\/pheomelanin ratio and melanosome maturation. Finally, immunodetection was performed to assess epidermal basal pigmentation, tyrosinase, and NNT expression in a human ex\u00a0vivo skin model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PPV significantly influenced melanin production in melanocytes and human ex\u00a0vivo skin. This effect was due to the inhibitory effect of PPV on the CREB\u2010MITF signaling pathway and the synergistic activation effect of PMBE, PSBE, and VC\u2010IP on the\n                      <jats:italic>NNT<\/jats:italic>\n                      gene expression in B16F10 cells. Activation of NNT led to a reduction in ROS levels and the NADP\n                      <jats:sup>+<\/jats:sup>\n                      \/NADPH ratio, ultimately inhibiting melanogenesis, tyrosinase activity, and melanosome maturation in B16F10 cells. Furthermore, PPV treatment reduced pigmentation and increased NNT expression in the aged ex\u00a0vivo skin model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PPV, synthesized from PMBE, PSBE, and VC\u2010IP, exhibited an anti\u2010melanogenic effect. This effect was attributed to the inhibition of CREB\u2010MITF\u2010mediated melanogenesis and the regulation of oxidative stress by NNT. The findings suggest PPV as a potential therapeutic agent for skin pigmentation disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.70606","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T07:00:07Z","timestamp":1766041207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Combination of\n                    <i>Pterocarpus marsupium<\/i>\n                    Bark Extract,\n                    <i>Pinus strobus<\/i>\n                    Bark Extract, and Ascorbyl Tetraisopalmitate Inhibits Melanogenesis via Nicotinamide Nucleotide Transhydrogenase Activation"],"prefix":"10.1111","volume":"24","author":[{"given":"Kejie","family":"Peng","sequence":"first","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro\u2010Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro\u2010Products Storage and Preservation of Ministry of Agriculture and Rural Affairs Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Mu","sequence":"additional","affiliation":[{"name":"Proya Cosmetics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumeng","family":"Li","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro\u2010Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro\u2010Products Storage and Preservation of Ministry of Agriculture and Rural Affairs Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhangtie","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro\u2010Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro\u2010Products Storage and Preservation of Ministry of Agriculture and Rural Affairs Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yansong","family":"Peng","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro\u2010Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro\u2010Products Storage and Preservation of Ministry of Agriculture and Rural Affairs Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro\u2010Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro\u2010Products Storage and Preservation of Ministry of Agriculture and Rural Affairs Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro\u2010Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro\u2010Products Storage and Preservation of Ministry of Agriculture and Rural Affairs Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010Hangzhou Global Scientific and Technological Innovation Center  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3116-7820","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Proya Cosmetics Co. 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