{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:51:40Z","timestamp":1787014300600,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intern J of Cosmetic Sci"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To demonstrate the synergistic effect of 4\u2010hexylresorcinol (4\u2010HR) with niacinamide in boosting anti\u2010melanogenic efficacy\n                      <jats:italic>in vitro<\/jats:italic>\n                      and establish the i\n                      <jats:italic>n vivo<\/jats:italic>\n                      efficacy and safety of the combination in a human trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4\u2010HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double\u2010blind, split\u2010face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12\u2010week study period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      tyrosinase enzyme activity studies showed that 4\u2010HR is one of the most potent tyrosinase inhibitors. The combination of 4\u2010HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model.\n                      <jats:italic>In vitro<\/jats:italic>\n                      as well as in the human trial, the combination of 4\u2010HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product\u2010related adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A formulation containing a combination of 4\u2010HR and niacinamide delivered superior skin tone and anti\u2010ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ics.12759","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T13:49:47Z","timestamp":1640612987000},"page":"103-117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Superior even skin tone and anti\u2010ageing benefit of a combination of 4\u2010hexylresorcinol and niacinamide"],"prefix":"10.1111","volume":"44","author":[{"given":"Rezwan","family":"Shariff","sequence":"first","affiliation":[{"name":"Unilever R&amp;D Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Du","sequence":"additional","affiliation":[{"name":"Unilever R&amp;D Shanghai 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