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In this study, electron spin resonance spectroscopy revealed that synephrine scavenged both hydroxyl and superoxide anion radicals. Several external stimuli, such as H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , X-rays, and ultraviolet (UV) radiation, cause stress-induced premature senescence (SIPS). As oxidative stress induces SIPS, we hypothesized that synephrine, an antioxidant, would suppress H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced premature senescence in WI-38 cells. Synephrine significantly decreased the reactive oxygen species levels induced by H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , thereby reducing lipid peroxidation, and oxidative DNA damage and preventing SIPS. Additionally, synephrine inhibited mitochondrial dysfunction in H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -treated WI-38 cells. The expression levels of p53, p21, and p16\n                    <jats:sup>-INK4A<\/jats:sup>\n                    , which are involved in the induction of cell cycle arrest in SIPS, were significantly lower in synephrine-treated cells than in untreated cells. Our results indicate that synephrine inhibits H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced oxidative stress and mitochondrial dysfunction, suppressing premature senescence by inhibiting activation of the p53\u2013p21 and p16\n                    <jats:sup>-INK4A<\/jats:sup>\n                    \u2013pRB pathways.\n                  <\/jats:p>","DOI":"10.1007\/s12013-025-01669-7","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T10:24:43Z","timestamp":1737368683000},"page":"2607-2622","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synephrine Inhibits Oxidative Stress and H2O2-Induced Premature Senescence"],"prefix":"10.1007","volume":"83","author":[{"given":"Hiroshi","family":"Abe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko P.","family":"Indo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki J.","family":"Majima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"issue":"8","key":"1669_CR1","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1177\/153537020422900802","volume":"229","author":"A Fugh-Berman","year":"2004","unstructured":"Fugh-Berman, A., & Myers, A. 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