{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:48:04Z","timestamp":1789422484143,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"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>Ferulic Acid (FA) is a highly abundant phenolic phytochemical which is present in plant tissues. FA has biological effects on physiological and pathological processes due to its anti-apoptotic and anti-oxidative properties, however, the detailed mechanism(s) of function is poorly understood. We have identified FA as a molecule that inhibits apoptosis induced by hydrogen peroxide (H2O2) or actinomycin D (ActD) in rat pheochromocytoma, PC12 cell. We also found that FA reduces H2O2-induced reactive oxygen species (ROS) production in PC12 cell, thereby acting as an anti-oxidant. Then, we analyzed FA-mediated signaling responses in rat pheochromocytoma, PC12 cells using antibody arrays for phosphokinase and apoptosis related proteins. This FA signaling pathway in PC12 cells includes inactivation of pro-apoptotic proteins, SMAC\/Diablo and Bad. In addition, FA attenuates the cell injury by H2O2 through the inhibition of phosphorylation of the extracellular signal-regulated kinase (ERK). Importantly, we find that FA restores expression levels of brain-derived neurotrophic factor (BDNF), a key neuroprotective effector, in H2O2-treated PC12 cells. As a possible mechanism, FA increases BDNF by regulating microRNA-10b expression following H2O2 stimulation. Taken together, FA has broad biological effects as a neuroprotective modulator to regulate the expression of phosphokinases, apoptosis-related proteins and microRNAs against oxidative stress in PC12 cells.<\/jats:p>","DOI":"10.3390\/molecules26010090","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T10:33:56Z","timestamp":1609151636000},"page":"90","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Protective Effect of Ferulic Acid against Hydrogen Peroxide Induced Apoptosis in PC12 Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-2650","authenticated-orcid":false,"given":"Hironao","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Medical Science and Technology, Hiroshima International University, Higashi-hiroshima, Hiroshima 739-2695, Japan"},{"name":"Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Technology, Hiroshima International University, Higashi-hiroshima, Hiroshima 739-2695, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erina","family":"Matsugi","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Technology, Hiroshima International University, Higashi-hiroshima, Hiroshima 739-2695, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Soda","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoka","family":"Hattori","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Hara","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayuki","family":"Usami","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Kusumoto","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Technology, Hiroshima International University, Higashi-hiroshima, Hiroshima 739-2695, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Higashiyama","sequence":"additional","affiliation":[{"name":"Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Toon, Shitsukawa, Ehime 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoyuki","family":"Kitaichi","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrd4002","article-title":"Modulation of oxidative stress as an anticancer strategy","volume":"12","author":"Gorrini","year":"2013","journal-title":"Nat. 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