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However, the neuroprotective potential of coffee bean-derived peptides remains largely unexplored. In this study, coffee bean protein hydrolysates (CBPH) exhibited protective effects against RSL3- and 6-OHDA-induced neuronal injury. Virtual screening and molecular docking targeting 15-lipoxygenase (ALOX15), a key enzyme involved in oxidative neuronal damage, identified eight candidate inhibitory peptides. Among them, FAR and FPSFRE showed significant ALOX15 inhibitory activity, reducing enzyme activity by 51.73 \u00b1 21.54% and 91.61 \u00b1 2.43%, respectively (p &amp;lt; 0.05). Consistently, both peptides significantly improved neuronal viability and attenuated oxidative stress-induced injury. Their direct interactions with ALOX15 were further confirmed by cellular thermal shift assay and molecular dynamics simulations. Moreover, FAR and FPSFRE ameliorated locomotor deficits in a 6-OHDA-induced zebrafish model, highlighting their potential as natural neuroprotective agents and functional food ingredients.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c07908","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:01:24Z","timestamp":1789059684000},"page":"29313-29327","source":"Crossref","is-referenced-by-count":0,"title":["ALOX15-Inhibitory\nPeptides Derived from Coffee Bean\nProtein Hydrolysates Confer Neuroprotection against Lipid Peroxidation"],"prefix":"10.1021","volume":"74","author":[{"given":"Xiao-Min","family":"Lin","sequence":"first","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]},{"name":"City University of Macau , , ,","place":["Macau, China, 999078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Jing","family":"Han","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine , , ,","place":["Kunming, China, 650500"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine , , ,","place":["Kunming, China, 650500"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ning","family":"Chen","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-Wei","family":"Su","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou Springsnow Biotechnology Co., Ltd , ,","place":["Guangzhou, China, 510670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Wen","family":"Ye","sequence":"additional","affiliation":[{"name":"Guangzhou Springsnow Biotechnology Co., Ltd , ,","place":["Guangzhou, China, 510670"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Guizhou Medical University , , ,","place":["Guian New Area, China, 561113"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Bi","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Biao","family":"Gong","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-5672","authenticated-orcid":true,"given":"Rong-Rong","family":"He","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]},{"name":"City University of Macau , , ,","place":["Macau, China, 999078"]},{"name":"Macau University of Science and Technology , , ,","place":["Macau, China, 999078"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"issue":"4","key":"2026092310085592700_cit1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1056\/NEJMra1816604","article-title":"Coffee, Caffeine,\nand Health","volume":"383","author":"van Dam","year":"2020","journal-title":"N. 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