{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:47:43Z","timestamp":1782110863836,"version":"3.54.5"},"reference-count":82,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Caffeic acid, a naturally occurring polyphenol found in various dietary sources, has gained considerable interest for its antioxidant, anti\u2010inflammatory, and neuroprotective properties. Preclinical studies suggest that caffeic acid may exert beneficial effects in models of Alzheimer's disease, Parkinson's disease, cerebral ischaemia, ageing, diabetes\u2010associated cognitive decline, and neuroinflammation. To assess the neuroprotective activity of caffeic acid in neurodegenerative diseases. After performing a detailed literature search across various databases, such as Google Scholar, Embase, PubMed, Scopus, and Cochrane, a total of 44 unique studies were identified based on the framed eligibility criteria. This meta\u2010analysis demonstrated that caffeic acid exerts significant effect on\u00a0neurobiomarker panel: amyloid\u2010\u03b2 accumulation (IV: \u22121.84 [\u22123.08, \u22120.61], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.004,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 8%), GFAP (IV: \u22122.03 [\u22122.91, \u22121.15], 95% CI,\n p<\/jats:italic>\n \u2009<\u20090.00001,), AchE (IV: \u22121.98 [\u22123.44, \u22120.52], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.008,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200985%), BDNF (IV: 1.14 [0.20, 2.09], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.02,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200957%); Oxidative stress markers such as MDA (IV: \u22124.60 [\u22126.66, \u22122.55], 95%CI,\n p<\/jats:italic>\n \u2009<\u20090.0001,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200999%) and LPO (IV: \u22122.12 [\u22123.49, \u22120.75], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.002,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200998%), SOD (IV: 4.90 [3.72, 6.08], 95% CI,\n p<\/jats:italic>\n \u2009<\u20090.00001,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200999%), CAT (IV: 21.35 [12.10, 30.61], 95% CI,\n p<\/jats:italic>\n \u2009<\u20090.00001,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 94%), GSH (IV: 6.86 [5.28, 8.44], 95% CI,\n p<\/jats:italic>\n \u2009<\u20090.00001,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 99%); Neuroinflammatory parameters including TNF\u2010\u03b1 (IV: \u22124.23 [\u22125.89, \u22122.57], 95% CI,\n p<\/jats:italic>\n \u2009<\u20090.00001,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200983%), IL\u20106 (IV: \u22123.07 [\u22124.69, \u22121.45], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.0002,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200978%) and IL\u20101\u03b2 (IV: \u22125.09 [\u22128.12, \u22122.07], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.0010,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200961%); Behavioural parameters like forced swim test (IV: \u22122.22 [\u22123.83, \u22120.61], 95% CI,\n p<\/jats:italic>\n = 0.007,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200986%), open field test\u2010 number of rearing's (IV: 12.50 [0.55, 24.45], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.04,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200989%), elevated plus maze test\u2010 time spent in open arms (IV: \u221230.45 [\u221253.67, \u22127.22], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.01,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200981%); Apoptosis (Caspase\u20103) parameters (IV: \u221228.46 [\u221252.22, \u22124.70], 95% CI,\n p<\/jats:italic>\n \u2009=\u20090.02,\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200995%). Caffeic acid showed significant neuroprotective activity in neurodegenerative diseases based on pre\u2010clinical evidence, making it a promising molecule for future RCTs.\n <\/jats:p>","DOI":"10.1002\/jbt.70959","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:26:16Z","timestamp":1781519176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010Neuroinflammatory and Neuroprotective Effects of Caffeic Acid in Experimental Models of Neurodegeneration: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"40","author":[{"given":"Radhika","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal Academy of Higher Education Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-8022","authenticated-orcid":false,"given":"Alosh","family":"Greeny","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal Academy of Higher Education Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-4888","authenticated-orcid":false,"given":"Gollapalle Lakshminarayanashastry","family":"Viswanatha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal Academy of Higher Education Manipal Karnataka India"},{"name":"Independent Researcher, Kengeri Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayesh","family":"Mudgal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal Academy of Higher Education Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9368-2672","authenticated-orcid":false,"given":"Shylaja","family":"Hanumanthappa","sequence":"additional","affiliation":[{"name":"Independent Researcher, Kengeri Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandakumar","family":"Krishnadas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal Academy of Higher Education Manipal Karnataka India"},{"name":"Center for Animal Research, Ethics and Training (CARET) Manipal Academy of Higher Education Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10062510"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199671618.003.0004"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2024-080952"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology13030157"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009258"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(97)00100-7"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.5.2283"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0352-8"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"issue":"5","key":"e_1_2_16_12_1","first-page":"562","article-title":"Anxiety, Depression, and Stress in Response to the Coronavirus Disease\u201019 Pandemic","volume":"88","author":"P\u00e9rez\u2010Cano H. 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