{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:34:54Z","timestamp":1794011694494,"version":"4.8.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007637","name":"German University in Cairo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007637","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Peroxisome proliferator-activated receptor gamma (PPAR\u03b3) is a nuclear receptor known to play a critical role in regulating neuroinflammation and neurodegenerative processes, including Alzheimer\u2019s disease. Prior studies from our group demonstrated that rice bran extract (RBE) enhances cognitive function and increases PPAR\u03b3 DNA-binding activity in the brain, effects that were abolished by PPAR\u03b3 antagonism. These findings suggest that bioactive constituents within RBE may modulate PPAR\u03b3 signaling. The current study aimed to provide additional evidence for the involvement of PPAR\u03b3 activation in the neuroprotective effects of RBE and to identify key RBE-derived components that may contribute to these effects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A neuroinflammatory mouse model was treated orally for 21 consecutive days with RBE. The brain CD36 and amyloid-beta (A\u03b2) protein levels were measured. HPLC and GC were used to assess the levels of RBE components. To measure alterations in fatty acid content after treatment with RBE, brain levels of DHA, EPA and AA were assessed using UHPLC\/MS-MS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>RBE treatment increased the brain levels of CD36, the direct PPAR\u03b3 target, and decreased A\u03b2 levels. A strong correlation was detected between the A\u03b2 and CD36 protein levels. As RBE was found to be rich in linolenic acid (ALA), linoleic acid (LA) and oleic acid, their metabolites concentrations in mice brain were measured, and results indicated higher concentration of EPA and DHA after RBE treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>RBE exerts neuroprotective effects potentially through activation of the PPAR\u03b3 pathway, as evidenced by CD36 upregulation and A\u03b2 reduction. The enrichment of RBE in polyunsaturated fatty acids (PUFAs), along with the observed increase in their brain-penetrant metabolites (EPA and DHA), suggests these lipids may contribute to the cognitive benefits of RBE.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12906-025-05097-1","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:33:02Z","timestamp":1759401182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective role of rice bran extract and its constituents in a neuroinflammatory mouse model"],"prefix":"10.1186","volume":"25","author":[{"given":"Sarah M. Abou","family":"El-Nagah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Abdel-Halim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola A.","family":"Heikal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham M.","family":"AbdelKader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"5097_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01486-5","author":"W Zhang","year":"2023","unstructured":"Zhang W, Xiao D, Mao Q, Xia H. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Ther. 2023. https:\/\/doi.org\/10.1038\/s41392-023-01486-5.","journal-title":"Signal Transduct Target Ther"},{"key":"5097_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3159","author":"M Ahmadian","year":"2013","unstructured":"Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. Ppar\u03b3 signaling and metabolism: the good, the bad and the future. Nat Med. 2013. https:\/\/doi.org\/10.1038\/nm.3159.","journal-title":"Nat Med"},{"key":"5097_CR3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.tips.2023.11.004","volume":"45","author":"C Titus","year":"2024","unstructured":"Titus C, Hoque MT, Bendayan R. Ppar agonists for the treatment of neuroinflammatory diseases. Trends Pharmacol Sci. 2024;45:9\u201323.","journal-title":"Trends Pharmacol Sci"},{"key":"5097_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/nri912","author":"RA Daynes","year":"2002","unstructured":"Daynes RA, Jones DC. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol. 2002. https:\/\/doi.org\/10.1038\/nri912.","journal-title":"Nat Rev Immunol"},{"key":"5097_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.06.016","author":"AR Pathan","year":"2008","unstructured":"Pathan AR, Gaikwad AB, Viswanad B, Ramarao P. Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats. Eur J Pharmacol. 2008. https:\/\/doi.org\/10.1016\/j.ejphar.2008.06.016.","journal-title":"Eur J Pharmacol"},{"key":"5097_CR6","doi-asserted-by":"crossref","unstructured":"Cheng H, Shang Y, Jiang L, Shi TL, Wang L. The peroxisome proliferators activated receptor-gamma agonists as therapeutics for the treatment of alzheimer\u2019s disease and mild-to-moderate alzheimer\u2019s disease: a meta-analysis. Int J Neurosci. 2016;126(4):299\u2013307.","DOI":"10.3109\/00207454.2015.1015722"},{"key":"5097_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00043-0","author":"DK Burns","year":"2021","unstructured":"Burns DK, Alexander RC, Welsh-Bohmer KA, Culp M, Chiang C, O\u2019Neil J, et al. Safety and efficacy of Pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer\u2019s disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2021. https:\/\/doi.org\/10.1016\/S1474-4422(21)00043-0.","journal-title":"Lancet Neurol"},{"key":"5097_CR8","unstructured":"Eggleton IJialalJS. Thiazolidinediones - StatPearls - NCBI Bookshelf. NCBI. 2020. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK551656\/"},{"key":"5097_CR9","doi-asserted-by":"publisher","first-page":"7SPart24","DOI":"10.1016\/j.jalz.2016.07.135","volume":"12","author":"J Didsbury","year":"2016","unstructured":"Didsbury J. P4-390: rapid onset of cognitive improvements in a subset of mild and moderate alzheimer\u2019s patients treated with T3D\u2010959: interim results of a phase 2A open label clinical trial. Alzheimer\u2019s Dement. 2016;12:7SPart24.","journal-title":"Alzheimer\u2019s Dement"},{"key":"5097_CR10","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.9.1470","author":"H Shimizu","year":"1998","unstructured":"Shimizu H, Tsuchiya T, Sato N, Shimomura Y, Kobayashi I, Mori M. Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients. Diabetes Care. 1998. https:\/\/doi.org\/10.2337\/diacare.21.9.1470.","journal-title":"Diabetes Care"},{"key":"5097_CR11","doi-asserted-by":"publisher","unstructured":"Arakawa K, Ishihara T, Aoto M, Inamasu M, Kitamura K, Saito A. An antidiabetic Thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in rats. Clin Exp Pharmacol Physiol. 2004;(1-2):8\u201313. https:\/\/doi.org\/10.1111\/j.1440-1681.2004.03954.x.","DOI":"10.1111\/j.1440-1681.2004.03954.x"},{"key":"5097_CR12","doi-asserted-by":"publisher","unstructured":"Pf\u00fctzner A, Weber MM, Forst T, Pioglitazone. Update on an oral antidiabetic drug with antiatherosclerotic effects. Expert Opin Pharmacother. 2007;8:1985\u201398. https:\/\/doi.org\/10.1517\/14656566.8.12.1985.","DOI":"10.1517\/14656566.8.12.1985"},{"key":"5097_CR13","volume-title":"A multi-center, randomized, double\u2010blind, placebo\u2010controlled phase 2 trial of the effects of T3D\u2010959 on safety, cognition, function and plasma biomarkers in mild to moderate Alzheimer\u2019s disease subjects: Rationale and study design","author":"J Didsbury","year":"2020","unstructured":"Didsbury J, Strittmatter W, Chamberlain S, Gabriel H, The PIONEER, Study. A multi-center, randomized, double\u2010blind, placebo\u2010controlled phase 2 trial of the effects of T3D\u2010959 on safety, cognition, function and plasma biomarkers in mild to moderate Alzheimer\u2019s disease subjects: Rationale and study design, vol. 16. Alzheimer\u2019s & Dementia; 2020."},{"key":"5097_CR14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06862.2000","author":"MT Heneka","year":"2000","unstructured":"Heneka MT, Klockgether T, Feinstein DL. Peroxisome proliferator-activated receptor-\u03b3 ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J Neurosci. 2000. https:\/\/doi.org\/10.1523\/JNEUROSCI.20-18-06862.2000.","journal-title":"J Neurosci"},{"key":"5097_CR15","doi-asserted-by":"publisher","unstructured":"Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE. Inflammatory mechanisms in alzheimer\u2019s disease: Inhibition of \u03b2- amyloid-stimulated Proinflammatory responses and neurotoxicity by PPAR\u03b3 agonists. J Neurosci. 2000;20(2):558\u201367. https:\/\/doi.org\/10.1523\/JNEUROSCI.20-02-00558.2000.","DOI":"10.1523\/JNEUROSCI.20-02-00558.2000"},{"key":"5097_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/nature07202","author":"SJ Bensinger","year":"2008","unstructured":"Bensinger SJ, Tontonoz P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature. 2008. https:\/\/doi.org\/10.1038\/nature07202.","journal-title":"Nature"},{"key":"5097_CR17","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-014-0101-6","author":"Y Yu","year":"2015","unstructured":"Yu Y, Ye RD. Microglial A\u03b2 receptors in alzheimer\u2019s disease. Cell Mol Neurobiol. 2015. https:\/\/doi.org\/10.1007\/s10571-014-0101-6.","journal-title":"Cell Mol Neurobiol"},{"key":"5097_CR18","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.3233\/JAD-170188","volume":"58","author":"M Tang","year":"2017","unstructured":"Tang M, Taghibiglou C, Liu J. The mechanisms of action of Curcumin in alzheimer\u2019s disease. J Alzheimers Dis. 2017;58:1003\u201316.","journal-title":"J Alzheimers Dis"},{"key":"5097_CR19","doi-asserted-by":"publisher","unstructured":"Wagdy R, Abdel-Kader RM, El-Khatib AH, Linscheid MW, Handoussa H, Hamdi N. Origanum Majorana L. protects against neuroinflammation-mediated cognitive impairment: a phyto-pharmacological study. BMC Complement Med Ther. 2023;23(1):165. https:\/\/doi.org\/10.1186\/s12906-023-03994-x.","DOI":"10.1186\/s12906-023-03994-x"},{"key":"5097_CR20","doi-asserted-by":"crossref","unstructured":"M\u00fcller WE, Abdel-Kader R, Fehske CJ, Leuner K. Effect on cellular energy centers: Principles of therapeutic use of EGb 761\u00ae. Pharm Unserer Zeit. 2009;38.","DOI":"10.1002\/pauz.200900328"},{"key":"5097_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.07.018","author":"L Wang","year":"2014","unstructured":"Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPAR\u03b3): a review. Biochem Pharmacol. 2014. https:\/\/doi.org\/10.1016\/j.bcp.2014.07.018.","journal-title":"Biochem Pharmacol"},{"key":"5097_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/s0090-6980(00)00071-x","author":"I Dussault","year":"2000","unstructured":"Dussault I, Forman BM. Prostaglandins and fatty acids regulate transcriptional signaling via the peroxisome proliferator activated receptor nuclear receptors. Prostaglandins Other Lipid Mediat. 2000. https:\/\/doi.org\/10.1016\/s0090-6980(00)00071-x.","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"5097_CR23","doi-asserted-by":"publisher","first-page":"4242","DOI":"10.1158\/1078-0432.CCR-08-3028","volume":"15","author":"JL Hong","year":"2009","unstructured":"Hong JL, Ju J, Paul S, So JY, DeCastro A, Smolarek A, et al. Mixed tocopherols prevent mammary tumorigenesis by inhibiting Estrogen action and activating PPAR-\u03b3. Clin Cancer Res. 2009;15:4242\u20139.","journal-title":"Clin Cancer Res"},{"key":"5097_CR24","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1471-2407-3-25","volume":"3","author":"SE Campbell","year":"2003","unstructured":"Campbell SE, Stone WL, Whaley SG, Qui M, Krishnan K. Gamma (\u03b3) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (\u03b3) expression in SW 480 human colon cancer cell lines. BMC Cancer. 2003;3:25.","journal-title":"BMC Cancer"},{"key":"5097_CR25","doi-asserted-by":"publisher","unstructured":"Fattah MAA, El, Abdelhamid YA, Elyamany MF, Badary OA, Heikal OA. Rice Bran extract protected against LPS-Induced neuroinflammation in mice through targeting PPAR-\u03b3 nuclear receptor. Mol Neurobiol. 2021;58(4):1504\u201316. https:\/\/doi.org\/10.1007\/s12035-020-02196-7.","DOI":"10.1007\/s12035-020-02196-7"},{"key":"5097_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2018.07.023","author":"AO Mostafa","year":"2018","unstructured":"Mostafa AO, Abdel-Kader RM, Heikal OA. Enhancement of cognitive functions by rice bran extract in a neuroinflammatory mouse model via regulation of PPAR\u03b3. J Funct Foods. 2018. https:\/\/doi.org\/10.1016\/j.jff.2018.07.023.","journal-title":"J Funct Foods"},{"key":"5097_CR27","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-016-8420-z","author":"S Hagl","year":"2016","unstructured":"Hagl S, Asseburg H, Heinrich M, Sus N, Blumrich EM, Dringen R, et al. Effects of long-term rice bran extract supplementation on survival, cognition and brain mitochondrial function in aged NMRI mice. Neuromol Med. 2016. https:\/\/doi.org\/10.1007\/s12017-016-8420-z.","journal-title":"Neuromol Med"},{"key":"5097_CR28","doi-asserted-by":"publisher","unstructured":"El-Din SS, Elwahab SA, Rashed L, Fayez S, Aboulhoda BE, Heikal OA et al. Possible role of rice Bran extract in microglial modulation through PPAR-gamma receptors in alzheimer\u2019s disease mice model. Metab Brain Dis. 2021;36(7):1903\u201315. https:\/\/doi.org\/10.1007\/s11011-021-00741-4.","DOI":"10.1007\/s11011-021-00741-4"},{"key":"5097_CR29","doi-asserted-by":"publisher","first-page":"816856","DOI":"10.1155\/2015\/816856","volume":"2015","author":"AJ Kroker","year":"2015","unstructured":"Kroker AJ, Bruning JB. Review of the structural and dynamic mechanisms of PPAR\u03b3 partial agonism. PPAR Res. 2015;2015:816856.","journal-title":"PPAR Res"},{"key":"5097_CR30","doi-asserted-by":"publisher","first-page":"17321","DOI":"10.1523\/JNEUROSCI.1569-12.2012","volume":"32","author":"M Yamanaka","year":"2012","unstructured":"Yamanaka M, Ishikawa T, Griep A, Axt D, Kummer MP, Heneka MT. PPAR\u03b3\/RXR\u03b1-induced and CD36-mediated microglial amyloid-\u03b2 phagocytosis results in cognitive improvement in amyloid precursor protein\/presenilin 1 mice. J Neurosci. 2012;32:17321\u201331.","journal-title":"J Neurosci"},{"key":"5097_CR31","doi-asserted-by":"publisher","unstructured":"Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW et al. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflamm. 2008;5:37. https:\/\/doi.org\/10.1186\/1742-2094-5-37. PMID: 18759972.","DOI":"10.1186\/1742-2094-5-37"},{"key":"5097_CR32","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-9088-8","author":"A Zakaria","year":"2016","unstructured":"Zakaria A, Hamdi N, Abdel-Kader RM. Methylene blue improves brain mitochondrial ABAD functions and decreases A\u03b2 in a neuroinflammatory alzheimer\u2019s disease mouse model. Mol Neurobiol. 2016. https:\/\/doi.org\/10.1007\/s12035-014-9088-8.","journal-title":"Mol Neurobiol"},{"key":"5097_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2023.01.006","author":"M Samir","year":"2023","unstructured":"Samir M, Abdelkader RM, Boushehri MS, Mansour S, Lamprecht A, Tammam SN. Enhancement of mitochondrial function using NO releasing nanoparticles; a potential approach for therapy of alzheimer\u2019s disease. Eur J Pharm Biopharm. 2023. https:\/\/doi.org\/10.1016\/j.ejpb.2023.01.006.","journal-title":"Eur J Pharm Biopharm"},{"key":"5097_CR34","doi-asserted-by":"publisher","DOI":"10.1111\/1750-3841.14587","author":"R Wagdy","year":"2019","unstructured":"Wagdy R, Abdelkader RM, El-Khatib AH, Linscheid MW, Hamdi N, Handoussa H. Neuromodulatory activity of dietary phenolics derived from Corchorus olitorius L. J Food Sci. 2019. https:\/\/doi.org\/10.1111\/1750-3841.14587.","journal-title":"J Food Sci"},{"key":"5097_CR35","doi-asserted-by":"publisher","DOI":"10.31487\/j.nnb.2021.04.01","author":"RM Abdel-Kader","year":"2021","unstructured":"Abdel-Kader RM, Fadel EA, Abdel-Kader RM. Pyrroloquinoline quinone enhances cognition of neuroinflammatory Alzheimer\u2019s disease mouse model via mitochondrial biogenesis regulation. Neurol Neurobiol. 2021. https:\/\/doi.org\/10.31487\/j.nnb.2021.04.01.","journal-title":"Neurol Neurobiol"},{"key":"5097_CR36","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.pnpbp.2012.08.002","volume":"47","author":"Z Xie","year":"2013","unstructured":"Xie Z, Xu Z. General anesthetics and \u03b2-amyloid protein. Prog Neuropsychopharmacol Biol Psychiatry. 2013;47:140\u20136.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"5097_CR37","first-page":"570","volume":"57","author":"SC Cartner","year":"2007","unstructured":"Cartner SC, Barlow SC, Ness TJ. Loss of cortical function in mice after decapitation, cervical dislocation, potassium chloride injection, and CO2 inhalation. Comp Med. 2007;57:570\u20133.","journal-title":"Comp Med"},{"key":"5097_CR38","doi-asserted-by":"publisher","unstructured":"Aguwa US, Eze CE, Obinwa BN, Okeke SN, Onwuelingo SF, Okonkwo DI, et al. Comparing the Effect of Methods of Rat Euthanasia on the Brain of Wistar Rats: Cervical Dislocation, Chloroform Inhalation, Diethyl Ether Inhalation and Formalin Inhalation. J Adv Med Med Res. 2020;32:8\u201316. https:\/\/doi.org\/10.9734\/jammr\/2020\/v32i1730636.","DOI":"10.9734\/jammr\/2020\/v32i1730636"},{"key":"5097_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.040","author":"T Zhang","year":"2016","unstructured":"Zhang T, Chen S, Syed I, St\u00e5hlman M, Kolar MJ, Homan EA, et al. A LC-MS-based workflow for measurement of branched fatty acid esters of hydroxy fatty acids. Nat Protoc. 2016. https:\/\/doi.org\/10.1038\/nprot.2016.040.","journal-title":"Nat Protoc"},{"key":"5097_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/molecules200916524","author":"S Hagl","year":"2015","unstructured":"Hagl S, Berressem D, Bruns B, Sus N, Frank J, Eckert GP. Beneficial effects of ethanolic and hexanic rice bran extract on mitochondrial function in PC12 cells and the search for bioactive components. Molecules. 2015. https:\/\/doi.org\/10.3390\/molecules200916524.","journal-title":"Molecules"},{"key":"5097_CR41","doi-asserted-by":"publisher","unstructured":"Bhatia HS, Baron J, Hagl S, Eckert GP, Fiebich BL. Rice Bran derivatives alleviate microglia activation: possible involvement of MAPK pathway. J Neuroinflamm. 2016;13(1):148. https:\/\/doi.org\/10.1186\/s12974-016-0615-6.","DOI":"10.1186\/s12974-016-0615-6"},{"key":"5097_CR42","doi-asserted-by":"publisher","unstructured":"Wilkinson K, Boyd JD, Glicksman M, Moore KJ, Khoury J, El. A high content drug screen identifies ursolic acid as an inhibitor of amyloid \u03b2 protein interactions with its receptor CD36. J Biol Chem. 2011;286(40):34914\u201322. https:\/\/doi.org\/10.1074\/jbc.M111.232116.","DOI":"10.1074\/jbc.M111.232116"},{"key":"5097_CR43","doi-asserted-by":"publisher","unstructured":"Khoury JB, El, Moore KJ, Means TK, Leung J, Terada K, Toft M et al. CD36 mediates the innate host response to \u03b2-amyloid. J Exp Med. 2003;197(12):1657\u201366. https:\/\/doi.org\/10.1084\/jem.20021546.","DOI":"10.1084\/jem.20021546"},{"key":"5097_CR44","doi-asserted-by":"publisher","unstructured":"Koenigsknecht J, Landreth G. Microglial phagocytosis of fibrillar \u03b2-amyloid through a \u03b21 integrin-dependent mechanism. J Neurosci. 2004;24(44):9838\u201346. https:\/\/doi.org\/10.1523\/JNEUROSCI.2557-04.2004.","DOI":"10.1523\/JNEUROSCI.2557-04.2004"},{"key":"5097_CR45","doi-asserted-by":"publisher","unstructured":"Hickman SE, Allison EK, Khoury J, El. Microglial dysfunction and defective \u03b2-amyloid clearance pathways in aging alzheimer\u2019s disease mice. J Neurosci. 2008;28(33):8354\u201360. https:\/\/doi.org\/10.1523\/JNEUROSCI.0616-08.2008.","DOI":"10.1523\/JNEUROSCI.0616-08.2008"},{"key":"5097_CR46","doi-asserted-by":"publisher","unstructured":"Dong S, Huang X, Zhen J, Halm-Lutterodt N, Van, Wang JJ, Zhou C et al. Dietary vitamin E status dictates oxidative stress outcomes by modulating effects of fish oil supplementation in alzheimer disease model APPswe\/PS1dE9 mice. Mol Neurobiol. 2018;55(12):9204\u20139219. https:\/\/doi.org\/10.1007\/s12035-018-1060-6.","DOI":"10.1007\/s12035-018-1060-6"},{"key":"5097_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jab.2017.05.001","author":"AB Jha","year":"2017","unstructured":"Jha AB, Panchal SS. Neuroprotection and cognitive enhancement by treatment with \u03b3-oryzanol in sporadic alzheimer\u2019s disease. J Appl Biomed. 2017. https:\/\/doi.org\/10.1016\/j.jab.2017.05.001.","journal-title":"J Appl Biomed"},{"key":"5097_CR48","doi-asserted-by":"publisher","unstructured":"Patrick RP. Role of phosphatidylcholine-DHA in preventing APOE4-associated alzheimer\u2019s disease. FASEB J. 2019;33(2):1554\u201364. https:\/\/doi.org\/10.1096\/fj.201801412R.","DOI":"10.1096\/fj.201801412R"},{"key":"5097_CR49","doi-asserted-by":"publisher","unstructured":"Escribano L, Sim\u00f3n AM, Gimeno E, Cuadrado-Tejedor M, Maturana RL, De, Garc\u00eda-Osta A et al. Rosiglitazone rescues memory impairment in alzheimer\u2019s Transgenic mice: mechanisms involving a reduced amyloid and Tau pathology. Neuropsychopharmacology. 2010;35(7):1593\u2013604. https:\/\/doi.org\/10.1038\/npp.2010.32.","DOI":"10.1038\/npp.2010.32"},{"key":"5097_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3820","author":"RP Bazinet","year":"2014","unstructured":"Bazinet RP, Lay\u00e9 S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014. https:\/\/doi.org\/10.1038\/nrn3820.","journal-title":"Nat Rev Neurosci"},{"key":"5097_CR51","doi-asserted-by":"publisher","unstructured":"Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR. Regional membrane phospholipid alterations in alzheimer\u2019s disease. Neurochem Res. 1998;23(1):81\u20138. https:\/\/doi.org\/10.1023\/a:1022457605436.","DOI":"10.1023\/a:1022457605436"},{"key":"5097_CR52","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.053371","author":"W Stonehouse","year":"2013","unstructured":"Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C, et al. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013. https:\/\/doi.org\/10.3945\/ajcn.112.053371.","journal-title":"Am J Clin Nutr"},{"key":"5097_CR53","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqab016","author":"A Sala-Vila","year":"2021","unstructured":"Sala-Vila A, Arenaza-Urquijo EM, S\u00e1nchez-Benavides G, Su\u00e1rez-Calvet M, Mil\u00e0-Alom\u00e0 M, Grau-Rivera O, et al. DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of alzheimer disease. Am J Clin Nutr. 2021. https:\/\/doi.org\/10.1093\/ajcn\/nqab016.","journal-title":"Am J Clin Nutr"},{"key":"5097_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(02)00046-1","author":"JC Vallv\u00e9","year":"2002","unstructured":"Vallv\u00e9 JC, Uliaque K, Girona J, Cabr\u00e9 A, Ribalta J, Heras M, et al. Unsaturated fatty acids and their oxidation products stimulate CD36 gene expression in human macrophages. Atherosclerosis. 2002. https:\/\/doi.org\/10.1016\/S0021-9150(02)00046-1.","journal-title":"Atherosclerosis"},{"key":"5097_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.11.030","author":"M Youssef","year":"2019","unstructured":"Youssef M, Ibrahim A, Akashi K, Hossain MS. PUFA-plasmalogens attenuate the LPS-induced nitric oxide production by inhibiting the NF-kB, p38 MAPK and JNK pathways in microglial cells. Neuroscience. 2019. https:\/\/doi.org\/10.1016\/j.neuroscience.2018.11.030.","journal-title":"Neuroscience"},{"key":"5097_CR56","doi-asserted-by":"publisher","unstructured":"peng Shi J, Fu W, Liu J. < Omega >-3 PUFA attenuates LPS-Induced Neuro-Injury of neonatal rats through the PI3K\/AKT pathway. Neuroscience. 2019;414.112\u201327. https:\/\/doi.org\/10.1016\/j.neuroscience.2019.06.027.","DOI":"10.1016\/j.neuroscience.2019.06.027"},{"key":"5097_CR57","doi-asserted-by":"publisher","first-page":"256","DOI":"10.4162\/nrp.2013.7.4.256","volume":"7","author":"KH Chung","year":"2013","unstructured":"Chung KH, Hwang HJ, Shin KO, Jeon WM, Choi KS. Effects of Perilla oil on plasma concentrations of cardioprotective (n-3) fatty acids and lipid profiles in mice. Nutr Res Pract. 2013;7:256.","journal-title":"Nutr Res Pract"},{"key":"5097_CR58","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11745-008-3240-z","volume":"44","author":"R Chopra","year":"2009","unstructured":"Chopra R, Sambaiah K. Effects of rice bran oil enriched with n-3 PUFA on liver and serum lipids in rats. Lipids. 2009;44:37\u201346.","journal-title":"Lipids"},{"key":"5097_CR59","doi-asserted-by":"publisher","DOI":"10.3390\/ani12213006","author":"KC Mowry","year":"2022","unstructured":"Mowry KC, Thomson-Parker TL, Morales C, Fikes KK, Stutts KJ, Leatherwood JL, et al. Effects of crude rice bran oil and a flaxseed oil blend in young horses engaged in a training program. Animals. 2022. https:\/\/doi.org\/10.3390\/ani12213006.","journal-title":"Animals"},{"key":"5097_CR60","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130131","author":"E Hjorth","year":"2013","unstructured":"Hjorth E, Zhu M, Toro VC, Vedin I, Palmblad J, Cederholm T, et al. Omega-3 fatty acids enhance phagocytosis of Alzheimer\u2019s disease-related amyloid-\u03b242 by human microglia and decrease inflammatory markers. J Alzheimers Dis. 2013. https:\/\/doi.org\/10.3233\/JAD-130131.","journal-title":"J Alzheimers Dis"},{"key":"5097_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.06.008","author":"S Hagl","year":"2013","unstructured":"Hagl S, Kocher A, Schiborr C, Eckert SH, Ciobanu I, Birringer M, et al. Rice bran extract protects from mitochondrial dysfunction in Guinea pig brains. Pharmacol Res. 2013. https:\/\/doi.org\/10.1016\/j.phrs.2013.06.008.","journal-title":"Pharmacol Res"},{"key":"5097_CR62","doi-asserted-by":"publisher","DOI":"10.1179\/1476830515Y.0000000040","author":"S Hagl","year":"2016","unstructured":"Hagl S, Berressem D, Grewal R, Sus N, Frank J, Eckert GP. Rice bran extract improves mitochondrial dysfunction in brains of aged NMRI mice. Nutr Neurosci. 2016. https:\/\/doi.org\/10.1179\/1476830515Y.0000000040.","journal-title":"Nutr Neurosci"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-025-05097-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12906-025-05097-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-025-05097-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:33:07Z","timestamp":1759401187000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-025-05097-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5097"],"URL":"https:\/\/doi.org\/10.1186\/s12906-025-05097-1","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]},"assertion":[{"value":"5 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were approved by the Ethics Committee of the German University in Cairo and were performed in accordance with the National Academies Guide for the Care and Use of Laboratory Animals (8th edition). Ethics approval number: PHTX-2017-03-RA.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"351"}}