{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:02:15Z","timestamp":1790542935511,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["No. 2018J05142"],"award-info":[{"award-number":["No. 2018J05142"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007834","name":"Natural Science Foundation of Ningbo","doi-asserted-by":"publisher","award":["No. 2019A610209"],"award-info":[{"award-number":["No. 2019A610209"]}],"id":[{"id":"10.13039\/100007834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81901133"],"award-info":[{"award-number":["No. 81901133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Foundation of Third Institute of Oceanography, Ministry of Natural Resources","award":["No. 2017007, No.2017026"],"award-info":[{"award-number":["No. 2017007, No.2017026"]}]},{"name":"the Key Technology R&amp;D Program of Fujian Province","award":["No.2018N0014"],"award-info":[{"award-number":["No.2018N0014"]}]},{"name":"Marine Economy Innovation Development Area Demonstration Project of Beihai","award":["Bhsfs009"],"award-info":[{"award-number":["Bhsfs009"]}]},{"name":"Xiamen Ocean Research and Development Institute co-construction project","award":["2020"],"award-info":[{"award-number":["2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA\u2013PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-\u03b1), and markedly reduced the production of TNF-\u03b1, IL-6, IL-1\u03b2, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor \u03b1 (PPAR-\u03b1) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-\u03b1 pathway.<\/jats:p>","DOI":"10.3390\/md18040222","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:48:52Z","timestamp":1587448132000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-2694","authenticated-orcid":false,"given":"Wenhui","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Biotechnology, Huaqiao University, Xiamen 361021, China"},{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Biotechnology, Huaqiao University, Xiamen 361021, China"},{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Fang","sequence":"additional","affiliation":[{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuan","family":"Hong","sequence":"additional","affiliation":[{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Technology Innovation Center for Exploitation of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Biotechnology, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kytikova, O., Novgorodtseva, T., Antonyuk, M., Denisenko, Y., and Gvozdenko, T. (2019). Molecular Targets of Fatty Acid Ethanolamides in Asthma. Medicina, 55.","DOI":"10.3390\/medicina55040087"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1146\/annurev-pharmtox-010818-021441","article-title":"Beyond THC and Endocannabinoids","volume":"60","author":"Pacher","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tutunchi, H., Saghafi-Asl, M., and Ostadrahimi, A. (2019). A systematic review of the effects of oleoylethanolamide, a high-affinity endogenous ligand of PPAR-alpha, on the management and prevention of obesity. Clin. Exp. Pharmacol. Physiol.","DOI":"10.1111\/1440-1681.13238"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111953","DOI":"10.1016\/j.ejmech.2019.111953","article-title":"A perspective review on fatty acid amide hydrolase (FAAH) inhibitors as potential therapeutic agents","volume":"188","author":"Tripathi","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbalip.2007.03.005","article-title":"Predominant expression of lysosomal N-acylethanolamine-hydrolyzing acid amidase in macrophages revealed by immunochemical studies","volume":"1771","author":"Tsuboi","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13565","DOI":"10.1038\/srep13565","article-title":"Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-alpha","volume":"5","author":"Yang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jid.2017.07.853","article-title":"The N-Acylethanolamine Acid Amidase Inhibitor ARN077 Suppresses Inflammation and Pruritus in a Mouse Model of Allergic Dermatitis","volume":"138","author":"Sasso","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.phrs.2018.03.011","article-title":"Inflammation-restricted anti-inflammatory activities of a N-acylethanolamine acid amidase (NAAA) inhibitor F215","volume":"132","author":"Li","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.3390\/md13063422","article-title":"Biological Properties of Fucoxanthin in Oil Recovered from Two Brown Seaweeds Using Supercritical CO2 Extraction","volume":"13","author":"Sivagnanam","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3390\/md10030604","article-title":"Fucoxantin: A treasure from the sea","volume":"10","author":"Gemello","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.foodchem.2018.07.142","article-title":"Inhibition of alpha-glucosidase activity by selected edible seaweeds and fucoxanthin","volume":"270","author":"Zaharudin","year":"2019","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.3390\/md13042196","article-title":"Anti-obesity activity of the marine carotenoid fucoxanthin","volume":"13","author":"Gammone","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jff.2018.07.048","article-title":"Fucoxanthin ameliorates hyperglycemia, hyperlipidemia and insulin resistance in diabetic mice partially through IRS-1\/PI3K\/Akt and AMPK pathways","volume":"48","author":"Zhang","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4784","DOI":"10.3390\/md13084784","article-title":"Fucoxanthin and Its Metabolite Fucoxanthinol in Cancer Prevention and Treatment","volume":"13","author":"Martin","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jpba.2018.10.033","article-title":"Determination of fucoxanthinol in rat plasma by liquid chromatography-tandem mass spectrometry","volume":"164","author":"Zhang","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.3892\/ijo.2013.2019","article-title":"Anticancer effects of marine carotenoids, fucoxanthin and its deacetylated product, fucoxanthinol, on osteosarcoma","volume":"43","author":"Rokkaku","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_17","first-page":"207","article-title":"Comparative effects between fucoxanthinol and its precursor fucoxanthin on viability and apoptosis of breast cancer cell lines MCF-7 and MDA-MB-231","volume":"35","author":"Rwigemera","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_18","first-page":"147","article-title":"Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells","volume":"18","author":"Maeda","year":"2006","journal-title":"Int. J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejphar.2010.09.032","article-title":"Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-kappaB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages","volume":"649","author":"Kim","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10753-013-9757-1","article-title":"First evidence for the anti-inflammatory activity of fucoxanthin in high-fat-diet-induced obesity in mice and the antioxidant functions in PC12 cells","volume":"37","author":"Tan","year":"2014","journal-title":"Inflammation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"906","DOI":"10.3389\/fphar.2019.00906","article-title":"Fucoxanthin, a Marine Xanthophyll Isolated From Conticribra weissflogii ND-8: Preventive Anti-Inflammatory Effect in a Mouse Model of Sepsis","volume":"10","author":"Su","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1021\/jf400015k","article-title":"Fucoxanthin ameliorates inflammation and oxidative reponses in microglia","volume":"61","author":"Pangestuti","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.3390\/md13084799","article-title":"Fucoxanthinol, Metabolite of Fucoxanthin, Improves Obesity-Induced Inflammation in Adipocyte Cells","volume":"13","author":"Maeda","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1074\/jbc.M116.737940","article-title":"Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells","volume":"292","author":"Hwang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Piomelli, D., Scalvini, L., Fotio, Y., Lodola, A., Spadoni, G., Tarzia, G., and Mor, M. (2020). N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition. J. Med. Chem.","DOI":"10.1021\/acs.jmedchem.0c00191"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E10032","DOI":"10.1073\/pnas.1811759115","article-title":"Molecular mechanism of activation of the immunoregulatory amidase NAAA","volume":"115","author":"Gorelik","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45034","DOI":"10.1074\/jbc.M306062200","article-title":"Lipopolysaccharide induces anandamide synthesis in macrophages via CD14\/MAPK\/phosphoinositide 3-kinase\/NF-kappaB independently of platelet-activating factor","volume":"278","author":"Liu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13345","DOI":"10.1073\/pnas.0601832103","article-title":"A biosynthetic pathway for anandamide","volume":"103","author":"Liu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1615\/CritRevImmunol.v31.i5.20","article-title":"LPS-induced cytokine production in human monocytes and macrophages","volume":"31","author":"Rossol","year":"2011","journal-title":"Crit. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.4049\/jimmunol.1501489","article-title":"Homeostatic PPARalpha Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine","volume":"196","author":"Manoharan","year":"2016","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1124\/jpet.108.136903","article-title":"Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury","volume":"326","author":"Genovese","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejphar.2009.04.022","article-title":"Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-kappaB nuclear signalling in dorsal root ganglia","volume":"613","author":"Russo","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.neuroscience.2009.11.069","article-title":"Intracellular mechanisms of N-acylethanolamine-mediated neuroprotection in a rat model of stroke","volume":"166","author":"Garg","year":"2010","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/10409238.2015.1092944","article-title":"Macrophage-derived lipid agonists of PPAR-alpha as intrinsic controllers of inflammation","volume":"51","author":"Pontis","year":"2016","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1016\/j.drudis.2014.06.007","article-title":"Harnessing the anti-inflammatory potential of palmitoylethanolamide","volume":"19","author":"Alhouayek","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.neuropharm.2018.11.013","article-title":"Inhibition of N-acylethanolamine acid amidase reduces nicotine-induced dopamine activation and reward","volume":"144","author":"Sagheddu","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104264","DOI":"10.1016\/j.phrs.2019.104264","article-title":"N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis","volume":"145","author":"Zhou","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4049\/jimmunol.1700223","article-title":"Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing","volume":"199","author":"Boniakowski","year":"2017","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1164\/rccm.201508-1545CI","article-title":"Macrophages, Inflammation, and Lung Cancer","volume":"193","author":"Conway","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-physiol-022516-034348","article-title":"Macrophages and the Recovery from Acute and Chronic Inflammation","volume":"79","author":"Hamidzadeh","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3430684","DOI":"10.1155\/2018\/3430684","article-title":"Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-kappaB Pathway","volume":"2018","author":"Muniandy","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2174\/18715281113129990053","article-title":"Anti-inflammatory treatments for chronic diseases: A review","volume":"12","author":"Laveti","year":"2013","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.abb.2010.05.031","article-title":"Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic\/obese KK-Ay mice","volume":"504","author":"Hosokawa","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.biochi.2010.01.006","article-title":"N-palmitoyl-ethanolamine: Biochemistry and new therapeutic opportunities","volume":"92","author":"Petrosino","year":"2010","journal-title":"Biochimie"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/sj.bjp.0704466","article-title":"Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat","volume":"135","author":"Conti","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1124\/mol.104.006353","article-title":"The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide","volume":"67","author":"Fu","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hong, F., Pan, S., Guo, Y., Xu, P., and Zhai, Y. (2019). PPARs as Nuclear Receptors for Nutrient and Energy Metabolism. Molecules, 24.","DOI":"10.3390\/molecules24142545"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","article-title":"Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease","volume":"62","author":"Pawlak","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.2337\/diabetes.54.8.2460","article-title":"Therapeutic roles of peroxisome proliferator-activated receptor agonists","volume":"54","author":"Staels","year":"2005","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.3389\/fmicb.2018.01936","article-title":"Inhibition of Nitric Oxide Production in Activated Macrophages Caused by Toxoplasma gondii Infection Occurs by Distinct Mechanisms in Different Mouse Macrophage Cell Lines","volume":"9","author":"Cabral","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1517\/14728222.2012.715633","article-title":"PPARalpha as a therapeutic target in inflammation-associated diseases","volume":"16","author":"Gervois","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32048","DOI":"10.1074\/jbc.274.45.32048","article-title":"Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1","volume":"274","author":"Delerive","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"36703","DOI":"10.1074\/jbc.M004045200","article-title":"Induction of IkappaBalpha expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-alpha activators","volume":"275","author":"Delerive","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nakano, Y., Uchiyama, M., Arima, T., Nagasaka, S., Igarashi, T., Shimizu, A., and Takahashi, H. (2018). PPARalpha Agonist Suppresses Inflammation after Corneal Alkali Burn by Suppressing Proinflammatory Cytokines, MCP-1, and Nuclear Translocation of NF-kappaB. Molecules, 24.","DOI":"10.3390\/molecules24010114"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e1397","DOI":"10.1038\/cddis.2014.361","article-title":"Peroxisome proliferator-activated receptor alpha activation attenuates the inflammatory response to protect the liver from acute failure by promoting the autophagy pathway","volume":"5","author":"Jiao","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1021\/acs.jnatprod.9b00705","article-title":"Aphidicolin Chemistry of the Deep-Sea-Derived Fungus Botryotinia fuckeliana MCCC 3A00494","volume":"82","author":"Niu","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.jchromb.2010.04.024","article-title":"Validation and application of an LC-MS\/MS method for quantitation of three fatty acid ethanolamides as biomarkers for fatty acid hydrolase inhibition in human plasma","volume":"878","author":"Jian","year":"2010","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/18\/4\/222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:45:03Z","timestamp":1760363103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/18\/4\/222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,21]]},"references-count":57,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["md18040222"],"URL":"https:\/\/doi.org\/10.3390\/md18040222","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,21]]}}}