{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:41:25Z","timestamp":1789432885507,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T00:00:00Z","timestamp":1654992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research and Researcher for Industry (RRi)","award":["PHD62I0008"],"award-info":[{"award-number":["PHD62I0008"]}]},{"name":"Thailand Science Research and Innovation","award":["PHD62I0008"],"award-info":[{"award-number":["PHD62I0008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Crocodile oil (CO) is generated from the fatty tissues of crocodiles as a by-product of commercial aquaculture. CO is extensively applied in the treatment of illnesses including asthma, emphysema, skin ulcers, and cancer, as well as wound healing. Whether CO has anti-inflammatory properties and encourages an immune response remains uncertain. The impact of CO on inflammatory conditions in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mechanisms behind it were examined in this work. Cells were treated with 0.125\u20132% CO dissolved in 0.5% propylene glycol with or without LPS. The production and expression of inflammatory cytokines and mediators were also examined in this research. CO reduced the synthesis and gene expression of interleukin-6 (IL-6). Consistently, CO inhibited the expression and synthesis of inflammatory markers including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO), and nuclear factor kappa B (NF-\u03baB). Furthermore, CO reduced the effects of DNA damage. CO also increased the cell-cycle regulators, cyclins D2 and E2, which improved the immunological response. CO might thus be produced as a nutraceutical supplement to help avoid inflammatory diseases.<\/jats:p>","DOI":"10.3390\/molecules27123784","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T22:37:20Z","timestamp":1655073440000},"page":"3784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Crocodile Oil Modulates Inflammation and Immune Responses in LPS-Stimulated RAW 264.7 Macrophages"],"prefix":"10.3390","volume":"27","author":[{"given":"Metas","family":"Ngernjan","sequence":"first","affiliation":[{"name":"Faculty of Fisheries Technology and Aquatic Resources, Maejo University, Chiang Mai 50290, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atcharaporn","family":"Ontawong","sequence":"additional","affiliation":[{"name":"Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-5365","authenticated-orcid":false,"given":"Narissara","family":"Lailerd","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriangsak","family":"Mengamphan","sequence":"additional","affiliation":[{"name":"Center of Excellence in Agricultural Innovation for Graduate Entrepreneur, Maejo University, Chiang Mai 50290, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sureeporn","family":"Sarapirom","sequence":"additional","affiliation":[{"name":"Applied Physics, Faculty of Science, Maejo University, Chiang Mai 50290, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doungporn","family":"Amornlerdpison","sequence":"additional","affiliation":[{"name":"Faculty of Fisheries Technology and Aquatic Resources, Maejo University, Chiang Mai 50290, Thailand"},{"name":"Center of Excellence in Agricultural Innovation for Graduate Entrepreneur, Maejo University, Chiang Mai 50290, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.exppara.2017.09.008","article-title":"Crocodiles and alligators: Antiamoebic and antitumor compounds of crocodiles","volume":"183","author":"Siddiqui","year":"2017","journal-title":"Exp. Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1111\/1440-1681.13524","article-title":"Potential of crocodile blood as a medication and dietary supplement: A systemic review","volume":"48","author":"Chook","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_3","unstructured":"(2004). Industry Interviews for Crocodile, Emu, Goat, Kangaroo and Rabbit Industries October 2004\u2013February 2005."},{"key":"ref_4","unstructured":"Shim-Prydon, G., and Camacho-Barreto, H. (2007). New Animal Products: New Uses and Markets for By-products and Co-products of Crocodile, Emu, Goat, Kangaroo and Rabbit."},{"key":"ref_5","unstructured":"Thailand, W.W.F. (2022, May 01). Buyer Beware: Focal Species: Reptiles: Crocodile. Available online: https:\/\/www.worldwildlife.org\/pages\/buyer-beware."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1553-2712.2012.01300.x","article-title":"Crocodile oil enhances cutaneous burn wound healing and reduces scar formation in rats","volume":"19","author":"Li","year":"2012","journal-title":"Acad. Emerg. Med."},{"key":"ref_7","first-page":"66","article-title":"The medicinal research and development prospects of crocodile","volume":"4","author":"Tang","year":"2007","journal-title":"World Health Digest"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"581","DOI":"10.4196\/kjpp.2016.20.6.581","article-title":"Evaluation of fish oil-rich in MUFAs for anti-diabetic and anti-inflammation potential in experimental type 2 diabetic rats","volume":"20","author":"Keapai","year":"2016","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.3892\/etm.2021.10657","article-title":"Anti-inflammatory effects and enhancing immune response of freshwater hybrid catfish oil in RAW264.7 cells","volume":"22","author":"Tongmee","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Levine, A.J. (2020). P53 and The Immune Response: 40 Years of Exploration-A Plan for the Future. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020541"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nm0598-575","article-title":"The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory injury","volume":"4","author":"Ophascharoensuk","year":"1998","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fcell.2019.00023","article-title":"Immunomodulatory Roles of Cell Cycle Regulators","volume":"7","author":"Laphanuwat","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1568010054022024","article-title":"Macrophages in inflammation","volume":"4","author":"Fujiwara","year":"2005","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1054\/bjoc.2001.1943","article-title":"Chronic immune activation and inflammation as the cause of malignancy","volume":"85","author":"Dalgleish","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4103\/aam.aam_56_18","article-title":"Inflammation and cancer","volume":"18","author":"Singh","year":"2019","journal-title":"Ann. Afr. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12933-015-0237-9","article-title":"Protective role of oleic acid against cardiovascular insulin resistance and in the early and late cellular atherosclerotic process","volume":"14","author":"Perdomo","year":"2015","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejphar.2015.03.098","article-title":"Fatty acids as modulators of neutrophil recruitment, function and survival","volume":"785","author":"Rodrigues","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves-de-Albuquerque, C.F., Medeiros-de-Moraes, I.M., Oliveira, F.M., Burth, P., Bozza, P.T., Castro Faria, M.V., Silva, A.R., and Castro-Faria-Neto, H.C. (2016). Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153607"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"614","DOI":"10.3389\/fimmu.2014.00614","article-title":"Molecular mechanisms that influence the macrophage m1-m2 polarization balance","volume":"5","author":"Wang","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1590\/S0102-865020150060000009","article-title":"Oil mixes omega 9, 6 and 3, enriched with seaweed, promoted reduction of thermal burned modulating NF-\u03baB and Ki-67","volume":"30","author":"Campelo","year":"2015","journal-title":"Acta Cir. Bras."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neulet.2009.08.040","article-title":"Oleic acid reduces lipopolysaccharide-induced expression of iNOS and COX-2 in BV2 murine microglial cells: Possible involvement of reactive oxygen species, p38 MAPK, and IKK\/NF-\u03baB signaling pathways","volume":"464","author":"Oh","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152789","DOI":"10.1016\/j.phymed.2018.12.012","article-title":"The enhancing immune response and anti-inflammatory effects of Anemarrhena asphodeloides extract in RAW 264.7 cells","volume":"59","author":"Ji","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature07202","article-title":"Integration of metabolism and inflammation by lipid-activated nuclear receptors","volume":"454","author":"Bensinger","year":"2008","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"728461","DOI":"10.1155\/2012\/728461","article-title":"New insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury","volume":"2012","author":"Neher","year":"2012","journal-title":"PPAR Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/01.shk.0000167108.88376.f2","article-title":"15-Deoxy-delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), a peroxisome proliferator activated receptor gamma ligand, reduces tissue leukosequestration and mortality in endotoxic shock","volume":"24","author":"Kaplan","year":"2005","journal-title":"Shock"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1097\/01.CCM.0000183161.81503.7D","article-title":"Rosiglitazone, a peroxisome proliferator-activated receptor-\u03b3 agonist, reduces acute lung injury in endotoxemic rats","volume":"33","author":"Liu","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6053492","DOI":"10.1155\/2018\/6053492","article-title":"Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis","volume":"2018","author":"Kurz","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1476-511X-9-68","article-title":"Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis","volume":"9","author":"Barros","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3329\/jhpn.v31i3.16826","article-title":"Protective effect of fish oil supplementation on DNA damage induced by cigarette smoking","volume":"31","author":"Ghorbanihaghjo","year":"2013","journal-title":"J. Health Popul. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3892\/br.2021.1449","article-title":"Coffea arabica bean extract inhibits glucose transport and disaccharidase activity in Caco-2 cells","volume":"15","author":"Ontawong","year":"2021","journal-title":"Biomed. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7948068","DOI":"10.1155\/2018\/7948068","article-title":"Immune Regulation of RAW264.7 Cells In Vitro by Flavonoids from Astragalus complanatus via Activating the NF-\u03baB Signalling Pathway","volume":"2018","author":"Li","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"26244","DOI":"10.1038\/srep26244","article-title":"Transcriptional repression of p27 is essential for murine embryonic development","volume":"6","author":"Teratake","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2131\/jts.36.191","article-title":"Cadmium toxicity is caused by accumulation of p53 through the down-regulation of Ube2d family genes in vitro and in vivo","volume":"36","author":"Tokumoto","year":"2011","journal-title":"J. Toxicol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yen, T.L., Chang, C.C., Chung, C.L., Ko, W.C., Yang, C.H., and Hsieh, C.Y. (2018). Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041100"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.ccr.2013.09.021","article-title":"Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors","volume":"24","author":"Zhao","year":"2013","journal-title":"Cancer Cell"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3784\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:28:24Z","timestamp":1760138904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,12]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["molecules27123784"],"URL":"https:\/\/doi.org\/10.3390\/molecules27123784","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,12]]}}}