{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:07:05Z","timestamp":1782490025564,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Korean Ministry of Environment","award":["2018002270002"],"award-info":[{"award-number":["2018002270002"]}]},{"name":"the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT &amp; Future Planning","award":["NRF-2020R1C1C1004911"],"award-info":[{"award-number":["NRF-2020R1C1C1004911"]}]},{"name":"the Basic Science Research Program through the National Research Foundation of Korea (NRF) founded by the Ministry of Education","award":["NRF-2021R1A6A1A03044242"],"award-info":[{"award-number":["NRF-2021R1A6A1A03044242"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The excessive synthesis of interleukin-6 (IL-6) is related to cytokine storm in COVID-19 patients. Moreover, blocking IL-6 has been suggested as a treatment strategy for inflammatory diseases such as sepsis. Sepsis is a severe systemic inflammatory response syndrome with high mortality. In the present study, we investigated the anti-inflammatory and anti-septic effects and the underlying mechanisms of Dracocephalum moldavica ethanol extract (DMEE) on lipopolysaccharide (LPS)-induced inflammatory stimulation in RAW 264.7 macrophages along with septic mouse models. We found that DMEE suppressed the release of inflammatory mediators NO and PGE2 and inhibited both the mRNA and protein expression levels of iNOS and COX-2, respectively. In addition, DMEE reduced the release of proinflammatory cytokines, mainly IL-6 and IL-1\u03b2, in RAW 264.7 cells by inhibiting the phosphorylation of JNK, ERK and p65. Furthermore, treatment with DMEE increased the survival rate and decreased the level of IL-6 in plasma in LPS-induced septic shock mice. Our findings suggest that DMEE elicits an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages and an anti-septic effect on septic mouse model through the inhibition of the ERK\/JNK\/NF-\u03baB signaling cascades and production of IL-6.<\/jats:p>","DOI":"10.3390\/nu13124501","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T21:32:40Z","timestamp":1639690360000},"page":"4501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Dracocephalum moldavica Ethanol Extract Suppresses LPS-Induced Inflammatory Responses through Inhibition of the JNK\/ERK\/NF-\u03baB Signaling Pathway and IL-6 Production in RAW 264.7 Macrophages and in Endotoxic-Treated Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Kyeong-Min","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Food Biotechnology and Environmental Science, School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1885-0540","authenticated-orcid":false,"given":"So-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Biotechnology and Environmental Science, School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamanna Jahan","family":"Mony","sequence":"additional","affiliation":[{"name":"Agriculture and Life Science Research Institute, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Jung","family":"Bae","sequence":"additional","affiliation":[{"name":"Agriculture and Life Science Research Institute, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Deok","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Food Biotechnology and Environmental Science, School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food Biotechnology and Environmental Science, School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hyuk","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food Biotechnology and Environmental Science, School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7581-0604","authenticated-orcid":false,"given":"Sun Hee","family":"Hong","sequence":"additional","affiliation":[{"name":"School of Applied Science in Natural Resources & Environment, Hankyong National University, Anseong 17579, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Deok","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Forest Science, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-5258","authenticated-orcid":false,"given":"Se Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food Biotechnology and Environmental Science, School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Korea"},{"name":"Agriculture and Life Science Research Institute, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","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":"2018","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ni.3123","article-title":"Control of adaptive immunity by the innate immune system","volume":"16","author":"Iwasaki","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.bcp.2012.04.020","article-title":"Echinocystic acid ameliorates lung inflammation in mice and alveolar macrophages by inhibiting the binding of LPS to TLR4 in NF-kappaB and MAPK pathways","volume":"84","author":"Joh","year":"2012","journal-title":"Biochem. Pharmacol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.intimp.2019.05.020","article-title":"Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-kappaB and MAPK signaling in in vitro and in vivo models","volume":"73","author":"Su","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1002\/1521-4141(200212)32:12<3689::AID-IMMU3689>3.0.CO;2-X","article-title":"IL-1beta-induced phosphorylation of PKB\/Akt depends on the presence of IRAK-1","volume":"32","author":"Neumann","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/s41598-018-37409-6","article-title":"Endogenous Neurosteroid (3alpha,5alpha)3-Hydroxypregnan-20-one Inhibits Toll-like-4 Receptor Activation and Pro-inflammatory Signaling in Macrophages and Brain","volume":"9","author":"Balan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e392","DOI":"10.1038\/emm.2017.156","article-title":"Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity","volume":"49","author":"Park","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/1744666X.2019.1629904","article-title":"Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome","volume":"15","author":"Kotch","year":"2019","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/jir.2019.0085","article-title":"Constitutive Inflammatory Cytokine Storm: A Major Threat to Human Health","volume":"40","author":"Gupta","year":"2020","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.7150\/thno.49713","article-title":"Immunopathogenesis and treatment of cytokine storm in COVID-19","volume":"11","author":"Kim","year":"2021","journal-title":"Theranostics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1136\/postgradmedj-2016-134519","article-title":"The recognition and management of sepsis and septic shock: A guide for non-intensivists","volume":"93","author":"Keeley","year":"2017","journal-title":"Postgrad. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1089\/sur.2017.221","article-title":"Early Goal-Directed Therapy: The History and Ongoing Impact on Management of Severe Sepsis and Septic Shock","volume":"19","author":"Weisberg","year":"2018","journal-title":"Surg. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13054-016-1233-5","article-title":"Sepsis-induced long-term immune paralysis\u2014Results of a descriptive, explorative study","volume":"20","author":"Arens","year":"2016","journal-title":"Crit. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/imj.14199","article-title":"Sepsis and septic shock: Current approaches to management","volume":"49","author":"Thompson","year":"2019","journal-title":"Intern. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.emc.2016.08.003","article-title":"Appropriate Antibiotic Therapy","volume":"35","author":"Allison","year":"2017","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_17","first-page":"CD011811","article-title":"Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults","volume":"4","author":"Roque","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Thao, P.T.N., Tra, T.T., Son, N.T., and Wada, K. (2018). Reduction in the IL-6 level at 24 h after admission to the intensive care unit is a survival predictor for Vietnamese patients with sepsis and septic shock: A prospective study. BMC Emerg. Med., 18.","DOI":"10.1186\/s12873-018-0191-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.2147\/IJN.S131893","article-title":"Development of solid lipid nanoparticles containing total flavonoid extract from Dracocephalum moldavica L. and their therapeutic effect against myocardial ischemia-reperfusion injury in rats","volume":"12","author":"Tan","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ptr.5494","article-title":"Badiranji Buya Keli, a Traditional Uyghur Medicine, Induces Vasodilation in Rat Artery: Signaling Mediated by Nitric Oxide Production in Endothelial Cells","volume":"30","author":"Miernisha","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3218","DOI":"10.1007\/s13197-017-2765-7","article-title":"Application of Moldavian dragonhead (Dracocephalum moldavica L.) leaves addition as a functional component of nutritionally valuable corn snacks","volume":"54","author":"Wojtowicz","year":"2017","journal-title":"J. Food Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6580","DOI":"10.1002\/fsn3.1949","article-title":"Process optimization of spray-dried Moldavian balm (Dracocephalum moldavica L.) extract powder","volume":"8","author":"Rahmati","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1093\/jpp\/rgaa033","article-title":"Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78\/IRE1alpha\/JNK pathway","volume":"73","author":"Zhang","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/SHK.0b013e3181a48e86","article-title":"Rosmarinic acid protects against experimental sepsis by inhibiting proinflammatory factor release and ameliorating hemodynamics","volume":"32","author":"Jiang","year":"2009","journal-title":"Shock"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s10753-012-9523-9","article-title":"Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo","volume":"36","author":"Lee","year":"2013","journal-title":"Inflammation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109752","DOI":"10.1016\/j.biopha.2019.109752","article-title":"Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs","volume":"123","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112680","DOI":"10.1016\/j.phytochem.2021.112680","article-title":"Abietane diterpenoids from Dracocephalum moldavica L. and their anti-inflammatory activities in vitro","volume":"184","author":"Nie","year":"2021","journal-title":"Phytochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"825","DOI":"10.3389\/fphys.2019.00825","article-title":"Atheroprotective Mechanisms of Tilianin by Inhibiting Inflammation Through Down-Regulating NF-kappaB Pathway and Foam Cells Formation","volume":"10","author":"Shen","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112651","DOI":"10.1016\/j.jep.2020.112651","article-title":"Dracocephalum moldavica attenuates scopolamine-induced cognitive impairment through activation of hippocampal ERK-CREB signaling in mice","volume":"253","author":"Deepa","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12994","DOI":"10.1111\/jfbc.12994","article-title":"Anti-inflammatory properties of fermented pine (Pinus morrisonicola Hay.) needle on lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells","volume":"43","author":"Chiu","year":"2019","journal-title":"J. Food Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.3892\/mmr.2016.4905","article-title":"Anti-inflammatory effects of essential oils extracted from Chamaecyparis obtusa on murine models of inflammation and RAW 264.7 cells","volume":"13","author":"Park","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ko, W.K., Lee, S.H., Kim, S.J., Jo, M.J., Kumar, H., Han, I.B., and Sohn, S. (2017). Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180673"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Baek, H.S., Min, H.J., Hong, V.S., Kwon, T.K., Park, J.W., Lee, J., and Kim, S. (2020). Anti-Inflammatory Effects of the Novel PIM Kinase Inhibitor KMU-470 in RAW 264.7 Cells through the TLR4-NF-kappaB-NLRP3 Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145138"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lfs.2014.08.017","article-title":"Anti-inflammatory effect of pyroglutamyl-leucine on lipopolysaccharide-stimulated RAW 264.7 macrophages","volume":"117","author":"Hirai","year":"2014","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.foodchem.2011.01.114","article-title":"Anti-inflammatory activities of tormentic acid from suspension cells of Eriobotrya Japonicaex vivo and in vivo","volume":"127","author":"Chang","year":"2011","journal-title":"Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.pnpbp.2015.06.008","article-title":"The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression","volume":"64","author":"Kim","year":"2016","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1093\/nar\/gkx064","article-title":"TLR4-induced NF-kappaB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a","volume":"45","author":"Nyati","year":"2017","journal-title":"Nucleic. Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1042\/CS20120668","article-title":"Septic shock: Desperately seeking treatment","volume":"126","author":"Huet","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1007\/s00134-016-4577-z","article-title":"Sepsis: Frontiers in diagnosis, resuscitation and antibiotic therapy","volume":"42","author":"Perner","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature01326","article-title":"The immunopathogenesis of sepsis","volume":"420","author":"Cohen","year":"2002","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/infdis\/163.6.1177","article-title":"The proinflammatory cytokines interleukin-1 and tumor necrosis factor anf treatment of the septic shock syndrome","volume":"163","author":"Dinarello","year":"1991","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jep.2019.02.039","article-title":"Sonchus oleraceus Linn protects against LPS-induced sepsis and inhibits inflammatory responses in RAW264.7 cells","volume":"236","author":"Chen","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41577-021-00553-8","article-title":"Is IL-6 a key cytokine target for therapy in COVID-19?","volume":"21","author":"Jones","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2217\/imt-2016-0020","article-title":"Immunotherapeutic implications of IL-6 blockade for cytokine storm","volume":"8","author":"Tanaka","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1002\/ptr.5846","article-title":"Effects of Tilianin on Proliferation, Migration and TGF-beta\/Smad Signaling in Rat Vascular Smooth Muscle Cells Induced with Angiotensin II","volume":"31","author":"Cao","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3109\/13880209.2012.711839","article-title":"Effects of total flavonoids from Dracocephalum moldavica on the proliferation, migration, and adhesion molecule expression of rat vascular smooth muscle cells induced by TNF-alpha","volume":"51","author":"Xing","year":"2013","journal-title":"Pharm. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1080\/15287394.2017.1367139","article-title":"The inhibitory effects of Dracocephalum moldavica L. (DML) on rat cerebral ischemia reperfusion injury","volume":"80","author":"Jia","year":"2017","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Han, Y., Yuan, C., Zhou, X., Han, Y., He, Y., Ouyang, J., Zhou, W., Wang, Z., Wang, H., and Li, G. (2021). Anti-Inflammatory Activity of Three Triterpene from Hippophae rhamnoides L. in Lipopolysaccharide-Stimulated RAW264.7 Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222112009"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"524","DOI":"10.5483\/BMBRep.2014.47.9.149","article-title":"Oleanolic acid regulates NF-kappaB signaling by suppressing MafK expression in RAW 264.7 cells","volume":"47","author":"Hwang","year":"2014","journal-title":"BMB Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.abb.2007.08.025","article-title":"Triterpenoid saponin, oleanolic acid 3-O-beta-d-glucopyranosyl(1\u21923)-alpha-l-rhamnopyranosyl(1\u21922)-alpha-l-arabinopy ranoside (OA) from Aralia elata inhibits LPS-induced nitric oxide production by down-regulated NF-kappaB in raw 264.7 cells","volume":"467","author":"Suh","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"So, Y., Lee, S.Y., Han, A.R., Kim, J.B., Jeong, H.G., and Jin, C.H. (2016). Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells. Molecules, 21.","DOI":"10.3390\/molecules21081083"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106436","DOI":"10.1016\/j.intimp.2020.106436","article-title":"Cryptochlorogenic acid attenuates LPS-induced inflammatory response and oxidative stress via upregulation of the Nrf2\/HO-1 signaling pathway in RAW 264.7 macrophages","volume":"83","author":"Zhao","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","first-page":"469","article-title":"Nitric oxide and superoxide in inflammation and immune regulation","volume":"54","author":"Guzik","year":"2003","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.tips.2012.02.004","article-title":"Prostaglandins and chronic inflammation","volume":"33","author":"Aoki","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/ptr.5150","article-title":"Triggering of p38 MAPK and JNK signaling is important for oleanolic acid-induced apoptosis via the mitochondrial death pathway in hypertrophic scar fibroblasts","volume":"28","author":"Chen","year":"2014","journal-title":"Phytother. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4501\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:41Z","timestamp":1760168981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,16]]},"references-count":55,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["nu13124501"],"URL":"https:\/\/doi.org\/10.3390\/nu13124501","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,16]]}}}