{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:59:56Z","timestamp":1784753996059,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Inflammatory diseases are a major threat to public health. Natural plant essential oils (EOs) possess anti-inflammatory and anti-oxidative activities. The objective of this study was to investigate the anti-inflammatory effect and mode of action of lemon essential oil (LEO), and its main active component, d-limonene, with different doses on intestinal inflammation of mice. Sixty-four 5-week-old male balb\/c mice weighing 22.0 \u00b1 1.5 g were randomly assigned into one of 8 treatments (<jats:italic>n<\/jats:italic> = 8\/treatment), including normal saline group (NS), <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) group, and either LEO and d-limonene essential oil (DEO) group supplemented at 300, 600, and 1,200 mg\/kg of BW, respectively. After the pre-feeding period, the mice were fasted for 12 h, the mice in the NS group and the <jats:italic>E. coli<\/jats:italic> group were gavaged with normal saline, and the mice in the LEO group and DEO group were gavaged with respective dose of EOs for 1 week. One hour after the end of gavage on the 7th day, except that the mice in the normal saline group were intraperitoneally injected with normal saline, the mice in the other groups were intraperitoneally injected with the same concentration of <jats:italic>E. coli<\/jats:italic> (10<jats:sup>8<\/jats:sup> cfu\/ml, 0.15 ml per mouse). The antioxidant indexes were measured including superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) in plasma obtained by taking blood from mouse eyeballs. The inflammatory indexes were measured including interleukin-6 (IL-6), interleukin-1\u03b2 (IL-1\u03b2), and tumor necrosis factor alpha (TNF-\u03b1) in plasma. The tight junction protein indicators were tested include zona occludens 1 protein (ZO-1), occludin and claudin in mouse duodenum. We found that all of the above indexes for <jats:italic>E. coli<\/jats:italic> group were different (<jats:italic>P<\/jats:italic>&amp;lt; <jats:italic>0.05<\/jats:italic>) with the NS group. The interaction of EO and dose (E \u00d7 D) were significant (<jats:italic>P<\/jats:italic> &amp;lt; 0.01) for all of the indexes. In addition, LEO at 300 mg\/kg BW and DEO at 600 mg\/kg BW had better antioxidant and anti-inflammation activity on the infected mice, which reduced (<jats:italic>P<\/jats:italic> &amp;lt; 0.05) the plasma concentrations of MDA, MPO, TNF-\u03b1, IL-1\u03b2, and IL-6, but increased (<jats:italic>P<\/jats:italic> &amp;lt; 0.01) the concentrations of SOD. Hematoxylin-eosin (H&amp;amp;E) staining of duodenum observation showed that LEO and DEO reduced inflammatory cell infiltration and maintain the orderly arrangement of epithelial cells. Moreover, supplementation of LEO at 600 mg\/kg and DEO at 300 mg\/kg BW alleviated (<jats:italic>P<\/jats:italic> &amp;lt; 0.05) intestinal barrier injury for increasing the relative expression of ZO-1, occludin and claudin mRNA in mice duodenum. These results showed that the pre-treatment with LEO and DEO had protection of intestinal tissue and inflammation in <jats:italic>E. coli<\/jats:italic> infected mice. Both LEO and DEO exhibited activity of antioxidant, anti-inflammatory and alleviating intestinal injury, whereas, compared with DEO, LEO can be active at a lower dosage. Furthermore, as the main active component of LEO, the d-limonene appeared to play not only the major role, but also the joint action with other active components of LEO.<\/jats:p>","DOI":"10.3389\/fnut.2022.843096","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:46Z","timestamp":1654167946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Protective Effect of Lemon Essential Oil and Its Major Active Component, D-Limonene, on Intestinal Injury and Inflammation of E. coli-Challenged Mice"],"prefix":"10.3389","volume":"9","author":[{"given":"Chen","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechao","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-020-2039-9","article-title":"Feeding-dependent VIP neuron-ILC3 circuit regulates the intestinal barrier","volume":"579","author":"Talbot","year":"2020","journal-title":"Nature."},{"key":"B2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12974-020-01873-7","article-title":"27-Hydroxycholesterol contributes to cognitive deficits in APP\/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction","volume":"17","author":"Wang","year":"2020","journal-title":"J Neuroinflammation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1038\/s41467-020-15735-6","article-title":"Aquaculture at the crossroads of global warming and antimicrobial resistance","volume":"11","author":"Reverter","year":"2020","journal-title":"Nat Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"17764","DOI":"10.1038\/s41598-020-74625-5","article-title":"Unveiling the effect of dietary essential oils supplementation in Sparus aurata gills and its efficiency against the infestation by Sparicotyle chrysophrii","volume":"10","author":"Firmino","year":"2020","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s11746-008-1204-3","article-title":"Physico-chemical characteristics of citrus seeds and seed oils from Pakistan","volume":"85","author":"Anwar","year":"2008","journal-title":"J Am Oil Chem Soc."},{"key":"B6","doi-asserted-by":"publisher","first-page":"8622","DOI":"10.18632\/aging.103179","article-title":"Lemon essential oil ameliorates age-associated cognitive dysfunction via modulating hippocampal synaptic density and inhibiting acetylcholinesterase","volume":"12","author":"Liu","year":"2020","journal-title":"Aging."},{"key":"B7","doi-asserted-by":"publisher","first-page":"62","DOI":"10.4103\/jcrt.JCRT_915_17","article-title":"In vitro cytotoxicity of cardamom oil, lemon oil, and jasmine oil on human skin, gastric, and brain cancer cell line","volume":"17","author":"Manjunath","year":"2019","journal-title":"J Cancer Res Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"108266","DOI":"10.1016\/j.ijfoodmicro.2019.108266","article-title":"Antimicrobial influence of nanoemulsified lemon essential oil and pure lemon essential oil on food-borne pathogens and fish spoilage bacteria","volume":"306","author":"Yazgan","year":"2019","journal-title":"Int J Food Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"71","DOI":"10.17221\/152\/2009-VETMED","article-title":"In vitro effects of essential oils on potential pathogens and beneficial members of the normal microbiota","volume":"55","author":"Ouwehand","year":"2010","journal-title":"Veterin\u00e1rn\u00ed Medic\u00edna"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2863","DOI":"10.3390\/molecules26102863","article-title":"Lemon oils attenuate the pathogenicity of Pseudomonas aeruginosa by quorum sensing inhibition","volume":"26","author":"Luciardi","year":"2021","journal-title":"Molecules."},{"key":"B11","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3390\/foods9030365","article-title":"Essential oils as potential alternative biocontrol products against plant pathogens and weeds: a review","volume":"9","author":"Raveau","year":"2020","journal-title":"Foods."},{"key":"B12","first-page":"42","article-title":"Antioxidant and antimicrobial activities of essential oil of lemon (Citrus limon) peel in vitro and in a food modell[J]","volume":"4","author":"Hassanzadeh","year":"2017","journal-title":"J Food Qual Hazards Control"},{"key":"B13","doi-asserted-by":"publisher","first-page":"17719","DOI":"10.1038\/s41598-019-54084-3","article-title":"Unraveling the selective antibacterial activity and chemical composition of citrus essential oils","volume":"9","author":"Ambrosio","year":"2019","journal-title":"Sci Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"770","DOI":"10.3390\/plants9060770","article-title":"Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain, in epithelial cells","volume":"9","author":"Senthil Kumar","year":"2020","journal-title":"Plants."},{"key":"B15","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1007\/s12011-017-1233-6","article-title":"Acute and cumulative effects of unmodified 50-nm nano-ZnO on mice","volume":"185","author":"Kong","year":"2018","journal-title":"Biol Trace Elem Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1134\/S0003683814010098","article-title":"Effects of low doses of essential oils on the antioxidant status of the erythrocytes, liver and the brain of mice","volume":"50","author":"Misharina","year":"2014","journal-title":"Appl Biochem Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1080\/00071668.2014.887830","article-title":"Effect of different concentrations of ginger root powder and its essential oil on growth performance, serum metabolites and antioxidant status in broiler chicks under heat stress","volume":"55","author":"Habibi","year":"2014","journal-title":"Br Poult Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"41540","DOI":"10.1007\/s11356-020-10066-x","article-title":"Protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity","volume":"27","author":"Abdel-Daim","year":"2020","journal-title":"Environ Sci Pollut Res Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"709","DOI":"10.3109\/13880209.2010.541924","article-title":"Antioxidant activity of Citrus limon essential oil in mouse hippocampus","volume":"49","author":"Campelo","year":"2011","journal-title":"Pharm Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"NP36","DOI":"10.1177\/2156587215616550","article-title":"Protective effect of Ocimum basilicum essential oil against acetic acid-induced colitis in rats","volume":"21","author":"Rashidian","year":"2016","journal-title":"J Evid Based Complementary Altern Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0153643","DOI":"10.1371\/journal.pone.0153643","article-title":"Anti-inflammatory properties and chemical characterization of the essential oils of four citrus species","volume":"11","author":"Amorim","year":"2016","journal-title":"PLoS ONE."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1901191","DOI":"10.1002\/mnfr.201901191","article-title":"Effects of short-peptide-based enteral nutrition on the intestinal microcirculation and mucosal barrier in mice with severe acute pancreatitis","volume":"64","author":"Zhang","year":"2020","journal-title":"Mol Nutr Food Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1136\/gut.2006.094375","article-title":"Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease","volume":"56","author":"Zeissig","year":"2007","journal-title":"Gut."},{"key":"B24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/foods9010037","article-title":"The essential oil and hydrolats from Myristica fragrans seeds with magnesium aluminometasilicate as excipient: antioxidant, antibacterial, and anti-inflammatory activity","volume":"9","author":"Matulyte","year":"2020","journal-title":"Foods."},{"key":"B25","doi-asserted-by":"publisher","first-page":"H87","DOI":"10.1111\/j.1750-3841.2010.01541.x","article-title":"Anti-inflammatory effects of limonene from yuzu (Citrus junos Tanaka) essential oil on eosinophils","volume":"75","author":"Hirota","year":"2010","journal-title":"J Food Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jep.2017.10.018","article-title":"The essential oil from Citrus limetta Risso peels alleviates skin inflammation: in-vitro and in-vivo study","volume":"212","author":"Maurya","year":"2018","journal-title":"J Ethnopharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/carcin\/12.1.115","article-title":"Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone carcinogenesis in mice by D-limonene and citrus fruit oils","volume":"12","author":"Wattenberg","year":"1991","journal-title":"Carcinogenesis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1023\/A:1010631030320","article-title":"Architecture and function of the gastroesophageal barrier in the piglet","volume":"46","author":"Vicente","year":"2001","journal-title":"Dig Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e28032","DOI":"10.1371\/journal.pone.0028032","article-title":"Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease","volume":"6","author":"Forsyth","year":"2011","journal-title":"PLoS ONE."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3031609","DOI":"10.1155\/2019\/3031609","article-title":"Histoprotective effect of essential oil from Citrus aurantifolia in testosterone-induced benign prostatic hyperplasia rat","volume":"2019","author":"Acheampong","year":"2019","journal-title":"Adv Urol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"111887","DOI":"10.1016\/j.jep.2019.111887","article-title":"Ameliorative effect of Atractylodes macrocephala essential oil combined with Panax ginseng total saponins on 5-fluorouracil induced diarrhea is associated with gut microbial modulation","volume":"238","author":"Wang","year":"2019","journal-title":"J Ethnopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.modgep.2004.10.009","article-title":"Gene expression pattern of Claudin-1 during chick embryogenesis","volume":"5","author":"Simard","year":"2005","journal-title":"Gene Expression Patterns."},{"key":"B33","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1007\/s00535-016-1207-z","article-title":"Gastrointestinal mucosal barrier function and diseases","volume":"51","author":"Oshima","year":"2016","journal-title":"J Gastroenterol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1152\/physrev.00003.2008","article-title":"Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer","volume":"91","author":"Fasano","year":"2011","journal-title":"Physiol Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/mi.2016.128","article-title":"Gut permeability and mucosal inflammation: bad, good or context dependent","volume":"10","author":"Ahmad","year":"2017","journal-title":"Mucosal Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4019","DOI":"10.1002\/jsfa.9629","article-title":"Effects of orange essential oil on intestinal microflora in mice","volume":"99","author":"Wang","year":"2019","journal-title":"J Sci Food Agric."},{"key":"B37","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1111\/jpn.13271","article-title":"Dietary supplementation of plant essential oil improves growth performance, intestinal morphology and health in weaned pigs","volume":"104","author":"Su","year":"2020","journal-title":"J Anim Physiol Anim Nutr."},{"key":"B38","doi-asserted-by":"publisher","first-page":"5436738","DOI":"10.1155\/2016\/5436738","article-title":"Oregano essential oil improves intestinal morphology and expression of tight junction proteins associated with modulation of selected intestinal bacteria and immune status in a pig model","volume":"2016","author":"Zou","year":"2016","journal-title":"Biomed Res Int."},{"key":"B39","doi-asserted-by":"publisher","first-page":"skaa245","DOI":"10.1093\/jas\/skaa245","article-title":"Eugenol attenuates inflammatory response and enhances barrier function during lipopolysaccharide-induced inflammation in the porcine intestinal epithelial cells","volume":"98","author":"Hui","year":"2020","journal-title":"J Anim Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1111\/jpn.12944","article-title":"Effects of oral administration of different dosages of carvacrol essential oils on intestinal barrier function in broilers","volume":"102","author":"Liu","year":"2018","journal-title":"J Anim Physiol Anim Nutr."},{"key":"B41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.molimm.2020.01.014","article-title":"Dapk1 improves inflammation, oxidative stress and autophagy in LPS-induced acute lung injury via p38MAPK\/NF-\u03baB signaling pathway","volume":"120","author":"Li","year":"2020","journal-title":"Mol Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"BSR20182297","DOI":"10.1042\/BSR20182297","article-title":"Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA\/ROCK signaling pathway","volume":"39","author":"Wang","year":"2019","journal-title":"Biosci Rep."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.843096\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:50Z","timestamp":1654167950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.843096\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":42,"alternative-id":["10.3389\/fnut.2022.843096"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.843096","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]},"article-number":"843096"}}