{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:05:46Z","timestamp":1780761946627,"version":"3.54.1"},"reference-count":52,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Perilla frutescens fruit oil (PFO) is rich in \u03b1-linolenic acid (ALA) and exhibits biological activities. We aimed to investigate analgesic, anti-inflammatory and anti-ulcer activities of PFO and PFO-supplemented soybean milk (PFO-SM) in animal models. Analgesic activity was assessed in acetic acid-induced writhing in mice, while anti-inflammatory activity was performed in ethyl phenylpropiolate (EPP)-induced ear edema and carrageenan-induced hind paw edema in rats. Anti-ulcer effects were conducted in water immersion stress, HCl\/ethanol and indomethacin-induced gastric ulcer in rats. Distinctly, PFO, containing 6.96 mg ALA and 2.61 mg LA equivalence\/g, did not induce acute toxicity (LD50 &amp;gt; 10 mL\/kg) in mice. PFO (2.5 and 5 mL\/kg) and PFO-SM (0.05 mL PFO equivalence\/kg) inhibited incidences of writhing (16.8, 18.0 and 32.3%, respectively) in acetic acid-induced mice. In addition, topical applications of PFO (0.1 and 1 mL\/ear) significantly inhibited EPP-induced ear edema (59.3 and 65.7%, respectively) in rats, while PFO-SM slightly inhibited ear edema (25.9%). However, PFO and PFO-SM did not inhibit carrageenan-induced hind paw edema in rats. Indeed, PFO (2.5 and 5 mL\/kg) significantly inhibited gastric ulcers in rats that induced by water immersion stress (92.4 and 96.6%, respectively), HCl\/ethanol (74.8 and 73.3%, respectively) and indomethacin (68.8 and 88.9%, respectively), while PFO-SM did not. PFO displayed potent analgesic, anti-inflammatory and anti-ulcer properties, while PFO-SM exerted only analgesic properties. Thus, Thai PFO and its functional drink offer potential benefits in treatment of analgesic, inflammatory diseases and gastric ulcer.<\/jats:p>","DOI":"10.1042\/bsr20203166","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T06:34:23Z","timestamp":1609914863000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Analgesic, anti-inflammatory and anti-ulcer properties of Thai <i>Perilla frutescence<\/i> fruit oil in animals"],"prefix":"10.1042","volume":"41","author":[{"given":"Narisara","family":"Paradee","sequence":"first","affiliation":[{"name":"Oxidative Stress Cluster, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimpisid","family":"Koonyosying","sequence":"additional","affiliation":[{"name":"Oxidative Stress Cluster, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winthana","family":"Kusirisin","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattanaporn","family":"Janthip","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Payap University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duangta","family":"Kanjanapothi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Payap University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kovit","family":"Pattanapanyasat","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8781","authenticated-orcid":false,"given":"Somdet","family":"Srichairatanakool","sequence":"additional","affiliation":[{"name":"Oxidative Stress Cluster, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"2021111620373774900_B1","doi-asserted-by":"publisher","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":"2021111620373774900_B2","doi-asserted-by":"publisher","first-page":"627","DOI":"10.14202\/vetworld.2018.627-635","article-title":"The crucial roles of inflammatory mediators in inflammation: a review","volume":"11","author":"Abdulkhaleq","year":"2018","journal-title":"Vet World"},{"key":"2021111620373774900_B3","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1038\/ni.3828","article-title":"Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities","volume":"18","author":"Liu","year":"2017","journal-title":"Nat. Immunol."},{"key":"2021111620373774900_B4","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.biopha.2018.12.002","article-title":"Oxyresveratrol ameliorates ethanol-induced gastric ulcer via downregulation of IL-6, TNF-alpha, NF-kB, and COX-2 levels, and upregulation of TFF-2 levels","volume":"110","author":"Aziz","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"2021111620373774900_B5","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1080\/13880209.2019.1682620","article-title":"Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival","volume":"57","author":"Lu","year":"2019","journal-title":"Pharm. Biol."},{"key":"2021111620373774900_B6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1254\/jphs.FP0070122","article-title":"Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats","volume":"105","author":"Dengiz","year":"2007","journal-title":"J. Pharmacol. Sci."},{"key":"2021111620373774900_B7","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3904\/kjim.2018.290","article-title":"Gastroprotective effects of irsogladine maleate on ethanol\/hydrochloric acid induced gastric ulcers in mice","volume":"36","author":"Kwon","year":"2019","journal-title":"Korean J. Intern. Med."},{"key":"2021111620373774900_B8","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/S0021-5198(19)52438-6","article-title":"Effect of polyamines on acidified ethanol-induced gastric lesions in rats","volume":"33","author":"Mizui","year":"1983","journal-title":"Jpn. J. Pharmacol."},{"key":"2021111620373774900_B9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s13596-011-0002-x","article-title":"Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant oils","volume":"11","author":"Asif","year":"2011","journal-title":"Orient. Pharm. Exp. Med."},{"key":"2021111620373774900_B10","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0952-3278(02)00271-5","article-title":"Bioavailability of omega-3 essential fatty acids from perilla seed oil","volume":"68","author":"Kurowska","year":"2003","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"2021111620373774900_B11","doi-asserted-by":"publisher","first-page":"259","DOI":"10.20307\/nps.2016.22.4.259","article-title":"Fatty acid content in Perilla cultivars and commercial oils determined by GC analysis","volume":"22","author":"Lee","year":"2016","journal-title":"Nat. Prod. Sci."},{"key":"2021111620373774900_B12","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1002\/ejlt.201100207","article-title":"Lipid components of flax, perilla, and chia seeds","volume":"114","author":"Ciftci","year":"2012","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"2021111620373774900_B13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1055\/s-2006-957062","article-title":"Anti-asthmatic effects of Perilla seed oil in the guinea pig in vitro and in vivo","volume":"73","author":"Deng","year":"2007","journal-title":"Planta Med."},{"key":"2021111620373774900_B14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.phrs.2010.01.005","article-title":"Plant derived omega-3-fatty acids protect mitochondrial function in the brain","volume":"61","author":"Eckert","year":"2010","journal-title":"Pharmacol. Res."},{"key":"2021111620373774900_B15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s11745-008-3171-8","article-title":"Dietary perilla oil inhibits proinflammatory cytokine production in the bronchoalveolar lavage fluid of ovalbumin-challenged mice","volume":"43","author":"Chang","year":"2008","journal-title":"Lipids"},{"key":"2021111620373774900_B16","doi-asserted-by":"publisher","first-page":"21","DOI":"10.5625\/lar.2014.30.1.21","article-title":"Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation","volume":"30","author":"Jang","year":"2014","journal-title":"Lab. Anim. Res."},{"key":"2021111620373774900_B17","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jnutbio.2004.02.010","article-title":"Suppression of hepatic fatty acid synthase by feeding alpha-linolenic acid rich perilla oil lowers plasma triacylglycerol level in rats","volume":"15","author":"Kim","year":"2004","journal-title":"J. Nutr. Biochem."},{"key":"2021111620373774900_B18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4103\/2221-1691.276316","article-title":"Thai Perilla frutescens fruit oil alleviates carbon tetrachloride-induced hepatotoxicities in rats","volume":"10","author":"Paradee","year":"2020","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"2021111620373774900_B19","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.foodchem.2014.10.096","article-title":"Evaluation of the chemical quality traits of soybean seeds, as related to sensory attributes of soymilk","volume":"173","author":"Ma","year":"2015","journal-title":"Food Chem."},{"key":"2021111620373774900_B20","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1093\/ajcn\/83.5.1118","article-title":"Soy isoflavones modulate immune function in healthy postmenopausal women","volume":"83","author":"Ryan-Borchers","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"2021111620373774900_B21","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1186\/s12906-019-2791-2","article-title":"Anti-inflammatory, analgesic and acute toxicity effects of fermented soybean","volume":"19","author":"Yusof","year":"2019","journal-title":"BMC Complement. Altern. Med."},{"key":"2021111620373774900_B22","doi-asserted-by":"publisher","first-page":"e22406","DOI":"10.1002\/jbt.22406","article-title":"In vivo anti-inflammatory efficacy of the combined Bowman-Birk trypsin inhibitor and genistein isoflavone, two biological compounds from soybean","volume":"33","author":"Sadeghalvad","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"2021111620373774900_B23","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1097\/FJC.0000000000000708","article-title":"Soy isoflavones inhibit endothelial cell dysfunction and prevent cardiovascular disease","volume":"74","author":"Yamagata","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"2021111620373774900_B24","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3390\/foods2020198","article-title":"Food quality improvement of soy milk made from short-time germinated soybeans","volume":"2","author":"Jiang","year":"2013","journal-title":"Foods"},{"key":"2021111620373774900_B25","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.3390\/molecules25112474","article-title":"Phytosterol, lipid and phenolic composition, and biological activities of guava seed oil","volume":"25","author":"Prommaban","year":"2020","journal-title":"Molecules"},{"key":"2021111620373774900_B26","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12906-016-1021-4","article-title":"Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa","volume":"16","author":"Bukhari","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"2021111620373774900_B27","first-page":"412","article-title":"Acetic acid-induced analgesic screening","volume":"18","author":"Koster","year":"1959","journal-title":"Fed. Proc."},{"key":"2021111620373774900_B28","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/0022-4731(82)90035-8","article-title":"Influence of 16 alpha, 17 alpha-acetal substitution and steroid nucleus fluorination on the topical to systemic activity ratio of glucocorticoids","volume":"16","author":"Brattsand","year":"1982","journal-title":"J. Steroid Biochem."},{"key":"2021111620373774900_B29","doi-asserted-by":"publisher","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"2021111620373774900_B30","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1248\/cpb.11.1282","article-title":"Studies on the drugs for peptic ulcer. Pharmacological studies on the effects of synthetic antispasmodics mixed with antacid","volume":"11","author":"Takagi","year":"1963","journal-title":"Chem. Pharm. Bull."},{"key":"2021111620373774900_B31","first-page":"265","article-title":"The production of acute gastric ulceration by indomethacin in the rat","volume":"4","author":"Djahanguiri","year":"1969","journal-title":"Scand. J. Gastroenterol."},{"key":"2021111620373774900_B32","doi-asserted-by":"publisher","first-page":"171","DOI":"10.5625\/lar.2016.32.3.171","article-title":"Anti-atherosclerotic effects of perilla oil in rabbits fed a high-cholesterol diet","volume":"32","author":"Cha","year":"2016","journal-title":"Lab. Anim. Res."},{"key":"2021111620373774900_B33","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1179\/1476830514Y.0000000132","article-title":"Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone spontaneously hypertensive rats","volume":"19","author":"Cai","year":"2016","journal-title":"Nutr. Neurosci."},{"key":"2021111620373774900_B34","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.yrtph.2019.01.035","article-title":"Acute and sub-chronic 90-day oral toxicity study of Perilla seed oil in rodents and Beagle dogs","volume":"103","author":"Zhang","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"2021111620373774900_B35","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0049-3848(03)00379-7","article-title":"The mechanism of action of aspirin","volume":"110","author":"Vane","year":"2003","journal-title":"Thromb. Res."},{"key":"2021111620373774900_B36","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.plefa.2009.05.020","article-title":"The essentiality of arachidonic acid and docosahexaenoic acid","volume":"81","author":"Le","year":"2009","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"2021111620373774900_B37","doi-asserted-by":"publisher","first-page":"784","DOI":"10.3390\/nu9070784","article-title":"Can early Omega-3 fatty acid exposure reduce risk of childhood allergic disease?","volume":"9","author":"Miles","year":"2017","journal-title":"Nutrients"},{"key":"2021111620373774900_B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2014.03.010","article-title":"Prostaglandin E3 metabolism and cancer","volume":"348","author":"Yang","year":"2014","journal-title":"Cancer Lett."},{"key":"2021111620373774900_B39","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2018.00146","article-title":"Omega-3 PUFA vs. NSAIDs for preventing cardiac inflammation","volume":"5","author":"Ye","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"2021111620373774900_B40","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jnutbio.2017.04.013","article-title":"Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors","volume":"46","author":"Djuric","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"2021111620373774900_B41","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2014.03.035","article-title":"Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy","volume":"72","author":"Jiang","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"2021111620373774900_B42","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/ajcn\/85.2.385","article-title":"Dietary \u03b1-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects","volume":"85","author":"Zhao","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"2021111620373774900_B43","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1016\/j.lfs.2004.09.037","article-title":"Inhibitory effect of vitamin E on proinflammatory cytokines-and endotoxin-induced nitric oxide release in alveolar macrophages","volume":"76","author":"Khanduja","year":"2005","journal-title":"Life Sci."},{"key":"2021111620373774900_B44","doi-asserted-by":"publisher","first-page":"675","DOI":"10.3177\/jnsv.45.675","article-title":"Vitamin E suppresses the induction of reactive oxygen species release by lipopolysaccharide, interleukin-1beta and tumor necrosis factor-alpha in rat alveolar macrophages","volume":"45","author":"Pathania","year":"1999","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"2021111620373774900_B45","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.4103\/1735-1995.172986","article-title":"Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training","volume":"20","author":"Sarir","year":"2015","journal-title":"J. Res. Med. Sci."},{"key":"2021111620373774900_B46","doi-asserted-by":"publisher","first-page":"128919","DOI":"10.1155\/2014\/128919","article-title":"Anti-inflammatory mechanism of polyunsaturated fatty acids in Helicobacter pylori-infected gastric epithelial cells","volume":"2014","author":"Lee","year":"2014","journal-title":"Mediators Inflamm."},{"key":"2021111620373774900_B47","doi-asserted-by":"publisher","first-page":"93","DOI":"10.4162\/nrp.2018.12.2.93","article-title":"Protective effects of perilla oil and alpha linolenic acid on SH-SY5Y neuronal cell death induced by hydrogen peroxide","volume":"12","author":"Lee","year":"2018","journal-title":"Nutr. Res. Pract."},{"key":"2021111620373774900_B48","doi-asserted-by":"publisher","first-page":"740687","DOI":"10.1155\/2011\/740687","article-title":"Effects of grape seed extract, vitamin c, and vitamin e on ethanol- and aspirin-induced ulcers","volume":"2011","author":"Cuevas","year":"2011","journal-title":"Adv. Pharmacol. Sci."},{"key":"2021111620373774900_B49","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.3109\/13880209.2014.902082","article-title":"Vitamin E: a potential therapy for gastric mucosal injury","volume":"52","author":"Kamisah","year":"2014","journal-title":"Pharm. Biol."},{"key":"2021111620373774900_B50","doi-asserted-by":"publisher","first-page":"4396","DOI":"10.1167\/iovs.12-9724","article-title":"Anti-inflammatory effects of alpha linolenic acid on human corneal epithelial cells","volume":"53","author":"Erdinest","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2021111620373774900_B51","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.immuni.2013.05.015","article-title":"Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation","volume":"38","author":"Yan","year":"2013","journal-title":"Immunity"},{"key":"2021111620373774900_B52","doi-asserted-by":"publisher","first-page":"e97957","DOI":"10.1371\/journal.pone.0097957","article-title":"Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-kappaB activation and enhancing autophagy","volume":"9","author":"Williams-Bey","year":"2014","journal-title":"PLoS ONE"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20203166\/902616\/bsr-2020-3166.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20203166\/902616\/bsr-2020-3166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T21:02:01Z","timestamp":1637096521000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/41\/1\/BSR20203166\/227473\/Analgesic-anti-inflammatory-and-anti-ulcer"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,29]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20203166","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1]]},"published":{"date-parts":[[2021,1]]},"article-number":"BSR20203166"}}