{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:52:27Z","timestamp":1788839547654,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["NSC101-2313-B-005-042-MY3 and MOST 107-2320-B-005-010-MY3"],"award-info":[{"award-number":["NSC101-2313-B-005-042-MY3 and MOST 107-2320-B-005-010-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007841","name":"Council of Agriculture","doi-asserted-by":"publisher","award":["110AS-14.1.1-ST-a4"],"award-info":[{"award-number":["110AS-14.1.1-ST-a4"]}],"id":[{"id":"10.13039\/100007841","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Menthone is rich in Mentha \u00d7 Piperita L. essential oil and it has anti-inflammatory properties; research shows that it is useful, via percutaneous absorption, in treating inflammation-related diseases. However, anti-allergic inflammatory effects of volatile menthone have not yet been used to treat allergic asthma, in vivo. We hypothesized that menthone inhalation may have anti-inflammatory and anti-allergic effects in patients with allergic asthma. Therefore, in our study, menthone inhalation was used to treat ovalbumin (OVA)-sensitized and challenged asthmatic mice. Allergic inflammation mediator changes in the lungs and airways, sera, splenocytes, and peritoneal macrophages of the mice were measured. Relative expression amounts of six receptor genes related to allergic inflammation of the lungs and airways were quantitated using a two-step real time quantitative polymerase chain reaction (qPCR). Results showed that menthone inhalation increased serum OVA-specific IgG2a\/IgG1 and IgG2a\/IgE ratios, increased Th1-type cytokine production in the bronchoalveolar lavage fluid, and decreased nitric oxide, protein, and eotaxin levels. Menthone inhalation inhibited mast cell and eosinophil degranulation, and chemokine (C-C motif) receptor 3 (Ccr3) gene expression amounts, but (relatively) increased Th1 cytokine secretion by splenocytes. Our results evidence that menthone inhalation alleviates local and systemic allergic inflammation in asthmatic mice.<\/jats:p>","DOI":"10.3390\/ijms23074011","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T06:01:34Z","timestamp":1649138494000},"page":"4011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Menthone Inhalation Alleviates Local and Systemic Allergic Inflammation in Ovalbumin-Sensitized and Challenged Asthmatic Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Yi-Hsuan","family":"Su","sequence":"first","affiliation":[{"name":"Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9209-7959","authenticated-orcid":false,"given":"Jin-Yuarn","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"ref_1","first-page":"16","article-title":"A Short review on management of asthma through alternative therapies","volume":"1","author":"Shivakumar","year":"2012","journal-title":"Int. J. Life Sci. Biotechnol. Pharma Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Miura, K., Inoue, K., Ogura, A., and Kaminuma, O. (2020). Role of CD4+ T cells in allergic airway diseases: Learning from murine models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207480"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/bph.12138","article-title":"Twenty-first century mast cell stabilizers","volume":"170","author":"Finn","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1080\/15321819.2020.1769129","article-title":"Mast cell activation markers for in vitro study","volume":"41","author":"Sahid","year":"2020","journal-title":"J. Immunoass. Immunochem."},{"key":"ref_5","first-page":"1073","article-title":"Investigation on the relationship among histamine, tryptase and beta-hexosaminidase in the process of mast cell degranulation","volume":"25","author":"Guo","year":"2009","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"ref_6","first-page":"1","article-title":"Use of natural products in asthma treatment","volume":"2020","author":"Oliveira","year":"2020","journal-title":"Evid. Based Complementary Altern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nakamura, T., Yoshida, N., Yamanoi, Y., Honryo, A., Tomita, H., Kuwabara, H., and Kojima, Y. (2020). Eucalyptus oil reduces allergic reactions and suppresses mast cell degranulation by downregulating IgE-Ec\u03b5RI signaling. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-77039-5"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.apjtm.2017.10.006","article-title":"Effects of 8-hydroxyisocapnolactone-2\u20133-diol and friedelin on mast cell degranulation","volume":"10","author":"Sahid","year":"2017","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/ptr.2164","article-title":"Phlomis umbrosa root inhibits mast cell-dependent allergic reactions and inflammatory cytokine secretion","volume":"22","author":"Shin","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/treephys\/tpx070","article-title":"An extended model of heartwood secondary metabolism informed by functional genomics","volume":"38","author":"Celedon","year":"2017","journal-title":"Tree Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s11101-005-5464-3","article-title":"Terpenoids from marine organisms: Unique structures and their pharmacological potential","volume":"5","author":"Gross","year":"2006","journal-title":"Phytochem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12950-015-0049-4","article-title":"Antioxidant and anti-inflammatory activity of Ocimum labiatum extract and isolated labdane diterpenoid","volume":"12","author":"Kapewangolo","year":"2015","journal-title":"J. Inflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.foodchem.2013.04.044","article-title":"Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1\/Th2 cytokine secretion profiles using murine primary splenocytes","volume":"141","author":"Ku","year":"2013","journal-title":"Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1021\/np049811x","article-title":"Anti-inflammatory phloroglucinols and terpenoids from Garcinia subelliptica","volume":"67","author":"Weng","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Kang, S., Yan, H., Lv, H.P., Zhang, Y., and Lin, Z. (2020). Enantiomeric distributions of volatile lactones and terpenoids in white teas stored for different durations. Food Chem., 320.","DOI":"10.1016\/j.foodchem.2020.126632"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3390\/molecules18011227","article-title":"A review on anti-inflammatory activity of monoterpenes","volume":"18","author":"Andrade","year":"2013","journal-title":"Molecules"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1080\/0972060X.2020.1828177","article-title":"Menthol, balance of menthol\/menthone, and essential oil contents of Mentha \u00d7 Piperita, L. under foliar-applied chitosan and inoculation of Arbuscular mycorrhizal fungi","volume":"23","author":"Goudarzian","year":"2020","journal-title":"J. Essent. Oil Bear. Plants"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.intimp.2014.12.001","article-title":"Research on choleretic effect of menthol, menthone, pluegone, isomenthone, and limonene in DanShu capsule","volume":"24","author":"Hu","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","first-page":"389","article-title":"Effect of Menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids","volume":"21","author":"Lan","year":"2016","journal-title":"Pharm. Dev. Technol."},{"key":"ref_20","first-page":"703","article-title":"The effects of vitamin C and menthone on acyclovir induced DNA damage in rat spermatozoa: An experimental study","volume":"16","author":"Toghiani","year":"2018","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0378-5173(01)00640-8","article-title":"Effect of menthone on the in vitro percutaneous absorption of tamoxifen and skin reversibility","volume":"219","author":"Zhao","year":"2001","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.pbb.2015.04.014","article-title":"L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters","volume":"134","author":"Xue","year":"2015","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fphar.2016.00170","article-title":"Anti-inflammatory properties of menthol and menthone in Schistosoma mansoni infection","volume":"7","author":"Zaia","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3389\/fphar.2017.00207","article-title":"CCR3 is associated with the death of a photoreceptor cell-line induced by light exposure","volume":"8","author":"Kuse","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1172\/JCI119145","article-title":"Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody","volume":"99","author":"Heath","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1073\/pnas.261462598","article-title":"The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness","volume":"99","author":"Humbles","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1309\/AJCPLSN0RQKHJX1A","article-title":"Evaluation of CCR3 as a basophil activation marker","volume":"140","author":"Khanolkar","year":"2013","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/mi.2014.46","article-title":"A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa","volume":"8","author":"Danilova","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1465-9921-11-17","article-title":"Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis","volume":"11","author":"Greiff","year":"2010","journal-title":"Respir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"696","DOI":"10.3892\/mmr.2016.6085","article-title":"Downregulation of mouse CCR3 by lentiviral shRNA inhibits proliferation and induces apoptosis of mouse eosinophils","volume":"15","author":"Zhu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Leon, B., and Ballesteros-Tato, A. (2021). Modulating Th2 cell immunity for the treatment of asthma. Front. Pharmacol., 12.","DOI":"10.3389\/fimmu.2021.637948"},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.fct.2009.01.017","article-title":"Dietary perilla oil lowers serum lipids and ovalbumin-specific IgG1, but increases total IgE levels in ovalbumin-challenged mice","volume":"47","author":"Chang","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10471","DOI":"10.1021\/jf902403p","article-title":"High dose Vitamin C supplementation increases the Th1\/Th2 cytokine secretion ratio, but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized and challenged mice","volume":"57","author":"Chang","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/ejlt.201100339","article-title":"Protective effect of dietary perilla oil on allergic inflammation in ovalbumin-challenged asthmatic mice","volume":"114","author":"Chang","year":"2012","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ku, C.M., and Lin, J.Y. (2015). Farnesol, a sesquiterpene alcohol in herbal plants, exerts anti-inflammatory and anti-allergic effects on ovalbumin-sensitized and challenged asthmatic mice. Evid. Based Complementary Altern. Med., 2015.","DOI":"10.1155\/2015\/387357"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.aller.2015.05.009","article-title":"Farnesol, a sesquiterpene alcohol in essential oils, ameliorates serum allergic antibody titres and lipid profiles in ovalbumin-challenged mice","volume":"44","author":"Ku","year":"2016","journal-title":"Allergol. Immunopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1021\/jf405630h","article-title":"Quercetin, but not its metabolite quercetin-3-glucuronide, exerts prophylactic immuno-stimulatory activity and therapeutic anti-inflammatory effect on lipopolysaccharide-treated mouse peritoneal macrophages ex vivo","volume":"62","author":"Liao","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yeh, T.H., and Lin, J.Y. (2020). Acorus gramineusand and Euodia ruticarpa steam distilled essential oils exert anti-inflammatory effects through decreasing Th1\/Th2 and pro-\/anti-inflammatory cytokine secretion ratios in vitro. Biomolecules, 10.","DOI":"10.3390\/biom10020338"},{"key":"ref_40","first-page":"121","article-title":"Splenocyte-conditioned media inhibit breast cancer MCF-7 cell growth, associated with increased Th2\/Th1 cytokines secretion ratio in the media using five selected polysaccharides","volume":"2","author":"Lin","year":"2017","journal-title":"J. Immunobiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yeh, T.H., and Lin, J.Y. (2021). Rutaecarpine administration inhibits cancer cell growth in allogenic TRAMP-C1 prostate cancer mice correlating with immune balance in vivo. Biomed. Pharmacother., 139.","DOI":"10.1016\/j.biopha.2021.111648"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lin, H.C., and Lin, J.Y. (2021). Pharmacological effects of guava (Psidium guajava L.) seed polysaccharides: GSF3 inhibits PC-3 prostate cancer cell growth through immunotherapy in vitro. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073631"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3390\/cimb43020071","article-title":"Active ingredients from Euodia ruticarpa steam distilled essential oil inhibit PC-3 prostate cancer cell growth via direct action and indirect immune cells conditioned media in vitro","volume":"4","author":"Yeh","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_44","first-page":"6","article-title":"Effects of antigen presentation of eosinophils on lung Th1\/Th2 imbalance","volume":"118","author":"Xie","year":"2005","journal-title":"Chin. Med. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.intimp.2005.01.001","article-title":"Cells isolated from bone-marrow and lungs of allergic BALB\/C mice and cultured in the presence of IL-5 are respectively resistant and susceptible to apoptosis induced by dexamethasone","volume":"5","author":"Maximiano","year":"2005","journal-title":"Int. Immunopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"83","DOI":"10.33549\/physiolres.931956","article-title":"Isolation of rat lung mast cells for purposes of one-week cultivation using novel Percoll variant Percoll PLUS","volume":"60","author":"Kubrycht","year":"2011","journal-title":"Physiol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.4049\/jimmunol.1302520","article-title":"Does \u03b2-hexosaminidase function only as a degranulation indicator in mast cells? The primary role of \u03b2-hexosaminidase in mast cell granules","volume":"193","author":"Fukuishi","year":"2014","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kono, R., Nakamura, M., Nomura, S., Kitano, N., Kagiya, T., Okuno, Y., Inada, K.I., Tokuda, A., Utsunomiya, H., and Ueno, M. (2018). Biological and epidemiological evidence of anti-allergic effects of traditional Japanese food ume (Prunus mume). Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30086-5"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.foodchem.2011.09.116","article-title":"Protective effect of isoquinoline alkaloid berberine on spontaneous inflammation in the spleen, liver and kidney of non-obese diabetic mice through down-regulating gene expression ratios of pro-\/anti-inflammatory or Th1\/Th2 cytokines","volume":"131","author":"Chueh","year":"2012","journal-title":"Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/j.intimp.2011.08.008","article-title":"Berberine down-regulates the Th1\/Th2 cytokine gene expression ratio in mouse primary splenocytes in the absence or presence of lipopolysaccharide in a preventive manner","volume":"11","author":"Lin","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.ijbiomac.2020.06.057","article-title":"GSF3, a polysaccharide from guava (Psidium guajava L.) seeds, inhibits MCF-7 breast cancer cell growth via increasing Bax\/Bcl-2 ratio or Fas mRNA expression levels","volume":"161","author":"Lin","year":"2020","journal-title":"Int. J. Biol. Macromol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/4011\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:47Z","timestamp":1760136587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/4011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,4]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23074011"],"URL":"https:\/\/doi.org\/10.3390\/ijms23074011","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,4]]}}}