{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:33:50Z","timestamp":1792118030011,"version":"4.4.0"},"reference-count":116,"publisher":"MDPI AG","issue":"11","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\/"}],"funder":[{"DOI":"10.13039\/501100003398","name":"Shanxi Scholarship Council of China","doi-asserted-by":"publisher","award":["HGKY2019075"],"award-info":[{"award-number":["HGKY2019075"]}],"id":[{"id":"10.13039\/501100003398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003398","name":"Shanxi Scholarship Council of China","doi-asserted-by":"publisher","award":["202003D03111123"],"award-info":[{"award-number":["202003D03111123"]}],"id":[{"id":"10.13039\/501100003398","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jinzhong Science and Technology Key R&amp;D Plan of Shanxi Province","award":["HGKY2019075"],"award-info":[{"award-number":["HGKY2019075"]}]},{"name":"Jinzhong Science and Technology Key R&amp;D Plan of Shanxi Province","award":["202003D03111123"],"award-info":[{"award-number":["202003D03111123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Perilla frutescens (L.) Britton, an important pharmaceutical and nutraceutical crop, is widely cultivated in East Asian countries. In this review, we present the latest research findings on the phytochemistry and pharmacological activities of P. frutescens. Different databases, including PubMed, Scopus, CNKI, Agricola, Scifinder, Embase, ScienceDirect, DOAJ, and Web of Science, were searched to present the best review. In this review, we clearly represent the active constituents responsible for each and every pharmacological activity, plausible mechanism of action, and maximum inhibitory concentrations, as well as IC50 values. Approximately 400 different bioactive compounds, including alkaloids, terpenoids, quinines, phenylpropanoids, polyphenolic compounds, flavonoids, coumarins, anthocyanins, carotenoids, neolignans, fatty acids, polycosanols, tocopherols, and sitosterols, have been reported in the leaves, seeds, roots, and aerial parts of P. frutescens. The bioactive constituents of P. frutescens exhibited different enzyme-inhibition properties, including antihyaluronidase effects and aldose reductase inhibitory, \u03b1-glucosidase inhibitory, xanthine oxidase inhibitory, and tyrosinase inhibitory properties. P. frutescens showed strong anti-inflammatory, antidepressant, anti-spasmodic, anticancer, antioxidant, antimicrobial, insecticidal, neuroprotective, and hepatoprotective effects. Hence, the active constituents of P. frutescens used in the treatment of diabetes and diabetic complications (retinopathy, neuropathy, and nephropathy), prevention of hyperuricemia in gout patients, hyper pigmentation, allergic conditions, skin inflammation, skin allergy, atopic dermatitis, periodontosis, androgenic alopecia, gastric inflammation, oesophagitis, carcinogenesis, cardiovascular, Alzheimer\u2019s, Parkinson\u2019s, and cerebral ischemic disorders. Furthermore, we revealed the most active constituents and possible mechanisms of the pharmacological properties of P. frutescens.<\/jats:p>","DOI":"10.3390\/molecules27113578","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"3578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["Perilla frutescens: A Rich Source of Pharmacological Active Compounds"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7939-7271","authenticated-orcid":false,"given":"Tianyu","family":"Hou","sequence":"first","affiliation":[{"name":"School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China"},{"name":"Jinzhong Institute of Industrial Technology and Innovation, North University of China, Jinzhong 030600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasudeva Reddy","family":"Netala","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9228-587X","authenticated-orcid":false,"given":"Hongjiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xing","sequence":"additional","affiliation":[{"name":"Graduate School of Humanities, Nagoya University, Nagoya 4648601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huizhen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China"},{"name":"Jinzhong Institute of Industrial Technology and Innovation, North University of China, Jinzhong 030600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China"},{"name":"Jinzhong Institute of Industrial Technology and Innovation, North University of China, Jinzhong 030600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.foodchem.2018.09.155","article-title":"Identification and quantification of essential oil content and composition total polyphenols and antioxidant capacity of Perilla frutescens (L.) Britt","volume":"275","author":"Ahmed","year":"2019","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1080\/0972060X.2016.1226962","article-title":"Active volatile constituents in Perilla frutescens essential oils and improvement of antimicrobial and anti-inflammatory bioactivity by fractionation","volume":"19","author":"Lin","year":"2016","journal-title":"J. Essen. Oil Bear. Plants"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.indcrop.2014.04.048","article-title":"Regional variation in components and antioxidant and antifungal activities of Perilla frutescens essential oils in China","volume":"59","author":"Tian","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_4","first-page":"32","article-title":"Chemical composition of the essential oil of Perilla frutescens","volume":"53","author":"Ito","year":"1999","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.indcrop.2014.11.043","article-title":"Essential oils of green and red Perilla frutescens as potential sources of compounds for mosquito management","volume":"1","author":"Tabanca","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1039\/b9ay00035f","article-title":"Rapid analysis of the essential oil components of dried Perilla frutescens (L) by magnetic nanoparticle-assisted microwave distillation and simultaneous headspace solid-phase microextraction followed by gas chromatography-mass spectrometry","volume":"1","author":"Ye","year":"2009","journal-title":"Anal. Methods"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00217-014-2242-8","article-title":"Chemical composition and insecticidal activities of the essential oil of Perilla frutescens (L) Britt aerial parts against two stored product insects","volume":"239","author":"You","year":"2014","journal-title":"Eur. Food Res. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.fitote.2018.08.006","article-title":"Anti-inflammatory constituents from Perilla frutescens on lipopolysaccharide-stimulated RAW2.647 cells","volume":"130","author":"Wang","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.fct.2013.12.031","article-title":"Induction of apoptosis by isoegomaketone from Perilla frutescens L in B16 melanoma cells is mediated through ROS generation and mitochondrial-dependent-independent pathway","volume":"65","author":"Kwon","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.indcrop.2019.03.025","article-title":"Phytochemical composition and bioactivities of essential oils from six Lamiaceae species","volume":"133","author":"Luo","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/jsfa.8552","article-title":"Microcapsules biologically prepared using Perilla frutescens (L) Britt essential oil and their use for extension of fruit shelf life","volume":"98","author":"Li","year":"2018","journal-title":"J. Sci. Food Agric."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11537","DOI":"10.1021\/jf902669d","article-title":"Characteristic aroma-active compounds of Korean perilla (Perilla frutescens Britton) leaf","volume":"57","author":"Seo","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ffj.1174","article-title":"Composition of the essential oil of Perilla frutescens (L) Britton from Turkey","volume":"18","author":"Baser","year":"2003","journal-title":"Flavour Fragr. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1271\/bbb.68.85","article-title":"Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects","volume":"68","author":"Banno","year":"2004","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11418-006-0015-9","article-title":"Cytotoxic activity of Perilla frutescens var japonica leaf extract is due to high concentrations of oleanolic and ursolic acids","volume":"60","author":"Akihisa","year":"2006","journal-title":"J. Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.jfda.2016.09.003","article-title":"Characterization of metabolite profiles from the leaves of green perilla (Perilla frutescens) by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and screening for their antioxidant properties","volume":"25","author":"Lee","year":"2017","journal-title":"J. Food Drug Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.bjp.2017.06.003","article-title":"Perillanolides A and B new monoterpene glycosides from the leaves of Perilla frutescens","volume":"27","author":"Liu","year":"2017","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4062\/biomolther.2013.088","article-title":"Inhibition of proinflammatory cytokine generation in lung inflammation by the leaves of Perilla frutescens and its constituents","volume":"22","author":"Lim","year":"2014","journal-title":"Biomol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1248\/cpb.43.920","article-title":"Inhibitory effect of perilloside A and C and related monoterpene glucosides on aldose reductase and their structure-activity relationships","volume":"43","author":"Fujita","year":"1995","journal-title":"Chem. Pharm. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/jcp.24243","article-title":"Barrier protective effects of rosmarinic acid on HMGB1-induced inflammatory responses in vitro and in vivo","volume":"228","author":"Yang","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.lwt.2008.04.006","article-title":"TLC bioautography-guided isolation of antioxidants from fruit of Perilla frutescens var acuta","volume":"42","author":"Gu","year":"2009","journal-title":"LWT Food Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.sajb.2019.03.015","article-title":"Comparative evaluation of phenolic phytochemicals from perilla seeds of diverse species and screening for their tyrosinase inhibitory and antioxidant properties","volume":"123","author":"Kim","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.foodchem.2012.05.104","article-title":"Isolation and identification of phenolic compounds from the seeds of Perilla frutescens (L) and their inhibitory activities against \u03b1-glucosidase and aldose reductase","volume":"135","author":"Ha","year":"2012","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.foodchem.2014.05.062","article-title":"Structural characterization and antioxidant activity evaluation of phenolic compounds from cold-pressed Perilla frutescens var arguta seed flour","volume":"164","author":"Zhou","year":"2014","journal-title":"Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"679463","DOI":"10.1155\/2013\/679463","article-title":"Rapid identification of aldose reductase inhibitory compounds from Perilla frutescens","volume":"2013","author":"Paek","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.foodchem.2009.07.020","article-title":"Isolation of caffeic acid from Perilla frutescens and its role in enhancing \u03b3-glutamylcysteine synthetase activity and glutathione level","volume":"119","author":"Park","year":"2010","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1271\/bbb.60.1093","article-title":"Novel antioxidants isolated from Perilla frutescens Britton var crispa (Thunb)","volume":"60","author":"Tada","year":"1996","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1080\/09168451.2014.962474","article-title":"A new flavanone and other flavonoids from green perilla leaf extract inhibit nitric oxide production in interleukin 1\u03b2-treated hepatocytes","volume":"79","author":"Nakajima","year":"2015","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.foodchem.2013.10.028","article-title":"Structural characterization of phenolic antioxidants from purple perilla (Perilla frutescens var acuta) leaves","volume":"148","author":"Jun","year":"2014","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s13596-011-0002-x","article-title":"Health effects of omega-369 fatty acids: Perilla frutescens is a good example of plant oils","volume":"11","author":"Asif","year":"2011","journal-title":"Orient. Pharm. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8141","DOI":"10.1021\/jf051360e","article-title":"Determination of phenolic compounds in Perilla frutescens L by capillary electrophoresis with electrochemical detection","volume":"53","author":"Peng","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.foodres.2018.05.017","article-title":"Characterization identification and quantification of phenolic compounds using UPLC-Q-TOF-MS and evaluation of antioxidant activity of 73 Perilla frutescens accessions","volume":"111","author":"Assefa","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1002\/fsn3.993","article-title":"Drying the leaves of Perilla frutescens increases their content of anticancer nutraceuticals","volume":"7","author":"Kagawa","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.crci.2008.04.011","article-title":"Polyphenol extraction from eight Perilla frutescens cultivars","volume":"12","author":"Meng","year":"2009","journal-title":"Comptes Rendus Chim."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1055\/s-2001-10878","article-title":"Inhibitory effect of decoction of Perilla frutescens on cultured murine mesangial cell proliferation and quantitative analysis of its active constituents","volume":"67","author":"Makino","year":"2001","journal-title":"Planta Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jff.2009.11.002","article-title":"Enhanced accumulation of caffeic acid rosmarinic acid and luteolin-glucoside in red perilla cultivated under red diode laser and blue LED illumination followed by UV-A irradiation","volume":"2","author":"Iwai","year":"2010","journal-title":"J. Funct. Foods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.foodchem.2012.08.057","article-title":"Identification characterization and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds of Korean perilla (Perilla frutescens) cultivars","volume":"136","author":"Lee","year":"2013","journal-title":"Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s13765-017-0260-5","article-title":"Determination of flavonoids from Perilla frutescens var japonica seeds and their inhibitory effect on aldose reductase","volume":"60","author":"Lee","year":"2017","journal-title":"Appl. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/0031-9422(93)85304-A","article-title":"Diglucuronoflavones from purple leaves of Perilla ocimoides","volume":"33","author":"Yoshida","year":"1993","journal-title":"Phytochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.phymed.2012.12.018","article-title":"Testing of Perilla frutescens extract and vicenin 2 for their antispasmodic effect","volume":"20","author":"Verspohl","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1080\/14786419.2018.1544981","article-title":"Isolation, characterization, and xanthine oxidase inhibitory activities of flavonoids from the leaves of Perilla frutescens","volume":"34","author":"Liu","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.bbrc.2016.12.083","article-title":"A flavanone derivative from the Asian medicinal herb (Perilla frutescens) potently suppresses IgE-mediated immediate hypersensitivity reactions","volume":"483","author":"Kamei","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.freeradbiomed.2012.06.021","article-title":"Isolation identification and biological evaluation of Nrf2-ARE activator from the leaves of green perilla (Perilla frutescens var crispa f viridis)","volume":"53","author":"Izumi","year":"2012","journal-title":"Free Rad. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9155","DOI":"10.3390\/molecules20059155","article-title":"Characterization of anthocyanins in Perilla frutescens var acuta extract by advanced UPLC-ESI-IT-TOF-MS method and their anticancer bioactivity","volume":"20","author":"He","year":"2015","journal-title":"Molecules"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0031-9422(02)00721-5","article-title":"Metabolomics and differential gene expression in anthocyanin chemo-varietal forms of Perilla frutescens","volume":"62","author":"Yamazaki","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0960-894X(01)00812-5","article-title":"Two neolignans from Perilla frutescens and their inhibition of nitric oxide synthase and tumor necrosis factor-\u03b1 expression in murine macrophage cell line Raw 2.647","volume":"12","author":"Ryu","year":"2002","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1021\/np990362o","article-title":"Two new prenylated 3-benzoxepin derivatives as cyclooxygenase inhibitors from Perilla frutescens var. acuta","volume":"63","author":"Liu","year":"2000","journal-title":"J. Nat. Prod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4168\/aard.2013.1.1.90","article-title":"Occupational asthma caused by inhaling smoke from roasting perilla seeds","volume":"1","author":"Jung","year":"2013","journal-title":"Allergy Asthma Respir. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5359","DOI":"10.1021\/jf060688k","article-title":"Policosanol content and composition in perilla seeds","volume":"54","author":"Adhikari","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1021\/jf204977x","article-title":"Metabolite profiling based on lipophilic compounds for quality assessment of perilla (Perilla frutescens) cultivars","volume":"60","author":"Kim","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"399","DOI":"10.4025\/actascitechnol.v38i4.27436","article-title":"Perilla frutescens: A potential ingredient for the enhancement of white bread as a source of Omega-3","volume":"38","author":"Bonafe","year":"2016","journal-title":"Acta Sci. Technol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0308-8146(99)00263-0","article-title":"Nutritional and short tem toxicological evaluation of Perilla seed oil","volume":"70","author":"Longvah","year":"2000","journal-title":"Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7324\/JAPS.2016.60201","article-title":"Impact of different pre-treatment strategies on the quality of fatty acid composition, tocols content and metabolic syndrome related activities of Perilla frutescens seed oil","volume":"6","author":"Sirilun","year":"2016","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s12272-011-0806-8","article-title":"Biological evaluation of isoegomaketone isolated from Perilla frutescens and its synthetic derivatives as anti-inflammatory agents","volume":"34","author":"Park","year":"2011","journal-title":"Arch. Pharm. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Nam, B., Yangkang, S., Kim, H.Y., Kim, J.B., Jin, C.H., and Han, A.R. (2017). A New Monoterpene from the leaves of a radiation mutant cultivar of Perilla frutescens var crispa with inhibitory activity on LPS-induced NO production. Molecules, 22.","DOI":"10.3390\/molecules22091471"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pbb.2013.10.026","article-title":"Effects of perillaldehyde on alternations in serum cytokines and depressive-like behaviour in mice after lipopolysaccharide administration","volume":"116","author":"Ji","year":"2014","journal-title":"Pharm. Biochem. Behav."},{"key":"ref_57","doi-asserted-by":"crossref","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":"ref_58","first-page":"409","article-title":"Preliminary analysis on essential oil composition of Perilla L cultivated in Lithuania","volume":"66","author":"Bumblauskiene","year":"2009","journal-title":"Acta Pol. Pharm. Drug Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1752-153X-7-61","article-title":"Determination of the content of rosmarinic acid by HPLC and analytical comparison of volatile constituents by GC-MS in different parts of Perilla frutescens (L.) Britt","volume":"7","author":"Liu","year":"2013","journal-title":"Chem. Cent. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11418-019-01363-y","article-title":"Bioconversion of essential oil components of Perilla frutescens by Saccharomyces cerevisiae","volume":"74","author":"Kimura","year":"2020","journal-title":"J. Nat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1006\/exer.1998.0624","article-title":"Cataract formation through the polyol pathway is associated with free radical production","volume":"68","author":"Kubo","year":"1999","journal-title":"Exp. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0167-4838(94)00182-G","article-title":"Residues affecting the catalysis and inhibition of rat lens aldose reductase","volume":"1246","author":"Carper","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1517\/13543784.8.12.2095","article-title":"Aldose reductase inhibitors: Therapeutic implications for diabetic complications","volume":"8","author":"Oates","year":"1999","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ghosh, S., and Collier, A. (2012). Section 3\u2014Management of Diabetes. Churchill\u2019s Pocketbook of Diabetes, Churchill Livingstone.","DOI":"10.1016\/B978-0-443-10081-9.00010-5"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ejmech.2017.04.031","article-title":"Xanthine oxidase inhibitors beyond allopurinol and febuxostat; an overview and selection of potential leads based on in silico calculated physico-chemical properties predicted pharmacokinetics and toxicity","volume":"135","author":"Smelcerovic","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1517\/13543776.2014.895325","article-title":"Analysis of patents on anti-gout therapies issued in China","volume":"24","author":"Yuan","year":"2014","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1177\/2047487313519346","article-title":"Uric acid and cardiovascular disease risk reclassification: Findings from NHANES III","volume":"22","author":"Zalawadiya","year":"2015","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1445-5994.2005.00790.x","article-title":"Risk estimates for drugs suspected of being associated with Stevens-Johnson syndrome and toxic epidermal necrolysis: A case-control study","volume":"35","author":"Lin","year":"2005","journal-title":"Intern. Med. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/sj.jid.5701033","article-title":"Stevens\u2013Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study","volume":"128","author":"Mockenhaupt","year":"2008","journal-title":"J. Investig. Derm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1248\/cpb.38.1772","article-title":"Two new potent inhibitors of xanthine oxidase from leaves of Perilla frutescens britton var Acuta Kudo","volume":"38","author":"Nakanishi","year":"1990","journal-title":"Chem. Pharm. Bull."},{"key":"ref_71","first-page":"2","article-title":"Tyrosinase and tyrosinase inhibitors","volume":"1","author":"Chang","year":"2012","journal-title":"J. Biocatal. Biotransform."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/1748-5967.12336","article-title":"Insecticidal and antifeeding activity of Perilla frutescens-derived material against the diamondback moth Plutella xylostella L.","volume":"49","author":"Kim","year":"2019","journal-title":"Entomol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1258\/ebm.2010.010252","article-title":"Effect of Perilla frutescens var. acuta Kudo and rosmarinic acid on allergic inflammatory reactions","volume":"236","author":"Oh","year":"2011","journal-title":"Exp. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mam.2011.10.015","article-title":"Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes","volume":"33","author":"Sbardella","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_75","first-page":"733","article-title":"Alleviation of atopic dermatitis-related symptoms by Perilla frutescens Britton","volume":"28","author":"Heo","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_76","first-page":"272","article-title":"Perilla leaf extract prevents atopic dermatitis induced by an extract of Dermatophagoides farinae in NC\/Nga mice","volume":"34","author":"Komatsu","year":"2016","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3109\/08923970009026007","article-title":"Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens","volume":"22","author":"Shin","year":"2000","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6941","DOI":"10.3390\/molecules19066941","article-title":"Anti-inflammatory and antipruritic effects of luteolin from Perilla (P frutescens L.) leaves","volume":"19","author":"Jeon","year":"2014","journal-title":"Molecules"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1021\/jf9802777","article-title":"Glycoprotein derived from the hot water extract of mint plant Perilla frutescens Britton","volume":"47","author":"Asada","year":"1999","journal-title":"J. Agric. Food Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"18204","DOI":"10.1038\/srep18204","article-title":"Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and calcium","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1365-2222.2004.01979.x","article-title":"Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen in a mouse model","volume":"34","author":"Sanbongi","year":"2004","journal-title":"Clin. Exp. Allergy"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/153537020422900305","article-title":"Extract of Perilla frutescens enriched for rosmarinic acid a polyphenolic phytochemical inhibits seasonal allergic rhinoconjunctivitis in humans","volume":"229","author":"Takano","year":"2004","journal-title":"Exp. Biol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/ptr.1115","article-title":"Antiallergic effect of Perilla frutescens and its active consti3tuents","volume":"17","author":"Makino","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_84","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_85","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0014-2999(02)02037-X","article-title":"Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice","volume":"449","author":"Takeda","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_86","first-page":"242","article-title":"Screening for mast cell histamine release inhibitory activity of Philippine medicinal plants Active constituent of Ehretia","volume":"41","author":"Rimando","year":"1987","journal-title":"Microphylla"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s002100000274","article-title":"Stimulatory effect of caffeic acid on \u03b1 1A-adrenoceptors to increase glucose uptake into cultured C 2 C 12 cells","volume":"362","author":"Cheng","year":"2000","journal-title":"Naunyn-Schmiedebergs Arch. Pharm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3181\/00379727-218-44309","article-title":"In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds","volume":"218","author":"Soliman","year":"1998","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0944-7113(00)80022-7","article-title":"Role of Salviae Miltiorrhizae Radix extract and its compounds in enhancing nitric oxide expression","volume":"7","author":"Yokozawa","year":"2000","journal-title":"Phytomedicine"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jep.2013.03.015","article-title":"Essential oil of Perilla frutescens-induced change in hippocampal expression of brain-derived neurotrophic factor in chronic unpredictable mild stress in mice","volume":"147","author":"Yi","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_91","first-page":"0753","article-title":"Antidepressant-like effect of essential oil of Perilla frutescens in a chronic unpredictable mild stress-induced depression model mice","volume":"12","author":"Ji","year":"2014","journal-title":"Chin. J. Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1248\/bpb.26.474","article-title":"Antidepressant-like effects of apigenin and 2 4 5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test","volume":"26","author":"Nakazawa","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/S0891-5849(02)00970-X","article-title":"Rosmarinic acid a major polyphenolic component of Perilla frutescens reduces lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-GalN)-sensitized mice","volume":"33","author":"Osakabe","year":"2002","journal-title":"Free Rad. Biol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.fct.2012.12.042","article-title":"The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage","volume":"55","author":"Yang","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s11418-017-1116-3","article-title":"The promotion of hair regrowth by topical application of a Perilla frutescens extract through increased cell viability and antagonism of testosterone and dihydrotestosterone","volume":"72","author":"Li","year":"2018","journal-title":"J. Nat. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.foodres.2010.09.035","article-title":"Hypolipidemic and antioxidant effects of total flavonoids of Perilla Frutescens leaves in hyperlipidemia rats induced by high-fat diet","volume":"44","author":"Feng","year":"2011","journal-title":"Food Res. Int."},{"key":"ref_97","first-page":"406","article-title":"Inotropic and lusitropic effects of Perilla frutescens (L) Britton extract on the rabbit myocardium","volume":"42","author":"Korotkich","year":"2006","journal-title":"Medicina"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.neurobiolaging.2010.02.013","article-title":"Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons","volume":"33","author":"Zhao","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1055\/s-2005-873145","article-title":"Luteolin inhibits LPS-stimulated inducible nitric oxide synthase expression in BV-2 microglial cells","volume":"72","author":"Kim","year":"2006","journal-title":"Planta Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"274","DOI":"10.4162\/nrp.2016.10.3.274","article-title":"Perilla frutescens var. japonica and rosmarinic acid improve amyloid-\u03b225\u201335 induced impairment of cognition and memory function","volume":"10","author":"Lee","year":"2016","journal-title":"Nutr. Res. Pract."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4062\/biomolther.2015.135","article-title":"The neuro-protective effect of the methanolic extract of Perilla frutescens var. japonica and rosmarinic acid against H2O2-induced oxidative stress in C6 glial cells","volume":"24","author":"Lee","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12272-001-1139-9","article-title":"\u03b2-Secretase (BACE1) inhibitors from Perilla frutescens var acuta","volume":"31","author":"Choi","year":"2008","journal-title":"Arch. Pharmacal Res."},{"key":"ref_103","first-page":"S256","article-title":"Neuroprotective effect of perilla extracts on PC12 cells","volume":"99","author":"Senavong","year":"2016","journal-title":"J. Med. Assoc. Thail."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.3892\/mmr.2014.2298","article-title":"Anti-inflammatory effects of Perilla frutescens leaf extract on lipopolysaccharide-stimulated RAW2647 cells","volume":"10","author":"Huang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"G32","DOI":"10.1152\/ajpgi.00294.2014","article-title":"Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines","volume":"308","author":"Urushima","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.fct.2013.06.003","article-title":"Rosmarinic acid down-regulates endothelial protein C receptor shedding in vitro and in vivo","volume":"59","author":"Ku","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"981372","DOI":"10.1155\/2013\/981372","article-title":"Effect of Perilla frutescens fixed oil on experimental esophagitis in albino wistar rats","volume":"2013","author":"Arya","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3389\/fphar.2018.01162","article-title":"Antioxidant and oxidative stress: A mutual interplay in age-related diseases","volume":"16","author":"Tan","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/ars.2006.8.99","article-title":"Nrf2: A potential molecular target for cancer chemoprevention by natural compounds","volume":"8","author":"Jeong","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jep.2007.05.008","article-title":"Growth inhibitory and apoptosis inducing effect of Perilla frutescens extract on human hepatoma HepG2 cells","volume":"112","author":"Lin","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4162\/nrp.2015.9.1.11","article-title":"Inhibitory activities of Perilla frutescens britton leaf extract against the growth migration and adhesion of human cancer cells","volume":"9","author":"Kwak","year":"2015","journal-title":"Nutr. Res. Pract."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1002\/1097-0142(19940415)73:8<2069::AID-CNCR2820730810>3.0.CO;2-1","article-title":"Colon cancer prevention with a small amount of dietary perilla oil high in alpha-linolenic acid in an animal model","volume":"73","author":"Narisawa","year":"1994","journal-title":"Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1002\/jcb.27491","article-title":"Perilaldehyde activates AMP-activated protein kinase to suppress the growth of gastric cancer via induction of autophagy","volume":"120","author":"Zhang","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1021\/jf00023a054","article-title":"Antimicrobial activity of the volatile constituents of Perilla frutescens and its synergistic effects with polygodial","volume":"40","author":"Kang","year":"1992","journal-title":"J. Agric. Food Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1271\/bbb.66.921","article-title":"Antimicrobial activity of Perilla seed polyphenols against oral pathogenic bacteria","volume":"66","author":"Yamamoto","year":"2002","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1007\/s42452-020-03323-8","article-title":"In silico evaluation of antimicrobial antihyaluronidase and bioavailability parameters of rosmarinic acid in Perilla frutescens leaf extracts","volume":"2","author":"Li","year":"2020","journal-title":"SN Appl. Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/11\/3578\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:47Z","timestamp":1760138627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/11\/3578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":116,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["molecules27113578"],"URL":"https:\/\/doi.org\/10.3390\/molecules27113578","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]}}}