{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:35:57Z","timestamp":1788867357543,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Mentha spicata is one of the most popular species in the genus, and it is of great interest as a gastrointestinal and sedative agent in the folk medicine system. In this study, different M. spicata extracts, obtained by the use of four solvents (hexane, chloroform, acetone and acetone\/water) were chemically characterized using HPLC-ESI-MS n, which allowed for identification of 27 phenolic compounds. The extracts\u2019 antioxidant and enzyme inhibitory properties were investigated. In addition, neuroprotective effects were evaluated in hypothalamic HypoE22 cells, and the ability of the extracts to prevent the hydrogen peroxide-induced degradation of dopamine and serotonin was observed. The best antioxidant effect was achieved for all the extraction methods using acetone\/water as a solvent. These extracts were the richest in acacetin, eriodictyol, hesperidin, sagerinic acid, naringenin, luteolin, chlorogenic acid, chrysoeriol and apigenin. The intrinsic antioxidant and enzyme inhibition properties of the acetone\/water extract could also explain, albeit partially, its efficacy in preventing prostaglandin E2 overproduction and dopamine depletion (82.9% turnover reduction) in HypoE22 cells exposed to hydrogen peroxide. Thus, our observations can provide a scientific confirmation of the neuromodulatory and neuroprotective effects of M. spicata.<\/jats:p>","DOI":"10.3390\/plants11020233","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T20:49:21Z","timestamp":1642452561000},"page":"233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Novel Perceptions on Chemical Profile and Biopharmaceutical Properties of Mentha spicata Extracts: Adding Missing Pieces to the Scientific Puzzle"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6548-7823","authenticated-orcid":false,"given":"Gokhan","family":"Zengin","sequence":"first","affiliation":[{"name":"Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, 42130 Konya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunes","family":"Ak","sequence":"additional","affiliation":[{"name":"Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, 42130 Konya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, 42130 Konya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-1719","authenticated-orcid":false,"given":"Sengul","family":"Uysal","sequence":"additional","affiliation":[{"name":"Halil Bayraktar Health Services Vocational College, Erciyes University, 38280 Kayseri, Turkey"},{"name":"Drug Application and Research Center, Erciyes University, 38280 Kayseri, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-5172","authenticated-orcid":false,"given":"Eulogio","family":"Llorent-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Physical and Analytical Chemistry, Campus Las Lagunillas, University of Ja\u00e9n, E-23071 Jaen, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-3848","authenticated-orcid":false,"given":"Simonetta Cristina","family":"Di Simone","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rapino","sequence":"additional","affiliation":[{"name":"Genetic Molecular Institute of CNR, Unit of Chieti, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-1413","authenticated-orcid":false,"given":"Alessandra","family":"Acquaviva","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8133-5691","authenticated-orcid":false,"given":"Maria Loreta","family":"Libero","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Chiavaroli","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Recinella","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Leone","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Cataldi","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giustino","family":"Orlando","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7346-7395","authenticated-orcid":false,"given":"Luigi","family":"Menghini","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-9407","authenticated-orcid":false,"given":"Claudio","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8042-6009","authenticated-orcid":false,"given":"Marwa","family":"Balaha","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El Sheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-993X","authenticated-orcid":false,"given":"Viviana","family":"di Giacomo","sequence":"additional","affiliation":[{"name":"Botanic Garden \u201cGiardino dei Semplici\u201d, Department of Pharmacy, \u201cGabriele d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mahendran, G., Verma, S.K., and Rahman, L.-U. (2021). The traditional uses, Phytochemistry and pharmacology of Spearmint (Mentha spicata L.): A review. J. Ethnopharmacol.","DOI":"10.1016\/j.jep.2021.114266"},{"key":"ref_2","unstructured":"G\u00fcner, A., and Aslan, S. (2012). T\u00fcrkiye Bitkileri Listesi: (Damarl\u0131 Bitkiler), Nezahat G\u00f6kyi\u01e7it Botanik Bah\u00e7esi Yay\u0131nlar\u0131."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14402","DOI":"10.3390\/molecules200814402","article-title":"Mentha spicata essential oil: Chemical composition, antioxidant and antibacterial activities against planktonic and biofilm cultures of Vibrio spp. strains","volume":"20","author":"Snoussi","year":"2015","journal-title":"Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Taylan, O., Cebi, N., and Sagdic, O. (2021). Rapid Screening of Mentha spicata Essential Oil and L-Menthol in Mentha piperita Essential Oil by ATR-FTIR Spectroscopy Coupled with Multivariate Analyses. Foods, 10.","DOI":"10.3390\/foods10020202"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Eftekhari, A., Khusro, A., Ahmadian, E., Dizaj, S.M., Hasanzadeh, A., and Cucchiarini, M. (2021). Phytochemical and nutra-pharmaceutical attributes of Mentha spp.: A comprehensive review. Arab. J. Chem., 14.","DOI":"10.1016\/j.arabjc.2021.103106"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.sajb.2021.05.014","article-title":"Mentha piperita phytochemicals in agriculture, food industry and medicine: Features and applications","volume":"141","author":"Gholamipourfard","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jtcme.2017.08.011","article-title":"Mentha spicata L. essential oil, phytochemistry and its effectiveness in flatulence","volume":"11","author":"Mahboubi","year":"2021","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yousuf, T., Akter, R., Ahmed, J., Mazumdar, S., Talukder, D., Nandi, N.C., and Nurulamin, M. (2021). Evaluation of acute oral toxicity, cytotoxicity, antidepressant and antioxidant activities of Japanese mint (Mentha arvensis L.) oil. Phytomedicine Plus, 1.","DOI":"10.1016\/j.phyplu.2021.100140"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Brand\u00e3o, F.R., Farias, C.F.S., de Melo Souza, D.C., de Oliveira, M.I.B., de Matos, L.V., Majolo, C., de Oliveira, M.R., Chaves, F.C.M., de Almeida O\u2019Sullivan, F.L., and Chagas, E.C. (2021). Anesthetic potential of the essential oils of Aloysia triphylla, Lippia sidoides and Mentha piperita for Colossoma macropomum. Aquaculture, 534.","DOI":"10.1016\/j.aquaculture.2020.736275"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Soltanbeigi, A., \u00d6zg\u00fcven, M., and Hassanpouraghdam, M.B. (2021). Planting-date and cutting-time affect the growth and essential oil composition of Mentha \u00d7 piperita and Mentha arvensis. Ind. Crops Prod., 170.","DOI":"10.1016\/j.indcrop.2021.113790"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yakoubi, R., Megateli, S., Hadj Sadok, T., and Gali, L. (2021). Photoprotective, antioxidant, anticholinesterase activities and phenolic contents of different Algerian Mentha pulegium extracts. Biocatal. Agric. Biotechnol., 34.","DOI":"10.1016\/j.bcab.2021.102038"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Juri\u0107, T., Mi\u0107i\u0107, N., Potkonjak, A., Milanov, D., Dodi\u0107, J., Trivunovi\u0107, Z., and Popovi\u0107, B.M. (2021). The evaluation of phenolic content, in vitro antioxidant and antibacterial activity of Mentha piperita extracts obtained by natural deep eutectic solvents. Food Chem., 362.","DOI":"10.1016\/j.foodchem.2021.130226"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sebai, E., Abidi, A., Serairi, R., Marzouki, M., Saratsi, K., Darghouth, M.A., Sotiraki, S., and Akkari, H. (2021). Essential oil of Mentha pulegium induces anthelmintic effects and reduces parasite-associated oxidative stress in rodent model. Exp. Parasitol., 225.","DOI":"10.1016\/j.exppara.2021.108105"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chraibi, M., Fadil, M., Farah, A., Lebrazi, S., and Fikri-Benbrahim, K. (2021). Antimicrobial combined action of Mentha pulegium, Ormenis mixta and Mentha piperita essential oils against S. aureus, E. coli and C. tropicalis: Application of mixture design methodology. LWT, 145.","DOI":"10.1016\/j.lwt.2021.111352"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gabetti, E., Sgorbini, B., Stilo, F., Bicchi, C., Rubiolo, P., Chialva, F., Reichenbach, S.E., Bongiovanni, V., Cordero, C., and Cavallero, A. (2021). Chemical fingerprinting strategies based on comprehensive two-dimensional gas chromatography combined with gas chromatography-olfactometry to capture the unique signature of Piemonte peppermint essential oil (Mentha x piperita var Italo-Mitcham). J. Chromatogr. A, 1645.","DOI":"10.1016\/j.chroma.2021.462101"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Spadaccino, G., Frabboni, L., Petruzzi, F., Disciglio, G., Mentana, A., Nardiello, D., and Quinto, M. (2021). Essential oil characterization of Prunus spinosa L., Salvia officinalis L., Eucalyptus globulus L., Melissa officinalis L. and Mentha x piperita L. by a volatolomic approach. J. Pharm. Biomed. Anal., 202.","DOI":"10.1016\/j.jpba.2021.114167"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Djamila, B., Fatima Zohra, K., Lahcene, K., and Zohra, R.F. (2021). Drying methods affect the extracts and essential oil of Mentha aquatica L.. Food Biosci., 41.","DOI":"10.1016\/j.fbio.2021.101007"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Eghbalian, M., Shavisi, N., Shahbazi, Y., and Dabirian, F. (2021). Active packaging based on sodium caseinate-gelatin nanofiber mats encapsulated with Mentha spicata L. essential oil and MgO nanoparticles: Preparation, properties, and food application. Food Packag. Shelf Life, 29.","DOI":"10.1016\/j.fpsl.2021.100737"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alsaraf, S., Hadi, Z., Akhtar, M.J., and Khan, S.A. (2021). Chemical profiling, cytotoxic and antioxidant activity of volatile oil isolated from the mint (Mentha spicata L.) grown in Oman. Biocatal. Agric. Biotechnol., 34.","DOI":"10.1016\/j.bcab.2021.102034"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, X., Han, H., Li, B., Zhang, D., Zhang, Z., and Xie, Y. (2021). Fumigant toxicity and physiological effects of spearmint (Mentha spicata, Lamiaceae) essential oil and its major constituents against Reticulitermes dabieshanensis. Ind. Crops Prod., 171.","DOI":"10.1016\/j.indcrop.2021.113894"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.aoas.2016.10.002","article-title":"Comparison of total phenolic and antioxidant activity of different Mentha spicata and M. longifolia accessions","volume":"61","author":"Abootalebian","year":"2016","journal-title":"Ann. Agric. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s10967-018-5976-0","article-title":"Chemical elements of Algerian Mentha spicata L. used in the treatment of digestive system disorders by employing instrumental neutron activation analysis technique","volume":"317","author":"Begaa","year":"2018","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1515\/tjb-2015-0034","article-title":"Comparison of total phenolic contents and antioxidant capacities in mint genotypes used as spices","volume":"40","author":"Elmastas","year":"2015","journal-title":"Turk. J. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Brahmi, F., Nury, T., Debbabi, M., Hadj-Ahmed, S., Zarrouk, A., Prost, M., Madani, K., Boulekbache-Makhlouf, L., and Lizard, G. (2018). Evaluation of antioxidant, anti-inflammatory and cytoprotective properties of ethanolic mint extracts from algeria on 7-ketocholesterol-treated murine RAW 264.7 macrophages. Antioxidants, 7.","DOI":"10.3390\/antiox7120184"},{"key":"ref_25","first-page":"73","article-title":"Antistress effect of Mentha piperita in rats and the role of brain serotonin and dopamine","volume":"2","author":"Parveen","year":"2012","journal-title":"Asian J. Pharm. Biol. Res. (AJPBR)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jep.2016.02.039","article-title":"Ethnopharmacological survey on medicinal plants used in herbal drinks among the traditional communities of Pakistan","volume":"184","author":"Ahmad","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.sajb.2021.04.009","article-title":"Chemical profiling, in vitro biological activities and Pearson correlation between phenolic contents and antioxidant activities of Caragana brachyantha Rech.f","volume":"140","author":"Ali","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_28","first-page":"58","article-title":"Ethnobotanical studies of aquatic plants of district Sialkot, Punjab (Pakistan)","volume":"2","author":"Ikram","year":"2014","journal-title":"J. Med. Plants"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.sajb.2016.01.001","article-title":"Ethnobotanical survey of culinary herbs and spices used in the traditional medicinal system of Nkonkobe Municipality, Eastern Cape, South Africa","volume":"104","author":"Afolayan","year":"2016","journal-title":"S. Afr. J. Bot."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Asadi-Samani, M., Moradi, M.-T., Mahmoodnia, L., Alaei, S., Asadi-Samani, F., and Luther, T. (2017). Traditional uses of medicinal plants to prevent and treat diabetes; an updated review of ethnobotanical studies in Iran. J. Nephropathol., 6.","DOI":"10.15171\/jnp.2017.20"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-018-2274-x","article-title":"Chemical composition, antioxidant, antimicrobial and Antiproliferative activities of essential oil of Mentha spicata L. (Lamiaceae) from Algerian Saharan atlas","volume":"18","author":"Bardaweel","year":"2018","journal-title":"BMC Complementary Altern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1515\/znc-2017-0150","article-title":"Evaluation of Lavandula stoechas L. subsp. stoechas L., Mentha spicata L. subsp. spicata L. essential oils and their main components against sinusitis pathogens","volume":"73","author":"Karaca","year":"2018","journal-title":"Z. F\u00fcr Nat. C"},{"key":"ref_33","first-page":"2383","article-title":"Comparative study of larvicidal activity of commercial essential oils from aromatic rosemary, vanilla, and spearmint against the mosquito Aedes aegypti","volume":"21","author":"Laojun","year":"2020","journal-title":"Biodiversitas J. Biol. Divers."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nardoni, S., Giovanelli, S., Pistelli, L., Mugnaini, L., Profili, G., Pisseri, F., and Mancianti, F. (2015). In vitro activity of twenty commercially available, plant-derived essential oils against selected dermatophyte species. Nat. Prod. Commun., 10.","DOI":"10.1177\/1934578X1501000840"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1080\/14786419.2019.1610755","article-title":"Antifungal activity of essential oil from Mentha spicata L. and Mentha pulegium L. growing wild in Sardinia Island (Italy)","volume":"35","author":"Piras","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1139\/apnm-2017-0144","article-title":"Protective effects of Mentha spicata against nicotine-induced toxicity in liver and erythrocytes of Wistar rats","volume":"43","author":"Rjeibi","year":"2018","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.physbeh.2016.08.013","article-title":"Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice","volume":"165","author":"Farr","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_38","first-page":"854","article-title":"Analgesic, anti-inflammatory and antipyretic effect of Mentha spicata (Spearmint)","volume":"3","author":"Yousuf","year":"2013","journal-title":"J. Pharm. Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1016\/j.fct.2008.08.027","article-title":"Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity in male rats\u2013Altered levels of gene expression, enzymes and hormones","volume":"46","author":"Kumar","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.3906\/kim-1712-3","article-title":"Quantification of flavonoids isolated from Mentha spicata in selected clones of Turkish mint landraces","volume":"42","author":"Erenler","year":"2018","journal-title":"Turk. J. Chem."},{"key":"ref_41","first-page":"1286","article-title":"Optimization of the process of polyphenol extraction from Mentha spicata with various solvents","volume":"98","author":"Najda","year":"2019","journal-title":"Przem. Chem."},{"key":"ref_42","first-page":"1447","article-title":"Extracts of M. pulegium (L.) and M. spicata (L.): Effect of Extraction Conditions on Phenolics and Flavonoids Contents and Their Antioxidant Power","volume":"64","author":"Zekri","year":"2021","journal-title":"Egypt. J. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ma, Y.-L., Sun, P., Feng, J., Yuan, J., Wang, Y., Shang, Y.-F., Niu, X.-L., Yang, S.-H., and Wei, Z.-J. (2021). Solvent effect on phenolics and antioxidant activity of Huangshan Gongju (Dendranthema morifolium (Ramat) Tzvel. cv. Gongju) extract. Food Chem. Toxicol., 147.","DOI":"10.1016\/j.fct.2020.111875"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rudke, A.R., Andrade, K.S., Mazzutti, S., Zielinski, A.A.F., Alves, V.R., Vitali, L., and Ferreira, S.R.S. (2021). A comparative study of phenolic compounds profile and in vitro antioxidant activity from buriti (Mauritia flexuosa) by-products extracts. LWT, 150.","DOI":"10.1016\/j.lwt.2021.111941"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, R., He, R., Li, Z., Lin, X., and Wang, L. (2021). HPLC-Q-Orbitrap-MS\/MS phenolic profiles and biological activities of extracts from roxburgh rose (Rosa roxburghii Tratt.) leaves. Arab. J. Chem., 14.","DOI":"10.1016\/j.arabjc.2021.103257"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5990","DOI":"10.1039\/c3ay41125g","article-title":"The Folin\u2013Ciocalteu assay revisited: Improvement of its specificity for total phenolic content determination","volume":"5","author":"Benavides","year":"2013","journal-title":"Anal. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/rcm.4047","article-title":"Analysis of underivatized oligosaccharides by liquid chromatography\/electrospray ionization tandem mass spectrometry with post-column addition of formic acid","volume":"23","author":"Verardo","year":"2009","journal-title":"Rapid Commun. Mass Spectrom. Int. J. Devoted Rapid Dissem. Up Minute Res. Mass Spectrom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0021-9673(00)00861-X","article-title":"Negative atmospheric pressure chemical ionisation low-energy collision activation mass spectrometry for the characterisation of flavonoids in extracts of fresh herbs","volume":"902","author":"Justesen","year":"2000","journal-title":"J. Chromatogr. A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1248\/cpb.53.677","article-title":"Multi-component HPLC fingerprinting of Radix Salviae Miltiorrhizae and its LC-MS-MS identification","volume":"53","author":"Hu","year":"2005","journal-title":"Chem. Pharm. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1039\/C6FO00841K","article-title":"Mentha spicata L. infusions as sources of antioxidant phenolic compounds: Emerging reserve lots with special harvest requirements","volume":"7","author":"Rita","year":"2016","journal-title":"Food Funct."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.foodchem.2011.03.037","article-title":"Identification of phenolic components in dried spices and influence of irradiation","volume":"128","author":"Nagy","year":"2011","journal-title":"Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Stanoeva, J.P., Stefova, M., Andonovska, K.B., and Stafilov, T. (2017). LC\/DAD\/MS n and ICP-AES Assay and Correlations between Phenolic Compounds and Toxic Metals in Endemic Thymus alsarensis from the Thallium Enriched Allchar Locality. Nat. Prod. Commun., 12.","DOI":"10.1177\/1934578X1701200206"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/ptr.4978","article-title":"In vitro inhibition of the transcription factor NF-\u03baB and cyclooxygenase by Bamboo extracts","volume":"28","author":"Haegeman","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pisoschi, A.M., Pop, A., Iordache, F., Stanca, L., Predoi, G., and Serban, A.I. (2021). Oxidative stress mitigation by antioxidants\u2014An overview on their chemistry and influences on health status. Eur. J. Med. Chem., 209.","DOI":"10.1016\/j.ejmech.2020.112891"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Guan, R., Van Le, Q., Yang, H., Zhang, D., Gu, H., Yang, Y., Sonne, C., Lam, S.S., Zhong, J., and Jianguang, Z. (2021). A review of dietary phytochemicals and their relation to oxidative stress and human diseases. Chemosphere, 271.","DOI":"10.1016\/j.chemosphere.2020.129499"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wairata, J., Fadlan, A., Setyo Purnomo, A., Taher, M., and Ersam, T. (2022). Total phenolic and flavonoid contents, antioxidant, antidiabetic and antiplasmodial activities of Garcinia forbesii King: A correlation study. Arab. J. Chem., 15.","DOI":"10.1016\/j.arabjc.2021.103541"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, Y., Pan, H., Hao, S., Pan, D., Wang, G., and Yu, W. (2021). Evaluation of phenolic composition and antioxidant properties of different varieties of Chinese citrus. Food Chem., 364.","DOI":"10.1016\/j.foodchem.2021.130413"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.indcrop.2013.07.007","article-title":"Antioxidant and antibacterial activities and composition of Brazilian spearmint (Mentha spicata L.)","volume":"50","author":"Scherer","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.24896\/eijppr.2016611","article-title":"Evaluation of bioactivity of Annona muricata, Piper betle and Mentha spicata","volume":"6","author":"Samrot","year":"2016","journal-title":"Int. J. Pharm. Phytopharm. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Qadir, M.A., Shahzadi, S.K., Bashir, A., Munir, A., and Shahzad, S. (2017). Evaluation of Phenolic Compounds and Antioxidant and Antimicrobial Activities of Some Common Herbs. Int. J. Anal. Chem., 2017.","DOI":"10.1155\/2017\/3475738"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ifset.2005.09.001","article-title":"The contribution of flavonoid C-ring on the DPPH free radical scavenging efficiency. A kinetic approach for the 3\u2032, 4\u2032-hydroxy substituted members","volume":"7","author":"Tsimogiannis","year":"2006","journal-title":"Innov. Food Sci. Emerg. Technol."},{"key":"ref_62","first-page":"55","article-title":"Structure-radical scavenging activity relationships of flavonoids","volume":"76","year":"2003","journal-title":"Croat. Chem. Acta"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0031-9422(98)00730-4","article-title":"Rosmarinic acid derivatives from Salvia officinalis","volume":"51","author":"Lu","year":"1999","journal-title":"Phytochemistry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1080\/1071576021000016463","article-title":"Interactions of flavonoids with iron and copper ions: A mechanism for their antioxidant activity","volume":"36","author":"Mira","year":"2002","journal-title":"Free Radic. Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Aleixandre, A., Gil, J.V., Sineiro, J., and Rosell, C.M. (2022). Understanding phenolic acids inhibition of \u03b1-amylase and \u03b1-glucosidase and influence of reaction conditions. Food Chem., 372.","DOI":"10.1016\/j.foodchem.2021.131231"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chen, X., Li, H., Lucero-Prisno, D.E., Abdullah, A.S., Huang, J., Laurence, C., Liang, X., Ma, Z., Mao, Z., and Ren, R. (2020). What is global health? Key concepts and clarification of misperceptions. Glob. Health Res. Policy, 5.","DOI":"10.1186\/s41256-020-00142-7"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lim, J., Ferruzzi, M.G., and Hamaker, B.R. (2022). Structural requirements of flavonoids for the selective inhibition of \u03b1-amylase versus \u03b1-glucosidase. Food Chem., 370.","DOI":"10.1016\/j.foodchem.2021.130981"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ozten, O., Zengin Kurt, B., Sonmez, F., Dogan, B., and Durdagi, S. (2021). Synthesis, molecular docking and molecular dynamics studies of novel tacrine-carbamate derivatives as potent cholinesterase inhibitors. Bioorg. Chem., 115.","DOI":"10.1016\/j.bioorg.2021.105225"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Srivastava, S., Ahmad, R., and Khare, S.K. (2021). Alzheimer\u2019s disease and its treatment by different approaches: A review. Eur. J. Med. Chem., 216.","DOI":"10.1016\/j.ejmech.2021.113320"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"The Lancet Global Health (2021). Global health 2021: Who tells the story?. Lancet Glob. Health, 9.","DOI":"10.1016\/S2214-109X(21)00004-8"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1080\/14756366.2017.1368503","article-title":"\u03b1-Glucosidase inhibition by flavonoids: An in vitro and in silico structure-activity relationship study","volume":"32","author":"Freitas","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s11101-019-09610-6","article-title":"Flavonoids as alpha-glucosidase inhibitors: Mechanistic approaches merged with enzyme kinetics and molecular modelling","volume":"19","author":"Sari","year":"2020","journal-title":"Phytochem. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s11064-012-0935-6","article-title":"Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer\u2019s disease and some pro-oxidant induced oxidative stress in rats\u2019 brain in vitro","volume":"38","author":"Oboh","year":"2013","journal-title":"Neurochem. Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Yang, W., Sun, W., Chen, S., Liu, D., Kong, X., Tian, J., and Ye, X. (2020). Inhibition of porcine pancreatic \u03b1-amylase activity by chlorogenic acid. J. Funct. Foods, 64.","DOI":"10.1016\/j.jff.2019.103587"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1515\/jbcpp-2013-0141","article-title":"Caffeic and chlorogenic acids inhibit key enzymes linked to type 2 diabetes (in vitro): A comparative study","volume":"26","author":"Oboh","year":"2015","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12940","DOI":"10.3390\/molecules190912940","article-title":"Effect of chlorogenic acid on melanogenesis of B16 melanoma cells","volume":"19","author":"Li","year":"2014","journal-title":"Molecules"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3233\/NUA-2012-0006","article-title":"Polyphenols as acetylcholinesterase inhibitors: Structural specificity and impact on human disease","volume":"1","author":"Roseiro","year":"2012","journal-title":"Nutr. Aging"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"22159","DOI":"10.1039\/D1RA03196A","article-title":"Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: A systematic review","volume":"11","author":"Obaid","year":"2021","journal-title":"RSC Adv."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.sajb.2021.10.024","article-title":"Phenolic profile, antioxidant and enzyme inhibitory properties of phenolic-rich fractions from the aerial parts of Mentha pulegium L.","volume":"146","author":"Abbou","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Bouyahya, A., Lagrouh, F., El Omari, N., Bourais, I., El Jemli, M., Marmouzi, I., Salhi, N., Faouzi, M.E.A., Belmehdi, O., and Dakka, N. (2020). Essential oils of Mentha viridis rich phenolic compounds show important antioxidant, antidiabetic, dermatoprotective, antidermatophyte and antibacterial properties. Biocatal. Agric. Biotechnol., 23.","DOI":"10.1016\/j.bcab.2019.101471"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cam, M., Basyigit, B., Alasalvar, H., Yilmaztekin, M., Ahhmed, A., Sagdic, O., Konca, Y., and Telci, I. (2020). Bioactive properties of powdered peppermint and spearmint extracts: Inhibition of key enzymes linked to hypertension and type 2 diabetes. Food Biosci., 35.","DOI":"10.1016\/j.fbio.2020.100577"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.sajb.2018.03.002","article-title":"Chemical composition, antioxidant activity and acetylcholinesterase inhibitory of wild Mentha species from northeastern Algeria","volume":"116","author":"Benabdallah","year":"2018","journal-title":"S. Afr. J. Bot."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1046\/j.1440-1681.2001.03439.x","article-title":"Changes in endogenous monoamines in aged rats","volume":"28","author":"Lee","year":"2001","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1196\/annals.1306.025","article-title":"Ironing iron out in Parkinson\u2019s disease and other neurodegenerative diseases with iron chelators: A lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28","volume":"1012","author":"Youdim","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Amat-ur-Rasool, H., Symes, F., Tooth, D., Schaffert, L.-N., Elmorsy, E., Ahmed, M., Hasnain, S., and Carter, W.G. (2020). Potential nutraceutical properties of leaves from several commonly cultivated plants. Biomolecules, 10.","DOI":"10.3390\/biom10111556"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.etap.2008.02.008","article-title":"Anti-inflammatory activity of four solvent fractions of ethanol extract of Mentha spicata L. investigated on acute and chronic inflammation induced rats","volume":"26","author":"Arumugam","year":"2008","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Cavar Zeljkovic, S., \u0160i\u0161kov\u00e1, J., Komz\u00e1kov\u00e1, K., De Diego, N., Kaffkov\u00e1, K., and Tarkowski, P. (2021). Phenolic Compounds and Biological Activity of Selected Mentha Species. Plants, 10.","DOI":"10.3390\/plants10030550"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Govindasamy, H., Magudeeswaran, S., Kandasamy, S., and Poomani, K. (2021). Binding mechanism of naringenin with monoamine oxidase\u2013B enzyme: QM\/MM and molecular dynamics perspective. Heliyon, 7.","DOI":"10.1016\/j.heliyon.2021.e06684"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.plefa.2015.11.006","article-title":"Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice","volume":"104","author":"Kiraly","year":"2016","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ojo, O.A., Ojo, A.B., Okolie, C., Nwakama, M.-A.C., Iyobhebhe, M., Evbuomwan, I.O., Nwonuma, C.O., Maimako, R.F., Adegboyega, A.E., and Taiwo, O.A. (2021). Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer\u2019s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches. Molecules, 26.","DOI":"10.3390\/molecules26071996"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.dmpk.2014.12.005","article-title":"Inhibition effects of Vernonia cinerea active compounds against cytochrome P450 2A6 and human monoamine oxidases, possible targets for reduction of tobacco dependence","volume":"30","author":"Prasopthum","year":"2015","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_92","first-page":"6467","article-title":"In silico drug design and molecular docking studies targeting Akt1 (RAC-alpha serine\/threonine-protein kinase) and Akt2 (RAC-beta serine\/threonine-protein kinase) proteins and investigation of CYP (cytochrome P450) inhibitors against MAOB (monoamine oxidase B) for OSCC (oral squamous cell carcinoma) treatment","volume":"39","author":"Sarker","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/etm.2021.10150","article-title":"Chrysoeriol ameliorates COX-2 expression through NF-\u03baB, AP-1 and MAPK regulation via the TLR4\/MyD88 signaling pathway in LPS-stimulated murine macrophages","volume":"22","author":"Yoon","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.phytol.2017.03.005","article-title":"In vitro enzyme inhibitory properties, antioxidant activities, and phytochemical profile of Potentilla thuringiaca","volume":"20","author":"Grochowski","year":"2017","journal-title":"Phytochem. Lett."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Uysal, S., Zengin, G., Locatelli, M., Bahadori, M.B., Mocan, A., Bellagamba, G., De Luca, E., Mollica, A., and Aktumsek, A. (2017). Cytotoxic and enzyme inhibitory potential of two Potentilla species (P. speciosa L. and P. reptans Willd.) and their chemical composition. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00290"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1080\/00032719.2020.1775628","article-title":"Spectrophotometric determination of the antioxidant properties and characterization of the phenolic content by high-performance liquid chromatography\u2013diode array detection\u2013tandem mass spectrometry (HPLC\u2013DAD\u2013MS\/MS) of Berberis hispanica Boiss. & Reut. leaves","volume":"54","year":"2021","journal-title":"Anal. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Rapino, M., Di Valerio, V., Zara, S., Gallorini, M., Marconi, G.D., Sancilio, S., Marsich, E., Ghinassi, B., di Giacomo, V., and Cataldi, A. (2019). Chitlac-coated thermosets enhance osteogenesis and angiogenesis in a co-culture of dental pulp stem cells and endothelial cells. Nanomaterials, 9.","DOI":"10.3390\/nano9070928"},{"key":"ref_98","first-page":"883","article-title":"Central apelin-13 administration modulates hypothalamic control of feeding","volume":"30","author":"Ferrante","year":"2016","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/ptr.5655","article-title":"An hydroalcoholic chamomile extract modulates inflammatory and immune response in HT29 cells and isolated rat colon","volume":"30","author":"Menghini","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Gu, L., Lu, J., Li, Q., Wu, N., Zhang, L., Li, H., Xing, W., and Zhang, X. (2020). A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer\u2019s disease and experimental validation. J. Ethnopharmacol., 251.","DOI":"10.1016\/j.jep.2019.112488"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Di Giacomo, V., Chiavaroli, A., Recinella, L., Orlando, G., Cataldi, A., Rapino, M., Di Valerio, V., Ronci, M., Leone, S., and Brunetti, L. (2020). Antioxidant and neuroprotective effects induced by cannabidiol and cannabigerol in rat CTX-TNA2 astrocytes and isolated cortexes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103575"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/2\/233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:02:55Z","timestamp":1760133775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/2\/233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,17]]},"references-count":101,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["plants11020233"],"URL":"https:\/\/doi.org\/10.3390\/plants11020233","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,17]]}}}