{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:16:51Z","timestamp":1783351011164,"version":"3.54.6"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:00:00Z","timestamp":1582588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"international Scientific Partnership Program ISPP at King Saud University","award":["ISPP# 008"],"award-info":[{"award-number":["ISPP# 008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Anaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been reported to cause anaphylactoid shock. Surprisingly, no therapeutic drugs are available which can directly target MRGPRX2 for treatment of anaphylactoid shock. Genistein is a non-steroidal polyphenol known for its diverse physiological and pharmacological activities. In recent studies, Genistein has been reported for its anti-inflammatory activity on mast cells. However, the effects and mechanistic pathways of Genistein on anaphylactoid reaction remain unknown. In the present study, we designed a battery of in-vitro, in-silico and in-vivo experiments to evaluate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action. The in-vitro results demonstrated the inhibitory activity of Genistein on MRGPRX2 activation. Further, a mouse model of anaphylactoid shock was used to evaluate the inhibitory activity of Genistein on blood vessel leakage and hind paw edema. Taken together, our findings have demonstrated a therapeutic potential of Genistein as a lead compound in the treatment of anaphylactoid shock via MRGPRX2.<\/jats:p>","DOI":"10.3390\/molecules25051028","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T03:21:16Z","timestamp":1582773676000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Protective Effect of Genistein against Compound 48\/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)"],"prefix":"10.3390","volume":"25","author":[{"given":"Mukesh","family":"Kumar","sequence":"first","affiliation":[{"name":"School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong,   China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong,   China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthi","family":"Duraisamy","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong,   China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Allam","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamaan","family":"Ajarem","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Kwok Chong CHOW","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong,   China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.3389\/fimmu.2018.03027","article-title":"Mas-related G protein-coupled receptor-X2 (MRGPRX2) in drug hypersensitivity reactions","volume":"9","author":"Porebski","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.iac.2007.03.013","article-title":"Mediators of anaphylaxis","volume":"27","author":"Ogawa","year":"2007","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_3","first-page":"138","article-title":"Anaphylactic and anaphylactoid reactions during the perioperative period","volume":"15","author":"Lagopoulos","year":"2011","journal-title":"Hippokratia"},{"key":"ref_4","first-page":"263","article-title":"Anaphylaxis during anaesthesia: Current aspects of diagnosis and prevention","volume":"11","author":"Fisher","year":"1994","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1093\/bja\/85.6.844","article-title":"Weal and flare responses to intradermal rocuronium and cisatracurium in humans","volume":"85","author":"Levy","year":"2000","journal-title":"Br. J. Anaesth."},{"key":"ref_6","first-page":"536","article-title":"Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999\u20132000","volume":"99","author":"Mertes","year":"2003","journal-title":"Anesthesiol. J. Am. Soc. Anesthesiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jaci.2008.09.043","article-title":"The etiology and incidence of anaphylaxis in Rochester, Minnesota: A report from the Rochester Epidemiology Project","volume":"122","author":"Decker","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.annfar.2004.10.013","article-title":"Anaphylactic and anaphylactoid reactions occurring during anaesthesia in France. Seventh epidemiologic survey (January 2001-December 2002)","volume":"23","author":"Mertes","year":"2004","journal-title":"Ann. Fr. D\u2019anesthesie Et De Reanim."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jaci.2003.11.033","article-title":"Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization","volume":"113","author":"Bohlke","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/thx.2004.038844","article-title":"Time trends in allergic disorders in the UK","volume":"62","author":"Gupta","year":"2007","journal-title":"Thorax"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1398-9995.2005.00785.x","article-title":"Epidemiology of life-threatening and lethal anaphylaxis: A review","volume":"60","author":"Morisset","year":"2005","journal-title":"Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jaci.2016.04.051","article-title":"Roles of Mas-related G protein\u2013coupled receptor X2 on mast cell\u2013mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases","volume":"138","author":"Subramanian","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1369\/0022155414545334","article-title":"Mast cell function: A new vision of an old cell","volume":"62","author":"Jamur","year":"2014","journal-title":"J. Histochem. Cytochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature14022","article-title":"Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions","volume":"519","author":"McNeil","year":"2015","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.bbrc.2006.08.177","article-title":"Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors","volume":"349","author":"Tatemoto","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1124\/pr.113.008425","article-title":"Pharmacology and signaling of MAS-related G protein\u2013coupled receptors","volume":"66","author":"Solinski","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alexander, S.P., Battey, J., Benson, H.E., Benya, R.V., Bonner, T.I., Davenport, A.P., Eguchi, S., Harmar, A., Holliday, N., and Jensen, R.T. (2019). Class A Orphans (version 2019.5) in the IUPHAR\/BPS Guide to Pharmacology Database. Iuphar\/Bps Guide Pharmacol. Cite, 2019.","DOI":"10.2218\/gtopdb\/F16\/2019.5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11628","DOI":"10.1038\/s41598-018-29965-8","article-title":"MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia","volume":"8","author":"Lafuente","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jaci.2018.01.034","article-title":"Mast cells signal their importance in health and disease","volume":"142","author":"Olivera","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s40629-014-0009-1","article-title":"Guideline for acute therapy and management of anaphylaxis","volume":"23","author":"Ring","year":"2014","journal-title":"Allergo J. Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Maleki, S.J., Crespo, J.F., and Cabanillas, B. (2019). Anti-inflammatory effects of flavonoids. Food Chem., 125124.","DOI":"10.1016\/j.foodchem.2019.125124"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, F.-C., Wang, C.-C., Lu, J.-W., Lee, C.-H., Chen, S.-C., Ho, Y.-J., and Peng, Y.-J. (2019). Chondroprotective Effects of Genistein against Osteoarthritis Induced Joint Inflammation. Nutrients, 11.","DOI":"10.3390\/nu11051180"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Abron, J.D., Singh, N.P., Price, R.L., Nagarkatti, M., Nagarkatti, P.S., and Singh, U.P. (2018). Genistein induces macrophage polarization and systemic cytokine to ameliorate experimental colitis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199631"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108665","DOI":"10.1016\/j.cbi.2019.05.031","article-title":"A review on protective role of genistein against oxidative stress in diabetes and related complications","volume":"310","author":"Weng","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jcjd.2019.04.007","article-title":"Effectiveness of genistein supplementation on metabolic factors and antioxidant status in postmenopausal women with type-2 diabetes mellitus","volume":"43","author":"Braxas","year":"2019","journal-title":"Can. J. Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1158\/1940-6207.CAPR-17-0289","article-title":"Genistein Prevents Development of Spontaneous Ovarian Cancer and Inhibits Tumor Growth in Hen Model","volume":"12","author":"Sahin","year":"2019","journal-title":"Cancer Prev. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3945\/an.114.008052","article-title":"Genistein and cancer: Current status, challenges, and future directions","volume":"6","author":"Spagnuolo","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4077\/CJP.2018.BAG518","article-title":"Genistein Suppressing the ROS-Induced Hypersensitivity of Rat Vagal Lung C-Fiber Afferents through an ER\u03b1-Mediated Mechanism","volume":"61","author":"Yeh","year":"2018","journal-title":"Chin. J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10616-017-0129-9","article-title":"A new method to evaluate anti-allergic effect of food component by measuring leukotriene B 4 from a mouse mast cell line","volume":"70","author":"Takasugi","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.3892\/ijmm.2014.1956","article-title":"Genistein inhibits pro-inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway","volume":"34","author":"Kim","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature25025","article-title":"Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727","volume":"553","author":"Robertson","year":"2018","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: Patterns of nonbonded atomic interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/0167-5699(90)90176-A","article-title":"Mast cells as a source of multifunctional cytokines","volume":"11","author":"Gordon","year":"1990","journal-title":"Immunol. Today"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/imr.12634","article-title":"Mast cells as sources of cytokines, chemokines, and growth factors","volume":"282","author":"Mukai","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00547","DOI":"10.1002\/prp2.547","article-title":"MrgX2 is a promiscuous receptor for basic peptides causing mast cell pseudo-allergic and anaphylactoid reactions","volume":"7","author":"Grimes","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.bcp.2017.12.017","article-title":"Saikosaponin A inhibits compound 48\/80-induced pseudo-allergy via the Mrgprx2 pathway in vitro and in vivo","volume":"148","author":"Wang","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/JLB.2AB1018-405R","article-title":"Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells","volume":"106","author":"Ogasawara","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.intimp.2018.11.025","article-title":"Quercetin inhibits Mrgprx2-induced pseudo-allergic reaction via PLC\u03b3-IP3R related Ca2+ fluctuations","volume":"66","author":"Ding","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153149","DOI":"10.1016\/j.phymed.2019.153149","article-title":"Inhibitory function of Shikonin on MRGPRX2-mediated pseudo-allergic reactions induced by the secretagogue","volume":"68","author":"Wang","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_40","first-page":"589","article-title":"Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay","volume":"48","author":"Alley","year":"1988","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/0471142735.im0738s91","article-title":"Measuring mast cell mediator release","volume":"91","author":"Kuehn","year":"2010","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.yexcr.2014.11.014","article-title":"Tryptase, a novel angiogenic factor stored in mast cell granules","volume":"332","author":"Ribatti","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0014-2999(85)90687-9","article-title":"Histamine release induced from mast cells by active components of compound 4880","volume":"115","author":"Koibuchi","year":"1985","journal-title":"Eur. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3844\/ajavsp.2016.61.69","article-title":"Development of a short-term canine full-thickness skin organ culture method under serum-free conditions","volume":"11","author":"Abramo","year":"2016","journal-title":"Am. J. Anim. Vet. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Schemann, M., Kugler, E.M., Buhner, S., Eastwood, C., Donovan, J., Jiang, W., and Grundy, D. (2012). The mast cell degranulator compound 48\/80 directly activates neurons. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052104"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1476-5381.2010.01127.x","article-title":"Principles of early drug discovery","volume":"162","author":"Hughes","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Li, J., Fu, A., and Zhang, L. (2019). An overview of scoring functions used for protein\u2013ligand interactions in molecular docking. Interdiscip. Sci. Comput. Life Sci., 1\u20139.","DOI":"10.1007\/s12539-019-00327-w"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/S0959-440X(96)80061-3","article-title":"Computational methods for biomolecular docking","volume":"6","author":"Lengauer","year":"1996","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: New development for protein structure and function predictions","volume":"43","author":"Yang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/bioinformatics\/18.11.1548","article-title":"Ramachandran plot on the web","volume":"18","author":"Sheik","year":"2002","journal-title":"Bioinformatics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jpba.2010.03.011","article-title":"Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC\u2013MS\/MS method: Application to an oral bioavailability study of genistein in mice","volume":"53","author":"Yang","year":"2010","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0014-2999(02)02449-4","article-title":"Genistein, an isoflavone included in soy, inhibits thrombotic vessel occlusion in the mouse femoral artery and in vitro platelet aggregation","volume":"455","author":"Kondo","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","first-page":"e50062","article-title":"An in vivo assay to test blood vessel permeability","volume":"73","author":"Radu","year":"2013","journal-title":"Jove (J. Vis. Exp.)"},{"key":"ref_54","first-page":"7","article-title":"Generation, isolation, and maintenance of human mast cells and mast cell lines derived from peripheral blood or cord blood","volume":"90","author":"Jensen","year":"2010","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0006-3002(63)90513-4","article-title":"Studies on succinate-tetrazolium reductase systems: III. Points of coupling of four different tetrazolium salts III. Points of coupling of four different tetrazolium salts","volume":"77","author":"Slater","year":"1963","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nsmb.3014","article-title":"PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome","volume":"22","author":"Kroeze","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"Th e protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: Protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_63","unstructured":"Schrodinger, L. (The PyMOL Molecular Graphics System, 2015). The PyMOL Molecular Graphics System, version 1.8."},{"key":"ref_64","unstructured":"Research, D.E.S. (2017). Desmond Molecular Dynamics System, D.\u2005E. Shaw Research, Schr\u00f6dinger. version 3.4."},{"key":"ref_65","unstructured":"Dassault Syst\u00e8mes BIOVIA (2017). Discovery Studio Modeling Environment, Dassault Syst\u00e8mes."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/5\/1028\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:01:38Z","timestamp":1760173298000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/5\/1028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,25]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["molecules25051028"],"URL":"https:\/\/doi.org\/10.3390\/molecules25051028","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,25]]}}}