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Luca Gallelli,1,2 Erika Cione,3 Tian Wang,4 Leiming Zhang4 1Department of Health Science, School of Medicine, Operative Unit of Clinical Pharmacology, Mater Domini University Hospital, Catanzaro, Italy; 2Research Center FAS@UMG, University Magna Graecia of Catanzaro, Catanzaro, Italy; 3Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018– 2022, University of Calabria, Rende, 87036, CS, Italy; 4Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, People’s Republic of ChinaCorrespondence: Luca GallelliDepartment of Health Science, School of Medicine, Operative Unit of Clinical Pharmacology, Mater Domini University Hospital, Catanzaro, ItalyTel +39 0961712322Email gallelli@unicz.itLeiming ZhangKey Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, People’s Republic of ChinaTel +86 5356706066Email zhangleiming2009@126.comAbstract: Saponins are a group of compounds used in clinical practice in the management of several diseases. Escin is a natural mixture of triterpene saponins which mainly consist of several isoforms, in which the α- and β-escin are predominant. β-escin is the major active compound that exerts a therapeutic effect by relieving tissue edema, promoting venous drainage, and reducing inflammation. In this review, we describe the features of its glucocorticoid-like activity that could explain its clinical effects. Using PubMed, Embase Cochrane library and reference lists for articles published until October 01, 2020, we documented that escin is likely able to exert its anti-inflammatory and anti-edematous effects through a glucocorticoid-like activity, but without the development of glucocorticoid-like adverse drug reactions.Keywords: escin, mechanism of action, glucocorticoid-like activity, clinical efficacy