Salehi B.Sharopov F.Tumer T.B.Ozleyen A.Rodrguez-Prez C.Ezzat S.M.Azzini E.Hosseinabadi T.Butnariu M.Sarac I.Bostan C.Acharya K.Sen S.Kasapoglu K.N.Da?kaya-Dikmen C.zelik B.Baghalpour N.Sharifi-Rad J.Fokou P.V.T.Cho W.C.Martins N.School of MedicineBam University of Medical SciencesBam44340847Iran; Department of Pharmaceutical TechnologyAvicenna Tajik State Medical UniversityRudaki 139Dushanbe734003Tajikistan; Department of Molecular Biology and GeneticsFaculty of Arts and ScienceCanakkale Onsekiz Mart UniversityCanakkale17020Turkey; Graduate Program of Biomolecular SciencesInstitute of Natural and Applied SciencesCanakkale Onsekiz Mart UniversityCanakkale17020Turkey; Department of Nutrition and Food ScienceUniversity of GranadaCampus of CartujaGranadaE-18071Spain; Institute of Nutrition and Food Technology (INYTA) 'Jos Mataix'Biomedical Research CentreUniversity of GranadaAvenida del Conocimiento s/nGranadaE-18071Spain; Pharmacognosy DepartmentFaculty of PharmacyCairo UniversityKasr El-Ainy StreetCairo11562Egypt; Department of PharmacognosyFaculty of PharmacyOctober University for Modern Science and Arts (MSA)6th October12566Egypt; Centre for Research on Food and NutritionCouncil for Agricultural Research and EconomicsRome546-00178Italy; Department of Pharmacognosy and BiotechnologySchool of PharmacyShahid Beheshti University of Medical SciencesTehran11369Iran; Banat's University of Agricultural Sciences and Veterinary Medicine King Michael I of Romania from TimisoaraCalea Aradului 119Timis300645Romania; Molecular and Applied Mycology and Plant Pathology LaboratoryDepartment of BotanyUniversity of CalcuttaKolkata700019India; Department of BotanyFakir Chand CollegeDiamond HarbourWest Bengal 743331India; Istanbul Technical UniversityChemical and Metallurgical Engineering FacultyFood Engineering DepartmentAyaza ga CampusMaslakIstanbul34469Turkey; Istanbul Gedik UniversityDepartment of Gastronomy and Culinary ArtsKartalIstanbul34876Turkey; Bioactive Research and Innovation Food Manufac.Indust. Trade Ltd.Katar StreetTeknokent ARI-3B110Sar?yerIstanbul34467Turkey; Phytochemistry Research CenterShahid Beheshti University of Medical SciencesTehran11369Iran; Zabol Medicinal Plants Research CenterZabol University of Medical SciencesZabol61615-585Iran; Antimicrobial and Biocontrol Agents UnitDepartment of BiochemistryFaculty of ScienceUniversity of Yaounde 1Ngoa EkelleAnnex Fac. SciYaounde812Cameroon; Department of Clinical OncologyQueen Elizabeth Hospital30 Gascoigne RoadHong KongHong Kong; Faculty of MedicineUniversity of PortoAlameda Prof. Hernni MonteiroPorto4200-319Portugal; Institute for Research and Innovation in Health (i3S)University of PortoPorto4200-135Portugal2020-01-092020-01-092019https://doi.org/10.3390/molecules24122272PubMedIDhttps://t.ly/GgxyrScopusMSA Google ScholarSymphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo. 2019 by the authors.Biological activityClinical trialsPhytochemistrySymphytum speciesantiinfective agentantioxidantphytochemicalanimalBoraginaceaechemistrydrug effectecosystemfood preservationhumanmusculoskeletal diseasephysiologytreatment outcomewound healingAnimalsAnti-Infective AgentsAntioxidantsBoraginaceaeEcosystemFood PreservationHumansMusculoskeletal DiseasesPhytochemicalsTreatment OutcomeWound Healinghttps://doi.org/10.3390/molecules24122272PubMedID