title: Efficacy of AdipoDren® in Reducing Interleukin-1-Induced Lymphatic Endothelial Hyperpermeability.
abstract: Lymphatic leakage can be seen as a detrimental phenomenon associated with fluid retention and deposition as well as gain of weight. Moreover, lymphatic dysfunction is associated with an inflammatory environment and can be a substrate for other health conditions. A number of treatments can ameliorate lymphatic vasculature: natural substances have been used as treatment options particularly suitable for their consolidated effectiveness and safety profile. Here we report the protective effect of AdipoDren®, an association of a series of plant-derived natural complexes, on lymphatic endothelium permeability promoted by interleukin-1 beta (IL-1β) and the associated molecular mechanisms. AdipoDren® demonstrated a protective effect on dermal lymphatic endothelial cell permeability increased by IL-1β. Reduced permeability was due to the maintenance of tight junctions and cell-cell localisation of occludin and zonula occludens-1 (ZO-1). Moreover, AdipoDren® reduced the expression of the inflammatory key element cyclooxygenase-2 (COX-2), while not altering the levels of endothelial and inducible nitric oxide synthases (eNOS and iNOS). The upregulation of antioxidant enzymatic systems (catalase and superoxide dismutase-1, SOD-1) and the downregulation of pro-oxidant markers (p22 phox subunit of NADPH oxidase) were also evident. In conclusion, AdipoDren® would be useful to ameliorate conditions of altered lymphatic vasculature and to support the physiological functionality of the lymphatic endothelium.
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Ciccone
authors.forename: Martina
authors.initials: M
authors.lastname: Monti
authors.forename: Giulia
authors.initials: G
authors.lastname: Antonini
authors.forename: Luisa
authors.initials: L
authors.lastname: Mattoli
authors.forename: Michela
authors.initials: M
authors.lastname: Burico
authors.forename: Francesca
authors.initials: F
authors.lastname: Marini
authors.forename: Anna
authors.initials: A
authors.lastname: Maidecchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Morbidelli
mesh_terms: D002199:Capillary Permeability / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008209:Lymphedema / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D012431:Rutin / Q000494:pharmacology; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C000618854:AdipoDren; D053583:Interleukin-1beta; C568985:OCLN protein, human; D062793:Occludin; D010936:Plant Extracts; D028321:Plant Preparations; C000606290:SOD1 protein, human; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D012431:Rutin; D002374:Catalase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; C086986:CYBA protein, human