title: St. John's wort extract and hyperforin protect rat and human pancreatic islets against cytokine toxicity.
abstract: The extract of Hypericum perforatum (St. John's wort, SJW) and its component hyperforin (HPF) were previously shown to inhibit cytokine-induced activation of signal transducer and activator of transcription-1 and nuclear factor κB and prevent apoptosis in a cultured β-cell line. Objective of this study was to assess the protection exerted by SJW and HPF on isolated rat and human islets exposed to cytokines in vitro. Functional, ultrastructural, biomolecular and cell death evaluation studies were performed. In both rat and human islets, SJW and HPF counteracted cytokine-induced functional impairment and down-regulated mRNA expression of pro-inflammatory target genes, such as iNOS, CXCL9, CXCL10, COX2. Cytokine-induced NO production from cultured islets, evaluated by nitrites measurement in the medium, was significantly reduced in the presence of the vegetal compounds. Noteworthy, the increase in apoptosis and necrosis following 48-h exposure to cytokines was fully prevented by SJW and partially by HPF. Ultrastructural morphometric analysis in human islets exposed to cytokines for 20 h showed that SJW or HPF avoided early β-cell damage (e.g., mitochondrial alterations and loss of insulin granules). In conclusion, SJW compounds protect rat and human islets against cytokine effects by counteracting key mechanisms of cytokine-mediated β-cell injury and represent promising pharmacological tools for prevention or limitation of β-cell dysfunction and loss in type 1 diabetes.
authors.forename: Michela
authors.initials: M
authors.lastname: Novelli
authors.forename: Pascale
authors.initials: P
authors.lastname: Beffy
authors.forename: Marta
authors.initials: M
authors.lastname: Menegazzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Tata
authors.forename: Luisa
authors.initials: L
authors.lastname: Martino
authors.forename: Anna
authors.initials: A
authors.lastname: Sgarbossa
authors.forename: Svetlana
authors.initials: S
authors.lastname: Porozov
authors.forename: Anna
authors.initials: A
authors.lastname: Pippa
authors.forename: Matilde
authors.initials: M
authors.lastname: Masini
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Masiello
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000633:toxicity*; D019610:Cytoprotection / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D020902:Hypericum / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007328:Insulin; D010936:Plant Extracts; D013729:Terpenes; D010696:Phloroglucinol; D005947:Glucose; C001654:hyperforin