title: Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice.
abstract: Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MS(n) ). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4(+) and activated CD4(+) CD25(+) T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.
authors.affiliation: Dept. of Immunology, Inst. for Biological Research "Sinisa Stankovic,", Univ. of Belgrade, 11060, Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Vujicic
authors.affiliation: Dept. of Immunology, Inst. for Biological Research "Sinisa Stankovic,", Univ. of Belgrade, 11060, Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Nikolic
authors.affiliation: Dept. of Chemistry, Section of Organic Chemistry and Biochemistry, Univ. of Ioannina, GR-45110, Ioannina, Greece.
authors.forename: Vassiliki G
authors.initials: VG
authors.lastname: Kontogianni
authors.affiliation: Dept. of Immunology, Inst. for Biological Research "Sinisa Stankovic,", Univ. of Belgrade, 11060, Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Saksida
authors.affiliation: Dept. of Chemistry, Section of Organic Chemistry and Biochemistry, Univ. of Ioannina, GR-45110, Ioannina, Greece.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Charisiadis
authors.affiliation: Dept. of Immunology, Inst. for Biological Research "Sinisa Stankovic,", Univ. of Belgrade, 11060, Belgrade, Serbia.
authors.forename: Bobana
authors.initials: B
authors.lastname: Vasic
authors.affiliation: Dept. of Immunology, Inst. for Biological Research "Sinisa Stankovic,", Univ. of Belgrade, 11060, Belgrade, Serbia.
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stosic-Grujicic
authors.affiliation: Dept. of Chemistry, Section of Organic Chemistry and Biochemistry, Univ. of Ioannina, GR-45110, Ioannina, Greece.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Gerothanassis
authors.affiliation: Dept. of Chemistry, Section of Organic Chemistry and Biochemistry, Univ. of Ioannina, GR-45110, Ioannina, Greece.
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
authors.affiliation: Dept. of Immunology, Inst. for Biological Research "Sinisa Stankovic,", Univ. of Belgrade, 11060, Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojanovic
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D005434:Flow Cytometry; D006115:Greece; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D031341:Origanum / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D013311:Streptozocin; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010936:Plant Extracts; D014157:Transcription Factors; D013311:Streptozocin
keywords: Origanum vulgare L. ssp. hirtum; T lymphocytes; immune modulation; macrophages; type 1 diabetes