title: Methanolic extract of Origanum vulgare ameliorates type 1 diabetes through antioxidant, anti-inflammatory and anti-apoptotic activity.
abstract: Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as a consequence of pancreatic β-cell destruction and results in hyperglycaemia. Since current T1D therapy mainly involves insulin replacement, the aim of the present study was to evaluate the therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano) leaf extract rich in biophenols for the treatment of T1D. The phytochemical profile of methanolic oregano extract (MOE) and aqueous oregano extract (AOE) was determined by liquid chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while their main compounds were quantified by HPLC with diode array detection. After establishing their potent in vitro antioxidant activity, the extracts were administered to C57BL/6 mice treated with multiple low doses of streptozotocin for diabetes induction. While prophylactic AOE therapy had no impact on diabetes induction, MOE reduced diabetes incidence and preserved normal insulin secretion. In addition, MOE scavenged reactive oxygen and nitrogen species and, therefore, alleviated the need for the up-regulation of antioxidant enzymes. MOE treatment specifically attenuated the pro-inflammatory response mediated by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T regulatory cells through the impact on specific signalling pathways and transcription factors. Importantly, MOE preserved β-cells from in vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a predominant compound in MOE, exhibited only partial protection from diabetes induction. In conclusion, acting as an antioxidant, immunomodulator and in an anti-apoptotic manner, MOE protected mice from diabetes development. Seemingly, there is more than one compound responsible for the beneficial effect of MOE.
authors: Department of Immunology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,Bulevar despota Stefana 142,11060Belgrade,Serbia.
authors: Milica
authors: M
authors: Vujicic
authors: Department of Immunology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,Bulevar despota Stefana 142,11060Belgrade,Serbia.
authors: Ivana
authors: I
authors: Nikolic
authors: Department of Chemistry,Section of Organic Chemistry and Biochemistry, University of Ioannina,GR-45110Ioannina,Greece.
authors: Vassiliki G
authors: VG
authors: Kontogianni
authors: Department of Immunology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,Bulevar despota Stefana 142,11060Belgrade,Serbia.
authors: Tamara
authors: T
authors: Saksida
authors: Department of Chemistry,Section of Organic Chemistry and Biochemistry, University of Ioannina,GR-45110Ioannina,Greece.
authors: Pantelis
authors: P
authors: Charisiadis
authors: Department of Physiology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,11060Belgrade,Serbia.
authors: Zorana
authors: Z
authors: Orescanin-Dusic
authors: Department of Physiology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,11060Belgrade,Serbia.
authors: Dusko
authors: D
authors: Blagojevic
authors: Department of Immunology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,Bulevar despota Stefana 142,11060Belgrade,Serbia.
authors: Stanislava
authors: S
authors: Stosic-Grujicic
authors: Department of Chemistry,Section of Organic Chemistry and Biochemistry, University of Ioannina,GR-45110Ioannina,Greece.
authors: Andreas G
authors: AG
authors: Tzakos
authors: Department of Immunology,Institute for Biological Research "Sinisa Stankovic", University of Belgrade,Bulevar despota Stefana 142,11060Belgrade,Serbia.
authors: Ivana
authors: I
authors: Stojanovic
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000975:Antioxidants / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000178:diet therapy / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects / Q000032:analysis; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D000432:Methanol / Q000737:chemistry; D008810:Mice, Inbred C57BL; D031341:Origanum / Q000737:chemistry*; D018384:Oxidative Stress; D010936:Plant Extracts / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D012997:Solvents; D000432:Methanol
keywords: T regulatory cells