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 ofOriganum vulgareL. 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 potentin vitroantioxidant 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 fromin vitroapoptosis 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.

Background and purpose:  The effects of hydrogen peroxide (H₂O₂) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca²⁺)‐induced] and the effect of such treatment on anti‐oxidative enzyme activities.Experimental approach:  Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca²⁺ (6 mM) and treated with H₂O₂ (2 µM–3 mM) over 2 h. Anti‐oxidative enzyme activities (manganese superoxide dismutase‐MnSOD, copper‐zinc superoxide dismutase‐CuZnSOD, catalase‐CAT, glutathione peroxidase‐GSHPx and glutathione reductase‐GR) in H₂O₂‐treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca²⁺‐induced contractions, without treatment with H₂O₂. The effect of inhibitors (propranolol, methylene blue, L‐NAME, tetraethylamonium, glibenclamide and 4‐aminopyridine) on H₂O₂‐mediated relaxation was explored.Key results:  H₂O₂ caused concentration‐dependent relaxation of both spontaneous and Ca²⁺‐induced uterine contractions. After H₂O₂ treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca²⁺‐induced rat uteri) were decreased. N^ω‐nitro‐L‐arginine methyl ester antagonized the effect of H₂O₂ on Ca²⁺‐induced contractions. H₂O₂‐induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4‐aminopyridine and glibenclamide, with the last compound being the least effective.Conclusions and implications:  H₂O₂ induced dose‐dependent relaxation of isolated rat uteri mainly via changes in voltage‐dependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti‐oxidative pathways may lead to new approaches to the management of dysfunctional uteri.