Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleAçık Erişim2026Scopus SJRQ1Effects of Melatonin Formulations on Caffeine-Evoked Cortical Activity and Pentobarbital-Induced Sleep in Mice
Sahin, Nurhan; Yabas, Mehmet; Er, Besir; Erten, Fusun; Kursun, Oznur Ece Durmaz; Cikim, Ismail Gurkan; Kaplan, Berkan; Erek, Gozde; Ozmen, Busra; Orhan, Cemal
Melatonin has chronobiotic, antioxidant, anti-inflammatory, and neuromodulatory properties, and its oral effects may vary according to formulation. This study compared conventional melatonin with a lipid-multiparticulate (LMP) formulation in two acute pharmacological mouse paradigms. Eighty-four male BALB/c mice were assigned to caffeine-evoked cortical activity or pentobarbital-induced sedative-hypnotic experiments. Mice received caffeine (7.5 mg/kg, i.p.) alone or with standard or LMP-melatonin (10 or 20 mg/kg, oral). ECoG recorded cortical electrical activity under urethane anaesthesia. In a separate cohort, latency to and duration of pentobarbital-induced loss of the righting reflex were measured. Circulating neurochemical and redox markers, as well as neurotransmitter- and inflammation-related gene and protein expression, were evaluated. Caffeine increased spike frequency and altered ECoG amplitude, together with unfavorable changes in circulating neurochemical and redox markers and in neurotransmitter receptor- and inflammation-related outcomes. Both melatonin formulations attenuated several of these changes in a dose-dependent manner, with the strongest effects generally observed in the high-dose LMP-melatonin group. Compared with conventional melatonin, LMP-melatonin produced greater modulation of ECoG activity, circulating biochemical markers, neurotransmitter-receptor expression, and IL-6 and TNF-α-related outcomes. LMP-melatonin also produced a greater reduction in the latency to and a greater prolongation of the duration of pentobarbital-induced loss of the righting reflex. LMP-melatonin produced greater formulation-dependent effects than conventional melatonin on caffeine-evoked cortical electrical activity, pentobarbital-induced sedative-hypnotic responses, and selected biochemical and molecular outcomes. However, pharmacokinetic exposure, physiological sleep stages, sleep architecture, sleep quality, and direct measures of neuronal injury were not assessed. Therefore, the findings do not directly establish enhanced bioavailability, physiological sleep promotion, or neuroprotection.
- MakaleAçık Erişim2024Scopus SJRQ1Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model
Sahin, Kazim; Gencoglu, Hasan; Korkusuz, Ahmet Kayhan; Orhan, Cemal; Aldatmaz, İsmail Ertuğ; Erten, Fusun; Er, Besir; Morde, Abhijeet; Padigaru, Muralidhara; Kilic, Ertugrul
Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.
AtıfScopus19OpenAlex19
İncele - MakaleAçık Erişim2021Scopus SJRQ2Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice
Gunal, Mehmet Yalcin; Sakul, Ayse Arzu; Caglayan, Ahmet Burak; Erten, Fusun; Kursun, Oznur Ece Durmaz; Kilic, Ertugrul; Sahin, Kazim
Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood–brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1β), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway.
AtıfScopus39OpenAlex40İncele