Sürdürülebilir Kalkınma Amaçları

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• MakaleAçık Erişim2026Scopus SJRQ1/r/munzur/1500
  Effects 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.

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• MakaleAçık Erişim2026Scopus SJRQ1/r/munzur/1310
  Modulation of SIRT1/PPARγ pathways and tight junction proteins by nicotinamide riboside under chronic variable stress

  Celik, Abdullah; Sahin, Nurhan; Orhan, Cemal; Er, Besir; Erten, Fusun; Ozmen, Busra; Tuzcu, Mehmet; Ozercan, Ibrahim Hanifi; Sahin, Kazim

  Abstract: Chronic stress disrupts homeostasis, leading to major health problems such as liver damage, intestinal barrier dysfunction, and impaired glucose metabolism. Although current treatments, including anxiolytics, sedatives, antidepressants, and beta blockers, are effective, their adverse effects emphasize the need for safer alternatives. Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), plays a central role in energy metabolism and oxidative stress regulation; elevated NAD + levels have been associated with reduced risk of chronic diseases such as obesity and type 2 diabetes. However, the effects of NR on liver metabolism, intestinal barrier integrity, and related protein pathways remain unclear. This study investigated the effects of NR supplementation in rats exposed to chronic variable stress (CVS). Fifty-six male Sprague Dawley rats were divided into normal and CVS groups and treated in a 2 × 4 factorial design with 0, 150, 300, or 600 mg/kg NR. Under CVS conditions, serum glucose, corticosterone, ACTH, and insulin levels increased, whereas NAD+, NADPH, nicotinamide (NAM), and nicotinic acid (NA) decreased significantly (p < 0.001). NR supplementation effectively corrected these biochemical imbalances and upregulated hepatic markers, including PPARγ, SIRT1, GLUT2, IRS1, and FASN (p < 0.001). Furthermore, the increased expression of key transport proteins such as PepT1, LAT2, EAAT3, FABP2, and FATP4 contributed to maintaining intestinal barrier integrity and improving gut health. NR also promoted the recovery of tight and adherens junction proteins. Notably, high-dose NR (600 mg/kg) markedly alleviated liver fibrosis, improved glucose metabolism, and strengthened intestinal barrier function, demonstrating its therapeutic potential as an alternative strategy against stress-induced metabolic disorders. Key points: • NR mitigated chronic stress-induced liver, intestinal, and glucose dysregulation. • NR improved glycemia and NAD⁺-related biomarkers under stress. • NR reduced hepatic fibrosis markers. • NR strengthened TJ/AJ proteins, supporting intestinal barrier integrity. • Findings support NR’s therapeutic potential in stress-related metabolism.

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• MakaleAçık Erişim2026Scopus SJRQ2/r/munzur/1258
  Effects of fenugreek and shatavari on vasomotor and hormonal balance in ovariectomized rats

  Erten, Füsun; Er, Beşir; Orhan, Cemal; Morde, Abhijeet A.; Padigaru, Muralidhara; Şahin, Kazim

  Trigonella foenum-graecum L. (fenugreek, TFG) and Asparagus racemosus Willd. (shatavari, AR) have been extensively used in Ayurvedic, Unani, and traditional folk medicine to support women’s health. TFG seeds are traditionally employed as galactagogues and hormonal modulators, while AR roots are valued as rejuvenating tonics with phytoestrogenic activity, prescribed for menopausal complaints and reproductive well-being. Both plants also exhibit antioxidant and hepatoprotective effects, suggesting their potential as safe, nonhormonal alternatives to conventional hormone replacement therapy. This study investigated the dose-dependent effects of TFG and AR, administered individually or in combination, on vasomotor symptoms, hormonal balance, oxidative stress, and neuroendocrine markers in an ovariectomized (OVX) rat model of menopause. Adult female rats underwent bilateral ovariectomy and were randomized into eight groups: Control, OVX, OVX+TFG (30 and 60 mg/kg), OVX+AR (30 and 60 mg/kg), and OVX+TFG/AR combinations. Treatments were administered orally for 8 days. Tail, core, and skin temperatures were recorded to assess thermoregulation, while blood and tissue samples were analyzed for hormone levels, oxidative stress, and molecular markers. OVX rats showed classical menopausal alterations, including increased follicle-stimulating hormone, luteinizing hormone, cortisol, and malondialdehyde, and decreased 17β-estradiol, progesterone, dopamine, and antioxidant enzymes, along with dysregulated neuroendocrine markers. All treatments partially reversed these changes, while the high-dose combination (TFG/AR 60 mg/kg each) demonstrated the most pronounced effects, normalizing hormone levels, reducing hot-flash-like temperature fluctuations, restoring antioxidant activity, downregulating neuroendocrine markers (c-FOS, GnRH, Kisspeptin, NKB, and TRPV1) expression, and elevating brain-derived neurotrophic factor levels (p < 0.05). High-dose combined supplementation of TFG and AR effectively alleviates vasomotor disturbances, restores hormonal and oxidative balance, and modulates neuroendocrine pathways in OVX rats. These findings validate their traditional use and highlight their potential as safe phytoestrogen-based, nonhormonal alternatives for the management of menopausal symptoms, warranting further clinical evaluation.

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• MakaleAçık Erişim2026Scopus SJRQ2/r/munzur/1254
  Water extracts of Fucus vesiculosus and Laminaria digitata enhance male reproductive parameters via antioxidant and NO/cGMP mechanisms in rats

  Gencoglu, Hasan; Erten, Fusun; Er, Besir; Orhan, Cemal; Acisu, Tutku Can; Sahin, Kazim

  Male sexual dysfunction is increasingly prevalent, driving interest in marine algal bioactives as potential natural modulators of reproductive physiology. Brown seaweeds such as Fucus vesiculosus and Laminaria digitata contain phlorotannins, fucoidans, and antioxidant compounds of applied relevance in phycology and biotechnology. This study assessed the effects of standardized water extracts of these two species on reproductive behavior, hormonal status, sperm quality, oxidative balance, and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling in male Sprague–Dawley rats. Animals received the seaweed extracts orally by gavage (300 mg kg⁻1 day⁻1) for 52 days. Both extracts improved male reproductive behavior by reducing the time required to initiate mounting, intromission, and ejaculation (mount latency, intromission latency, and ejaculation latency), while increasing the number of these sexual behaviors during the test period (p < 0.05). Serum follicle-stimulating hormone and testosterone concentrations increased, alongside higher testicular superoxide dismutase, catalase, and glutathione peroxidase activities and lower malondialdehyde levels. Sperm count and motility improved, particularly with L. digitata extract. Western blot analyses revealed phosphorylated phosphodiesterase-5, endothelial NO synthase, and cGMP levels, with reduced endothelin-1 in testicular and epididymal tissues (p < 0.05–0.001). These findings indicate that extracts of F. vesiculosus and L. digitata, chosen for their well-documented antioxidant and phlorotannin-rich profiles, confer protective and prosexual effects associated with enhanced antioxidant defense and upregulation of NO/cGMP-related pathways, with the L. digitata extract exhibiting comparatively stronger activity.

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• MakaleYalnız künye2026Scopus SJRQ1/r/munzur/1022
  Boron source–dependent regulation of bone mineralization and osteogenic molecular pathways in broilers with tibial dyschondroplasia

  Orhan, Cemal; Sahin, Emre; Erten, Fusun; Er, Besir; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Kom, Mustafa; Akdemir, Fatih; Balci, Tansel Ansal; Denli, Muzaffer

  Rapid genetic selection for growth rate and slaughter weight in broilers has been associated with a higher incidence of skeletal disorders, particularly tibial dyschondroplasia (TD), which causes considerable economic losses in poultry production. We investigated the effects of boric acid (BA) and sodium pentaborate pentahydrate (SPP) on growth performance, bone mineralization, tibial histopathology, and osteogenic protein expression in broilers with manganese (Mn) deficiency-induced TD. A total of 360 Ross 308 broiler chicks were used in a 2 × 2 × 3 factorial design with TD status (normal or Mn deficiency–induced TD), boron source (BA or SPP), and supplemental boron level (0, 4.37, and 8.74 mg elemental B/kg diet). Birds were randomly allocated to 12 groups with six replicates of five birds each. Clinical and histopathological findings confirmed TD induction. TD decreased body weight, feed intake, and carcass weight, while increasing feed conversion ratio (p < 0.05). Boron supplementation improved tibial mineral density and content in a dose-dependent manner (p < 0.05). In TD broilers, serum osteocalcin (OCN) concentrations were higher with high-level SPP supplementation than with BA supplementation (p = 0.012). Boron source and level significantly affected serum and bone boron concentrations, bone calcium concentrations (p < 0.05). In TD broilers, tibial osteoprotegerin levels were markedly elevated in the high-level SPP group (p < 0.001), whereas SRY-box transcription factor 9, hypoxia-inducible factor-1α, and tumor necrosis factor-α were reduced (p < 0.05). These findings indicate that SPP exerts regulatory effects on bone metabolism and osteogenic signaling pathways in TD-affected broilers.

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• MakaleAçık Erişim2025Scopus SJRQ1/r/munzur/938
  Effects of Integrated Extracts of Trigonella foenum-graecum and Asparagus racemosus on Hot Flash-like Symptoms in Ovariectomized Rats

  Erten, Fusun; Er, Besir; Ozmen, Ramazan; Tokmak, Muhammed; Gokdere, Ebru; Orhan, Cemal; Morde, Abhijeet A.; Padigaru, Muralidhara; Sahin, Kazim

  Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for alleviating menopausal symptoms in ovariectomized rats. Following bilateral ovariectomy, the animals were randomly assigned to nine groups: (1) Control, (2) Ovariectomy (OVX), (3) OVX+TA1 (TA: Combination of Trigonella and Asparagus; TFG 30 mg/kg + AR 30 mg/kg), (4) OVX+TA2 (TFG 30 mg/kg + AR 15 mg/kg), (5) OVX+TA3 (TFG 15 mg/kg + AR 30 mg/kg), (6) OVX+TA4 (TFG 40 mg/kg + AR 30 mg/kg), (7) OVX+TA5 (TFG 30 mg/kg + AR 40 mg/kg), (8) OVX+IAT1 (IAT: Integrated Asparagus and Trigonella; TFG+AR integrated extract, 30 mg/kg), and (9) OVX+IAT2 (TFG+AR integrated extract, 60 mg/kg). On the 8th day of treatment, tail and skin temperatures were recorded every 30 min for 24 h. Ovariectomized rats exhibited menopausal symptoms, such as hormonal imbalances and elevated skin temperature. Administration of AR, TFG, and IAT significantly decreased serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol while increasing estradiol, progesterone, and dopamine (p < 0.0001), effectively alleviating hot flash-like symptoms. Additionally, they mitigated ovariectomy-induced oxidative stress by lowering malondialdehyde (MDA) levels and restoring antioxidant enzyme activity. Ovariectomized rats exhibited increased expression of a proto-oncogene (c-FOS), gonadotropin-releasing hormone (GnRH), Kisspeptin, Neurokinin B (NKB), and Transient receptor potential vanilloid 1 (TRPV1), along with reduced expressing brain-derived neurotrophic factor (BDNF) levels, which were reversed by treatment, especially with the IAT2 combination. The AR and TFG combination, particularly in IAT formulations, showed strong potential in alleviating menopausal symptoms in ovariectomized rats. These findings suggest that the combination of AR and TFG extracts could be a natural alternative for managing postmenopausal symptoms by restoring reproductive hormone levels, regulating lipid profiles, and enhancing antioxidant defense systems.

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  AtıfScopus8·WoS8·OpenAlex6

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• MakaleAçık Erişim2024Scopus SJRQ1/r/munzur/1974
  Impact 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.

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  AtıfScopus19·OpenAlex19

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• MakaleAçık Erişim2023Scopus SJRQ1/r/munzur/2518
  Effects of a Combination of Arginine Silicate Inositol Complex and a Novel Form of Biotin on Hair and Nail Growth in a Rodent Model

  Demir, Betul; Cicek, Demet; Orhan, Cemal; Er, Besir; Erten, Fusun; Tuzcu, Mehmet; Ozercan, Ibrahim Hanifi; Sahin, Nurhan; Komorowski, James; Ojalvo, Sara Perez

  The purpose of this study was to examine the effects of a combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on hair and nail growth in an animal model. Twenty-eight female Sprague–Dawley rats (8 weeks old) were randomized into one of the following groups: (i) group (control), shaved; (ii) group (ASI), shaved + ASI (4.14 mg/rat/day); (iii) group (ASI + MgB I), shaved + ASI (4.14 mg/rat/day) + MgB (48.7 μg/rat/day); and (iv) group (ASI + MgB II), shaved + ASI (4.14 mg/rat/day) + MgB (325 μg/rat/day). On day 42, compared with the control group, while hair density (p < 0.05, p < 0.01, and p < 0.0001, respectively) and anagen ratio (p < 0.01, p < 0.01, and p < 0.001) increased in the ASI, ASI + MgB I, and ASI + MgB II groups, telogen ratio decreased (p < 0.01, p < 0.01, and p < 0.001, respectively). In the molecular analysis, VEGF, HGF, and KGF-2 increased in the ASI (p < 0.01, p < 0.01, and p < 0.05, respectively), ASI + MgB I (p < 0.0001 for all), and ASI + MgB II (p < 0.0001 for all) groups when compared to the control group. FGF-2 (p < 0.01) and IGF-1 (p < 0.001) were found to be increased in the ASI + MgB I and ASI + MgB II groups. SIRT-1 and β-catenin increased in the ASI (p < 0.05 and p < 0.01), ASI + MgB I (p < 0.001 for both), and ASI + MgB II (p < 0.0001 for both) groups. Wnt-1 increased in the ASI + MgB I (p < 0.001) and ASI + MgB II (p < 0.0001) groups. In conclusion, the combination of ASI and MgB could promote hair growth by regulating IGF-1, FGF, KGF, HGF, VEGF, SIRT-1, Wnt, and β-catenin signal pathways. It was also established that ASI did not affect nail growth, whereas the MgB combination was effective using a higher dose of biotin.

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  AtıfScopus11·WoS9·OpenAlex11

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• MakaleAçık Erişim2023Scopus SJRQ1/r/munzur/2314
  Evaluation of pea/rice and amylopectin/chromium as an alternative protein source to improve muscle protein synthesis in rats

  Ozdemir, Oguzhan; Erten, Fusun; Er, Besir; Orhan, Cemal; Komorowski, James R.; Sylla, Sarah; Perez Ojalvo, Sara; Sahin, Kazim

  Background: A preclinical study reported that the combination of an amylopectin/chromium complex (ACr) of branched-chain amino acids (BCAA) significantly enhanced muscle protein synthesis (MPS). This study was conducted to determine the effects of the addition of ACr complex to a pea/rice (PR) protein on MPS, insulin, muslin levels, and the mTOR pathway in exercised rats. Methods: Twenty-four rats were divided into three groups: (i) exercise (Ex); (ii) Ex + PR 1:1 blend (0.465 g/kg BW); (iii) Ex + PR + ACr (0.155 g/kg BW). On the day of single-dose administration, after the animals were exercised at 26/m/min for 2 h, the supplement was given by oral gavage. The rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of deuterium-labeled phenylalanine to determine the protein fractional synthesis rate (FSR) one h after consuming the study product. Results: The combination of PR and ACr enhanced MPS by 42.55% compared to the Ex group, while Ex + PR alone increased MPS by 30.2% over the Ex group (p < 0.0001) in exercised rats. Ex + PR plus ACr significantly enhanced phosphorylation of mTOR and S6K1 (p < 0.0001), and 4E-BP1 (p < 0.001) compared to the Ex (p < 0.0001). PR to ACr also significantly increased insulin and musclin levels (p < 0.0001) in exercised rats. Additionally, compared to Ex + PR alone, Ex + PR + ACr enhanced mTOR (p < 0.0001) and S6K1 (p < 0.0001) levels. Conclusion: These data suggested that PR + ACr may provide an alternative to animal proteins for remodeling and repairing muscle by stimulating MPS and mTOR signaling pathways in post-exercised rats. More preclinical and clinical human studies on combining pea/rice and amylopectin/chromium complex are required.

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  AtıfScopus4·OpenAlex4

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• MakaleAçık Erişim2021Scopus SJRQ3/r/munzur/3569
  Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats

  Orhan, Cemal; Erten, Füsun; Er, Beşir; Tuzcu, Mehmet; Şahin, Nurhan; Durmaz Kurşun, Öznur Ece; Juturu, Vijaya; Şahin, Kazim

  Background/aim: This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats. Materials and methods: Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results: Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (p < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group. Conclusion: These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.

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  AtıfScopus15·WoS13·OpenAlex14

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