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Yayınlar
- MakaleAçık Erişim2026Scopus SJRQ1Ellagic Acid Mitigates Lead (Pb)-Induced Toxicity in Cyprinus carpio: A Multi-Biomarker Assessment of Hematological, Immunological, and Oxidative Stress Responses Supported by Molecular Docking
Eroglu, Mucahit; Cakmak, Mehmet Nuri; Pala, Aysegul; Uslu, Harun; Yonar, Serpil Mise; Ispir, Unal; Orhan, Cemal; Yonar, Muhammet Enis
Lead (Pb) is a widespread environmental pollutant that induces systemic toxicity in aquatic organisms primarily through oxidative stress, hematological disruption, and immune dysfunction. This study investigated the protective effects of ellagic acid (EA) against Pb-induced toxicity in common carp (Cyprinus carpio) using a multi-biomarker approach and molecular docking. Fish were assigned to six experimental groups: control, EA-treated, Pb-I, Pb-I + EA, Pb-II, and Pb-II + EA. Fish in the Pb-I and Pb-II groups were exposed to 2.5 and 5 mg/L Pb, respectively, while EA was administered via diet at 100 mg/kg for 14 days. At the end of the exposure period, hematological indices, innate immune parameters, and oxidative stress biomarkers were assessed in blood, liver, kidney, and gill tissues. Pb exposure caused marked hematological impairment, suppressed immune responses, increased malondialdehyde levels, and disrupted antioxidant defense by reducing SOD, CAT, GSH-Px, and GSH levels while increasing GST activity. In contrast, dietary EA supplementation significantly mitigated Pb-induced alterations, improved hematological and immunological responses, reduced lipid peroxidation, restored antioxidant capacity, and normalized GST activity to control levels. Molecular docking analyses further showed that EA interacts with hemoglobin and immunoglobulin M, supporting its potential role in preserving oxygen transport and immune functions under Pb-induced stress. Overall, the findings demonstrate that Pb-induced toxicity involves coordinated disruption of redox homeostasis and immune function, whereas EA exerts a multi-target protective effect through biochemical and molecular mechanisms. This study provides mechanistic insight into chemical-biological interactions and supports the potential application of natural bioactive compounds in mitigating heavy metal-induced toxicity.
- 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 Erişim2026Scopus SJRQ2Synergistic Effects of Caffeine and Paclitaxel in Breast Cancer Cells: Mechanistic Insights Into NF-κB and Nrf2 Signaling
Gencoglu, Hasan; Delioglu, Saime; Nergiz, Mehmet Akif; Metin, Rumeysa; Erten, Fusun; Tokmak, Muhammed; Orhan, Cemal; Sahin, Kazim
Breast cancer remains one of the most prevalent malignancies among women. Recent studies have explored the potential of phytochemicals such as caffeine as chemosensitizing agents in enhancing the efficacy of standard chemotherapeutics like paclitaxel. This study aimed to investigate the cytotoxic, apoptotic, inflammatory, and oxidative stress-related effects of caffeine alone and in combination with paclitaxel in MCF-7 cells. Cells were treated with various concentrations of caffeine (1–100 mM), paclitaxel (0–350 µg/mL), and their combinations for 24, 48, and 72 h. Cell viability was assessed using the MTS assay, and IC₅₀ values were calculated. The expression levels of Bax, Bcl-2, NF-κB, and Nrf2 proteins were analyzed by Western blotting. Both caffeine and paclitaxel induced time- and dose-dependent reductions in MCF-7 cell viability. The combination treatment showed synergistic cytotoxicity, with significantly lower IC₅₀ values compared to single-agent treatments. Western blot analysis showed that both treatments boosted pro-apoptotic Bax and decreased anti-apoptotic Bcl-2, with slightly less effect in the combination group. NF-κB levels increased considerably in caffeine and paclitaxel groups, but were lower in the combination group compared to paclitaxel alone, suggesting a possible reduction in inflammatory signaling. Nrf2 expression increased significantly with caffeine, suggesting oxidative stress responses. In MCF-7 cells, caffeine enhanced paclitaxel's pro-apoptotic and cytotoxic actions and modified inflammation and oxidative stress pathways in a complicated, dose-dependent manner. Cytotoxicity was synergistic; however, apoptotic and stress indicators may be antagonistic. In clinical circumstances, caffeine may be an adjuvant in breast cancer treatment, however mechanistic and in vivo investigations are needed.
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İncele - MakaleAçık Erişim2026Scopus SJRQ1Modulation 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.
- MakaleAçık Erişim2026Scopus SJRQ2Effects 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.
- MakaleAçık Erişim2026Scopus SJRQ2Water 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.
- MakaleYalnız künye2026Scopus SJRQ1Boron 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.
- MakaleAçık Erişim2025Scopus SJRQ1Effects 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.
AtıfScopus8WoS8OpenAlex6İncele - 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.
AtıfScopus19OpenAlex19İncele - MakaleAçık Erişim2023Scopus SJRQ3The effect of different boron compounds on nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism
Şahin, Emre; Orhan, Cemal; Erten, Füsun; Şahin, Fikrettin; Şahin, Nurhan; Şahin, Kazim
Background/aim: Gastrointestinal health is essential for maintaining a healthy lifestyle. Improving nutrient absorption and energy metabolism are the critical targets for intestinal health. This study aimed to determine the effects of different boron (B) derivatives on nutrient digestibility, intestinal nutrient transporters, and lipid metabolism in rats. Materials and methods: Twenty-one rats were allocated to three groups (n = 7) as follows: (i) Control, (ii) Sodium pentaborate pentahy-drate (SPP), and (iii) boric acid (BA). The rats were fed a chow diet (AIN-93M) and supplemented with 8 mg/kg elemental B from SPP (45.2 mg/kg BW) and BA (42.7 mg/kg BW) via oral gavage every other day for 12 weeks. The nutrient digestibility of rats in each group was measured using the indigestible indicator (chromium oxide, Cr2 O3, 0.20%). At the end of the experiment, animals were decapitated by cervical dislocation and jejunum, and liver samples were taken from each animal. The nutrient transporters and lipid-regulated transcription factors were determined by RT-PCR. Results: The nutrient digestibility (except for ash) was increased by SPP and BA supplementation (p < 0.05). SPP and BA-supplemented rats had higher jejunal glucose transporter 1 (GLUT1), GLUT2, GLUT5, sodium-dependent glucose transporter 1 (SGLT1), fatty acid transport protein-1 (FATP1), and FATP4 mRNA expression levels compared to nonsupplemented rats (p < 0.0001). BA-supplemented rats had remarkably higher peroxisome proliferator-activated receptor gamma (PPARγ) levels than nonsupplemented rats (p < 0.0001). In contrast, sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptor alpha (LxR-α), and fatty acid synthase (FAS) levels decreased by SPP supplementation compared to other groups (p < 0.05). Conclusion: SPP and BA administration enhanced nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism in rats.
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İncele - MakaleAçık Erişim2023Scopus SJRQ1Effects 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.
AtıfScopus11WoS9OpenAlex11İncele - MakaleAçık Erişim2023Scopus SJRQ1Evaluation 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.
AtıfScopus4OpenAlex4İncele - MakaleAçık Erişim2023Scopus SJRQ1The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats
Sahin, Emre; Orhan, Cemal; Erten, Fusun; Saiyed, Zainulabedin; Azari, Elnaz Karimian; Durkee, Shane; Sahin, Kazim
We investigated whether different doses of undenatured type II collagen (undenatured collagen, UC-II) help improve monosodium iodoacetate (MIA)-induced (osteoarthritis) OA in young and old rats. A total of 70 rats were divided into five groups: (1) control; (2) MIA (a single intra-articular injection of MIA); (3)–(5) MIA+ Undenatured Collagen with various oral doses (0.66, 1.33, and 2 mg/kg). The results showed that all doses of undenatured collagen in both age groups reduced knee diameter, while the two higher doses (1.33 mg/kg and 2 mg/kg) reduced the Mankin score and increased most gait measurements as early as day 14 compared to the MIA rats. However, the 2 mg/kg dose showed the best efficacy in improving Mankin score and gait measurements by 28 days post-OA induction. In young but not old rats, all doses of undenatured collagen reduced the Kellgren-Lawrence score compared to the MIA group. Undenatured collagen reduced the levels of most inflammatory and cartilage breakdown markers in serum and knee joint cartilage in both age groups. In conclusion, this data suggests that while all doses of undenatured collagen supplementation may ameliorate MIA-induced OA symptoms, the higher doses showed faster improvement in gait measurements and were more efficacious for overall joint health in rats.
AtıfScopus17WoS17OpenAlex15İncele - MakaleAçık Erişim2023Scopus SJRQ1Lutein/Zeaxanthin Isomers and Quercetagetin Combination Safeguards the Retina from Photo-Oxidative Damage by Modulating Neuroplasticity Markers and the Nrf2 Pathway
Sahin, Emre; Orhan, Cemal; Sahin, Nurhan; Padigaru, Muralidhara; Morde, Abhijeet; Lal, Mohan; Dhavan, Nanasaheb; Erten, Fusun; Bilgic, Ahmet Alp; Ozercan, Ibrahim Hanifi
Exposure to light-emitting diode (LED) light is a primary cause of retinal damage, resulting in vision loss. Several plant-derived substances, such as lutein and quercetagetin (QCG), show promise in supporting eye health. In this study, the impact of lutein/zeaxanthin (L/Z, Lutemax 2020) and QCG were evaluated individually and together in a rat model of LED-induced retinal damage. A total of 63 Wistar rats were allocated into nine groups (n = 7). For 28 days, the rats received L/Z (10 or 20 mg/kg BW), quercetin (QC, 20 mg/kg BW), QCG (10 or 20 mg/kg BW), or a mixture of different lutein and QCG dosages, after which they were exposed to LED light for 48 h. LED exposure led to a spike in serum malondialdehyde (MDA) and inflammatory cytokines, as well as an increase in retinal NF-κB, ICAM, GFAP, and MCP-1 levels (p < 0.0001 for all). It also reduced serum antioxidant enzyme activities and retinal Nrf2, HO-1, GAP43, NCAM, and outer nuclear layer (ONL) thickness (p < 0.0001 for all). However, administering L/Z and QCG, particularly a 1:1 combination of L/Z and QCG at 20 mg/kg, effectively reversed these changes. The treatment suppressed NF-κB, ICAM, GFAP, and MCP-1 while enhancing Nrf2, HO-1, GAP43, and NCAM and preventing ONL thickness reduction in LED-induced retinal damage rats. In conclusion, while LED light exposure caused retinal damage, treatment with L/Z, QC, and QCG, particularly a combined L/Z and QCG regimen, exhibited protective effects on the retina. This is possibly due to the modulation of neuroplasticity markers and nuclear transcription factors in the rats’ retinal cells.
AtıfScopus22OpenAlex22İncele - MakaleAçık Erişim2021Scopus SJRQ3Lutein/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.
AtıfScopus15WoS13OpenAlex14İncele - MakaleYayıncıda açık erişim2021Scopus SJRQ4Effects of magnesium biotinate supplementation on serum insulin, glucose and lipid parameters along with liver protein levels of lipid metabolism in rats
Sahin, Kazim; Orhan, Cemal; Kucuk, Osman; Erten, Fusun; Tuzcu, Mehmet; Sahin, Nurhan; Ojalvo, Sara Perez; Komorowski, James Richard
The objective of this study was to investigate the effects of a novel form of biotin (magnesium biotinate) on serum glucose, lipid profile, and hepatic lipid metabolism-related protein levels in rats. Forty-two rats were divided into six groups and fed a standard diet-based egg white powdered diet supplemented with either d-biotin at 0.01, 1, or 100 mg/kg BW or magnesium biotinate at 0.01, 1, or 100 mg/kg BW for 35 days. Neither form of biotin influenced (p > 0.05) serum glucose or insulin concentrations. Serum total cholesterol and triglyceride decreased with biotin from both sources (p < 0.05). Concentrations were lower with magnesium biotinate when comparing the 1 mg/kg dose (p < 0.05). Serum, liver, and brain biotin and liver cyclic guanosine monophosphate (cGMP) concentrations were greater when rats were treated with magnesium biotinate versus d-biotin, particularly when comparing the 1 and 100 mg/kg dose groups (p < 0.05). Both biotin forms decreased the liver SREBP-1c and FAS and increased AMPK-a1, ACC-1, ACC-2, PCC, and MCC levels (p < 0.05). The magnitudes of responses were more emphasized with magnesium biotinate. Magnesium biotinate, compared with a commercial d-biotin, is more effective in reducing serum lipid concentrations and regulating protein levels of lipid metabolism-related biomarkers.
AtıfScopus5WoS5OpenAlex5İncele - MakaleAçık Erişim2021Scopus SJRQ1Magnesium picolinate improves bone formation by regulation of rank/rankl/opg and bmp-2/runx2 signaling pathways in high-fat fed rats
Sahin, Emre; Orhan, Cemal; Balci, Tansel Ansal; Erten, Fusun; Sahin, Kazim
Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, de-creasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteo-genetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.
AtıfScopus21WoS20OpenAlex21İncele - MakaleAçık Erişim2021Scopus SJRQ1Next‐generation ultrasol curcumin boosts muscle endurance and reduces muscle damage in treadmill‐exhausted rats
Sahin, Emre; Orhan, Cemal; Erten, Fusun; Er, Besir; Acharya, Manutosh; Morde, Abhijeet A.; Padigaru, Muralidhara; Sahin, Kazim
Curcumin positively affects performance during exercise and subsequent recovery. However, curcumin has limited bioavailability unless consumed in larger doses. In the current study, we examined the impact of a new formulation of curcumin, Next‐Generation Ultrasol Curcumin (NGUC), which is relatively more bioavailable than natural curcumin on exhaustion time, grip strength, muscle damage parameters, and serum and muscle proteins. A total of 28 rats were randomly grouped as control (C, non‐supplemented), exercise (E, non‐supplemented), E+NGUC100 (supplemented with 100 mg/kg BW NGUC), and E+NGUC200 (supplemented with 200 mg/kg NGUC). Grip strength and exhaustion time were increased with NGUC supplementation (p < 0.0001). Creatine kinase (CK), lactate dehydrogenase (LDH), lactic acid (LA), myoglobin, malondialdehyde (MDA) concentrations were reduced in serum, and muscle tissue in NGUC supplemented groups (p < 0.05). In contrast, NGUC supplementation elevated the antioxidant enzyme levels compared to the non‐supplemented exercise group (p < 0.01). Additionally, inflammatory cytokines were inhibited with NGUC administration (p < 0.05). NGUC decreased PGC‐1α, p‐4E‐BP1, p‐mTOR, MAFbx, and MuRF1 proteins in muscle tissue (p < 0.05). These results indicate that NGUC boosts exercise performance while reducing muscle damage by targeting antioxidant, anti‐inflammatory, and muscle mass regulatory pathways.
AtıfScopus9WoS9OpenAlex9İncele - MakaleAçık Erişim2020Scopus SJRQ2Salacia chinensis exerts its antidiabetic effect by modulating glucose-regulated proteins and transcription factors in high-fat diet fed-streptozotocin-induced type 2 diabetic rats
Erten, Fusun; Orhan, Cemal; Tuzcu, Mehmet; Er, Besir; Defo Deeh, Patrick Brice; Sahin, Nurhan; Özercan, Ibrahim Hanifi; Juturu, Vijaya; Sahin, Kazim
This study aimed to investigate the properties of Salacia chinensis (Celastraceae, SC) and its molecular mechanism in the type 2 diabetic rats. Forty-two Wistar rats were divided into six groups (n = 7): control, SC (100 mg/kg, per os), high-fat diet (HFD), HFD + SC (100 mg/kg), HFD + streptozotocin (STZ, 40 mg/kg, i.p.), and HFD + STZ+SC. SC decreased serum glucose, insulin, triglycerides, free fatty acid, and malondialdehyde levels, but increased serum total antioxidant capacity (0.33 ± 0.02 versus. 0.79 ± 0.03), compared with the untreated group (p <.001). Additionally, SC elevated the expression of glucose-regulated proteins GLUT2, PPAR-ɣ, p-IRS, and Nrf2, but downregulated NF-κB in the liver and kidney (p <.001). In conclusion, SC could improve insulin resistance by modulation of glucose-regulated proteins and transcription factors in diabetic rats. Practical applications: Present data has contributed to the current ethnomedicinal benefits of SC, through which the SC intake regulated the carbohydrate metabolism and increased the antioxidant capacity. The balance of transcription factors can mediate these efficacies partially and various key proteins involved in energy metabolism, along with oxidative stress and insulin sensitivity.
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