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A novel structure of exopolysaccharide from the Lactic Acid Bacteria (LAB) Lacticaseibacillus rhamnosus ACS5, isolated from home-made Turkish cheese, is described. After lyophilization, the L-EPS-ACS5 was characterized in production and functional activities in vitro, including antioxidant and antidiabetic activities. The physicochemical characterizations of the L-EPS-ACS5 were determined through molecular weight, UV, FTIR, SEM, TGA, HPLC, NMR, methylation, and GC-MS analysis. Strong antioxidant activities of L-EPS-ACS5 were confirmed from the results obtained in the hydroxyl radical, DPPH, ABTS, FRAP, superoxide anion radical, total antioxidant activity, and DNA damage protective effect, and also the L-EPS-ACS5 exhibited high antidiabetic activity (60 %). This study isolated L-EPS-ACS5 from a home-made cheese L. rhamnosus strain, demonstrating its novel and enhanced functionalities compared to existing strains. This opens exciting avenues for its development in the fields of biomedicine and pharmaceuticals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Derya OnaDarilmaz reports financial support was provided by The Scientific and Technological Research Council of Turkey. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant-antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant-antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH-SY5Y (a human neuroblastoma cell line), HT-29 (a human colorectal adenocarcinoma cell line), and PCS-201-012 (a human primary dermal fibroblast cell line) cells. Consequently, the half-maximal inhibitory concentration (IC 50 ) values of compound 3a were determined to be 218.72, 202.85, and 227.86 μM while the IC 50 values of compound 3b were defined to be 227.42, 199.27, and 250.11 μM in PCS-201-012, HT-29, and SH-SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS-201-012 cells as compared to the other cell lines., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

In this study, the performance of a novel organic tea compost developed for the first time in the world from raw tea waste from tea processing factories and enriched with worms, beneficial microorganisms, and enzymes was tested in comparison to chemical fertilizers in tea plantations in Rize and Artvin provinces, where the most intensive tea cultivation is carried out in Turkey. In the field trials, the developed organic tea vermicompost was incorporated into the root zones of the plants in the tea plantations in amounts of 1000 (OVT1), 2000 (OVT2) and 4000 (OVT4) (kg ha -1 ). The experimental design included a control group without OVT applications and positive controls with chemical fertilizers (N: P: K 25:5:10, (CF) 1200 kg ha -1 ) commonly used by local growers. The evaluation included field trials over two years. The average yields obtained in two-year field trials in five different areas were: Control (6326), OVT1 (7082), OVT2 (7408), OVT4 (7910), and CF (8028) kg ha -1 . Notably, there was no significant statistical difference in yields between the organic (at 4000 kg ha -1 ) and chemical fertilizers (at 1200 kg ha -1 ). The highest nutrient contents were obtained when CF and OVT4 were applied. According to the average values across all regions, the application of OVT4 increased the uptake of 63% N, 18% K, 75% P, 21% Mg, 19% Na, 29% Ca, 28% Zn, 11% Cu and 24% Mn compared to the control group. The application of chemical fertilizers increased the uptake of 75% N, 21% K, 75% P, 21% Mg, 28% Na, 27% Ca, 30% Zn, 18% Cu and 31% Mn compared to the control group. The organic fertilizer treatment had the lowest levels of antioxidants compared to the control groups and the chemical fertilizers. It was also found that the organic fertilizer increased the levels of amino acids, organic acids and chlorophyll in the tea plant. Its low antioxidant activity and proline content prepared them for or protected them from stress conditions. With these properties, the biotechnologically developed organic tea compost fertilizer has proven to be very promising for tea cultivation and organic plant production., (© 2024. The Author(s).)

Inhibiting aldose reductase (ALR2, AR) as well as maintaining a concomitant antioxidant (AO) activity via dual-acting agents may be a rational approach to prevent cellular glucotoxicity and at least delay the progression of diabetes mellitus (DM). This study was aimed at evaluating the dual-acting AR inhibitor (ARI) cemtirestat (CMTI) on tissue oxidative stress (OS) and carbonyl stress (CS) biomarkers in rats exposed to fructose alone (F) or fructose plus streptozotocin (D; type-2 diabetic). D and F rats were either untreated or treated daily with low- or high-dose CMTI, ARI drug epalrestat (EPA) or antioxidant stobadine (STB) for 14 weeks. Malondialdehyde (MDA), glutathione S-transferase (GST), nitric oxide synthase (NOS), and catalase (CAT) were increased in the sciatic nerve of F and D. These increases were attenuated by low doses of CMTI and STB in D, but exacerbated by low-dose EPA and high-dose CMTI in F. STB and CMTI and to a lesser extent EPA improved MDA, protein-carbonyl, GST and CAT in the hearts and lungs of F and D. CMTI and STB were more effective than EPA in improving the increased MDA and protein-carbonyl levels in the kidneys of F and especially D. CMTI ameliorated renal GST inhibition in D. In the lungs, hearts, and kidneys of F and D, the GSH to GSSG ratio decreased and caspase-3 activity increased, but partially resolved with treatments. In conclusion, CMTI with ARI/AO activity may be advantageous in overcoming OS, CS, and their undesirable consequences, with low dose efficacy and limited toxicity, compared to ARI or antioxidant alone.

Alzheimer's disease (AD), the most frequent neurodegenerative disease within dementias, affects the CNS, leading to gradual memory issues and cognitive dysfunction. Oxidative stress in AD contributes to ongoing neuronal loss and hastens disease progression. Notably, the potent antioxidant compounds morin and hesperidin have demonstrated significant effectiveness in addressing oxidative stress. This study explores the impact of morin and hesperidin on behavior and oxidative stress in the streptozotocin (STZ)-induced AD rat model. The experiment involved five groups: control, STZ, STZ+morin, STZ+hesperidin, and STZ+morin+hesperidin. The rat model of AD was created by injecting STZ with the stereotaxic surgery. Morin and hesperidin were applied to the groups for 7-days. After the applications, the Morris water maze (MWM) and novel object recognition (NOR) tests were used and the rats were sacrificed. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), and protein carbonyl (PC) levels were measured. In the STZ group, the levels of NOx and PC exhibited a noteworthy increase compared to the control. Conversely, the application of morin and/or hesperidin treatments reduced NOx and PC levels compared to the STZ group. The co-administration of morin and hesperidin improved the antioxidant status and decreased lipid peroxidation in STZ-induced rats. In the STZ group, serum advanced oxidation protein products (AOPP) levels were statistically elevated compared to the control. However, in the treatment groups, morin and/or hesperidin successfully decreased AOPP levels to those observed in the control. The combined use of these flavonoids may have a neuroprotective effect regarding memory problems and decreasing oxidative/nitrosative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the nutrient intake and dietary antioxidant capacity of children and adolescents with ASD. The study included 38 children and adolescents with ASD aged 6-18 years and 38 gender and age-matched peers without ASD. Caregivers of participants who met inclusion criteria completed a questionnaire form, three-day food consumption record and antioxidant nutrient questionnaire. There were 26 (68.4%) boys and 12 (31.6%) girls in both groups and mean age of participants with and without ASD was 10.9 ± 4.03 years versus 11.1 ± 4.09 years, respectively. The average intake of carbohydrates, vitamin D, calcium, sodium and selenium was lower in participants with ASD than in participants without ASD (p < 0.05). In both groups, dietary fiber, vitamin D, potassium, calcium and selenium intake insufficiency were high, and there was a significant difference between the two groups in terms of carbohydrate, omega 3, vitamin D and sodium intake insufficiency. Considering the antioxidant intakes of the participants, the median value of dietary antioxidant capacity from food consumption record of participants with and without ASD was 3.2 (1.9) mmol versus 4.3 (1.9) mmol, respectively, whereas the dietary antioxidant capacity from antioxidant nutrient questionnaire was 3.5 (2.9) mmol versus 4.8 (2.7) mmol, respectively (p < 0.05). It is predicted that providing nutritional counseling and regulation of diet, especially keeping the antioxidant capacity of diets high, may be effective in reducing some of the symptoms of ASD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Propolis is a resinous mixture produced by honeybees which has been used since ancient times for its useful properties. However, its chemical composition and bioactivity may vary, depending on the geographical area of origin and the type of tree bees use for collecting pollen. In this context, this research aimed to investigate the total phenolic content (using the Folin-Ciocalteu assay) and the total antioxidant capacity (using the FRAP, DPPH, and ABTS assays) of three black poplar ( Populus nigra L.) propolis (BPP) solutions (S1, S2, and S3), as well as the chemical composition (HPLC-ESI-MS n ) and biological activities (effect on cell viability, genotoxic/antigenotoxic properties, and anti-inflammatory activity, and effect on ROS production) of the one which showed the highest antioxidant activity (S1). The hydroalcoholic BPP solution S1 was a prototype of an innovative, research-type product by an Italian nutraceutical manufacturer. In contrast, hydroalcoholic BPP solutions S2 and S3 were conventional products purchased from local pharmacy stores. For the three extracts, 50 phenolic compounds, encompassing phenolic acids and flavonoids, were identified. In summary, the results showed an interesting chemical profile and the remarkable antioxidant, antigenotoxic, anti-inflammatory and ROS-modulating activities of the innovative BPP extract S1, paving the way for future research. In vivo investigations will be a possible line to take, which may help corroborate the hypothesis of the potential health benefits of this product, and even stimulate further ameliorations of the new prototype.

Coenzyme Q10 (KQ10) and curcumin (KUR) supplements are extensively used for their potential antioxidant, anticancer, and antiapoptotic properties. The present study investigated the neuroprotective potential of KQ10 and KUR against the side effect of cyclophosphamide (SF) (150 mg/kg) on the hippocampus of male Wistar albino rats. Forty-nine 10-12 weeks old rats were randomly divided into seven groups: control, olive oil (OL), SF, KQ10, KUR, SF+KQ10, and SF+KUR. Our biochemical finding showed a significant decrease in superoxide dismutase (SOD) level in the SF group compared to the control group (p < 0.05). There was also a significant reduction in the total number of the hippocampal pyramidal neurons in the CA1, CA2, and CA1-3 regions in the SF group compared to the control group (p < 0.05). In the SF+KQ10 group, we found a significant increase in serum SOD level and the total number of the hippocampal pyramidal neurons in the CA1, CA2, and CA1-3 regions compared to the SF group (p < 0.05). Immunohistochemical and histopathological examination exhibited noteworthy findings in the hippocampus tissues. Our findings showed that KQ10 administration significantly mitigated the hippocampal alteration caused by SF through enhancing antioxidant enzyme activity and reducing apoptosis. However, we found no protective activity of KUR on the hippocampus tissue, which may be due to its weak antioxidative activity., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The current research centers on exploring the antioxidant, antimicrobial, and antidiabetic features of Schinus molle L. grown in Turkey., Methods: Quantitative analysis of chlorogenic acid, caffeic acid, and hyperoside levels in leaf, ripe fruit, and raw fruit extracts was conducted using High-Performance Liquid Chromatography (HPLC) in a 70% methanol-water mixture. Among the extracts, the methanol extract from ripe fruits displayed the highest chlorogenic acid concentration, measuring at 2.040% ± 0.172% standard deviation (SD). Moreover, analysis of their total phenolic and flavonoid contents was carried out. Antioxidant power was assessed through different chemical assays, together with their antimicrobial and anti-diabetic properties., Results: The results of DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and reducing power assays showed that leaf and ripe fruit alcoholic extract exhibited peak performance. While the MIC ( minimum inhibitory concentration) values of the extracts were determined to have moderate bactericidal effects on Staphylococcus aureus , Escherichia coli , and Candida albicans it was observed that none of the extracts displayed biofilm inhibition. The inhibition percentage of α-glucosidase enzyme activity for the methanol extract of raw fruits was determined to be 99.11 ± 1.61. In diabetic β-TC cells, glucose level was measured as 129 ± 2.03 mg/dL, and insulin amount was measured as 37.2 ± 0.02 mg/dL., Conclusions: The findings of our study seem to have important implications for future research, as Schinus molle L. may be a potential pharmaceutical candidate with important pharmacological activities., Competing Interests: The authors declare no conflict of interest. Esra Küpeli Akkol was one of the Guest editors of this journal. We declare that Esra Küpeli Akkol had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Daniela Rigano., (© 2023 The Author(s). Published by IMR Press.)

As the use of plastic-containing materials in our daily lives becomes increasingly common, exposure to nanoplastics accordingly becomes inevitable. Micro and nanoplastics released from large amounts of plastic waste constitute a serious environmental problem. Therefore, this study aimed to examine the effects of polystyrene nanoplastic (PS-NP) on the hippocampus. MATERIAL AND METHOD: Thirty Wistar albino rats, 15 male and 15 female, aged 6-8 weeks, were used in the research. These were randomly divided into three groups of five males and five females each. A five-minute open field test was applied to all rats on the first and last days of the study. Three groups of rats (Control, NP1 and NP2) received the standard chow and water. Additionally, rats in the first neoplastic group (NP1) received 25 mg/kg PS-NP and rats in the second nanoplastic group (NP2) received 50 mg/kg PS-NP, at the same time each day by oral gavage. The rats were sacrificed under deep anesthesia at the end of four weeks. The hippocampi were removed and subjected to histopathological and biochemical analyses. RESULTS: Green fluorescent dots were detected in the hippocampi of both dose groups receiving nanoplastics (NPs) administered orally to female and male rats. Histopathological examination revealed neuronal degeneration in the hippocampi of male and female rats from both dose groups. However, while no significant difference was observed among the groups in terms of changes in antioxidant enzyme values and open-field test data in male rats, significant differences in peroxidase (POD) and glutathione S-transferase (GST) values and fecal boli and grooming numbers were determined in female rats exposed to NPs. In conclusion, exposure to NP substances extend as far as the hippocampus, causing neuronal damage and behavioral problems., Competing Interests: Declaration of Competing Interest There is no conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fructose, endogenously produced as a consequence of activation of the polyol pathway under hyperglycemic conditions, contribute to formation of advanced glycoxidation end products (AGEs) and carbonyl stress. Oxidative stress is increased in diabetes (DM) due to AGEs formation and the utilization of NADPH by aldo-keto reductase, AKR1B1(AR), the first enzyme in polyol pathway. Since inhibition of AR is an attractive approach for the management of diabetic eye diseases, we aimed to compare the effects of a novel AR inhibitor (ARI)/antioxidant (AO) compound cemtirestat on eye tissues with the effects of ARI drug epalrestat and AO agent stobadine in rat model for glycotoxicity. One group of rats was fed high fructose (10% drinking water; 14 weeks), while type-2 DM was induced in the other group of rats with fructose plus streptozotocin (40 mg/kg-bw/day). Diabetic (D) and nondiabetic fructose-fed rats (F) were either untreated or treated with two different doses of cemtirestat (2.5 and 7.5 mg/kg-bw/day), epalrestat (25 and 50 mg/kg-bw/day), or stobadine (25 and 50 mg/kg-bw/day) for 14 weeks. Cemtirestat, epalrestat, and stobadine elaviate the increase in TNF-α, IL-1β, NF-ƙB, and caspase-3 in retina, lens, cornea, and sclera of F and D rats. Both glycotoxicity models resulted in a decrease in GSH to GSSG ratio and a change in glutathione S-transferase activity in eye tissues, but these alterations were improved especially with cemtirestat and stobadine. Lens D-sorbitol of D rats increased more than that of F rats, this increase was only attenuated by cemtirestat and epalrestat. Epalrestat was more effective than cemtirestat and stobadine in inhibiting the increase of vascular endothelial growth factor (VEGF) in the retina of F and D rats. Cemtirestat and stobadine but not epalrestat decreased high level of Nε-(carboxymethyl)lysine in the lens and retina of F and D rats. Cemtirestat is a potential therapeutic in protecting the rat eye against glycotoxicity insults., (© 2023 John Wiley & Sons Ltd.)

Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips, and so on. One of them is octyl gallate. The purpose of this study was to evaluate the potential genotoxicity of octyl gallate in human lymphocytes, using in vitro chromosomal abnormalities (CA), sister chromatid exchange (SCE), cytokinesis block micronucleus cytome (CBMN-Cyt), micronucleus-FISH (MN-FISH), and comet tests. Different concentrations (0.031, 0.063, 0.125, 0.25, and 0.50 μg/ml) of octyl gallate were used. A negative (distilled water), a positive (0.20 μg/ml Mitomycin-C), and a solvent control (8.77 μl/ml ethanol) were also applied for each treatment. Octyl gallate did not cause changes in chromosomal abnormalities, micronucleus, nuclear bud (NBUD), and nucleoplasmic bridge (NPB) frequency. Similarly, there was no significant difference in DNA damage (comet assay), percentage of centromere positive and negative cells (MN-FISH test) compared to the solvent control. Moreover, octyl gallate did not affect replication and nuclear division index. On the other hand, it significantly increased the SCE/cell ratio in three highest concentrations compared to solvent control at 24 h treatment. Similarly, at 48 h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/ml). An important reduction was detected in mitotic index values in the highest concentration at 24 h treatment and almost all concentrations (except 0.031 and 0.063 µg/ml) at 48 h treatment. The results obtained suggest that octyl gallate has no important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

The present study aimed to perform the validity and reliability study of the Food Frequency Questionnaire (FFQ) on the frequency of foods rich in antioxidant nutrients and used in Age-Related Eye Diseases (AREDs). In the first interview of the study, the first application of FFQ was carried out, and blank forms of Dietary Records (DRs) were given. For the validity of the FFQ, a total of 12 d (3 days * 4 weeks) of DR were taken. For the reliability of the FFQ, a test-retest application was made with an interval of 4 weeks. The daily intake means of antioxidant nutrients, omega 3 and total antioxidant capacity data obtained from both the FFQ and DR were calculated, and the concordance between the two methods was evaluated with the Pearson Correlation Coefficient (PCC) and Bland-Altman graphs. The present study was carried out at Ege University İzmir/Turkey, Department of Ophthalmology, Retina Unit. The study was conducted with individuals aged ≥50 years who suffered from Age-Related Macular Degeneration ( n 100, 72⋅0 ± 8⋅03 years). The values obtained from the test-retest applications for FFQ reliability were the same. The nutrient intake means obtained from the FFQ were similar or significantly higher than DR ( P < 0⋅05). In the Bland-Altman graphical approach, the nutrient data were within the limits of agreement, and the PCCs between the two methods were moderately related. Considered together, this FFQ is a suitable tool for determining the dietary intakes of antioxidant nutrients in the Turkish population., (© The Author(s) 2023.)

This study aims to determine whether exposure to non-ionizing radiofrequency fields could induce an adaptive response (AR) in adult mice and to reveal potential molecular mechanisms triggered by RF-induced AR. The study was performed on 24 adult male Swiss-Albino mice. The average mass of the mice was 37 g. Four groups of adult mice, each consisting of 6, were formed. The radiofrequency group (R) and the adaptive response group (RB) were exposed to 900 MHz of global system for mobile communications (GSM) signal at 0.339 W/kg (1 g average specific absorption rate) 4 h/day for 7 days, while the control group (C) and the bleomycin group (B) were not exposed. 20 minutes after the last radiofrequency field (RF) exposure, the mice in the B and RB groups were injected intraperitoneal (ip) bleomycin (BLM), 37.5 mg/kg. All the animals were sacrificed 30 minutes after the BLM injection. Oxidative damage and antioxidant mechanism were subsequently investigated in the blood samples. Changes in the expression of the genes involved in DNA repair were detected in the liver tissue. TUNEL method was used to determine the apoptosis developed by DNA fragmentation in the liver tissue. The RB group, which produced an adaptive response, was compared with the control group. According to the results, the increase of reactive oxygen species (ROS) in the RB group may have played an important role in triggering the adaptive response and producing the required minimum stress level. Furthermore, tumor suppressor 53(p53), oxo guanine DNA glycosylase (OGG-1) levels responsible for DNA repair mechanism genes expression were increased in conjunction with the increase in ROS. The change in the poly (ADP-ribose) polymerase 1 (PARP-1) and glutathione peroxidase 1 (GPx-1) gene expression were not statistically significant. The antioxidant enzyme levels of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were decreased in the group with adaptive response. According to the data obtained from terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, apoptosis was decreased in the RB group due to the decrease in cell death, which might have resulted from an increase in gene expression responsible for DNA repair mechanisms. The results of our study show that exposure to RF radiation may create a protective reaction against the bleomycin. The minimal oxidative stress due to the RF exposure leads to an adaptive response in the genes that play a role in the DNA repair mechanism and enzymes, enabling the survival of the cell.

The aim of this study was to evaluate the postoperative analgesic and antioxidant effects of butorphanol given in the preoperative or early postoperative period. Twenty-seven healthy female dogs undergoing ovariohysterectomy were randomly divided into three groups as before surgery group (BSG, n = 7) received butorphanol 30 min before preanesthetic administration, after surgery group (ASG, n = 10) received butorphanol during the last skin suture and the control group (CG, n = 10) received no butorphanol. Pain was assessed with short form of the Glasgow composite pain scale (CMPS-SF). Serum concentration of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase activities (GPx) were quantified by spectrophotometric methods to assess oxidative stress status. The pain score increased rapidly at 1 h after surgery and then decreased gradually towards to 24 h in all groups. There was no statistical difference among the groups in terms of CMPS-SF scores (P > 0.05). Serum concentration of MDA was lower in ASG than in BSG and CG from 1 h to 24 h after surgery. Serum activity of GPx was higher in ASG than in BSG and CG from 2 h to 24 h (P < 0.05). Serum activity of SOD was higher in ASG than in BSG and CG from 1 h to 24 h after surgery (P < 0.05). Serum SOD activity at different time points in ASG did not differ compared to preoperative level though it decreased significantly from 1 h onwards both in CT and BSG. The results indicate that single butorphanol administration either before or after the operation might not provide sufficient analgesia, however, it seems that it has antioxidant potential and may protect tissues by reducing oxidative stress when administered early postoperative period following ovariohysterectomy., (Copyright © 2022. Published by Elsevier Inc.)

In this study, a series of bis- and tetrakis-1,2,3-triazole derivatives were synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry in 73-95% yield. The bis- and tetrakis-1,2,3-triazoles exhibited significant DNA cleavage activity while the tetrakis-1,2,3-triazole analog 6g completely degraded the plasmid DNA. Molecular docking simulations suggest that compound 6g acts as minor groove binder of DNA by binding through several noncovalent interactions with base pairs. All bis- and tetrakis-1,2,3-triazole derivatives were screened for antibacterial activity against E. coli, B. cereus, S. aureus, P. aeruginosa, E. hirae, L. pneumophila subsp. pneumophila strains and antifungal activity against microfungus C. albicans and C. tropicalis strains. Compound 4d exhibited the best antibacterial activity among bis-1,2,3-triazoles against E. coli and E. hirae, while 6c exhibited the best antibacterial activity among tetrakis-1,2,3-triazoles against E. hirae. Furthermore, the best antifungal activity against C. albicans and C. tropicalis was reported for the compound 5, while 6d displayed the best antifungal activity against C. tropicalis and C. albicans. Reasonable iron chelating activities and DPPH radical scavenging abilities were found for some of the compounds. Finally, the acid dissociation constants (pK a ) of the bis-1,2,3-triazoles were also determined with the help of HYPERQUAD program using the data obtained from potentiometric titrations. The reported data here concludes that the bis- and tetrakis-1,2,3-triazoles are important cores that should be considered for further development of especially new anticancer agents acting through the DNA cleavage activity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Medicinal uses of natural phenolic acids and their synthetic derivatives have been augmented in recent years. Phenolic acids are chemically defined secondary plant metabolites and being moieties or leads are much versatile in nature with a wide scope of biological activities which seek the attention of researchers across the world to synthesize different derivatives of phenolic acids and screen them for their various biological properties. These compounds are of meticulous interest due to the properties they possess and their occurrence. Based on the convincing evidence reported in the literature, it is suggested that phenolic acids and their derivatives are promising molecules as a drug., Objectives: The present review article aims to bring together the information on the biosynthesis, metabolism, and sources of phenolic acids and emphasize the therapeutic potential of phenolic acid and its synthetic derivatives to comprehensively portray the current scenery for researchers interested in designing drugs for furthering this study., Conclusion: Phenolic acids being moieties or lead, are much versatile in nature as they possess a wide range of biological activities like antimicrobial, antioxidant, antiviral, antiulcer, antiinflammatory, antidiabetic, anticancer and many more offers researchers to explore more about these or many untapped benefits in the medicinal field. The information mentioned in this article will be helpful to the forthcoming researchers working in this area. Phenolic acids have massive potential to be investigated for novel medicinal possibilities and for the development of new chemical moieties to treat different diseases of clinical importance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Molineria capitulata is an ornamental plant that has traditionally been used to treat several chronic diseases. The present study was designed to examine the antioxidant, cytotoxic, thrombolytic, anti-inflammatory, and analgesic activities of a methanolic extract of M. capitulata leaves (MEMC) using both experimental and computational models. Previously established protocols were used to perform qualitative and quantitative phytochemical screening in MEMC. A computational study, including molecular docking and ADME/T analyses, was performed. The quantitative phytochemical analysis revealed the total phenolic and flavonoid contents as 148.67 and 24 mg/g, respectively. Antioxidant activity was assessed by examining the reducing power of MEMC, resulting in absorbance of 1.87 at 400 µg/mL, demonstrating a strong reduction capacity. The extract exhibited significant protection against blood clotting and showed the highest protein denaturation inhibition at 500 µg/mL. In both the acetic acid-induced writhing and formalin-induced paw-licking models, MEMC resulted in significant potential pain inhibition in mice. In the computational analysis, 4-hydroxybenzaldehyde, orcinol glucoside, curcapital, crassifogenin C, and 2,6-dimethoxy-benzoic acid displayed a strong predictive binding affinity against the respective receptors. These findings indicated that M. capitulata possesses significant pharmacological activities to an extent supported by computational studies.

Aldose reductase (AR) catalyzes the conversion of glucose to sorbitol in a NADPH-dependent reaction, thereby increasing the production of reactive oxygen species (ROS). Since AR activation is linked to redox dysregulation and cell damage in neurodegenerative diseases, AR inhibitors (ARIs) constitute promising therapeutic tools for the treatment of these disorders. Among these compounds, the novel substituted triazinoindole derivatives cemtirestat (CMTI) and COTI, as well as the clinically employed epalrestat (EPA) and the pyridoindole-antioxidant stobadine (STB), were tested in both PC12 cells and BV2 microglia exposed to four different neurotoxic models. These include (1) oxidative stress with hydrogen peroxide (H 2 O 2 ), (2) mitochondrial complex IV inhibition with NaN 3 , (3) endoplasmic reticulum-stress and lipotoxicity induced by palmitic acid/bovine serum albumin (PAM/BSA), and (4) advanced carbonyl compound lipotoxicity by 4-hydroxynonenal (4-HNE). All toxic compounds decreased cell viability and increased ROS formation in both PC12 and BV2 cells in a concentration-dependent manner (1-1000 μM; NaN 3  < H 2 O 2 ≈PAM/BSA < 4-HNE). In PC12 cells, EPA increased cell viability in all toxic models only at 1 μM, whereas CMTI restored baseline viability in all toxic models. COTI afforded protection against lipotoxicity, while STB only prevented H 2 O 2 -induced toxicity. Except for the 4-HNE model, EPA prevented ROS generation in all other toxic models, whereas CMTI, COTI, and STB prevented ROS production in all toxic models. In BV2 cells, EPA and CMTI restored baseline cell viability in all toxic models tested, while COTI and STB did not prevent the loss of viability in the NaN 3 model. All ARIs and STB efficiently prevented ROS formation in all toxic models in a concentration-independent manner. The differential protective effects evoked by the novel ARIs and STB on the toxic models tested herein provide novel and relevant comparative evidence for the design of specific therapeutic strategies against neurodegenerative events associated with neurological disorders.

It is aimed to investigate the cytotoxic effects of the various extracts from the leaf and seed of Centaurea derderiifolia on the growth human cervical adenocarcinoma (HeLa) cells by xCELLigence method and to isolate the cytotoxic constituents. The results showed that subfractions 2 and 3 exhibited remarkable inhibitory effect against HeLa (IC 50  < 10 µg/mL). The chloroform extract of leaf displayed the highest cytotoxic effect on HeLa cells (IC 50  < 50 µg/mL) and was therefore subjected to a bioassay-guided multistep separation procedure. The pure compounds were elucidated by spectroscopic and mass-spectrometric analyses, including 1 D-, 2 D-NMR. In addition to cytotoxic effects of the isolated constituents, their antioxidant activities were also studied. On the other hand, subfraction 4 exhibited the highest DPPH radical scavenging activity (IC 50  = 0.76 ± 0.03 mg/mL). β-sitosterol-3-O-β-d-glucopyranoside was isolated for the first time from this plant and three compounds from the bioactive subfractions were identified.

Aldose reductase (AR, ALR2), the first enzyme of the polyol pathway, is implicated in the pathophysiology of diabetic complications. Aldose reductase inhibitors (ARIs) thus present a promising therapeutic approach to treat a wide array of diabetic complications. Moreover, a therapeutic potential of ARIs in the treatment of chronic inflammation-related pathologies and several genetic metabolic disorders has been recently indicated. Substituted indoles are an interesting group of compounds with a plethora of biological activities. This article reviews a series of indole-based bifunctional aldose reductase inhibitors/antioxidants (ARIs/AOs) developed during recent years. Experimental results obtained in in vitro, ex vivo, and in vivo models of diabetic complications are presented. Structure-activity relationships with respect to carboxymethyl pharmacophore regioisomerization and core scaffold modification are discussed along with the criteria of 'drug-likeness". Novel promising structures of putative multifunctional ARIs/AOs are designed.

The paper reports anticholinesterase and antioxidant activities of extracts, fractions from aerial parts, roots, flowers, fruits of Ferula longipedunculata Pe ş men (Apiaceae). Phenolic content, antioxidant activities of samples were carried out using Folin-Ciocalteu, DPPH, TBA methods. Anticholinesterase activity was actualised through Ellman's method. The utmost and least total phenolic content were detected in root MeOH extract (36.4 mg GAE g -1 DW) and aerial part (23.74 mg GAE g -1 DW), respectively. Hexane fraction of root exhibited significant inhibition against AChE (37.99%) and BuChE (81.66%) at 20 μg/mL as well as remarkable antioxidant and anticholinesterase activities. However, investigations on roots will be substantial for improved usage of F. longipedunculata for pharmaceutical and food search needs.

The aim of the current study is to investigate the effect of daily long-term radio-frequency electromagnetic field (RF-EMFs) exposure on thiol/disulphide homeostasis and oxidant-antioxidant status in the serum of rats. Fourteen male Sprague Dawley rats were divided into two equal groups (n = 7). They were grouped as group 1 (sham-control) and group 2 (2100 MHz exposed). Group 2 rats were exposed to GSM-like signals for 5 h/day, 7 days per week for 14 days. In serum of blood samples, the native, total and native/total thiol levels and antioxidant-oxidant parameters were analyzed. The study revealed that the mean serum total thiol levels of GSM exposure group was rather higher than sham-control group ( p = 0,219); the mean serum native thiol levels of GSM exposure group was rather higher than sham-control group ( p = 0,416), and the mean serum disulphide levels of GSM exposure group was rather higher than sham-control group ( p = 0,566). On the other hand, the mean serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of GSM exposure group were higher than sham-control group. There are no data in the literature, that examine the effects of RF-EMFs on thiol/disulphide homeostasis. The results of this study, indicate that RF-EMFs did not cause oxidative stress and statistically changes in thiol/disulphide homeostasis. More sample sizes and longer-term exposures are needed to confirm the results of this study.

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: To detect antioxidant and antiinflammatory efficacy of Curcumin (Cur) on lung tissue in rats with sepsis., Methods: Totally 32 rats were divided into 4 groups; the rats in Group 1 (control group) had abdominal incision under sterile conditions following anesthesia and the abdomen was sutured. Abdominal incision was performed in the rats in Group 2 (Cur group) under sterile conditions following anesthesia and the abdomen was closed. Cur was given to this group after dissolving within dimethylsulphoxide as 100 mg/kg through oral gavage and started for 3 d before surgical procedure. Group 3 (CLP group) had caecal ligation and punction (CLP) under sterile conditions to create sepsis following anesthesia and the abdomen was sutured. CLP was performed in the rats in Group 4 (CLP + Cur group) under sterile conditions following anesthesia to create a sepsis model and the abdomen was closed. Cur was also given to this group after dissolving within dimethylsulphoxide as 100 mg/kg through oral gavage and started for 3 d before surgical procedure. All the rats were sacrificed through blood aspiration from the heart under sterile conditions following anesthesia and lung tissues were removed after 24 h following the surgical procedures. The tissue samples were homogenizated for biochemical analyses; and malondialdehyde (MDA), nitric okxide (NO), myeloperoxidase (MPO), superoxidedysmutase (SOD) nd catalase (CAT) were analyzed through spectrophotometric method, immunhistochemical iNOS staining was performed to assess the inflammation; and histopathological differences between the groups were evaluated., Results: A statistically significant decrease was detected in the CLP + Cur group when compared with the CLP group of which Cur was not given in terms of MDA, MPO and NO levels (P < 0.05) whereas a statistically significant elevation was fpund in the CLP + Cur group when compared with the CLP group in terms of SOD and CAT levels (P < 0.05)., Conclusion: The study outcomes revealed that supplementation of Cur presents an antioxidant effect by reducing the free radical level and increasing the antioxidant enzyme levels; and an antiinflammatory effect by reducing iNOS level.

Neuroprotective action of the novel aldose reductase (AR) inhibitor cemtirestat (CMT), 2-(3-thioxo-2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid, was recently proved in experimental rat models of diabetes. The in vivo results indicated that the antioxidant activity of this compound might have participated on its effects. The aim of this study was to explore in a greater detail the putative antioxidant mechanisms potentially involved in CMT mediated neuroprotection. Antioxidant efficacy per se of CMT was proved by a ferric reducing antioxidant power (FRAP) test and CMT was found to scavenge reactive oxygen species (ROS) generated in water phase chemically with decreasing efficacy as follows ROO > H 2 O 2  > O 2 - . Studies in liposomes revealed the ability of CMT to inhibit lipid peroxidation more efficiently than melatonin, yet less effectively than Trolox. In the rat brain cortical slices, CMT reduced the loss of cell viability/mitochondrial function induced by quinolinic acid (QUIN), and inhibited lipid peroxidation. In addition, CMT normalized the GSH/GSSG ratio which could be explained, at least partially, by the ability of this compound to release free GSH from the pool of endogenously bound disulfides. Neuronal cell damage induced by QUIN or H 2 O 2 was reduced by CMT as proved by significant drop in propidium iodide incorporation into cells. On balance then, our results corroborated the notion of a multifunctional action of CMT as a drug combining AR inhibition with direct antioxidant and ROS scavenging activity. Moreover, the ability of CMT to restore thiol-disulfide homeostasis was proved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist that is commonly used as a sedative and anesthetic. The protective effects of DEX against oxidative damage under both in vitro and in vivo conditions have been demonstrated. It was aimed to evaluate and compare the protective effects of DEX and vitamin C (Vit C) on DNA against H2O2-induced DNA damage in human lymphocyte cell cultures in vitro by alkaline Comet assay., Materials and Methods: Lymphocyte cell cultures were divided into 5 groups, as the negative control, solvent control, positive control, hydrogen peroxide (H2O2; 150 μM) + DEX (1 μM; 2.5 μM; 5 μM), and H2O2 (150 μM) + Vit C (1 μM; 2.5 μM; 5 μM), and incubated at 37 °C for 1 h. Cell viability was measured using the Trypan blue test. DNA damage was measured using the Alkali Comet Technique and the % percent tail intensity was evaluated. Statistical analysis was performed using 1-way ANOVA and the Tukey multiple comparison test., Results: It was observed that H2O2 significantly induced DNA damage in the lymphocytes and this damage was decreased significantly with Vit C and DEX. It was observed that Vit C at doses of 1 μM and 2.5 μM had a significantly stronger antioxidant effect, but there was no significant difference between the antioxidant effects of Vit C and DEX with a dose of 5 μM. The dose of 5 μM DEX was found to be the most effective in reducing oxidative DNA damage., Conclusion: There is limited data on the protective effects of DEX against oxidative DNA damage. The primary effect might be cytoprotection. The results herein showed that DEX was protective against H2O2-induced in vitro oxidative DNA damage in lymphocyte cell cultures in a dose-dependent manner. DEX might have a potential therapeutic value in the prevention of oxidative DNA damage in patients., Competing Interests: The authors declare no conflicts of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Carotenoids are natural fat-soluble pigments synthesized by plants, algae, fungi and microorganisms. They are responsible for the coloration of different photosynthetic organisms. Although they play a role in photosynthesis, they are also present in non-photosynthetic plant tissues, fungi, and bacteria. These metabolites have mainly been used in food, cosmetics, and the pharmaceutical industry. In addition to their utilization as pigmentation, they have significant therapeutically applications, such as improving immune system and preventing neurodegenerative diseases. Primarily, they have attracted attention due to their antioxidant activity. Several statistical investigations indicated an association between the use of carotenoids in diets and a decreased incidence of cancer types, suggesting the antioxidant properties of these compounds as an important factor in the scope of the studies against oxidative stress. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. Numerous of bioactive compounds such as marine carotenoids have low stability, are poorly absorbed, and own very limited bioavailability. The new technique is nanoencapsulation, which can be used to preserve marine carotenoids and their original properties during processing, storage, improve their physiochemical properties and increase their health-promoting effects. This review aims to describe the role of marine carotenoids, their potential applications and different types of advanced nanoformulations preventing and treating oxidative stress related disorders.

Monovalent thallium (Tl + ) is a cation that can exert complex neurotoxic patterns in the brain by mechanisms that have yet to be completely characterized. To learn more about Tl + toxicity, it is necessary to investigate its major effects in vivo and its ability to trigger specific signaling pathways (such as the antioxidant SKN-1 pathway) in different biological models. Caenorhabditis elegans (C. elegans) is a nematode constituting a simple in vivo biological model with a well-characterized nervous system, and high genetic homology to mammalian systems. In this study, both wild-type (N2) and skn-1 knockout (KO) mutant C. elegans strains subjected to acute and chronic exposures to Tl + [2.5-35 μM] were evaluated for physiological stress (survival, longevity, and worm size), motor alterations (body bends), and biochemical changes (glutathione S-transferase regulation in a gst-4 fluorescence strain). While survival was affected by Tl + in N2 and skn-1 KO (worms lacking the orthologue of mammalian Nrf2) strains in a similar manner, the longevity was more prominently decreased in the skn-1 KO strain compared with the wild-type strain. Moreover, chronic exposure led to a greater compromise in the longevity in both strains compared with acute exposure. Tl + also induced motor alterations in both skn-1 KO and wild-type strains, as well as changes in worm size in wild-type worms. In addition, preconditioning nematodes with the well-known antioxidant S-allylcysteine (SAC) reversed the Tl + -induced decrease in survival in the N2 strain. GST fluorescent expression was also decreased by the metal in the nematode, and recovered by SAC. Our results describe and validate, for the first time, features of the toxic pattern induced by Tl + in an in vivo biological model established with C. elegans, supporting an altered redox component in Tl + toxicity, as previously described in mammal models. We demonstrate that the presence of the orthologous SKN-1 pathway is required for worms in evoking an efficient antioxidant defense. Therefore, the nematode represents an optimal model to reproduce mammalian Tl + toxicity, where toxic mechanisms and novel therapeutic approaches of clinical value may be successfully pursued.

We investigated using immunohistochemistry the possible protective effects of ascorbic acid, α-tocopherol and selenium during chemotherapy treatment with cyclophosphamide. Thirty female Wistar rats were divided into five groups of six: group 1, untreated control; group 2, 75 µg/kg cyclophosphamide; group 3, 75 µg/kg cyclophosphamide + 150 µg/kg/day α-tocopherol; group 4, 75 µg/kg cyclophosphamide + 200 µg/kg/day ascorbic acid and group 5, 75 µg/kg cyclophosphamide + 40 ppm/kg/day selenium. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and AT 1 was used to evaluate structural damage. Caspase-8, caspase-9 and caspase-3 signal molecules were used to investigate apoptosis. In group 2, epithelium, alveolar macrophages, infiltrated lymphocytes and connective tissue were immunostained moderately to strongly with PCNA. Bronchus, alveolar wall and infiltrated lymphocytes were immunostained moderately to strongly with AT 1 and diffuse strong caspase immunoreactions were observed throughout the lung tissue. AT 1 and caspase immunoreactions in groups 4 and 5 were similar to group 2. In group 3, PCNA immunoreactivity was strong in the bronchiolus epithelium, endothelial cell nuclei and in stacks of infiltrated lymphocyte cell nuclei. In group 3, AT 1 and caspase immunoreactions were identical to group 1. It appears that α-tocopherol inhibits lung tissue damage in rats during chemotherapy.

Alzheimer's disease (AD) is a disease characterized by cerebral neuronal degeneration and loss in a progressive manner. Amyloid beta (Aβ) in the brain is toxic to neurons, being a main risk factor for initiation and continuation of cognitive deterioration in AD. Neurotoxicity of Aβ origin is also linked to oxidative stress characterized by excessive lipid peroxidation, protein oxidation, changes in antioxidant systems, and cerebral DNA damage in AD. Furthermore, Aβ can induce oxidative neuronal cell death by a mitochondrial dysfunction. Cellular injury caused by oxidative stress can be possibly prevented by boosting or promoting bodily oxidative defense system by supplying antioxidants in diet or as medications. However, most synthetic antioxidants are found to have cytotoxicity, which prevents their safe use, and limits their administration. For this reason, more attention has been paid to the natural non-toxic antioxidants. One of the most promising groups of non-toxic antioxidative compounds is thought to be polysaccharides. This study investigated the characterization and protective action exerted by exopolysaccharides (EPSs) originated from Lactobacillus delbrueckii ssp. bulgaricus B3 and Lactobacillus plantarum GD2 to protect from apoptotic activity exerted by Aβ 1-42 among SH-SY5Y cells. We characterized EPSs by elemental analysis, FTIR, AFM, SEM, and XRD. The antioxidant effects of EPSs were determined by the DPPH free radical scavenging activity, hydroxyl radical scavenging activity, metal ion chelating activity, lipid peroxidation inhibitory activity, and superoxide anion scavenging activity method. The protective effects of EPSs were determined by flow cytometry and RT-PCR. Mannose ratio, molecular weight, functional groups, surface morphology, and amorphous character structure of EPSs are thought to play a role in the protective effect of EPSs. EPSs reduced apoptotic activity of Aβ 1-42 in addition to their depolarizing effect on mitochondrial membrane potential in concentration-dependent manner. These observations contribute the inclusion of EPSs among the therapeutic options used to manage various neurological disorders in the traditional medicine in a scientific manner, indicating that EPSs may be promising natural chemical constituents that need advanced research and development for pharmacological therapy of AD.

The presented work reports anticholinesterase and antioxidant activities of extracts, fractions from aerial parts, fruits, flowers, roots and isolated compounds of roots from Leiotulus dasyanthus (bergapten, pimpinellin, umbelliferone, quercetin, rutin and kaempferol). Phenolic contents, antioxidant activities of samples were carried out by Folin-Ciocalteu, DPPH, TBA methods. Anticholinesterase activity was evaluated by Ellman's method. The highest and lowest total phenolic content were detected in root MeOH extract (88.6 mg GAE g -1 DW) and aerial part (51.83 mg GAE g -1 DW), respectively. The highest antioxidant activity among isolated secondary metabolites got coumarins umbelliferone, bergapten and pimpinellin. Pimpinellin (66.55%) and umbelliferone (61.09%) demonstrated strong inhibition towards acetylcholinesterase and butyrylcholinesterase, respectively. Dichloromethane fraction of root demonstrated significant inhibition against AChE (49.66%) and BuChE (92.21%) at 20 µg/mL. Dichloromethane fractions of roots had a notableness antioxidant and anticholinesterase activities. The further studies on roots will be important for development use of this plant for pharmaceutical and food research needs.[Formula: see text].

Ethnopharmacological Relevance: In Turkish folk medicine, leaves of Sorbus domestica are used for the treatment of burns, cough, stomachache, bradyuria, kidney stone. The fruits of this plant are used for diarrhoea., Aim of the Study: This study was carried out to investigate the effect of S. domestica on ulcerative colitis induced by acetic acid in rats., Materials and Methods: The crude methanolic extract of fruits was sequentially fractionated into five subextracts; dichloromethane, diethyl ether, ethyl acetate, n-butanol and aqueous extracts. Effects of the extract, subextracts and fractions were investigated in acetic acid-induced rat colitis model. The colonic interleukin-6 (IL-6), tumor necrosis factor (TNF-α), nitrite, superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO), catalase (CAT), and malondialdehyde (MDA) levels as well as the caspase-3 and myeloperoxidase (MPO) activities were measured to determine the activity. Histopathological analyzes were also performed on the colon tissue of rats., Results: The methanolic extract and diethylether subextract have led to a noteworthy decrease in MPO, caspase-3, IL-6, TNF-α, MDA, and nitrite levels in the colon tissue and blood. In addition, histopathological analysis results were supported by biochemical parameters. After confirmation of the activity against ulcerative colitis, the diethyl ether subextract was subjected to more chromatographic separation for the isolation of compounds 1, 2 and 3. The structures of these three compounds were elucidated as vanillic acid 4-O-α-L-rhamnopyranoside (1), protocateuic acid anhydrite (2) and trivanilloyl-(1,3,4-trihydroxybenzol) ester (3)., Conclusion: In this study, the potential of S. domestica in the treatment of colitis was investigated. Fruits of this plant were found to have important anti-inflammatory and antioxidant activities. Through isolation techniques, vanillic acid 4-O-α-L-rhamnopyranoside, protocateuic acid anhydrite and trivanilloyl-(1,3,4-trihydroxybenzol) ester were determined as the main active components of the fruits. Consequently, S domestica might be a promising candidate for upcoming use the prevention and treatment of various disorders, such as inflammatory bowel diseases, irritable bowel syndrome and Clostridium difficile infection., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study investigated the capability of an essential oil mix (MO: 1% and 3%) in ameliorating amnesia and brain oxidative stress in a rat model of scopolamine (Sco) and tried to explore the underlying mechanism. The MO was administered by inhalation to rats once daily for 21 days, while Sco (0.7 mg/kg) treatment was delivered 30 min before behavioral tests. Donepezil (DP: 5 mg/kg) was used as a positive reference drug. The cognitive-enhancing effects of the MO in the Sco rat model were assessed in the Y-maze, radial arm maze (RAM), and novel object recognition (NOR) tests. As identified by gas chromatography-mass spectrometry (GC-MS), the chemical composition of the MO is comprised by limonene (91.11%), followed by γ-terpinene (2.02%), β-myrcene (1.92%), β-pinene (1.76%), α-pinene (1.01%), sabinene (0.67%), linalool (0.55%), cymene (0.53%), and valencene (0.43%). Molecular interactions of limonene as the major compound in MO with the active site of butyrylcholinesterase (BChE) was explored via molecular docking experiments, and Van der Waals (vdW) contacts were observed between limonene and the active site residues SER198, HIS438, LEU286, VAL288, and PHE329. The brain oxidative status and acetylcholinesterase (AChE) and BChE inhibitory activities were also determined. MO reversed Sco-induced memory deficits and brain oxidative stress, along with cholinesterase inhibitory effects, which is an important mechanism in the anti-amnesia effect. Our present findings suggest that MO ameliorated memory impairment induced by Sco via restoration of the cholinergic system activity and brain antioxidant status.

Ethnopharmacological Relevance: The ethnobotanical studies conducted in Turkey and other countries have revealed that Cornus mas L., from the family Cornaceae have been used against stomachache, diarrhea and colitis., Aim of the Study: The objective the present study is to determine the possible activity of C. mas in experimentally induced ulcerative colitis in rats and to identify its phytochemical feature., Materials and Methods: 2,4,6-Trinitrobenzene sulfonic acid-induced colitis model was induced in rats. The rats were orally treated with different doses (50, 100, 200 and 400 mg/kg) of C. mas 80% methanol extract for 14 days. Increase in body weight, consumed amount of feed, form of the stool, presence of rectal prolapse were followed every day. At the end of the experiment, colon tissues were removed and wet weights for each animal were measured and colon damages were scored. Total antioxidant and total oxidant status, cytokine (TNF-α and IL-1β) and protein levels of colon tissues were evaluated and histopathological analyses were carried out. After the detection of the effective dose as 400 mg/kg, the aqueous methanol extract was fractionated by using liquid-liquid fractionation technique and the sub-extracts were also tested for in vivo biological activities. High Performance Liquid Chromatography analyses were conducted to determine the phytochemical profile of the active crude extract and n-butanol sub-extract., Results: Amount of feed consumed per day and increase in body weight were the lowest in the control group, while those values were determined to be the highest in 80% methanol extract (at 400 mg/kg dose), n-butanol sub-extract and reference groups. Following colitis induction, it was determined that the fecal form was yellow-slippery in all groups and returned to normal after the treatment with C. mas extracts. Rectal prolapse score was less in the extract (400 mg/kg) and n-butanol sub-extract treated groups. Total antioxidant, total oxidant status, cytokine and protein levels were found to be in parallel with macroscopic findings. 80% methanol extract (400 mg/kg) and n-butanol sub-extract provided the best healing according to the wet weight measurements and colon damage scoring performed on the removed colon tissues. These findings supported the results of histopathological analysis. According to the chromatographic analysis, ellagic acid was determined in both extracts and its amount was quantified., Conclusions: The present study has verified the ethnomedical use of C. mas for the treatment of ulcerative colitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bendiocarb is a pesticide carbamate which is used to protect agricultural products and animals. In this study, rats were given orally with bendiocarb and also other chemicals via gavage. Male rats were randomly divided into eight groups (n = 6): group 1 served as controls; group 2 received vitamin C (100 mg/kg bw); group 3 received vitamin E (100 mg/kg bw); group 4 received vitamins C plus E; group 5 received bendiocarb (0.8 mg/kg 1/50 LD 50 ); group 6 received both bendiocarb and vitamin C; group 7 received both bendiocarb and vitamin E; and group 8 received both bendiocarb and vitamin C and E via oral gavage. Degenerative changes and biochemical differences in rat kidney were investigated after 4 weeks of especially bendiocarb treatment. While biochemical values were normal in the control group, it was observed that CAT, SOD, GPx, and GST values decreased, while MDA, creatine, urea, and uric acid values increased in the pesticide-treated groups. It was also reported that bendiocarb caused cytopathological and histopathological changes in rat kidney. We have shown that the application of vitamins has a therapeutic effect on the evaluated parameters.

This study reported the genetic and oxidative effects of aqueous and methanol extracts from two edible mushrooms, Lepista nuda (Bull.) Cooke and Pleurotus ostreatus (Jacq.) P. Kummer, in cultured human lymphocytes. Chromosome aberration (CA) and micronucleus (MN) assays were used for genotoxic influences estimation. In addition, the changes of total antioxidant capacity (TAC) and total oxidative stress (TOS) in the cells were monitored. The fungal extracts at all applied concentrations did not indicate significant differences (p > 0.05) in CA and MN analyses. Furthermore, while the treatments with maximum concentration of aqueous extract of L. nuda statistically (p < 0.05) increased TAC especially, TOS levels in the cells were reduced by them in comparison with negative control. Based on TAC analysis, low IC50 values belonging to aqueous (5.43 mg/L) and methanol (10.88 mg/L) extracts of L. nuda were remarkable. Our data demonstrated that the extracts obtained from P. ostreatus and especially L. nuda can be a new resource for therapeutics with their nonmutagenic and antioxidant features.

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer's disease and its potential as a lead compound in clinical applications.

This study focused on the concept of the possible protective effect of some honey types against HCl/ethanol-induced gastric ulcers in male Wistar albino rats. Rats were pretreated with rhododendron, chestnut, and oak honey orally with doses of 1.25 and 2.5 g/kg, bw (body weight) for three consecutive days. On fourth day, nothing was applied, and after the administration of anesthesia on the fifth day, their stomachs were surgically removed to investigate the histopathological examinations. Besides analyses of some blood serum profiles and antioxidant parameters of gastric tissue, some biochemical properties of honeys were investigated to support the histopathological results. The degrees of ulcer lesions in all groups revealed a statistically significant difference (p = .011). Although this difference originated from the additional ulcerative inducing effect of some honeys, the lower concentration rhododendron honey indicated more promising data than the positive control group (pantoprazole) in consequence of the microscopic and macroscopic evaluations. PRACTICAL APPLICATIONS: As being a member of natural products, honey has acquired fame among the studies in recent years due to its versatility as a source of food and complementary medicine. For contributing to this argument, this comprehensive study was performed and results were focused on the lower concentration of rhododendron honey thanks to its clinical potential with protecting the gastric mucosa. According to the obtained results, our suggestion came into prominence that this honey might be protecting the mucosa, better than the different concentrations of chestnut and oak honeys, by being better-absorbed through the gastric mucosa., (© 2019 Wiley Periodicals, Inc.)

Endometritis is an inflammatory disorder of the endometrial lining of the uterine tissue in postpartum stage. Endometritis mostly progresses subclinically and causes infertility through the disruption of the hormonal balance. It has been shown in many studies that resveratrol has anti-inflammatory and antioxidant properties. However, the possible beneficial effects of resveratrol in endometritis have not been determined yet. The aim of the present study is to evaluate the treatment potential of resveratrol in an experimentally induced endometritis model in rats. Endometritis was induced in 12-week-old female, nonpregnant, Sprague Dawley rats. The animals were divided into six groups: control (NaCl 0.9%) and endometritis (NaCl 0.9%), marbofloxacin + PGF 2α , marbofloxacin, marbofloxacin + resveratrol, and resveratrol groups. To induce endometritis, 5 mg/kg/s.c. progesterone was given for 5 days, and then Escherichia coli (50 μl, 1 × 10 5  cfu/rat) was injected in the right cornu uteri following laparotomy. Sixteen hours after bacterial inoculation, the treatment protocol was applied for 14 days. At the end of the experiment, the total oxidant status (TOS) and total antioxidant status (TAS) were examined spectrophotometrically in uterus tissues. The severity of inflammation in uterus samples and follicular activity in ovarian tissues were histopathologically evaluated. In addition, serum cytokine levels were determined. While TAS in uterine tissue significantly increased in the resveratrol group when compared to that of the other groups (p < 0.05), there was no difference between the groups in TOS (p > 0.05). The inflammation of the endometrium and the numbers of corpus luteum in the endometritis group were highly significant when compared to those of the other groups (p < 0.05). The recovery of inflammation and follicular activity were similar to those of the other groups in resveratrol group. However, it was realized that resveratrol administration reduced serum cytokine levels. According to the results of the current study, resveratrol was found to be effective in the treatment of endometritis with its antioxidant and anti-inflammatory functions.

Bisphenol A (BPA) is an estrogenic endocrine disrupting chemical to which humans are frequently exposed during routine daily life. Curcumin and taurine are natural products that have also been used as antioxidants against different environmental toxin-induced hepatotoxicity. Furthermore, they have protective and therapeutic effects against various diseases. The present investigation has been conducted to evaluate the therapeutic potential of curcumin (100 mg kg -1 ) and taurine (100 mg kg -1 ) for their hepatoprotective efficacy against BPA (130 mg kg -1 )-induced liver injury in rat. BPA significantly elevated the levels of malondialdehyde (MDA), while it reduced the activities of catalase (CAT), total glutathione S-transferase (GST), total glutathione peroxidase (GPx), and total superoxide dismutase (SOD). Besides, these biochemical changes were accompanied by histopathological alterations marked by the destruction of normal liver structure. The histological examinations showed that exposure of BPA caused dilatation of sinusoids, inflammatory cell infiltration, congestion, and necrosis in liver parenchyma. The BPA-induced histopathological alterations in liver were minimized by curcumin and taurine treatment. Furthermore, no necrosis was observed in the liver tissues of curcumin plus BPA and taurine plus BPA-treated rats. Oral administration of curcumin and taurine to BPA-exposed rats significantly reversed the content of lipid peroxidation products, as well as enhanced the activities of GPx and GST, CAT, and SOD enzymes. These findings have indicated that curcumin and taurine might have a protective effect against BPA-induced hepatotoxicity in rats.

Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Thymus sipyleus Boiss. subsp. rosulans (Borbas) Jalas (TS) is a commonly used plant in the treatment of various complaints, including skin wounds in Turkish folk medicine. Despite the widespread traditional use of TS, there is not any scientific report confirming the effectiveness of this plant on the healing process. This research aimed to investigate the effects of different extracts obtained from TS on biological events during wound healing, on a cellular basis. In this context, proliferative activities of the extracts, as well as the effects on wound closure and hydroxyproline synthesis, were determined. In addition to wound healing properties, the antioxidant, antibacterial and anti-inflammatory activities of the extracts were evaluated. Decoction (D) and infusion (I) extracts contained the highest amount of phenolic content and showed the most potent activity against DPPH radical. All extracts exhibited complete protection against the damage induced by hydrogen peroxide (H 2 O 2 ) by increasing cell viability compared to only H 2 O 2 -treated groups, both in co-treatment and pre-treatment protocols. None of the extracts exhibited cytotoxic activity, and most of the extracts from the TS stimulated fibroblast proliferation and migration. All TS extracts exert anti-inflammatory activity by suppressing the overproduction of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO). The most pronounced activity on hydroxyproline synthesis was observed in D extract. In summary, it was observed that TS extracts can promote the healing process by enhancing fibroblast migration, proliferation and collagen synthesis as well as suppressing pro-inflammatory cytokines. The obtained data in this work support the traditional use of TS as a valuable plant-based compound for the treatment of wounds.

Purpose: Contrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN., Methods: Twenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp + CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500 mg/kg for 5 days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp + CIN groups, L-NAME (10 mg/kg), tenoxicam (0.5 mg/kg) and sodium amidotrizoate (10 ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected., Results: When the Dexp + CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels., Conclusions: Dexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.

Bisphenol A (BPA) is a chemical found in environmental xenoestrogen. In the present study, olive oil, curcumin, taurine, BPA, curcumin plus BPA, and taurine plus BPA were exposed to rats for 4 weeks via gavage. Content of malondialdehyde and activities of antioxidant enzymes (GPx, GST, SOD, CAT) and also histopathological and cytopathological changes of heart were studied. No significant changes in all studied parameters were seen between control, olive oil, curcumin, and taurine-treated groups. However, there were significant differences in levels of malondialdehyde and activities of antioxidant enzymes in BPA-exposed rats and some histo/cytopathological changes determined. In curcumin plus BPA-exposed and taurine plus BPA-exposed groups, we measured the preventive effects on some parameters but not exactly. As a result, curcumin and taurine significantly minimized BPA-induced cardiotoxicity in rats.

We aimed to investigate the effect of melatonin and curcumin treatment on oxidative stress, apoptosis, and histology of testicular tissue in our study. Four groups were formed using young (4 months old, n = 6) and aged (20-22 months old, n = 18) male Wistar albino rats: (a) Young control (1% ethanol:phosphate-buffered saline [PBS], subcutaneously [s.c.]); (b) Aged control (CTL; n = 6, 1% ethanol:PBS, s.c.); (c) Aged Melatonin (MLT; n = 6, 10 mg/kg, s.c.); (d) Aged Curcumin (CUR; n = 6, 30 mg/kg, i.p.). At the end of 21 days, the rats were sacrificed, and testicular tissues were removed. Malondialdehyde (MDA) in the testicular tissue was determined with thiobarbituric acid reactive substances formation, and glutathione (GSH) was determined with modified Ellman method; testosterone level was determined with chemiluminescence method and histologic changes were determined with Haematoxylin-Eosin and Johnsen's scoring; Apoptotic cell counts were made with TUNEL staining of seminiferous tubule in testis. With ageing, MDA level increased in testicular tissue, but GSH and blood testosterone levels decreased. Melatonin treatment for aged rats significantly decreased Paired total testicular/body weight ratio compared to aged control group (p < 0.05). Curcumin treatment for aged rats significantly increased GSH level compared to the aged control group (p < 0.05). Besides, melatonin and curcumin treatment significantly decreased the number of apoptotic cells and significantly increased Johnsen's score (p < 0.05)., (© 2018 Blackwell Verlag GmbH.)

Objective: This study investigated effects of S-allylmercaptocysteine (SAMC), diallyl disulfide (DADS), and vitamin B 12 on inner ear functions and morphology after long-period high-level broadband noise exposure., Materials and Methods: Twenty-four healthy rats were randomly divided into four groups. First group was chosen as the control group. Vitamin B 12 , SAMC, and DADS were applied to other groups for 4 weeks. On the 14th day, each group was exposed to broadband noise. Auditory brainstem response test was performed before and immediately after noise exposure and repeated on the 2nd and 14th day., Results: Permanent threshold shifts were significantly lower in groups treated with vitamin B 12 , SAMC, and DADS. Histologically, cochleae of SAMC and DADS groups were found to be better preserved than the cochleae of vitamin B 12 and control groups., Conclusion: Physiologically and histologically, SAMC and DADS reduced the long-term effects of noise. However, physiological recovery was not consistent with the morphological findings in vitamin B 12 group., Competing Interests: None

Background: The aim of this study was to evaluate the degradation of tryptophan (Trp), neopterin production and antioxidant capacity in patients with benign and malignant thyroid disease., Methods: For this reason, the levels of tryptophan, kynurenine (Kyn) and neopterin, and superoxide dismutase (SOD) and catalase (CAT) enzyme activities in 67 thyroid patients were evaluated in our study and the results were compared with 30 healthy controls., Results: Tryptophan and kynurenine levels in thyroid patients decreased compared to the control group. Patients with thyroid disease had lower CAT activity than the control group. The neopterin and tryptophan levels in malignant and benign patients were also significantly different., Conclusion: The results of the present study suggest that thyroid disorders may lead to changes in tryptophan degradation, neopterin production and CAT enzyme activities., (© 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

The purpose of this study was to determine the effects of resveratrol and regular aerobic exercise on vascular functions and biomarkers related to vessel responsiveness in an age and gender-dependent manner. The study used young (3 months) and old (12 months) male and female Wistar albino rats. Resveratrol was given in the drinking water (0.05 mg/ml; approximately 7.5 mg/kg) for 6 weeks. In the exercise group, all rats performed treadmill running at 20 m/min on a 0° incline, 40 min/day, 3 times a week, for 6 weeks. Acetylcholine-induced, endothelium-dependent and sodium nitroprusside-mediated, endothelium-independent relaxations of rat thoracic aorta and blood levels of biomarkers were separately changed by resveratrol intake and exercise-training in an age and gender-dependent manner. Antioxidant enzymes and eNOS expressions in vessels were elevated by resveratrol and exercise. Resveratrol and exercise enhanced gene expressions of non-selective PDE1, 2, 3 and cAMP selective PDE4 but not cGMP selective PDE5 in the aorta. In addition, the aortic mRNA expression of inflammation markers were altered by resveratrol and exercise-training. The results of the study demonstrated that vessel responsiveness and biomarkers related to vascular functions were altered by resveratrol consumption and exercise-training in an age and gender-dependent manner., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We studied the effects of treatment with SMe1EC, a hexahydropyridoindole antioxidant, on vascular reactivity, endothelial function, and oxidonitrosative stress level of thoracic aorta in young and old rats with or without diabetes mellitus. The rats were grouped as young control (YC 3 months old), old control (OC 15 months old), young diabetic (YD), old diabetic (OD), young control treated (YCT), old control treated (OCT), young diabetic treated (YDT), and old diabetic treated (ODT). Diabetes was induced by streptozotocin injection and subsequently SMe1EC2 (10 mg/kg/day, p.o.) was administered to YCT, OCT, YDT, and ODT rats for 5 months. In young and old rats, diabetes resulted in hypertension, weight loss, hyperglycemia, and hypertriglyceridemia, which were partially prevented by SMe1EC2. SMe1EC2 also inhibited the diabetes-induced increase in aorta levels of AGEs (advanced glycosylation end-protein adducts), 4-HNE (4-hydroxy-nonenal-histidine), 3-NT (3-nitrotyrosine), and RAGEs (receptors for AGEs). The contractions of the aorta rings to phenylephrine (Phe) and KCL did not significantly change, but acetylcholine (ACh) and salbutamol relaxations were reduced in OC compared to YC rats. Diabetes induction increased Phe contractions in YC and OC rats, KCL contractions in YC rats, and did not cause further inhibition in already inhibited ACh and salbutamol relaxations in OC rats. We have achieved the lowest levels of ACh relaxation in YD rats compared to other groups. SMe1EC2 did not change the response of aorta to ACh, salbutamol and Phe in YC rats, and ameliorated ACh relaxations in OC and YD but not in OD rats. In YDT and ODT rats, increased Phe and KCL contractions, high blood pressure, and impaired salbutamol relaxations were amended by SMe1EC2. Phe contractions observed in YD and OD rats as well as KCl contractions observed in OC rats were the lowest levels when the rats were treated with SMe1EC2. When the bath solution was shifted to cyclopiazonic acid (CYP) or CYP plus Ca 2+ -free medium, the contraction induced by a single dose of Phe (3 × 10 -6  M) was more inhibited in YD and OD than in YC but not in OC rats. In SMe1EC2-treated rats, neither the presence of CFM nor CFM plus CYP exhibited a significant change in response of aorta to a single dose of Phe. These findings suggest that α1-adrenergic receptor signaling is activated in both age groups of diabetic rats, diabetes activates K + -depolarization and calcium mobilization via Ca V especially in the aorta of young rats, and sensitizes the aorta of old rats to the regulating effect of SMe1EC2. ACh relaxations were inhibited in YC rats, increased in OC rats and unchanged in YD and OD rats when aortic rings pretreated with TEA, an inhibitor of calcium-activated K + channels (K Ca ), or 4-aminopyridine (4-AP), an inhibitor of voltage-sensitive K + channels (K V ). ACh relaxations were inhibited in YCT, OCT, and YDT rats in the presence of 4-AP or TEA. In ODT rats, 4-AP did not change ACh relaxation but TEA inhibited. These findings suggest that the contribution of K v and K Ca to ACh relaxation is likely upregulated by SMe1EC2 when the relaxations were inhibited by aging or diabetes. We conclude that SMe1EC2 might be a promising agent for aging and diabetes related vascular disorders.