Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells

We investigated antigenotoxic and antioxidative effects of newly derivatized compound naringenin-oxime (NG-Ox) compared to its mother compound naringenin (NG) against oxidative damage induced by hydrogen peroxide (HP) in human peripheral blood mononuclear cells (PBMC). Antigenotoxic activity was assessed using alkaline single cell gel electrophoresis assay (comet assay). Oxidative status was evaluated by measurement of total antioxidant status, total oxidant status and lipid hydroperoxide levels in the cells. Oxidative stress index was also calculated. Both NG and NG-Ox show a protective effect against HP-induced oxidative damage on PBMC and are able to reduce oxidative stress. The percentage of antigenotoxic and antioxidant potential progressively increased in a dose-dependent manner. However, these activities were found to be more significant in NG-Ox-treated cells than in NG-treated cells. Taken together, these observations provide evidences indicating that both NG and NG-Ox are able to protect cells against oxidative damage and apparently NG-Ox is more effective than NG.     

Apoptotic activity and anti-Toxoplasma effects of artemether on the tachyzoites and experimental infected Vero and J774 cell lines by Toxoplasma gondii

Objectives:

Drugs used for toxoplasmosis have limited efficacy and also severe side effects. A new drug with good efficacy and limited side effects is need of the hour. We studied the effects of artemether on Toxoplasma gondii in vitro conditions.

Materials and Methods:

Artemether (methyl-ether-qinghaosu) was tested for tachyzoites, J774, and Vero cell lines infected by T. gondii. For evaluating the effect of drugs on Vero cells infected with T. gondii, we designed two separate experiments; in the first experiment, the Vero cells were infected with tachyzoites and then treated with artemether; while in the second one, the tachyzoites were exposed to artemether and then Vero cells were infected with treated tachyzoites. For evaluating the apoptotic effect of artemether on tachyzoites and infected J774 macrophages cell line with T. gondii, we used flow cytometry method. Inhibitory concentration (IC₅₀) was evaluated by intracellular replication of tachyzoites in Vero cells.

Results:

IC₅₀ for infected Vero cells with tachyzoites was determined as 49.13 μg/ml. In pretreated tachyzoites with artemether before entering into Vero cells, IC₅₀ was calculated as 13.15 μg/ml. In both experiments, artemether showed a higher inhibitory effect than sulfadiazine (positive control). Artemether even at the highest concentrations only showed low cytotoxicity on Vero and J774 cell lines. Apoptosis in tachyzoites rise with an increasing concentration of artemether.

Conclusions:

Our findings indicate that artemether is effective to control the tachyzoites of T. gondii in vitro and maybe a good alternative drug for toxoplasmosis.KEY WORDS: Apoptosis, artemether, in vitro, J774, Toxoplasma gondii, Vero     

The structural HCV genes delivered by MPG cell penetrating peptide are directed to enhance immune responses in mice model

One of the significant problems in vaccination projects is the lack of an effective vaccine against hepatitis C virus (HCV). The goal of the current study is to evaluate and compare two DNA constructs encoding HCV core and coreE1E2 genes alone or complexed with MPG peptide as a delivery system for stimulation of antibody responses and IFN-γ secretion in Balb/c mice model. Indeed, MPG cell penetrating peptide was used to improve DNA immunization in mice. Our results demonstrated that MPG forms stable non-covalent nanoparticles with pcDNA-core and pcDNA-coreE1E2 at an N/P ratio of 10:1. The in vitro transfection efficiency of core or coreE1E2 DNA using MPG and TurboFect delivery systems was confirmed by western blot analysis. The results indicated the expression of the full-length core (～21?kDa), and coreE1E2 (～83?kDa) proteins using an anti-His monoclonal antibody. In addition, the expression of HCV core and coreE1E2 proteins was performed in bacteria and the purified recombinant proteins were injected to mice with Montanide 720 adjuvant. Our data showed that the immunized mice with HCV core and coreE1E2 proteins generated the mixture of sera IgG1 and IgG2a isotypes considerably higher than other groups. Furthermore, DNA constructs encoding core and coreE1E2 complexed with MPG could significantly induce IFN-γ secretion in lower concentrations than the naked core and coreE1E2 DNAs. Taken together, the DNA formulations as well as protein regimens used in this study triggered high-level IFN-γ production in mice, an important feature for the development of Th1 immune responses.     

Chemical composition along with anti-leishmanial and cytotoxic activity of Zataria multiflora

Context: Natural products and their compounds are some of the most interesting sources of new drugs. Reviews have reported various pharmacological properties such as antimicrobial effects of Zataria multiflora Boiss (Lamiaceae).

Objective: The present study investigates the chemical composition of Z. multiflora essential oil and evaluates its cytotoxic effects and anti-leishmanial activities against Leishmania tropica in an in vitro model.

Materials and methods: The components of Z. multiflora oil were identified by gas chromatography/mass spectroscopy (GC/MS) analysis. Anti-leishmanial effects of the essential oil (0–100?μL/mL) and methanol extract of Z. multiflora (0–100 μg/mL) on promastigote forms as well as their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 h. The leishmanicidal activity against amastigote forms of L. tropica was evaluated at the concentrations of 0–50 μg/mL in a macrophage model for 48 h.

Results: The chemical analyses demonstrated that the main components of essential oil were thymol (41.81%), carvacrol (28.85%), and p-cymene (8.36%). Regarding leishmanicidal activity, the IC₅₀ values for the essential oil and methanol extract were 3.2?μL/mL and 9.8 μg/mL against promastigote forms and 8.3?μL/mL and 34.6 μg/mL against amastigote forms, respectively. Essential oil (CC₅₀ 89.3?μL/mL) indicated a higher cytotoxic effect than the methanol extract (CC₅₀ 591.6 μg/mL) of Z. multiflora.

Conclusion: The present study revealed the chemical composition of Z. multiflora that might be a natural source of new anti-leishmanial agents in terms of use against cutaneous leishmaniasis.     

Efficacy of Probiotics in Irritable Bowel Syndrome: A Meta-Analysis of Randomized,Controlled Trials

Purpose  This study was designed to evaluate whether probiotics improve symptoms in patients with irritable bowel syndrome. Methods  PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy of probiotics in the management of irritable bowel syndrome. Clinical improvement was the key outcome of interest. Data were searched within the time period of 1966 through September 2007. Results  Eight randomized, placebo-controlled, clinical trials met our criteria and were included in the analysis. Pooling of eight trials for the outcome of clinical improvement yielded a significant relative risk of 1.22 (95 percent confidence interval, 1.07–1.4; P = 0.0042). Conclusions  Probiotics may improve symptoms of irritable bowel syndrome and can be used as supplement to standard therapy.     

Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid Peroxidation in Type 2 Diabetes: A Randomized Double‐Blind Placebo‐Controlled Clinical Trial

This study aimed to examine the effects of hesperidin supplement on the glycemic parameters, oxidative DNA damage, and lipid peroxidation in patients with type 2 diabetes. Sixty‐four patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on glycemic parameters, total antioxidant capacity (TAC), 8‐hydroxydeoxyguanosine (8‐OHDG), and malondialdehyde (MDA) were collected at the baseline and at the end of the study. In hesperidin group, TAC increased (0.74 ± 0.16 vs. 0.82 ± 0.18), while serum froctoseamin (5.79 ± 5.86 vs. 5.01 ± 4.95; p  = 0.001), 8‐OHDG (14.32 ± 6.4 vs. 11.00 ± 7.0; p  = 0.000), and MDA (5.78 ± 1.76 vs. 4.60 ± 0.75; p  = 0.000) decreased in comparison with the baseline values. There was a significant difference in percent change of TAC (13.35 ± 19.21 vs. 3.13 ± 10.02; p  = 0.043), froctoseamin (?10.10 ± 16.84 vs. 4.27 ± 34.646), 8‐OHDG (?25.11 ± 28.23 vs. 8.69 ± 35.41; p  = 0.000), and MDA (?16.46 ± 18.04 vs. ?1.82 ± 22.63; p  = 0.007) between hesperidin and control groups following intervention in adjusted models. These results suggest that hesperidin may improve TAC and alleviate serum froctoseamin, 8‐OHDG, and MDA levels in type 2 diabetes. Copyright © 2017 John Wiley & Sons, Ltd.