Safety assessment of European cranberrybush (Viburnum opulus L.) fruit juice: Acute and subacute oral toxicity.

European cranberrybush (ECB) (Viburnum opulus L.) fruits are abundant in phenolic compounds associated with various health benefits. However, the toxicity and safety of ECB juice have not been systematically studied. In the present study, acute and subacute oral toxicities of ECB fruit juice were evaluated on Sprague-Dawley rats and BALB/c mice to establish a toxicity profile. In acute tests, a single administration of 2000 mg/kg body weight of extract to rats exhibited no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) was over 2000 mg/kg. In subacute tests, repeated administration for 28 days at 0 (control), 500, and 2000 mg/kg doses of extract in mice did not display adverse clinical signs or deaths. However, in the 2000 mg/kg subacute group, platelet counts were significantly high, which correlated with histopathological analyses revealing that ECB extract at 2000 mg/kg was toxic to the kidney, liver, and adipose tissue. The NOAEL value of ECB extract was found as 500 mg/kg/day, but further sub-chronic and chronic toxicity studies are warranted to comprehensively evaluate the long-term safety implications. The study's results emphasize the importance of considering the dosage of dietary supplements containing high levels of phenolic compounds over an extended period to avoid potential cumulative effects from prolonged consumption of high doses.

Chewable tablet with herbal extracts and propolis arrests Wuhan and Omicron variants of SARS-CoV-2 virus.

Prevention of COVID-19 is of paramount importance for public health. Some natural extracts might have the potential to suppress COVID-19 infection. Therefore, this study aimed to design a standardised, efficient, and safe chewable tablet formulation (with propolis and three herbal extracts) for possible prevention against two variants (Wuhan B.1.36 and Omicron BA.1.1) of SARS-CoV-2 virus and other viral infections. Green tea, bilberry, dried pomegranate peel, and propolis extracts were selected for this purpose. Cytotoxicity and antiviral activity of each component, as well as the developed chewable tablet, were examined against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus using Vero E6 cells with the xCELLigence real-time cell analyser-multiple plates system. Anti-inflammatory and analgesic activities, as well as mutagenicity and anti-mutagenicity of the chewable tablet were also analysed. Compared to the control, it was observed that the chewable tablet at concentrations of 110 and 55 µg/mL had antiviral activity rates of 101% and 81%, respectively, for the Wuhan variant and 112% and 35%, respectively, for the Omicron variant. The combination of herbal extracts with propolis extract were synergically more effective (∼7-fold higher) than that of individual extract. The present work suggests that a combination of herbal extracts with propolis at suitable concentrations can effectively be used as a food supplement for the prevention of both variants of the SARS-CoV-2 virus in the oral cavity (the first entry point of the SARS-CoV-2 virus).

A comprehensive study to evaluate the wound healing potential of okra (Abelmoschus esculentus) fruit.

ETHNOPHARMACOLOGICAL RELEVANCE: Okra fruit (Abelmoschus esculentus (L.) Moench) has been extensively used for the treatment of skin damage and subcutaneous tissue abscess for many years in Turkish folk medicine. AIM OF STUDY: In this study, we aimed to investigate the wound healing potential of okra fruit by in vitro and in vivo experimental models in detail. Furthermore, based on the results of experiments, a wound healing formulation was developed and its activity profile was studied. MATERIALS AND METHODS: For this purpose, the phenolic, flavonoid and proanthocyanidin contents and chemical profile of aqueous and ethanolic extracts prepared from okra fruits cultivated in two different locations of Turkey, i.e. Aegean and Kilis regions, were comparatively determined and the tryptophan levels, which is known to be an influential factor in wound healing, were measured. Antioxidant activity of the okra fruit extracts was determined by DPPH test, ABTS radical scavenger activity, iron-binding capacity, total antioxidant capacity and copper reduction capacity assays. Moreover, antibacterial activity potentials of the aqueous and ethanolic extracts of okra fruits were determined. The protective effect of the extracts against H2O2-induced oxidative stress and anti-inflammatory activity were assessed in HDF (human dermal fibroblast) cells and in RAW 264.7 murine macrophages, respectively. The biocompatibility of the gel formulations prepared with the best performing extract were evaluated by human Epiderm™ reconstituted skin irritation test model. Wound-healing activity was investigated in rats by in vivo excision model and, histopathological examination of tissues and gene expression levels of inflammation markers were also determined. RESULTS: According to our findings, the aqueous and ethanolic extracts of okra fruits were found to possess a rich in phenolic content. Besides, isoquercitrin was found to be a marker component in ethanolic extracts of okra fruits. Both extracts exhibited antioxidant activity with significant protective effect against H2O2-induced damage in HDF cells by diminishing the MDA level. Also, the highest dose of ethanolic extracts has displayed a potent anti-inflammatory activity on LPS-induced RAW264.7 cells. Besides, both water and ethanolic extracts were shown to possess antimicrobial activity. On the other hand, the formulations prepared from the extracts were found non-irritant on in vitro Epiderm™-SIT. In vivo excision assay showed that tissue TGF-ß and IL-1ß levels were significantly decreased by the 5% okra ethanolic gel formulation. The histopathological analysis also demonstrated that collagenisation and granulation tissue maturation were found higher in 5% (w/v) okra ethanolic extract-treated group. CONCLUSION: 5% of okra ethanolic extract might be suggested as a potent wound healing agent based on the antimicrobial, antioxidant and anti-inflammatory tests. The proposed activity was also confirmed by the histopathological findings and gene expression analysis.

Protective Effect of Nigella sativa and Nigella damascena Fixed Oils Against Aflatoxin Induced Mutagenicity in the Classical and Modified Ames Test.

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography-mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC2 . The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.

The screening of the safety profile of polymeric based amoxicillin nanoparticles in various test systems.

Nanotechnology-based drugs show superiority over conventional medicines because of increased bioavailability, lower accumulation in non-target tissues, and improved therapeutic index with increased accumulation at target sites. However, it is important to be aware of possible problems related to the toxicity of these products, which have therapeutically superior properties. Accordingly, the present study was designed to investigate the safety profile of amoxicillin nanoparticles (AmxNPs) that we developed to increase the oral bioavailability of amoxicillin (Amx) in poultry. In the first part of the study, the genotoxicity potential of AmxNPs was evaluated using the Ames test and the in vitro comet assay. The results of Ames test showed that none of the tested concentrations of Amx and AmxNPs cause a significant increase in the revertant number of Salmonella typhimurium strains TA98, and TA100, either with or without metabolic activation. Similarly, the comet assay revealed that AmxNPs did not induce DNA damage at any of the concentrations used, whereas high-dose (200 µg/mL) of Amx caused a significant increase in the percentage of DNA in the tail. In the second part of the study, the toxicity potential of AmxNPs on broilers was investigated by measuring biochemical parameters. In vivo results demonstrated that AmxNps did not cause a significant change in biochemical parameters, whereas Amx increased ALT, glucose, and cholesterol levels at certain sampling times. The obtained findings suggest that AmxNPs could be a safe promising potential drug in drug delivery systems.

A Realistic Approach for Anti-Inflammatory, Antinociceptive and Antimutagenic Activities, and Risk Assessment of the Aqueous Extract of Platanus orientalis L. Leaves.

BACKGROUND: Oriental planetree (Platanus orientalis L.) leaf was recorded as a remedy against inflammatory problems and to stop the pain, i.e. toothache or knee pain in "The Canon of Medicines" by Avicenna and was also being documented in the Iranian Traditional Medicine. Although such a utilization has not been described in reliable sources, recently use of its leaves as herbal tea has become popular among laypeople. Previous studies have shown that only the nonpolar extract from the leaves may have such efficacy, while possible benefits when it is used as herbal tea have not been investigated. OBJECTIVE: The present study aims to reveal the possible efficacy and safety profile of aqueous extract from P. orientalis leaf. METHODS: Aqueous extract of the leaves was submitted to in vivo and in vitro tests to determine its anti-inflammatory, antinociceptive, antimutagenic activities and also reveal its safety profile. RESULTS: The aqueous extract (400 mg/kg) procured weak and non-significant anti-inflammatory and antinociceptive activities. Meanwhile, the aqueous extract demonstrated antimutagenic activity in very high concentrations. On the other hand, results of safety evaluation showed that no concern had been observed from the viewpoint of public health. CONCLUSION: Despite the popularity of the herbal tea prepared from the leaves of Oriental planetree among the people suffering joint problems to relieve pain, this study has proven that such application would not help them to alleviate their complaints when used as herbal tea.

Ameliorating Effects of ß-Glucan on Epigastric Artery Island Flap Ischemia-Reperfusion Injury.

BACKGROUND: Ischemia-reperfusion injury has been one of the culprits of tissue injury and flap loss after island flap transpositions. Thus, significant research has been undertaken to study how to prevent or decrease the spread of ischemia-reperfusion injury. Preventive effects of ß-glucan on ischemia-reperfusion injury in the kidney, lung, and small intestine have previously been reported. In this study, we present the ameliorating effects of ß-glucan on ischemia-reperfusion injury using the epigastric artery island-flap in rats. MATERIALS AND METHODS: Thirty Wistar-Albino rats were equally divided into three groups: sham, experimental model, and treatment groups. In the sham group, an island flap was elevated and sutured back to the original position without any ischemia. In the experimental model group, the same-sized flap was elevated and sutured back with 8 h of ischemia and consequent 12 h of reperfusion. In the treatment group, 50 mg per kilogram ß-glucan was administered to the rats using an orogastric tube for 10 d before the experiment. The same-sized flap is elevated and sutured back to its original position with 8 h of ischemia and 12 h of consequent reperfusion in the treatment group. Tissue biopsies were taken on the first day of the experimental surgery. Tissue neutrophil aggregation and vascular responses were evaluated by histological examinations. Tissue oxidant and antioxidant enzyme levels are evaluated biochemically after tissue homogenization. Topographic follow-up and evaluation of the flaps were maintained, and photographs were taken on the first and seventh day of the experimental surgery. RESULTS: Topographic flap survival was significantly better in the ß-glucan administered group. The neutrophil number, malondialdehyde, and myeloperoxidase levels were significantly lower while glutathione peroxidase and superoxide dismutase levels were significantly higher in the ß-glucan administered group respective to the experimental model group. CONCLUSIONS: Based on the results of our study, we can conclude that ß-glucan is protective against ischemia-reperfusion injury. Our study presents the first experimental evidence of such an effect on skin island flaps.

The integrated use of in silico methods for the hepatotoxicity potential of Piper methysticum.

Herbal products as supplements and therapeutic intervention have been used for centuries. However, their toxicities are not completely evaluated and the mechanisms are not clearly understood. Dried rhizome of the plant kava (Piper methysticum) is used for its anxiolytic, and sedative effects. The drug is also known for its hepatotoxicity potential. Major constituents of the plant were identified as kavalactones, alkaloids and chalcones in previous studies. Kava hepatotoxicity mechanism and the constituent that causes the toxicity have been debated for decades. In this paper, we illustrated the use of computational tools for the hepatotoxicity of kava constituents. The proposed mechanisms and major constituents that are most probably responsible for the toxicity have been scrutinized. According to the experimental and prediction results, the kava constituents play a substantial role in hepatotoxicity by some means or other via glutathione depletion, CYP inhibition, reactive metabolite formation, mitochondrial toxicity and cyclooxygenase activity. Some of the constituents, which have not been tested yet, were predicted to involve mitochondrial membrane potential, caspase-3 stimulation, and AhR activity. Since Nrf2 activation could be favorable for prevention of hepatotoxicity, we also suggest that these compounds should undergo testing given that they were predicted not to be activating Nrf2. Among the major constituents, alkaloids appear to be the least studied and the least toxic group in general. The outcomes of the study could help to appreciate the mechanisms and to prioritize the kava constituents for further testing.

Clinicopathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer following definitive therapy.

OBJECTIVE: To demonstrate the effect of clinicopathological factors on 68Ga-PSMA-11 PET/CT positivity at the time of biochemical recurrence (BCR) of localized prostate cancer (PCa) following definitive therapy. METHODS: We retrospectively reviewed our institutional database for PCa patients who had BCR and subsequently underwent 68Ga-PSMA-11 PET/CT between April 2014 and February 2018. A total of 51 patients who were metastasis-free before PSMA imaging and previously treated with definitive therapy (radical prostatectomy or external beam radiotherapy) for localized disease (pT1c-T3b pN0-1 cM0) were included. RESULTS: 37 out of 51 patients (72.5%) had positive 68Ga-PSMA-11 PET/CT scans. Age at diagnosis, Gleason score (GS), D'Amico risk status of PCa, initial PSA level before treatment and PSA doubling time were not associated with PSMA positivity. Pre-scan PSA levels of > 0.2 ng/ml and PSA velocity of ≥ 1 ng/ml/year were significantly associated with increased PSMA positivity, whereas history of androgen deprivation therapy showed a trend towards significance. The optimal cutoffs for distinguishing between positive and negative scans were ≥ 0.71 ng/ml for pre-scan PSA and ≥ 1.22 ng/ml/yr for PSA velocity. In multivariable analysis, log pre-scan PSA and pre-scan PSA level > 0.2 ng/ml remained significant predictors for PSMA positivity, whereas the association of PSA velocity and of ADT was lost. CONCLUSIONS: In BCR of localized PCa following definitive therapy, pre-scan PSA was strongly associated with positive 68Ga-PSMA-11 scan, even at PSA levels ranging from 0.2 to 1.0 ng/ml. Therefore, clinical and pathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer need to be further elucidated.

Hydroxytyrosol: The Phytochemical Responsible for Bioactivity of Traditionally used Olive Pits.

The fruits of Olea europaea L. is widely consumed as food, and olive pits are utilized in folk medicine to relieve gastric disturbances. In the present study, the possible anti-inflammatory, analgesic and antioxidant activities of aqueous extracts of black (BP) and green olive (GP) pit prepared at gastric fed state pH were evaluated in vitro. Moreover, the bioactive compound, hydroxytyrosol (HT), was isolated from the extracts for the first time. According to results, GP extract (62.5 to 1000 µg/mL) showed significant anti-inflammatory activity in a dose-dependent manner and HT displayed significant nitrite inhibition at 100 µM with slight analgesic activity. Extracts and HT showed a significant antioxidant activity according to Total Antioxidant Capacity (TOAC), cupric ion reducing antioxidant capacity (CUPRAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. As a conclusion, a proper formulation containing HT might be a potential remedy to relieve gastric disturbances and olive pits, can be utilized as a valuable industrial tool for the low-cost production of HT. How to cite this article: Reis R, Sipahi H, Zeybekoglu G, Celik N, Kirmizibekmez H, Kaklikkaya N, Aydin A. Hydroxytyrosol: The Factor Responsible for Bioactivity of Traditionally used Olive Pits. Euroasian J Hepatogastroenterol, 2018;8(2):126-132.

Energy Drink Induced Lipid Peroxidation and Oxidative Damage in Rat Liver and Brain When Used Alone or Combined with Alcohol.

Energy drinks (ED) are containing large doses of metabolic stimulants and its use with ethanol has increased dramatically among young adults. In this study, we examined the effects of ED exposure either alone or in combination with ethanol on oxidative stress parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and lipid peroxidation parameter malondialdehyde (MDA) in rat. Some histopathological findings were also evaluated. ED exposure led to a dose-dependent increase in liver MDA compared to the control indicating oxidative damage. Histopathological findings also revealed that ED alone may generate liver damage. Ethanol exposure increased MDA level and SOD, CAT, and GSH-Px activity in both the brain and the liver. The combination of ethanol and ED produced greater damage which is considered by further increases in SOD and GSH-Px activity in the brain. Similar results for MDA were observed in both the liver and brain as well. Our findings suggest that ED consumption alone or combination with ethanol may represent a significant public health concern.

Antimutagenic and anticlastogenic effects of Turkish Black Tea on TA98 and TA100 strains of Salmonella typhimurium (in vitro) and mice (in vivo).

CONTEXT: Black tea has been reported to have significant antimutagenic and anticarcinogenic properties associated with its polyphenols theaflavins (TF) and thearubigins (TR). Similarly, Turkish black tea (TBT) also contains a considerable amount of TF and TR. OBJECTIVE: This study investigated the mutagenic, antimutagenic and anticlastogenic properties of TBT. MATERIALS AND METHODS: The mutagenic and antimutagenic effects of TBT (10 to 40000 µg/plate) were investigated in vitro on Salmonella strains TA98 and TA100 with and without S9 fraction. Anticlastogenic effect was studied at concentrations of 300-1200 mg/kg TBT extract by chromosomal aberrations (CA) assay from bone marrow of mice. RESULTS: The results of this study did not reveal any mutagenic properties of TBT. On the contrary, TBT extract exhibited antimutagenic activity at >1000 µg/plate concentrations in TA98 strain with and without S9 activation (40% inhibition with S9 and 27% without S9). In TA100 strain, the antimutagenic activity was observed at >20,000 µg/plate TBT extracts without S9 activation (28% inhibition) and at >1000 µg/plate with S9 activation (59% inhibition). A significant decrease in the percentage of aberrant cells (12.33% ± 1.27) was observed in dimethylbenz(a)anthracene (DMBA) plus highest concentration (1200 mg/kg) of TBT extract-treated group when compared to only DMBA-treated group (17.00% ± 2.28). DISCUSSION AND CONCLUSION: Results indicated that TBT can be considered as genotoxically safe, because it did not exert any mutagenic and clastogenic effects. As a result, TBT exhibited antimutagenic effects more apparently after metabolic activation in bacterial test system and had an anticlastogenic effect in mice.

Substance Abuse Profiles of Patients Admitted to the Alcohol and Drug Addiction Research, Treatment, and Education Center in Turkey.

OBJECTIVES: To determine the substance abuse profiles of patients treated a Drug Addiction Research, Treatment, and Education Center (AMATEM) in association with the percentage of substance use distribution and multiple substance use in their urine samples. For this, we retrospectively evaluated the urine sample analysis reports of 600 male and female patients aged 13 to 65 years who were treated at the AMATEM unit of Istanbul Neuropsychiatry Hospital between January 1st, 2015, and December 12th, 2015. MATERIALS AND METHODS: The urine samples were sent to Üsküdar University Advanced Toxicology Analysis Laboratory and were analyzed using a UPLC tandem mass spectrometer (UPLC-MS/MS). To determine the substance use profiles of the patients applying to AMATEM, statistical assessment was performed on the analysis reports of the patients. RESULTS: When the analysis reports of the 600 urine samples were examined, 293 patients were identified to have used addictive substances. The substances most frequently detected in the urine samples were respectively: cannabis, alcohol, morphine, cocaine, synthetic cannabinoids, 3,4-Methylenedioxymethamphetamine, and amphetamine. CONCLUSION: The findings in our study resemble the rates of cannabis use by the young population throughout the world. Our results show differences to the literature regarding the consumption of synthetic cannabinoids because the variety of synthetic cannabinoids change rapidly around the world each year.

Safety evaluation of styrax liquidus from the viewpoint of genotoxicity and mutagenicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Styrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. AIM OF STUDY: In spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of the present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. MATERIALS AND METHODS: In vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10- 30,000µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500-2000mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. RESULTS: Genotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95mg/g), while in its ethanolic extract not only p-coumaric acid (11.46mg/g), but also gallic acid (1.60mg/g) were found to the main components. CONCLUSION: The findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity.

Effect of a hypercholesterolemia as a starting factor on spinal degeneration in rabbits and role of Vitamin E (α-tocopherol).

BACKGROUND: To identify the role of the hypercholesterolemia as a starting factor in discovertebral degeneration that ultimately causes lower back pain, and investigate the role of Vitamin E in this process. METHODS: The rabbits (n = 32) were divided into two broad experimental groups: A control group, and a hypercholesterolemia group, namely cholesterol, and cholesterol plus Vitamin E groups and they were fed sequentially for 4 or 8 weeks. Serum cholesterol and Vitamin E (α-tocopherol) levels were determined; vascular tissue was prepared for histopathological analyses and vertebra was decalcified for the study. RESULTS: Cholesterol diet group resulted approximately 44-fold of increase plasma cholesterol levels over the 4-week control values. Additional supplementation with Vitamin E group induced a plasma cholesterol level increase of only 37-fold as compared to the control group. In the cholesterol groups, light microscope examination revealed atherosclerotic plaque in major arteries. However, in the cholesterol plus Vitamin E treatment groups, no lipid accumulation or foam cell formation was visible in the abdominal aorta and vertebral segmental artery. In histopathological examination, we found degenerative changes in the discovertebral unit in cholesterol treated groups. CONCLUSION: Hypercholesterolemia causes fat accumulation in the disc endplate and vertebral body that causes blood supply disturbances which might be a starting factor of discovertebral degeneration. This event was not reversed by the elimination of cholesterol from the diet. Vitamin E supplementation was not effective in reducing fat accumulation in vertebral bone marrow. As a result, we conclude that degeneration of the discovertebral unit is not related to atherosclerotic changes in the major blood vessels.

Bioactivites of two common polyphenolic compounds: Verbascoside and catechin.

CONTEXT: Natural products can present remarkable biological and pharmacological activities. In traditional medicine, plants have been used historically in treating cancer, infections, and other inflammatory conditions. OBJECTIVE: Verbascoside and catechin are widespread polyphenolic plant compounds that could play a role in the anti-inflammatory and health-promoting effects of plants and plant extracts. MATERIALS AND METHODS: This study compares the potential cytotoxic effects of polyphenols verbascoside and catechin (6.25-200 µM) on human peripheral blood mononuclear cells (PBMC) for 48 h and myelomonocytic THP-1 and THP-1 Blue cells for 24 h. The effects of the compounds on immune activation markers such as indoleamine 2,3-dioxygenase (IDO) activity as well as on neopterin formation and nuclear factor-κB (NF-κB) activation were investigated. Cytotoxicity of the compounds was tested using Cell-Titer Blue assay. RESULTS: Verbascoside exhibited significant suppressive effects in mitogen-stimulated PBMC on tryptophan breakdown (>50 µM; IC50 value: 58.6 µM) and the production of neopterin (>6.25 µM; IC50 value: 217 µM). These effects correlated with a decline in cell viability, while THP-1 Blue cells were less sensitive. NF-κB activity was slightly enhanced at lower concentrations (<50 µM verbascoside) in stimulated cells and at the highest concentration used in unstimulated cells. Catechin had no relevant effects on cell viability and on the tested inflammation markers, except NF-κB activation in THP-1 Blue cells. DISCUSSION AND CONCLUSION: The results obtained show that verbascoside and catechin represent effective compounds which interfere with immunobiochemical pathways that are highly relevant for immunosurveillance and competing virus infections.

The fruit extract of Berberis crataegina DC: exerts potent antioxidant activity and protects DNA integrity.

BACKGROUND: Dried fruits of Berberis crataegina (Berberidaceae) have been frequently consumed as food garniture in Turkish cuisine, while its fruit paste has been used to increase stamina and in particular to prevent from cardiovascular dysfunctions in Northeastern Black Sea region of Turkey. This study investigated this folkloric information in order to explain the claimed healing effects as well as to evaluate possible risks. METHODS: Total phenolic, flavonoid and proanthocyanidin contents and antioxidant capacity of the methanolic fruit extract were evaluated through several in vitro assays. The cytotoxic and genotoxic effects of B. crataegina fruit extract were also assessed in both cervical cancer cell line (HeLa) and human peripheral blood lymphocytes. RESULTS: The extract showed protective effects against ferric-induced oxidative stress and had a relatively good antioxidant activity. It also ameliorated the H2O2 mediated DNA damage in lymphocytes, suggesting the protective effect against oxidative DNA damage. CONCLUSION: The methanolic extract of B. crataegina fruits may be a potential antioxidant nutrient and also may exert a protective role against lipid peroxidation as well as oxidative DNA damage.

Malondialdehyde, antioxidant enzymes, and renal tubular functions in children with iron deficiency or iron-deficiency anemia.

We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-ß-D-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.