The antidiabetic effect of superparamagnetic iron oxide nanoparticles highlights the role of WNT/AMPK/mTOR/FOXO1/mitochondrial DNA in muscle and kidney.

Aim: To explore the antidiabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs)-PEG-550 and its related metabolic pathways in muscles and kidney. Materials & methods: Diabetes was induced in 5-day neonatal rats; after confirming diabetes, treatment with SPIONs-PEG-550 started at different doses for 4 weeks. Routine analysis of glucose, insulin, adipocytokines, urea and creatinine was performed. The expression of several genes involved in metabolic pathways and the corresponding protein levels were examined. Results & conclusion: SPIONs-PEG-550 normalized the disturbed glucose homeostasis, reversed insulin resistance, adjusted the serum level of adipocytokines, and improved several disturbed downstream effectors of the insulin signaling and WNT pathway in both tissues. Histological examination of the muscle and pancreas has shown almost normal functional characteristics without remarkable adverse effects on the kidney.

Exploring the Chemical Constituents, Antioxidant, Xanthine Oxidase and COX Inhibitory Activity of Commiphora gileadensis Commonly Grown Wild in Saudi Arabia.

The use of the synthetic drugs has increased in the last few decades; however, these drugs exhibit various side effects. Scientists are therefore seeking alternatives from natural sources. Commiphora gileadensis has long been used to treat various disorders. It is commonly known as bisham or balm of Makkah. This plant contains various phytochemicals, including polyphenols and flavonoids, with biological potential. We found that steam-distilled essential oil of C. gileadensis exhibited higher antioxidant activity (IC50, 22.2 µg/mL) than ascorbic acid (IC50, 1.25 µg/mL). The major constituents (>2%) in the essential oil were ß-myrcene, nonane, verticiol, ß-phellandrene, ß-cadinene, terpinen-4-ol, ß-eudesmol, α-pinene, cis-ß-copaene and verticillol, which might be responsible for the antioxidant and antimicrobial activity against Gram-positive bacteria. The extract of C. gileadensis exhibited inhibitory activity against cyclooxygenase (IC50, 450.1 µg/mL), xanthine oxidase (251.2 µg/mL) and protein denaturation (110.5 µg/mL) compared to standard treatments, making it a viable treatment from a natural plant source. LC-MS analysis revealed the presence of phenolic compounds such as caffeic acid phenyl ester, hesperetin, hesperidin, chrysin and transient amounts of catechin, gallic acid, rutin and caffeic acid. The chemical constituents of this plant can be explored further to investigate its wide variety of therapeutic potential.

Volatile Composition and Biological Activity of Jordanian Commercial Samples of R. coriaria L. Fruits.

The present paper reports the GC-HS-SPME analysis of volatile emission and GC-MS analysis of chemical composition of essential oil of R. coriaria fruits of eight different samples of R. coriaria L. fruits ("sumac" folk name), collected from Jordanian agricultural field and the local market. The analyses show an important variability among the Sumac samples probably due to the origin, cultivation, harvesting period, drying, and conservation of the plant material. The main class of component present in all samples was monoterpenes (43.1 to 72.9%), except for one sample which evidenced a high percentage of sesquiterpene hydrocarbons (38.5%). The oxygenated monoterpenes provided a contribution to total class of monoterpenes ranging from 10.1 to 24.3%. A few samples were rich in monoterpene hydrocarbons. Regarding the single components present in all the volatile emissions, ß-caryophyllene was the main compound in most of the analyzed samples, varying from 34.6% to 7.9%. Only two samples were characterized by α-pinene as the main constituent (42.2 and 40.8% respectively). Essential oils were collected using hydro-distillation method. Furfural was the main constituent in almost all the analyzed EOs (4.9 to 48.1%), except in one of them, where ß-caryophyllene was the most abundant one. ß-caryophyllene ranged from 1.2 to 10.6%. Oxygenated monoterpenes like carvone and carvacrol ranged from 3.2-9.1% and 1.0-7.7% respectively. Cembrene was present in good amount in EO samples EO-2 to EO-8. The antioxidant capacities of the fruit essential oils from R. coriaria were assessed using spectrophotometry to measure free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and inhibition of ß-carotene bleaching (BCB). The essential oils from the fruits of the different samples of R. coriaria exhibited the MIC value ranging from 32.8 to 131.25 µg/mL against S. aureus ATCC 6538 and 131.25 to 262.5 µg/mL against E. coli ATCC 8739. The MIC values of ciprofloxacin were 0.59 and 2.34 µg/mL against S. aureus ATCC 6538 and E. coli ATCC 8739, respectively.

Fatty Acid Analysis, Chemical Constituents, Biological Activity and Pesticide Residues Screening in Jordanian Propolis.

Propolis is a resinous natural product collected by honeybees (Apis mellifera and others) from tree exudates that has been widely used in folk medicine. The present study was carried out to investigate the fatty acid composition, chemical constituents, antioxidant, and xanthine oxidase (XO) inhibitory activity of Jordanian propolis, collected from Al-Ghour, Jordan. The hexane extract of Jordanian propolis contained different fatty acids, which are reported for the first time by using GC-FID. The HPLC was carried out to identify important chemical constituents such as fatty acids, polyphenols and α-tocopherol. The antioxidant and xanthine oxidase inhibitory activities were also monitored. The major fatty acid identified were palmitic acid (44.6%), oleic acid (18:1∆9cis, 24.6%), arachidic acid (7.4%), stearic acid (5.4%), linoleic acid (18:2∆9-12cis, 3.1%), caprylic acid (2.9%), lignoceric acid (2.6%), cis-11,14-eicosaldienoic acid (20:2∆11-14cis, 2.4%), palmitoleic acid (1.5%), cis-11-eicosenoic acid (1.2%), α-linolenic acid (18:3∆9-12-15cis, 1.1%), cis-13,16-docosadienoic acid (22:2∆13-16cis, 1.0%), along with other fatty acids. The major chemical constituents identified using gradient HPLC-PDA analysis were pinocembrin (2.82%), chrysin (1.83%), luteolin-7-O-glucoside (1.23%), caffeic acid (1.12%), caffeic acid phenethyl ester (CAPE, 0.79%), apigenin (0.54%), galangin (0.46%), and luteolin (0.30%); while the minor constituents were hesperidin, quercetin, rutin, and vanillic acid. The percentage of α-tocopherol was 2.01 µg/g of the lipid fraction of propolis. Antioxidant properties of the extracts were determined via DPPH radical scavenging. The DPPH radical scavenging activities (IC50) of different extracts ranged from 6.13 to 60.5 µg/mL compared to ascorbic acid (1.21 µg/mL). The xanthine oxidase inhibition (IC50) ranged from 75.11 to 250.74 µg/mL compared to allopurinol (0.38 µg/mL). The results indicate that the various flavonoids, phenolic compounds, α-tocopherol, and other constituents which are present in propolis are responsible for the antioxidant and xanthine oxidation inhibition activity. To evaluate the safety studies of propolis, the pesticide residues were also monitored by LC-MS-MS 4500 Q-Trap. Trace amounts of pesticide residue (ng/mL) were detected in the samples, which are far below the permissible limit as per international guidelines.

Comparative pharmacokinetics of salbutamol inhaled from a pressurized metered dose inhaler either alone or connected to a newly enhanced spacer design.

BACKGROUND: Coordination between actuation of a pressurized metered dose inhaler (pMDI) and inhalation is a critical manoeuvre that many patients fail to perform correctly. pMDIs connected to spacers do not require hand-lung coordination. This study evaluated the relative lung and systemic bioavailability and oropharyngeal deposition of salbutamol post-inhalation from Ventolin® Evohaler® (GlaxoSmithKline) either alone following verbal inhaler technique counselling (VC) or connected to a newly improved Able Spacer® (AS). METHODS: In a two-period, randomized crossover study, 16 healthy adults inhaled 2 × 100 µg salbutamol puffs (1 min gap) from Ventolin using VC or AS. Immediately after each puff inhalation, each subject gargled with 20 mL water for oropharyngeal deposition (OD) determination. Urine samples were collected 0.5 h (pre-) and 0.5, 1.0 and 2.0 h post-inhalation. Urine was then pooled 2-24 h post-inhalation. The relative lung bioavailability (0-0.5 h urinary salbutamol excretion - USAL0.5) and systemic bioavailability (0-24 h urinary excretion of salbutamol and its metabolite - USALMET24) were determined. A one week washout separated VC and AS use. RESULTS: The mean (SD) USAL0.5 of VC and AS was 5.36 (4.48) and 12.80 (10.83) µg, respectively. The mean (SD) OD was 11.35 (3.37) and 0.48 (0.30) µg, respectively. VC and AS were significantly different in USAL0.5 and OD (p<0.001). USALMET24 was comparable (p>0.05). CONCLUSIONS: Compared with VC, AS doubled the inhaled salbutamol lung dose and minimised its precipitation in the oral cavity. The results suggest this inhalation aid can add therapeutic and safety benefits particularly in patients with continued pMDI technique issues despite repeated VC.

Improving hepatic mitochondrial biogenesis as a postulated mechanism for the antidiabetic effect of Spirulina platensis in comparison with metformin.

Various nutritional and medicinal potencies have been accredited to metabolites from the cyanobacteria, Spirulina platensis (Arthrospira platensis) sp. Hence, our study was designed to examine whether the Spirulina supplementation would possess beneficial effects in type 2 diabetes mellitus (T2DM) in comparison with metformin. High-fat diet/low-dose streptozotocin (HFD/STZ) model was adopted and the diabetic rats were orally treated with metformin (200 mg/kg) or Spirulina (250 or 500 or 750 mg/kg) for 30 days. Spirulina ameliorated the HFD/STZ-induced elevation of fasting blood glucose, insulin, and hepatic enzymes. Moreover, Spirulina successfully rectified disrupted serum lipid profile and exhibited an anti-inflammatory effect via tumor necrosis factor-α and adiponectin modulation. On the molecular level, Spirulina reduced the expression of hepatic sterol regulatory element binding protein-1c (SREBP-1c), confirming its lipotropic effect. Furthermore, Spirulina amended compromised hepatic mitochondrial biogenesis signaling by significantly increasing peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (Tfam), and mitochondrial DNA (mtDNA) copy number. On almost all parameters, the highest dose of Spirulina showed the best effects, which were comparable to that of metformin. To our knowledge, our study is the first to attribute the various aspects of the effect of Spirulina to the SREBP-1c and PGC-1α/Tfam/mtDNA pathways in liver. The present results clearly proved that Spirulina modulated glucose/lipid profile and exhibited prominent anti-inflammatory properties through SREBP-1c inhibition and hepatic mitochondrial biogenesis enhancement. Thus, Spirulina can be considered as an add-on to conventional antidiabetic agents and might influence the whole dynamics of the therapeutic approaches in T2DM.

Corrigendum to "Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes".

[This corrects the article DOI: 10.1155/2016/9354937.].

Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Background. Our aim was to evaluate the protective effect of lipoic acid (LA) on fetal outcome of diabetic mothers. Methods. Diabetes was induced in female rats using streptozotocin and rats were made pregnant. Pregnant control (group 1; n = 9; and group 2; n = 7) or pregnant diabetic (group 3; n = 10; and group 4; n = 8) rats were treated daily with either LA (groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the fetuses, placentas, and membranes were dissected, examined morphologically, and then homogenized, to measure cyclooxygenase (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2α (PGFM) levels. The level of total glutathione was measured in the maternal liver and plasma and in all fetuses. Results. Supplementation of diabetic rats with LA was found to significantly (p < 0.05) reduce resorption rates in diabetic rats and led to a significant (p < 0.05) increase in liver, plasma, and fetuses total glutathione from LA-TD rats as compared to those from V-TD. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas, and membranes were characteristic of experimental diabetic gestation associated with malformation. The levels of PGEM in malformed fetuses from LA-TD mothers was significantly (p < 0.05) higher than those in malformed fetuses from V-TD rats. Conclusions. LA treatment did not completely prevent the occurrence of malformations. Thus, other factors may be involved in the pathogenesis of the diabetes-induced congenital malformations.

The hypocholesterolemic and antioxidative effect of dietary diosgenin and chromium chloride supplementation on high-cholesterol fed Japanese quails.

The current study investigated the effect of natural diosgenin extracted from fenugreek seeds, in comparison with the pure standard diosgenin, plus chromium chloride (CrCl3) supplementation on high-cholesterol fed Japanese quails. Quails were randomly divided into four groups. Group one (n = 25) fed experimental diet only (control; contained basal diet supplemented with 1% cholesterol), group 2 (n = 20) fed experimental diet supplemented with CrCl3 only (400 microg kg(-1) of body weight), groups 3 and 4 (n = 30 per group) were fed experimental diet supplemented with either 0.5% (w/w) of extracted diosgenin plus CrCl3 or pure standard diosgenin (0.5%) plus CrCl3 respectively, for 12 days. Blood samples were collected at days 0 and 12 for measuring levels of lipid profile. The work was carried out at Applied Science University and Amman University, Amman, Jordan during the period from October 2009 through October 2010. The mean levels of total cholesterol (TC) in control quails at d12 was significantly (p < 0.01) increased compare to those at d0. Supplementation of diet with CrCl3 alone or CrCl3 with diosgenin either extracted or pure standard for 12 days showed a significant (p < 0.01) decrease in TC and low density lipoprotein cholesterol (LDL-C) levels as compared to those in the control quails. While, high density lipoprotein cholesterol (HDL-C) increased significantly (p < 0.01) in quails supplemented with diosgenin and CrCl3. At d12, the mean Superoxide Dismutase (SOD) activities in erythrocytes of quails in all supplemented groups was significantly (p < 0.01) increased as compared to those in control group and was more pronounced in erythrocytes of quails supplemented with pure standard diosgenin plus CrCl3. These results indicated that the combined diosgenin and CrCl3 supplementation to high-cholesterol fed quails might induce a protective effect by both regulating lipid and antioxidative damage.

Diabetic hand syndromes as a clinical and diagnostic tool for diabetes mellitus patients.

Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia with various complications including diabetic hand syndrome (DHS); a condition characterized by association of distinct entities; limited joint mobility (LJM), Dupuytren's disease (DD), flexor tenosynovitis (FTS) and carpal tunnel syndrome (CTS) resulting in significant morbidity and mortality. The aim of this study was to evaluate the prevalence of these changes and their association to diabetes duration. We studied 142 type 2 and 45 type 1 DM patients and investigated the presence of these hand changes and peripheral neuropathy (PNP). The prevalence of LJM was 29.4%, DD was 17.6%, FTS was 10.7% and CTS 41.7% in all diabetics. The prevalence of CTS was more in type 2 DM (83.3%) as compared to type 1 DM (24.4%). Age and duration of diabetes were clearly related to these changes. A clear association between these changes and PNP was observed. The prevalence of CTS and hand changes was higher in type 2 diabetics. The association of DD and PNP suggests that common factors could contribute to their pathogenesis. Consequently, clinical examination for diabetic hand should not ignore it.

Smoking practices in Jordanian people and their impact on semen quality and hormonal levels among adult men.

Despite worldwide anti-smoking campaigns, cigarette smoking prevalence is increasing in the third-world countries. It is now regarded as the most important public health issue. Here, we study the current smoking situation and investigate the impact of cigarette smoking on semen quality and hormonal levels among adult people. Furthermore, we suggest various strategies to reduce smoking consumption among young individuals. Across-sectional data from 804 adult smoker subjects (male n = 530 and female n = 274) aged between 15 and 45 years were analyzed. One hundred and eleven males were agreed for further evaluation of their semen quality and hormones compared with 93 age-matched non-smoking males. This study showed that the majorfactors initiating smoking among women were friends' influence (49%), life pressures (16%) and parental imitation (14%). The major reasons in men was friends' influence (65%). Furthermore, 61% ofwomen and 89% of men smoke in public implying social acceptance oreven encouragement of this habit. This study also found that low-income Jordanians consume more tobacco materials than those in the middle- and higher income. Furthermore, smokers had significantly lower (p < 0.001) sperm concentration and motility values and higher (p < 0.001) serum testosterone and luteinizing hormone (LH) levels than non-smokers.

The levels of vascular endothelial growth factor-A and placental growth factor-2 in embryopathy associated with experimental diabetic gestation.

The objective of this study was to investigate the role of vascular endothelial growth factor-A (VEGF-A) and placental growth factor-2 (PlGF-2) in fetal malformations associated with maternal diabetes. Diabetes was induced in female rats. Diabetic and control female rats were made pregnant. On Day 15 of gestation, rats were sacrificed and embryos and their placentas and membranes were dissected out of the uterine horns. Following morphological examination, embryos and their placentas and membranes were homogenized and used for assayed of VEGF-A and PlGF-2 levels. Embryos of diabetic mothers, exhibited significantly (P < 0.05) shorter crown-to-rump lengths, smaller weights, and heavier placental weights. Experimentally induced maternal diabetes was accompanied by decreased VEGF-A in embryos and associated structures. The levels of PlGF-2 in non-malformed embryos of diabetic gestation and their placentas were significantly (P < 0.05) lower than the average of controls. These results might indicate defective vascularization with a consequent morphological or anatomical anomalies or more subtle biochemical or metabolic changes. In diabetic mothers, a statistically significant (P < 0.05) decrease was noted in the level of VEGF-A in plasma of diabetic rats with a small non-significant decrease in PlGF-2. Like many other diabetic complications, diabetes-induced embryopathies might have vascular origin and correcting the disturbances in these angiogenic factors might help decrease the incidence of malformation in diabetic gestation.