ß-lapachone protects against doxorubicin-induced hepatotoxicity through modulation of NAD+ /SIRT-1/FXR/p-AMPK/NF-kB and Nrf2 signaling axis.

Doxorubicin (DOX) is a widely used antineoplastic drug, but its clinical use is limited by significant toxicities, such as hepatotoxicity. In this study, we evaluated the effects of ß-lapachone (ß-LAP), a natural quinone-containing compound, in a mouse model of DOX-induced hepatotoxicity. ß-LAP was orally administered at 1.25, 2.5, and 5 mg/kg for 4 days, and a single dose of DOX (20 mg/kg) was injected intraperitoneally on the second day. Histopathological changes, liver function markers, antioxidant and inflammatory markers were assessed. ß-LAP ameliorated liver injury and liver function markers evoked by DOX. ß-LAP also downregulated the mRNA expression of nuclear factor-kB-corresponding genes including interleukin-6, interleukin-1ß, and tumor necrosis factor-α. Moreover, ß-LAP increased the nuclear factor erythroid 2-related factor 2 target genes heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1, along with antioxidant enzymes including reduced glutathione, catalase, and superoxide dismutase with simultaneous reduction in the lipid peroxidation product malondialdehyde. Meanwhile, it recovered NAD+ /NADH ratios and subsequently elevated the protein levels of sirtuin-1 (SIRT-1), farnesoid X receptor (FXR), and phosphorylated AMP-activated protein kinase (p-AMPK). Collectively, these findings suggest a protective role of ß-LAP against DOX-induced hepatotoxicity by partly regulating the NAD+ /SIRT-1/FXR/p-AMPK axis.

Chronic Kombucha Beverage Consumption Attenuates Inflammatory Markers and Histopathology of Brain Tissue in Transnet Global Brain Ischemia in Rats.

There is evidence that kombucha beverage (KB), a traditional fermented beverage, has a preventive effect on experimental brain ischemia. According to our previous studies, pre-treatment of KB attenuates brain edema and improves motor skills and oxidative stress in a rat model of global brain ischemia. This study was designed to evaluate the effects of the pre-treatment of KB, as a novel agent, on pro-inflammatory parameters and brain histopathology changes following global brain ischemia. Adult male Wistar rats were randomly divided into the sham, the control, and the groups treated with kombucha (KB1 and KB2 groups). KB at doses 1 and 2 mL/kg was prescribed two-week consecutive days before induction of global brain ischemia. Global brain ischemia was induced by blocking common carotid arteries for 60 min and the following reperfusion by 24 h. The serum and brain levels of tumor necrosis factor-α(TNF-α), IL-1ß, histopathological change, and infarct volume are determined using the ELISA, hematoxylin and eosin (H&E), and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, respectively. This study indicated that pre-treatment of KB significantly reduced infarct volume, the serum, and brain levels of TNF-α and IL-1ß. The histopathological finding of the brain tissue confirmed a protective role for pre-treatment KB in the ischemic rats. Thus, the present study showed that the beneficial effects of KB pre-treatment on brain ischemic may be mediated by decreasing pro-inflammatory parameters.

Hematotoxicity induced by simultaneous exposure to noise and toluene in New Zealand white rabbits: Synergistic and antagonistic effects.

Exposure to numerous pollutants is prevalent in workplaces. Examination of combined exposure to different harmful physical factors and chemicals has offered new insights into toxicology in recent years. This study aimed to investigate the hematological alterations caused by exposure to noise and toluene. Twenty-four New Zealand white rabbits were exposed to 1000 ± 50 ppm toluene and/or 100 ± 5 dB noise for 14 consecutive days. Exposure to noise and toluene changed a number of parameters of white blood cells (WBC), red blood cells (RBC), and platelets on different days after the exposure. Simultaneous exposure to noise and toluene increased WBC, and exposure to noise and toluene alone decreased RBC. Exposure to noise and toluene alone increased basophile, monocyte, and neutrophil counts. The coefficient of variation of red blood cell distribution width (RDW-CV) and the standard deviation of red blood cell distribution width (RDW-SD) significantly increased after co-exposure to noise and toluene. Platelet levels increased in the noise-exposed and the co-exposed groups and decreased in the toluene-exposed group. Furthermore, co-exposure to noise and toluene induced dissimilar synergistic and antagonistic effects on the hematological indices. According to the results of this study, simultaneous exposure to toluene and noise can aggravate some hematotoxic effects compared to exposure to noise or toluene alone. The results also demonstrated the vital role of the modulatory mechanisms of the body in controlling the detrimental effects of stressors.

Effects of sulfur dioxide, ozone, and ambient air pollution on lung histopathology, oxidative-stress biomarkers, and apoptosis-related gene expressions in rats.

PURPOSE OF THE STUDY: Ambient air pollution (AAP) has become an important health problem globally. Besides, several pieces of evidence indicate that air pollutants such as sulfur dioxide (SO2) and ozone (O3) are major contributors to a wide range of non-communicable diseases. The present study investigated the effects of AAP, sulfur dioxide, and ozone on oxidative stress, histopathology, and some apoptosis-related genes expressions of lung tissue in a rat model. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly divided into the control, AAP, sulfur dioxide (10 ppm), and ozone (0.6 ppm) groups. After five consecutive weeks' exposure to the selected pollutants (3 h/day), lung tissues were harvested and immediately fixed with formalin. The samples were routinely processed, sectioned, stained with hematoxylin and eosin (H&E), and finally assessed for presence of pathological changes. Expression changes of BAX, p-53, EGFR, caspase-3, caspase-8 and caspase-9 were assayed using the RT-qPCR method. One hundred milligrams of lung tissues were extracted and the supernatants were used for assaying malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase activities. RESULTS: GPx activity was increased in the ozone (P = 0.05) and AAP (P < 0.001) groups and also MDA level in sulfur dioxide group (P = 0.008). Pathological lesions were mild, moderate, and severe in the sulfur dioxide, ozone, and AAP groups, respectively, as compared to control group (P ˂ 0.05). Exposure to AAP and sulfur dioxide enhanced BAX (P = 0.002) and caspase-8 (P < 0.001) mRNA expression, respectively. Caspases-3 and -8 mRNA expressions were elevated in ozone group (P < 0.001). CONCLUSIONS: The results indicated induction of oxidative stress. Our results suggest the apoptosis stimuli effect of AAP and also the extrinsic apoptotic pathway trigger effect of sulfur dioxide and ozone in the lung tissue in the concentrations used in the present study. The histopathological and the genes expression changes may be a result of the induced oxidative stress in the lung tissues.

Evaluation of a novel bioactive wound dressing: an in vitro and in vivo study.

OBJECTIVE: Hard-to-heal wounds, such as pressure ulcers and diabetic ulcers, are a major challenge for wound dressings. The aim of this study was to develop a bioactive dressing based on polymers and natural materials with unique biological and therapeutic properties. METHOD: The dressing was composed of an active layer containing polyvinyl alcohol (PVA), honey, curcumin and keratin, and an upper layer with lower hydrophilicity comprising PVA to induce flexibility. Physicochemical properties of the dressing were characterised by Fourier transform infrared spectroscopy, field emission scanning electron microscopy, swelling behaviour and antibacterial measurements. A wound healing study was performed using an experimental rat model and two different compositions of the bioactive dressing were compared with a commercial wound dressing (Comfeel, Coloplast, Denmark). Histopathological evaluation was conducted for this purpose. RESULTS: Characterisation results showed that a smooth bilayer film with two homogenous but distinct layers was produced. The dressing also provided adequate moisture to the wound environment without infection and adhesion due to dryness occurring. Our results exhibited significant bactericidal activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and improved the wound healing process without any scarring. Histopathological findings demonstrated a significant higher healing rate in vivo together with well-formed epidermis, granulation tissue formation and tissue contraction, when compared with the commercial wound dressing. CONCLUSION: Our results demonstrated acceptable physical and healing effects for the novel bioactive wound dressing; however, more investigations are recommended.

Dietary quality indices modifies the effects of melanocortin-4 receptor (MC4R) rs17782313 polymorphism on cardio-metabolic risk factors and hypothalamic hormones in obese adults.

BACKGROUND: Although the Melanocortin-4 Receptor (MC4R) gene rs17782313 C/T has been consistently related to obesity risk, the interaction between MC4R polymorphism and diet quality indices on cardio-metabolic risk factors has not yet investigated. Therefore we aimed to test this hypothesis. METHODS: This cross-sectional study recruited 188 (96 males and 92 females) healthy obese adults aged 20-50 years. Diet quality indices including Healthy Eating Index-2015 (HEI-2015) and Diet Quality Index-International (DQI-I) were constructed using data from a validated food frequency questionnaire. MC4R s17782313 were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The interaction between MC4R polymorphism and diet quality indices was tested by Analysis of covariance (ANCOVA) multivariate interaction model. RESULTS: There were significant gene-diet interactions between rs17782313 and HEI-2015 (P Interaction < 0.05) in modulating low-density lipoprotein cholesterol (LDL-C) levels among female group; rare allele heterozygotes of rs17782313 had highest mean of LDL-C concentration when placed in second tertile of HEI (P < 0.05). Moreover, rs17782313 and both indices (HEI and DQI-I) had significant interaction on serum glucose concentrations, systolic and diastolic blood pressure (SBP, DBP) in males (P Interaction < 0.05); when adherence to these indices was low, the obesity risk allele was associated with serum glucose concentrations, SBP and DBP. These gene-diet interactions remained significant even after adjustment for potential confounders. CONCLUSION: Our study showed that MC4R rs17782313 interacts with adherence to the dietary quality indices (HEI and DQI-I) to influence several cardio-metabolic risk factors in obese male and females. Further large prospective studies are warranted to confirm our findings.

Effects of Cornus mas Fruit Hydro-Methanolic Extract on Liver Antioxidants and Histopathologic Changes Induced by Cisplatin in Rats.

Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. The present study was aimed to investigate whether Cornus mas fruit hydro-methanolic extract (CMFE) can modulate the cisplatin-induced changes in liver antioxidant enzymes and histological structure. Forty Wistar rats were divided into a control group, cisplatin (Cis) group, CMFE group, CMFE 300 + Cis group, and the CMFE 700 + Cis group. After the intervention, blood and tissue samples were taken for biochemical and histopathological analysis. Cis caused reduction in the activity of liver antioxidant enzymes including SOD, GPx, TAC, and CAT and increased that of MDA. Moreover, exposure to Cis caused a reduction in serum level of AST, ALT, and ALP and a rise in serum level of GGT. Oral administration of CMFE for 16 days in the two different dosages at 300 and 700 mg/kg improved the Cis-induced changes of liver enzymes activity and serum enzymes level. Evaluating the histological structure of liver tissue, it was found that treatment by CMFE could ameliorate the Cis-induced changes to near normal histology. The results showed antioxidant and phenol contents in Cornus mas fruit could improve Cis-induced oxidative stress and liver histologic changes in rats.

Empagliflozin Attenuates Renal and Urinary Markers of Tubular Epithelial Cell Injury in Streptozotocin-induced Diabetic Rats.

Empagliflozin, a SGLT-2 inhibitor, improves diabetic nephropathy through its pleiotropic anti-inflammatory effects. The present study aims to evaluate empagliflozin effects on renal and urinary levels of tubular epithelial cell injury markers in streptozotocin-induced diabetic rats. Empagliflozin at 10 mg/kg (p.o.) was administered for 4 weeks, beginning 8 weeks after induction of diabetes. Renal function as well as markers of renal tubular epithelial cell injury were assessed in kidney tissue homogenates and urine. Empagliflozin was able to ameliorate diabetes induced elevations in serum cystatin C levels. It also alleviated renal KIM-1/NGAL levels and urinary albumin, α-GST, and RBP excretions. In addition to decreasing urinary levels of cell cycle arrest indices i.e. TIMP-2 and IGFBP7, empagliflozin mitigated acetylated NF-κB levels in renal tissues of diabetic rats. As a whole, these findings reveal empagliflozin capability in improving diabetic nephropathy via ameliorating indices of renal inflammation, injury, and cell cycle arrest on streptozotocin-induced diabetic rats.

Quercetin mitigates anxiety-like behavior and normalizes hypothalamus-pituitary-adrenal axis function in a mouse model of mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is a major public health risk for developing anxiety-related disorders and hypothalamus-pituitary-adrenal (HPA) axis dysregulation in humans. Extensive research has shown that dietary intake or supplementation of the natural flavonoid quercetin might be useful for treating anxiety-related symptoms. The objectives of this study were to determine whether quercetin treatment can attenuate anxiogenic-like behaviors and normalize HPA axis function in mice with mTBI. Animals subjected to mTBI were treated daily with quercetin (50 mg/kg) or diazepam (positive control, 3 mg/kg) for 14 days. Four behavioral tests (open field, plus maze, light-dark box, and zero maze) were used to assess anxiety-related behaviors in mice. To evaluate HPA axis function, adrenocorticotropic hormone and corticosterone were measured in the serum of mice after the anxiety tests. Quercetin treatment was found to significantly reduce anxiety-like behaviors in mTBI-induced mice. A strength of this study is the consistency of results among anxiety tests. The dysregulation of the HPA axis in mTBI-induced mice treated with quercetin was also attenuated, with decreased levels of adrenocorticotropic hormone and corticosterone. The effects of quercetin were comparable with those of diazepam treatment. Taken together, these results suggest that quercetin might be useful for treating anxiety-related symptoms and HPA axis hyperreactivity in patients with mTBI.

Serotonin 5-HT1A receptors modulate depression-related symptoms following mild traumatic brain injury in male adult mice.

Traumatic brain injury is a complex phenomenon leading to neurological diseases and persistent disability that currently affects millions of people worldwide. Increasing evidence shows that a wide range of patients with mild traumatic brain injury (mTBI) suffer from depression during the initial stages of injury and the post-acute stages of recovery. However, the underlying mechanisms involved in depression following mTBI are still not fully understood. The aim of this study was to determine whether serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor is involved in the regulation of depression-related behaviors following mild traumatic brain injury in mice. Mice with or without mTBI received intracerebroventricular injections of 5-HT1A receptor agonist (8-OH-DPAT) or antagonist (WAY-100635) for 5 days, then animals were subjected to behavioral tests. Four behavioral tests including novelty-suppressed feeding test, forced swim test, sucrose preference test and tail suspension test were used to evaluate depression-related symptoms in animals. Our results indicated that mTBI induction increased depression-like symptoms through altering serotonin 5-HT1A receptor activity in the brain. Activation of 5-HT1A receptor by a subthreshold dose of 8-OH-DPAT led to a significant decrease in depression-like behaviors, whereas blockade of 5-HT1A receptor by a subthreshold dose of WAY-100635 resulted in a considerable increase in depression-like phenotypes in mTBI-induced mice. The major strength of the present study is that depression-related symptoms were assessed in four behavioral tests. The present study supports the idea that disturbances in the function of serotonergic system in the brain following mTBI can play an important role in the regulation of depression-related behaviors.

Oral administration of alpha-lipoic acid did not affect lipid peroxidation and antioxidant biomarkers in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which oxidative stress could play a substantial pathological role. Alpha-lipoic acid (ALA) has been known as a "universal" and "ideal" antioxidant. The purpose of this study was to investigate the effects of oral administration of Alpha-lipoic acid (ALA) on lipid peroxidation and antioxidant biomarkers in Rheumatoid arthritis (RA) patients. The study was a randomized, double-blinded, placebo-controlled clinical trial. 70 RA patients were randomized 1:1 to two groups using blocked randomization method and received 1200 mg/day ALA or placebo for 8 weeks. Fasting blood samples were obtained before and after the intervention to analyze total antioxidant capacity (TAC), antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and arylesterase (ARE) activities] and malondialdehyde (MDA). We observed significant increase in serum TAC (0.11 mmol/L; p=0.033) and ARE (13.76 U/mL; p=0.046) and significant decline in MDA (-0.36 nmol/L; p=0.002), in ALA group. However, these changes in ALA-treated group were not statistically significant when compared with placebo-treated group (p > 0.05). Also, within- and between-group differences of whole blood SOD and GSH-Px were not statistically significant (p > 0.05). In conclusion, unexpectedly, ALA therapy did not affect the oxidative status of RA patients in the present clinical trial. It seems that more comprehensive clinical trials in RA patients are still warranted to clarify the effectiveness of ALA which has been known as a potent antioxidant.

Ethambutol-Loaded Solid Lipid Nanoparticles as Dry Powder Inhalable Formulation for Tuberculosis Therapy.

Ethambutol hydrocloride (EMB) is an anti-tuberculosis drug, which is commonly used as a protection agent against of unrecognized resistance to other drugs employed to treat this disease. Since oral form of EMB has some side effects and cellular toxicity, direct administration of EMB into lungs seems to be an attractive and reasonable option in order to overcome these side effects. Our main goal in this study was assessment of pulmonary administration through dry powder inhaler (DPI) using EMB-loaded solid lipid nanoparticles (SLNs). We prepared EMB-loaded SLNs using two techniques (hot homogenization and ultrasonication). DPI formulations were made by spray drying of EMB-loaded SLNs with and without mannitol. For investigation of flowbility of the prepared powders, Carr's index and Hausner ratio, and for in vitro deposition of the powders, Next Generation Impactor (NGI) analysis were used. The encapsulation efficiency and particle size of obtained particles were higher than 98% and sub-100 nm, respectively. Toxicity investigation of EMB-loaded SLNs via MTT assay showed biocompatibility and non-toxicity of the SLNs. Results of flowability and aerodynamic traits assessment of EMB-loaded SLN DPI powder confirmed the suitability of prepared powders. Overall, the attained results showed that EMB-loaded SLN DPI has high potential for direct treatment of tuberculosis.

The effects of vitamin D administration on brain inflammatory markers in high fat diet induced obese rats.

BACKGROUND: Obesity induced brain inflammation is associated with cognitive disorders. We aimed to investigate the influence of vitamin D on hypothalamus and hippocampus inflammatory response in high-fat diet induced obese rats. METHODS: In the beginning of the study, 40 rats were divided into two groups: control diet and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: N, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. IL-6, IL-1ß, NF-Kß and acetylcholine (ACH) and brain derived neurotropic factor (BDNF) concentrations in hippocampus and hypothalamus homogenate samples were measured by commercial ELISA kits. RESULTS: Vitamin D administration, reduced food intake and weight gain in studied groups (P < 0.001). Vitamin D reduced hippocampus acetylcholine concentrations in ND + vitamin D group (P < 0.001). High fat diet increased hippocampus IL-6 concentrations significantly (P < 0.05) compared with normal diet receiving groups. Vitamin D could not have significant effects on IL-6 concentrations. Vitamin D administrations reduced IL-1ß, NF-Kß and acetylcholine concentration and BDNF concentrations in ND + vitamin D compared with ND group. These reductions were not significant in HFD + vitamin D versus HFD group. CONCLUSION: According to our results, vitamin D reduced food intake and weight gain and modulated the HFD induced inflammatory response in hippocampus and hypothalamus of high fat diet induced obesity. Therefore, this neurosteroid, can be suggested as a supplemental therapeutic tool in prevention of obesity related cognitive and neurodegenerative problems.

Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats.

BACKGROUND: Obesity is associated with numerous metabolic and inflammatory disorders. The current study was aimed to evaluate the effects of vitamin D administration on the markers of oxidative stress and inflammation in the cardiac tissue of high-fat diet induced obese rats. METHODS: In the beginning of the study, 40 male Wistar rats were divided into two groups: normal diet (ND) and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: ND, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α concentration and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) concentrations in the cardiac tissue and serum concentrations of lipids in rats were determined using ELISA kits and spectrophotometry methods respectively. RESULTS: According to our results, GPx activity in ND and ND + vitamin D group was significantly higher compared with HFD group. Similarly, SOD activity was also significantly increased in ND + vitamin D group compared with ND and HFD groups. Moreover, vitamin D administration, significantly reduced catalase activity in ND + vitamin D and HFD + vitamin D groups (P < 0.05). TNF-α concentration in heart tissue in ND + vitamin D group significantly reduced compared with ND group. Cardiac tissue MDA concentration in baseline or after vitamin D administration did not changed significantly. CONCLUSION: Vitamin D improved cardiac oxidative stress and inflammatory markers in HFD induced obese rats. Further studies in human models are needed to further confirm the use of this nutrient in daily clinical practice.

Assessing the effect of 5-hydroxymethylfurfural on selected components of immune responses in mice immunised with ovalbumin.

BACKGROUND: 5-Hydroxymethylfurfural (5-HMF) is one of the most important products of the Maillard reaction. In recent years, many profitable biological effects of this compound have been demonstrated. This study sought to elucidate the anti-allergic effect of 5-HMF by investigating some selected components of the immune response in BALB/c mice immunised with ovalbumin (OVA). RESULTS: Immunised animals had an increased level of serum total and OVA-specific antibodies when compared to the control (P < 0.01).We found that the OVA-induced increase in serum IgE and OVA-specific IgE were significantly suppressed in the groups treated with 5-HMF (P < 0.05). Moreover, interleukin-4 (IL-4) and interferon gamma (IFN-γ) were significantly reduced in a dose-independent manner when compared to the sensitised group (P < 0.05). CONCLUSION: 5-HMF inhibited the up-regulation of total and OVA-specific IgE through the suppression of the Th2-type immune response in immunised BALB/c mice. 5-HMF could therefore be a novel therapeutic approach for the prevention of IgE-mediated allergic diseases. © 2017 Society of Chemical Industry.

Effects of Alpha-Lipoic Acid Supplementation on Inflammatory Biomarkers and Matrix Metalloproteinase-3 in Rheumatoid Arthritis Patients.

OBJECTIVE: Although many studies have considered alpha-lipoic acid (ALA) as a potent antioxidant with anti-inflammatory functions in oxidative stress-associated inflammatory diseases, few studies have evaluated its efficacy in rheumatoid arthritis (RA). Therefore, we aimed to examine the effects of ALA on serum biomarkers of joint damage and inflammation in women with RA. METHODS: We performed a randomized, double-blind, placebo-controlled clinical trial in which RA patients (n = 70) aged 20-50 years were randomly assigned 1:1 to receive either ALA (1200 mg/day) or placebo for 8 weeks. Fasting blood samples were taken before and after the study to analyze inflammatory biomarkers including serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and serum matrix metalloproteinase-3 (MMP-3) as a marker of joint erosion. Moreover, 3-day dietary records, the International Physical Activity Questionnaire (IPAQ), and the Spielberger State-Trait anxiety inventory form Y (STAI-Y) were assessed before and after the intervention. RESULTS: Sixty-five RA patients completed the trial. No statistically significant differences were observed in serum levels of hs-CRP, TNF-α, IL-6, and MMP-3 within and between the ALA and placebo groups (p > 0.05). There were no statistically significant differences in dietary intakes, physical activity, and anxiety levels between groups at baseline and they remained statistically unchanged during the study period (p > 0.05). CONCLUSION: Although in theory ALA supplementation could serve as a beneficial nutraceutical in RA patients, in the present study serum inflammatory biomarkers and MMP-3 were not significantly affected by 8 weeks of ALA supplementation.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients. METHODS: In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention. RESULTS: A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05). CONCLUSIONS: In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.

Association Between Sex Hormone-Binding Globulin, Atherogenic Indices of Plasma Among Young Sedentary Males.

Background: Males are more likely than females to suffer from cardiovascular disease (CVD). So, sex hormones may modify these variations and affect the lipid profile. We examined the relationship between sex hormone-binding globulin (SHBG) and CVD risk factors among young males in this study. Methods: Using a cross-sectional design, we measured total testosterone, SHBG, lipids, glucose, insulin, antioxidant parameters, and anthropometric factors in 48 young males in the age range of 18 to 40 years. Atherogenic indices of plasma were calculated. In this study, a partial correlation analysis was carried out to assess the relationship between SHBG and other variables after adjustment for confounders. Results: According to the results of multivariable analyses adjusted for age and energy, SHBG had a negative correlation with total cholesterol (r = -.454, P =.010), low-density lipoprotein cholesterol (r = -.496, P =.005), quantitative insulin-sensitivity check index, and positive correlation with high-density lipoprotein cholesterol (r = .463, P =.009). No significant correlation was observed between SHBG and triglycerides (P >.05). Several atherogenic indices of plasma have a negative correlation with SHBG levels. These include Atherogenic Index of Plasma (r = -.474, P = .006), Castelli Risk Index (CRI)1 (r = -.581, P < .001), CRI2 (r = -.564, P = .001), and Atherogenic Coefficient (r = -.581, P < .001). Conclusion: Among young men, high plasma SHBG was associated with reduced CVD risk factors, modified lipid profile and atherogenic ratios, and better glycemic markers. Therefore, reduced SHBG concentrations could be a prognostic marker of CVD among young sedentary males.

Protective effects of di- and tri-peptides containing proline, glycine, and leucine on liver enzymology and histopathology of diabetic mice.

CONTEXT: Small peptides as multifunctional biomolecules can prevent the metabolic disorders such as diabetes. OBJECTIVE: The purpose of this study was to investigate the effects of small peptides on the enzymes and histopathology of the liver in mice exposed to diabetes. METHODS: Di- and tri-peptides containing proline, glycine, and leucine were produced by solid phase peptide synthesis (SPPS) protocol. The effects of produced peptides as well as carnosine (Ala-His) and glutathione (Glu-Cys-Gly) were evaluated on hepatic enzymes activity by enzymatic method and histopathology of liver using hematoxylin and eosin and TUNEL staining to assess histologic changes and apoptosis in diabetes induced by multiple low doses of streptozotocin (MLDS). RESULTS: The Ala-His, Leu-Gly and Pro-Gly-Pro peptides had the higher protective effects against the effects of diabetes on the enzymes and histologic changes of liver in mice. CONCLUSION: These peptides can be raised as considerable pharmaceutical preventive agent against diabetes development.