HEPATOPROTECTIVE ACTIVITY OF MONASCUS PURPUREUS (RED RICE YEAST) IN DIABETIC RATS ALONE OR IN COMBINATION WITH PIOGLITAZONE: AN EFFECT MEDIATED THROUGH CYTOKINES, ANTIOXIDANTS AND LIPID BIOMARKERS

Objective: Diabetes induces many complications such as cardiovascular problems, cataracts, kidney damage and polyneuropathy. Streptozotocin (STZ) induced diabetes is considered one of the most common animal models in rats. The present study investigated the effects of Monascus purpureus (MP) alone or in combination with pioglitazone on glucose level and on liver in streptozotocin (STZ) diabetic rats.Methods: In this study were divided into five experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with Monascus purpureus (500 mg/kg B. W, oral), treated STZ-diabetic with pioglitazone (10 mg/kg B.W., oral) and treated STZ-diabetic with MP (250 mg/kg B. W, oral)+pioglitazone (10 mg/kg B.W., oral)). Treatment continued for 14 d then blood sampling was done to assess blood glucose. At the end of the study, the animals were fasted overnight, anesthetized with sodium pentobarbital (60 mg/kg i.p.), and sacrificed to collect tissues samples (liver, pancreases).Results: Throughout the experimental period, all treatments significantly (P<.05) lowered serum glucose, triglycerides, cholesterol, c-peptide and IL-6. In addition, hepatic cholesterol and triglycerides levels were also lowered. Moreover, the treated diabetic rats showed higher activity of reduced glutathione (P<.05) in the liver compared with the diabetic control rats and inhibited diabetes induced elevation in the level of malondialdehyde in liver.Conclusion: The results of this study clearly demonstrated that MP act by many ways, including anti-hyperglycemic, antioxidant effects and pancreatic β-cell protection. From these points, it seems that MP may be a useful supplement to alleviate the development of diabetes and its complications

Genistein Ameliorates Cyclophosphamide - Induced Hepatotoxicity by Modulation of Oxidative Stress and Inflammatory Mediators

AIM: The present study investigated the protective effect of the phytoestrogen, genistein (GEN), against (CP)-induced acute hepatotoxicity in rats.MATERIAL AND METHODS: Male adult rats were randomly assigned into five groups. Normal control group received the vehicles; CP group received a single dose of CP (200 mg/kg, i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and liver tissues were collected forty-eight hours after CP injection for assessment of liver function enzymes (ALT and AST) in rat sera, the hepatic oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1β, and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and histopathological examination of liver tissues were also conducted.RESULTS: The CP-induced acute liver damage was evidenced by elevated serum ALT and AST accompanied by increased hepatic oxidative stress and inflammatory biomarkers. Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP group with distortion of liver architecture. GEN-pretreatment significantly ameliorated the deterioration of liver function and exerted significant anti-oxidant and anti-inflammatory activity with a marked decline in hepatic cyclooxygenase-2 expression in a dose dependent-manner.CONCLUSION: The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced liver damage

HPLC-DAD-MS/MS profiling of phenolics from Securigera securidaca flowers and its anti-hyperglycemic and anti-hyperlipidemic activities

AbstractSecurigera securidaca (L.) Degen & Döefl., Fabaceae, has been widely used in the Iranian, Indian and Egyptian folk medicine as antidiabetic and anti-hyperlipidemic remedy. Phenolic profiling of the ethanolic extract (90%) of the flowers of S. securidaca was performed via HPLC-DAD-MS/MS analysis in the positive and negative ion modes. The total polyphenols and flavonoids in the flowers were determined colorimetrically, and the quantification of their components was carried out using HPLC-UV. Total phenolics and flavonoids estimated as gallic acid and rutin equivalents were 82.39±2.79mg/g and 48.82±1.95mg/g of the dried powdered flowers, respectively. HPLC-DAD-MS/MS analysis of the extract allowed the identification of 39 flavonoids and eight phenolic acids. Quantitative analysis of some flavonoids and phenolics (mg/100g powdered flowers) revealed the presence of isoquercetrin (3340±2.1), hesperidin (32.09±2.28), naringin (197.3±30.16), luteolin (10.247±0.594), chlorogenic acid (84.22±2.08), catechin (3.94±0.57) and protocatechuic acid (34.4±0.15), in the extract. Moreover, the acute toxicity, hypoglycemic and hypolipidemic effects of the extract were investigated using alloxan induced diabetes in rats in a dose of 100, 200, and 400mg/kgbwt. The ethanolic extract was safe up to a dose of 2000mg/kg. All tested doses of the flower extract showed marked decrease in blood glucose level by 31.78%, 66.41% and 63.8% at 100, 200 and 400mg/kgbwt, respectively, at p<0.05. Regarding the anti-hyperlipidemic effect, a dose of 400mg/kg of the flower extract showed the highest reduction in serum triacylglycerides and total cholesterol levels (68.46% and 51.50%, respectively at p<0.05). The current study proved the folk use of the flowers of S. securidaca as anti-diabetic and anti-hyperlipidemic agent which could be attributed to its high phenolic content

ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

New pyridine and chromene scaffolds as potent vasorelaxant and anticancer agents

Based on studies that have reported the association between cancer and cardiovascular diseases, new series of pyridine- (3a-o) and/or chromene- (4a-e) carbonitrile analogous were designed, synthesized and screened for their vasodilation and cytotoxic properties. The majority of the new chemical entities demonstrated significant vasodilation efficacies, compounds 3a, 3h, 3j, 3m, 3o, 4d and 4e exhibited the most promising potency with IC50 = 437.9, 481.0, 484.5, 444.8, 312.1, 427.6 and 417.2 µM, respectively, exceeding prazosin hydrochloride (IC50 = 487.3 μM). Compounds 3b-e, 3k and 3l also, revealed moderate vasodilation activity with IC50 values ranging from 489.7 to 584.5 µM. In addition, the anti-proliferative activity evaluation of the experimental compounds at 10 µM on the MCF-7 and MDA-MB 231 breast cancer cell lines illustrated the excellent anti-proliferative properties of derivatives 3d, 3g and 3i. Compound 3d was the most potent analogue with IC50 = 4.55 ± 0.88 and 9.87 ± 0.89 µM against MCF-7 and MDA-MB 231, respectively. Moreover, compound 3d stimulated apoptosis and cell cycle arrest at the S phase in MCF-7 cells in addition to its capability in accumulation of cells in pre-G1phase and activating caspase-3. Furthermore, the molecular docking of 3d was performed to discover the binding modes within the active site of caspase-3. 3d, as the only common bi-functional agent among the tested hits, demonstrated that new pyridine-3-carbonitrile derivatives bearing cycloheptyl ring systems offer potential as new therapeutic candidates with combined vasodilation and anticancer properties

Structural and electrochemical studies of proton conducting biopolymer blend electrolytes based on MC:Dextran for EDLC device application with high energy density

This study shows preparation and characterization of solid biopolymer electrolyte based on glycerolized methylcellulose (MC): dextran-doped with ammonium thiocyanate (NH4SCN). The nature of electrolyte composition in terms of interaction is characterized using Fourier transform infrared (FTIR) technique. Lowering and shifting in the intensity of the bands are observed with increasing the quantity of glycerol as a plasticizer, confirming complexation between electrolyte components. Ion transport parameters are determined using both of the methods of EIS and FTIR where the parameters are found to be increased with glycerol concentration. The transport number measurement indicates that ions are the primary charge carrier in the conduction mechanism where tion is found to be 0.961. The maximum DC ionic conductivity value is achieved that found to be 1.63 � 10�3 S cm�1. The ESR values are ranged from 300 to 580 O throughout 450 cycles. The technique of linear sweep voltammetry (LSV) shows the electrochemical stability window of 2 V for the conducting samples. The response of cyclic voltammetry (CV) shows an almost rectangular shape without Faradaic peaks. A galvanostatic charge–discharge investigation has shown the initial specific capacitance, energy density, and power density are 133 F g�1, 18.3 Wh Kg�1, and 680 W Kg�1, respectively

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe