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The present study was hypothesized to evaluated the antihyperlipidemic effect of diosmin (DS) on lipid metabolism in experimental diabetic rats. Diabetes was induced male albino Wistar rats by intraperitoneal administration of streptozotocin (STZ) (45 mg/kg b.w.) 15 min after the ip administration of nicotinamide (NA) (110 mg/kg b.w.). DS were administered to diabetic rats intragastrically at 100 mg/kg b.w. for 45 days. The levels of plasma and tissue lipids (cholesterol, triglycerides) (TGs), free fatty acids (FFAs) and phospholipids (PLs), low density, very low-density lipoproteins (LDL and VLDL), and high-density-cholesterol (HDL-C) were measured. The activities of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were assayed. The levels of plasma and tissue lipids decreased with significant increase in HDL-C levels. The altered activities of lipid metabolic enzymes were restored to near normal. The present findings suggest that DS can potentially ameliorate lipid abnormalities in experimental diabetes.
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... juice was shown to positively influence serum lipid levels and to decrease coronary heart disease risk . Their hypolipidemic effects can be due to the presence of flavonoids, pectins and ascorbic acid, which have a high antioxidant potential and may interfere with cholesterol metabolism . ...
... Many studies demonstrated a relationship between the intake of flavonoid-rich foods and a reduced risk for cardiovascular disease . Bergamot fruit is very rich in many peculiar bioactive flavonoids compared to other Citrus fruits , hence their evaluation as metabolic regulators might represent an attractive strategy in drug discovery. The aim of this review is to provide an overview on all flavonoids detected in C. bergamia Risso and on the current knowledge of their hypolipidemic effects , summarizing the results obtained from different in vivo studies [61,75,77,89]. ...
Elevated serum cholesterol, triglycerides and LDL levels are often associated with an increased incidence of atherosclerosis and coronary artery disease. The most effective therapeutic strategy against these diseases is based on statins administration, nevertheless some patients, especially those with metabolic syndrome fail to achieve their recommended LDL targets with statin therapy, moreover, it may induce many serious side effects. Several scientific studies have highlighted a strong correlation between diets rich in flavonoids and cardiovascular risk reduction. In particular, Citrus bergamia Risso, also known as bergamot, has shown a significant degree of hypocholesterolemic and antioxidant/radical scavenging activities. In addition, this fruit has attracted considerable attention due to its peculiar flavonoid composition, since it contains some flavanones that can act as natural statins. Hence, the study of bergamot flavonoids as metabolic regulators offers a great opportunity for screening and discovery of new therapeutic agents. Cholesterol metabolism, flavonoid composition and potential therapeutic use of C. bergamia Risso will be discussed in the following review.
... Eugenol (4-allyl-2-methoxyphenol) is a naturally existing phenolic secondary metabolite found in various fruits, vegetables, and other plant-based foods that can help manage or prevent DM. Cloves, turmeric, oregano, basil, black pepper, and nutmeg are the primary sources of eugenol, a widely occurring fragrant oil component (Srinivasan and Pari 2013;Raja et al. 2015). In STZ-induced diabetic rats, the anti-hyperglycemic potential of eugenol was investigated by monitoring the activity of the key enzymes involved in glucose metabolism. ...
Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic syndrome defined through the dysfunction of pancreatic β-cells driven by a confluence of genetic and environmental elements. Insulin resistance, mediated by interleukins and other inflammatory elements, is one of the key factors contributing to the progression of T2DM. Many essential oils derived from dietary plants are beneficial against various chronic diseases. We reviewed the anti-diabetic properties of dietary plant-derived essential oil compounds, with a focus on their molecular mechanisms by modulating specific signaling pathways and other critical inflammatory mediators involved in insulin resistance. High-quality literature published in the last 12 years, from 2010 to 2022, was collected from the Scopus, Web of Science, PubMed, and Embase databases using the search terms "dietary plants," "essential oils," "anti-diabetic," "insulin resistance," "antihyperglycemic," "T2DM," "anti-diabetic essential oils," and anti-diabetic mechanism." According to the results, the essential oil compounds, including cinnamaldehyde, carvacrol, zingerone, sclareol, zerumbone, myrtenol, thujone, geraniol, citral, eugenol, thymoquinone, thymol, citronellol, α-terpineol, and linalool have been demonstrated to contain strong anti-diabetic effects via modulating various signal transduction pathways linked to glucose metabolism. Additionally, in diabetes-related animal models, they can also considerably reduce the expression of TNF-α, IL-1β, IL-4, IL-6, iNOS, and COX-2. The main signaling molecules regulated by these compounds include AMPK, GLUT4, Caspase-3, PPARγ, PPARα, NF-κB, p-IκBα, MyD88, MCP-1, SREBP-1c, AGEs, RAGE, VEGF, Nrf2/HO-1, and SIRT-1. They can also significantly inhibit the generation of TBARS and MDA, reduce oxidative stress, increase insulin levels, adiponectin, and glycoprotein enzymes, boost antioxidant enzymes like SOD, CAT, and GPx, as well as reduce glutathione and vital glycolytic enzymes. Besides, they can significantly lower the levels of liver enzymes and lipid profile markers. Moreover, most essential oil compounds are generally safe based on animal studies. In conclusion, dietary plant-derived essential oil compounds have potential anti-diabetic effects by influencing different signaling pathways and molecular targets linked to glucose metabolism, and should be safe and beneficial against diabetes and related complications.
... LCAT was an enzyme that was responsible for the formation of most cholesterol esters and was also important for the maturation of HDL metabolism. Increased LCAT activity induced by increased production of Apo A1 will increase HDL-C levels so that it can fight atherosclerosis (Srinivasan & Pari, 2013;Tenda & Toyo, 2021). The content of quercetin in mulberry leaves was known to reduce the activity of HMG-CoA reductase which affects cholesterol synthesis (Deng et al., 2020). ...
... MM has the advantage that it can increase its solubility in water, has improved stability and pharmacokinetic properties, and can make the drug circulation time longer when compared to conventional micelles (made from single copolymers)  Diabetes mellitus causes hyperglycemia and impaired glucose metabolism, causing an increase in lipid and lipoprotein levels and the production of free radicals . Based on the results of phytochemical screening, both extracts contain flavonoids, phenols, and terpenoids, which are generally claimed to be useful for antidiabetic activity and antihyperlipidemic activity, according to previous reports . ...
Phytochemicals or secondary metabolites are substances produced by plants that have been shown to have many biological activities, providing a scientific basis for using herbs in traditional medicine. In addition, the use of herbs is considered to be safe and more economical compared to synthetic medicine. However, herbal medicines have disadvantages, such as having low solubility, stability, and bioavailability. Some of them can undergo physical and chemical degradation , which reduces their pharmacological activity. In recent decades, nanotechnology-based herbal drug formulations have attracted attention due to their enhanced activity and potential for overcoming the problems associated with herbal medicine. Approaches using nanotechnology-based delivery systems that are biocompatible, biodegradable, and based on lipids, polymers, or nanoemulsions can increase the solubility, stability, bioavailability, and pharmacological activity of herbals. This review article aims to provide an overview of the latest advances in the development of nanotechnology-based herbal drug formulations for increased activity, as well as a summary of the challenges these delivery systems for herbal medicines face.
... Previous studies have reported a significant decrease in C-reactive protein (CRP), HbA1c, and levels of plasma lipids such as triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL-CHO), very low-density lipoprotein cholesterol (VLDL-CHO), phospholipids, and free fatty acids . Diosmin increased the activity of antioxidant enzymes, such as GPx, and SOD . Diosmin possesses neuroprotective effects against long-term potentiation deficits and TBI-induced memory due to a decrease in the pro-inflammatory cytokine TNF-α level in the hippocampus . ...
The absence of a treatment efficient in the control of type 2 diabetes mellitus requires more functional products to assist treatment. Luteolin (LU) and diosmin (DIO) have been known as bioactive molecules with potential for the treatment of diabetes. This work aimed to establish the role that a combination of LU and DIO in selenium nanoparticles (SeNPs) played in streptozotocin (STZ)- induced diabetes mice. Green synthesis of Se NPs was performed by mixing luteolin and diosmin with the solution of Na2SeO3 under continuous stirring conditions resulting in the flavonoids conjugated with SeNPs. The existence of flavonoids on the surface of SeNPs was confirmed by UV-Vis spectra, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) images, and DLS graphs via Zetasizer. The average diameter of GA/LU/DIO-SeNPs was 47.84 nm with a PDI of −0.208, a zeta potential value of −17.6, a Se content of 21.5% with an encapsulation efficiency of flavonoids of 86.1%, and can be stabilized by gum Arabic for approximately 175 days without any aggregation and precipitation observed at this time. Furthermore, The C57BL/6 mice were treated with STZ induced-diabetes and were exposed to LU/DIO, SeNPs, and GA/LU/DIO-SeNPs for six weeks. The treatment by nanospheres (GA/LU/DIO-SeNPs) in the mice with diabetes for a period of 6 weeks restored their blood glucose, lipid profile, glycogen, glycosylated hemoglobin, and insulin levels. At the same time, there were significant changes in body weight, food intake, and water intake compared with the STZ- untreated induced diabetic mice. Moreover, the GA/LU/DIO-SeNPs showed good antioxidant activity examined by catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) in liver and kidney and can prevent the damage in the liver evaluated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. The nanospheres exhibited a significant anti-diabetic activity with a synergistic effect between the selenium and flavonoids. This investigation provides novel SeNPs nanospheres prepared by a high-efficiency strategy for incorporating luteolin and diosmin to improve the efficiency in type 2 diabetes.
... Hypercholesterolemia, accumulation of lipids in hepatic tissues, altered plasma lipid and lipoprotein profile are hallmarks of metabolic dyslipidemia associated with type 2 diabetes (Farmer, 2008;Shepherd, 2005). Diosmin treatment effectively normalized the altered levels of plasma lipids, tissue lipids (cholesterol, TGs, FFAs and PLs) and plasma lipoproteins (LDL, VLDL) (Srinivasan and Pari, 2013). Diosmin also reverses the changes in glycoprotein profile associated with type 2 diabetes. ...
Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them.Online databases, previous studies, and reviews have been used to gather information onanti-oxidant,immunomodulatory, anti-cancer,anti-parasitic, and anti-microbialproperties of diosmin.Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids.
... It possesses diverse pharmacological activities, mainly due to its free radical scavenging ability. These include anti-inflammatory , anticancer [29,30], antiulcer , antihyperlipidemic , and antihyperglycemic activities . Additionally, it has been reported that DSN exerted a hepatoprotective activity against iron-induced liver damage  and reduced the liver injury caused by carbon tetrachloride and γ-radiation . ...
Diosmin (DSN) exhibits poor water solubility and low bioavailability. Although nanocrystals (NCs) are successful for improving drug solubility, they may undergo crystal growth. Therefore, DSN NCs were prepared, employing sonoprecipitation utilizing different stabilizers. The optimum stabilizer was combined with chitosan (CS) as an electrostatic stabilizer. NCs based on 0.15% w/v poloxamer 188 (PLX188) as a steric stabilizer and 0.04% w/v CS were selected because they showed the smallest diameter (368.93 ± 0.47 nm) and the highest ζ-potential (+40.43 ± 0.15 mV). Mannitol (1% w/v) hindered NC enlargement on lyophilization. FT-IR negated the chemical interaction of NC components. DSC and XRD were performed to verify the crystalline state. DSN dissolution enhancement was attributed to the nanometric rod-shaped NCs, the high surface area, and the improved wettability. CS insolubility and its diffusion layer may explain controlled DSN release from CS-PLX188 NCs. CS-PLX188 NCs were more stable than PLX188 NCs, suggesting the significance of the combined electrostatic and steric stabilization strategies. The superiority of CS-PLX188 NCs was indicated by the significantly regulated biomarkers, pathological alterations, and inducible nitric oxide synthase (iNOS) expression of the hepatic tissue compared to DSN suspension and PLX188 NCs. Permeation, mucoadhesion, and cellular uptake enhancement by CS may explain this superiority.
... However, in case of diabetes, LLE is not stimulated due to an insulin insufficiency that results in increased synthesis of TGs by the liver and a disproportion in the liberation and rate of clearance of VLDL-C by LLE . Thus, TGs are usually used as indicators of intracellular aggregation of lipids . Consistent with this, the results of the present study showed significantly higher levels of TGs, TC, and VLDL-C and reduced HDL-C levels in the STZ-control group compared to non-diabetic rats. ...
Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second–fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth–seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.
... In the present study, we observed an increase in the levels of PLs in the plasma and liver of STZinduced diabetic rats. In this context, a previous report (Srinivasan and Pari 2013) also revealed an increased PLs level in the plasma and tissues of diabetic rats, which could be due to the increased levels of FFAs and TC (Dawaliby et al. 2016). We noticed decreased levels of PLs by the treatment of tyrosol may be due to an increase in insulin secretion that ultimately led to a decrease in the synthesis of TC and FFAs. ...
We investigated the antihyperlipidemic effects of tyrosol in streptozotocin (STZ)-induced diabetic rats. Rats were injected intraperitoneally with STZ (40 mg/kg), and these established experimental rats were treated with tyrosol (20 mg/kg) and glibenclamide (600µg/kg) for 45 days. The observed results revealed that tyrosol treatment significantly reduced plasma glucose, plasma, and liver total cholesterol, triglycerides, free fatty acids, phospholipids, plasma low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, and significantly increased plasma insulin and high-density lipoprotein cholesterol in STZ-induced diabetic rats. The activity of
3-hydroxy 3-methylglutaryl coenzyme A reductase significantly reduced in the liver, whereas the activities of lipoprotein lipase and lecithin cholesterol acyltransferase were significantly increased in the plasma of tyrosol treated STZ-induced diabetic rats. Histological examination showed that tyrosol treatment remarkably reduced lipid accumulation in the liver of STZ-induced diabetic rats. The present study revealed that tyrosol exhibits potent antihyperlipidemic effects in STZ-induced diabetic rats.
... Specifically, its main constituents are phenolics, including flavonoids, phenolic acids, and esters . Attributed to strong biological properties, previous research has noted that the phenolic compounds of propolis seem to play a critical role in the regulation of lipid metabolism [25,26]. ese studies only concentrated on evaluating the lipid-lowering activities of flavonoids [27,28]. ...
Lipid metabolism disorder is one of the significant risk factors for a multitude of human diseases and has become a serious threat to human health. The present study aimed to evaluate the effects of phenolics from poplar-type propolis on regulating lipid metabolism by using cell models of steatosis induced by palmitic acid (PA). Our study shows that phenolic esters have higher lipid-lowering activities than phenolic acids, especially for three caffeic acid esters, including caffeic acid phenethyl ester (CAPE), caffeic acid cinnamyl ester (CACE), and caffeic acid benzyl ester (CABE). Most notably, CACE presents prominent properties to prevent intracellular lipid accumulation and to amend extracellular adipokine secretion abnormalities. In addition, our results firstly reveal that CACE can alleviate lipid metabolism disorder through mediating protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6) signaling pathway-associated protein expression, suppressing endoplasmic reticulum (ER) stress, and activating peroxisome proliferator-activated receptors (PPARs) by distinct upregulation of PPARα and downregulation of PPARγ.
... Although STZ and alloxan are highly toxic to β cells, the effect is short-lived and when there are surviving cells, chronic hyperglycemia can be a toxic factor . The increase in insulin levels in diabetic animals treated with eugenol may be due to the anti-hyperglycemic potential of eugenol, mediated by its enhancement of increased secretion of existing residual β-cells [32,59,92]. However, we believe that this effect does not occur in human diabetes because while experimental diabetes provides models for studying the disease, it is not equivalent to the human disease condition. ...
Diabetes is a highly prevalent health condition affecting many people worldwide. In vitro studies have described the positive effects of cloves and its major compound, eugenol, in the treatment of diabetes. However, it is unclear whether the effects of this compound are negative, neutral, or positive, on hyperglycemic animals. Therefore, a meta-analytical review was conducted to determine the magnitude of effects of eugenol on variables directly and indirectly related to diabetes. This study revealed that eugenol treatment decreased the glucose levels and the activity of carbohydrate-metabolizing enzymes, ameliorated the lipid profile, and reduced the oxidative, renal, and hepatic damages in hyperglycemic rodents. Moreover, eugenol alleviated the weight loss and restored the activity of the antioxidant defense system. Insulin levels was not affected by eugenol treatment. Also, mixed model analyses revealed that the use of purified or non-purified eugenol and the concentrations administered significantly affected the treatment outcome. In conclusion, our findings indicate that eugenol may have potential therapeutic effects in the treatment of diabetes. Furthermore, this study can direct future preclinical and clinical trials, with important implications for human health.
... Currently, it is a medication mainly used for the treatment of diseases, such as chronic venous insufficiency and hemorrhoids . The effect of diosmin on lipid metabolism was evaluated using an animal model of streptozotocin (STZ)-induced diabetes . Interestingly, it was shown to attenuate biochemical markers, such as fasting plasma glucose concentrations, glycosylated hemoglobin (HbA1c), and C-reactive protein (CRP). ...
The consumption of plant-based food is important for health promotion, especially concerning the prevention and management of chronic diseases. Flavonoids are the main bioactive compounds in citrus fruits, with multiple beneficial effects, especially antidiabetic effects. We systematically review the potential antidiabetic action and molecular mechanisms of citrus flavonoids based on in vitro and in vivo studies. A search of the PubMed, EMBASE, Scopus, and Web of Science Core Collection databases for articles published since 2010 was carried out using the keywords citrus, flavonoid, and diabetes. All articles identified were analyzed, and data were extracted using a standardized form. The search identified 38 articles, which reported that 19 citrus flavonoids, including 8-prenylnaringenin, cosmosiin, didymin, diosmin, hesperetin, hesperidin, isosiennsetin, naringenin, naringin, neohesperidin, nobiletin, poncirin, quercetin, rhoifolin, rutin, sineesytin, sudachitin, tangeretin, and xanthohumol, have antidiabetic potential. These flavonoids regulated biomarkers of glycemic control, lipid profiles, renal function, hepatic enzymes, and antioxidant enzymes, and modulated signaling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications. Citrus flavonoids, therefore, are promising antidiabetic candidates, while their antidiabetic effects remain to be verified in forthcoming human studies.
... Further, the antihyperlipidemic activity of extracts might be attributed to the presence of flavonoids and phenols in accordance with the previous reports. 40,41 The elevated blood glucose level (hyperglycemia) in diabetes facilitates the free radical's production and depletes the natural antioxidants. 42 The SOD, CAT, and GSH are important enzymes that scavenge the free radicals and protect the cells against oxidative stress injury. ...
Background and aim
Herbal medicine combined with nanotechnology is widely proposed to improve the oral bioavailability, reduce the required dose and side effects, and improve the pharmacological efficacy of extracts. Thus, this study evaluated the in vivo antidiabetic and antihyperlipidemic activities of ethanolic leaf extracts of Argyreia pierreana (AP) and Matelea denticulata (MP) plants in comparison with their micellar nanoformulations.
Materials and methods
The mixed micelles (MMs) loaded with and crude extracts (CEs) of AP and MD (AP-MMs and MD-MMs) were prepared using a film dispersion technique. Type 2 diabetes was induced in rats using high-fat diet (HFD) and low-dose (35 mg/kg) streptozotocin (STZ) injection. The pharmacological actions of CE, AP-MMs and MD-MMs were determined in type 2 diabetic Sprague-Dawley rats.
Oral treatments with low-dose AP-MMs and MD-MMs having a mean particle size of 163 ± 10 nm and 145 ± 8 nm respectively, resulted in significantly decreased fasting blood glucose level and increased serum insulin, glucokinase levels, and normalized the elevated levels of hemoglobin A1C and glucose-6-phosphatase. Both extracts significantly decreased serum total cholesterol, triglycerides, and low-density lipoprotein, as well as elevated high-density lipoprotein levels. Additionally, improvements in antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and malondialdehyde levels were evidenced clearly in tested vital organs (brain, heart, liver).
This is the first report of the antidiabetic and antihyperlipidemic activities of ethanolic leaf extracts of AP and MP plants. Our findings indicate the potential utility of nanotechnology in improving the oral therapeutic efficacy of herbal extracts.
... The increase in HDL-C by P. vulgaris may have been mediated through increase in the activity of lecithin cholesterol acyltransferase, which play a key role in incorporating free cholesterol to HDL for hepatic transport. Flavonoids have been shown to enhance the activity of LCAT (Srinivasan and Pari, 2013) and may account for the observed higher HDL by the extracts of P. vulgaris. ...
Phaseolus vulgaris is used in ethnomedicine for the management of overweight and cardiovascular disorders with claims of efficacy. This motivated this study in which the antihyperlipidemic activities of the extracts of P. vulgaris and its antioxidant activities were evaluated. Methanol/methylene chloride (1:1) extract was screened and further partitioned into n-hexane, ethyl acetate and butanol solvent fractions. HPLC "fingerprinting" technique showed the abundance of catechin in the crude extract. Oral median lethal dose (LD50) was estimated to be greater than 5000 mg/kg. Short term treatment with the crude extract and ethyl acetate fraction significantly (p < 0.05) lowered the levels of serum triglyceride, total cholesterol, LDL-C and VLDL-C in hyperlipidemic condition induced in rats with Triton WR-1339, Triton X-100 and high fat diet. Similarly, sub-acute treatment of the animals with crude extract and ethyl acetate fractions produced dose-dependent and significant (p < 0.05) decrease in serum triglyceride, total cholesterol and VLDL-C levels in high fat hyperlipidemic model. Antioxidant activities of the extract and fractions were determined in vitro using DPPH assay while liver malondialdehyde and serum antioxidant enzyme activities were used to assess the in vivo antioxidant potentials in CCl4-intoxicated rats. DPPH median inhibitory concentrations (IC50) of the extract and fractions ranged from 79.84-98.49 μg/ml. The extract and its fractions produced significant (p < 0.05) inhibition of lipid peroxidation and significant (p < 0.05) higher levels of catalase and glutathione peroxidase enzyme activities. This investigation showed that the extract and fractions of Phaseolus vulgaris possess some anti-hyperlipidemic and
... Diosmin is different from hesperidin by the presence of a double bond between two carbon atoms in the C-ring of the molecule, which contains a sugar molecule bound to the tri-ring flavonoid structure. In addition, diosmin may be produced following the extraction of hesperidin, and this is in the form of the conversion of hesperidin to diosmin (Bogucka-Kocka et al. 2013;Patel et al. 2013;Srinivasan and Pari 2013;Suică-Bunghez et al. 2015;Bertozzi et al. 2017;Buddhan and Manoharan 2017;Mirshekar et al. 2017). Diosmin rapidly converts to diosmetin in the form of aglycone in the intestinal flora. ...
In this study, the effect of diosmin against the adverse effects of lead exposure in rats was investigated. Wistar Albino race 40 male rats weighing 150–200 g 2–3 months were used. A total of 4 groups were assigned, one of which was control and the other 3 were trial groups. The rats in the control group were treated with dimethyl sulfoxide, which was used only as a vehicle in diosmin administration. Groups 2, 3, and 4 from the experimental group were given diosmin at a dose of 50 mg/kg.bw, lead acetate at the dose of 1000 ppm, lead acetate at the dose of 1000 ppm, and diosmin at a dose of 50 mg/kg.bw for 6 weeks, respectively. Application of lead acetate with drinking water and also diosmin was performed by oral catheter. At the end of the experimental period, blood was taken to dry and with heparin by puncture to the heart under light ether anesthesia. Following the blood samples, some organs of the rats (the liver, kidney, brain, heart, and testis) were removed. Some biochemical parameters (glucose, triglyceride, cholesterol, BUN, creatinine, uric acid, LDH, AST, ALT, ALP, total protein, albumin) were measured in serum. Some oxidative stress parameters in tissue samples and blood (MDA, NO, SOD, CAT, GSH-Px, GSH) were evaluated. Body and organ (the liver, kidney, brain, heart, and testis) weights were also evaluated at the end of the study. No significant change was observed in the parameters examined in the diosmin alone-treated group by comparison to control group. On the other hand, significant changes were found in the values of lead acetate-treated group comparing control group. It was observed that the values approached the values of the control group in the combination of lead and diosmin. Exposure to lead acetate at a dose of 1000 ppm for 6 weeks causes organ damage; however the diosmin application at a dose of 50 mg/kg.bw had a positive effect on the regression of tissue damage.
... Different parts of C. asiatica were found to contain high phenolic contents (quercetin, kaempherol, catechin, rutin, apigenin and naringin and volatile oils (caryophyllene, farnesol and elemene), which exhibit strong association with its antioxidative activities 9 . Diabetes mellitus poses a major health problem on both clinical and social plans also, for the onset of serious invaliding complications that frequently appear 10 . Accordingly, this study was designed to investigate the possible protective effects of C. asiatica on the diabetic complications and antioxidant status of hepatic, cardiac, renal and testicular tissues of STZ-diabetic rats, which are often prone to secondary complications of the disease. ...
Effects of Centella asiatica upon oxidative stress and dysfunctions of liver, heart, kidney and testis in STZ-diabetic rats were investigated. Animals were divided into four groups Group 1, Control; Group 2, streptozotocin (STZ); Group 3, C. asiatica treated plus streptozotocin and Group 4, C. asiatica. Toxicological parameters including AST, ALT, ALP, LDH and CK-MB were significantly improved after treatment with C. asiatica (250 mg/kg BW, orally) in diabetic rats. Co-administration of C. asiatica ameliorated higher levels of plasma total cholesterol, triglycerides, total lipids and low density lipoprotein cholesterol (LDL-C) and increased the level of high density lipoprotein cholesterol (HDL-C). While, urea, creatinine and uric acid levels were decreased. A significant reduction of plasma Na +1 , K +1 , Mg +2 and Ca +2 that improved by C. asiatica in diabetic rats compared to non diabetics. C. asiatica treatment restored testosterone, FSH, LH, PRL and sperm count near to normal values in diabetic rats. In addition, SOD, CAT, GPX activities and GSH levels were restored by C. asiatica administration and consequently, the levels of lipid peroxidation were reduced in the selected organs as compared to diabetic animals. Also, treatment of rats Centella asiatica ameliorated DNA fragmentation. The protective effect of C. asiatica is mainly attributed to its antioxidant properties and pharmaceutical potent. These findings demonstrated the protective effect of C. asiatica on the antioxidant tissue defense system during streptozotocin-induced diabetes and its beneficial effect in preventing diabetic complications.
... Diabetes mellitus is the name given to a group of disorders with different etiologies. It is characterized by disarrangements in carbohydrates, proteins and fat metabolism caused by the complete or relative insufficiency of insulin secretion and/or insulin action . Diabetes mellitus is characterized by hyperglycemia, hypercholesterolemia and hypertriglyceridemia resulting from defects in insulin secretion followed by dysfunction and failure of organs especially the eyes, kidneys, nerves, heart and arteries. ...
Background: Flax seeds have been shown to have multiple benefits in cardiovascular disorders. Objective: To evaluate Antihyperlipidemic activity of methanolic fraction of flax lignan concentrate (MF-FLC) obtained from Linum usitatissium L., Linaceae in nicotinamide-STZ induced diabetic hyperlipidemia rats. Methods: Male Wistar rats were used for the study. The IAEC of Poona college of Pharmacy approved the proposal. Protocol no. CPCSEA/01/14. Diabetes was induced in rats by nicotinamide-STZ. Diabetic animals were divided into five groups: Diabetic atherosclerosis control, Atorvastatin (10 mg/kg), MF-FLC (200 mg/kg), MF-FLC (400 mg/kg), and MF-FLC (800 mg/kg). After the confirmation of diabetes, rats were treated with cholesterol (4% w/w) and cholic acid (1% w/w) for 45 days. After 15 days of cholesterol treatment, atorvastatin and MF-FLC treatment was given to respective groups for 30 days. Non-diabetic atherosclerosis group received cholesterol-cholic acid treatment alone. The control group was given coconut oil as vehicle. Results: Treatment of MF-FLC (400 mg/kg) and atorvastatin (10 mg/kg) significantly reduced systolic blood pressure (p<0.01), diastolic blood pressure (p<0.01), mean arterial blood pressure (p<0.001) and left ventricular end diastolic pressure (p<0.001) whereas there was significant increase in Max dp/dt (p<0.001) and Min dp/dt (p<0.01) indicating the effect on cardiac contractility. These findings were confirmed in histopathology. MF-FLC (400 mg/kg) showed significant (p<0.01) reduction in the glucose level. MF-FLC (400 mg/kg) was found to be effective, increase in the dose (800 mg/kg) there showed a ceiling effect. Conclusion: The treatment with MF-FLC showed significant increase in the both max and min dp/dt. Atorvastatin (10 mg/kg) also showed significant increase in the both max and min dp/dt. This suggests that MF-FLC provides sufficient contractile reserve to ameliorate the detrimental effects of diabetes on cardiac contractility. MF-FLC had additional benefit of anti-hyperglycemic effect when compared to atorvastatin.
... This antidiabetic potential of GGEAE could be due to i) Enhance insulin sensitivity and improve glucose utilisation as insulin levels are not raised significantly however glucose levels were decreased, which resembles the observation done in other studies (Paoli et al., 2013;Sendrayaperumal et al., 2014;Zhang et al., 2012). ii) Improved lipids and carbohydrate metabolism as discussed by other authors (Prasath and Subramanian, 2014;Srinivasan and Pari, 2013). iii) Antioxidant activity which is evident from elevated levels of SOD, catalase and alleviated levels of TBARS in pancreas, liver, and kidney of extract treated groups which are in agreement with others observations (Pietta, 2000). ...
... 172 Amentoflavone, daidzein, luteolin and luteolin 7-O-glucoside have been proved to be the strongest inhibitors of α-glucosidase among the twenty-one tested compounds. 173 Orientoside too was shown to impede α-glycosidase function. The lowest possible level of blood glucose is achieved after 4 h of dosing of quercetin. ...
... This effect seems to be because of the amino acid composition of sp or flavonoids of lz, such as Quercetin (Prasath and Subramanian, 2014) or Fisetin and taurine (Wang et al., 2013). Our results are in concordance with those of Srinivasan and Pari (2012) who found that Diosmin (flavonoid of citrus fruits) reduces TBARS in kidney of diabetic rat and with Abdel-Moneim et al. (2015) who found that combining between taurine and Silymarin (polyphenolic flavonoid) reduces the values of hepatic TBARS, and other studies have found that dietary flavonoids (quercetin/catechin, 2:1) significantly reduced the VLDL/LDL oxidation in rats fed diets rich in polyunsaturated fatty acids (Frémont et al., 1998). In addition, the ingestion of a tea rich in catechins reduces the values of LDL malondialdehyde in men (Nagao et al., 2005). ...
This paper aims to study the effect of green lemon zest combined with sardine proteins in diabetic hypertensive rats (DHRs).
Male Wistar rats (n = 30) weighing 250 ± 10 g were divided into five groups. The first group consumed a diet containing 20 per cent casein (C). The other four groups are rendered diabetic by intraperitoneal injection of streptozotocin (40 mg/kg body weight), then hypertensive by subcutaneous implantation controlled time-release pellet containing ouabain (0.25 mg/pellet). One untreated group (DHR) consumed 20 per cent casein and the three other groups consumed the same diet supplemented with 2 per cent green lemon zest (DHR-lz), or with 20 per cent of sardine protein (group DHR-sp) or with the combination of both sardine proteins and green lemon zest (group DHR-sp + lz).
DHRs feeding on the combination of both sardine protein (sp) and lemon zest (lz) induced a significant decrease of diastolic blood pressure and heart rates values compared with DHR (p < 0.05). The HDLC values were increased by +55 per cent in DHR-sp + lz compared with DHR group. Moreover, plasma non-HDLC concentrations were decreased significantly compared to DHR, DHR-lz, DHR-sp and C groups. In DHR-sp + lzvs DHR group, TBARS values were decreased by −25 per cent in the liver. Moreover, kidney TBARS were significantly reduced by −66, −51, −65 and −67 per cent compared with C, DHR, DHR-lz and DHR-sp, respectively.
These results suggest that consumption of green lemon zest combined with sardine proteins can reduce blood pressure and tissue oxidative damage and, therefore, help to prevent cardiovascular complications in hypertensive diabetic patients.
... As a flavonoid, it also exhibits antihemorroidal, antioxidant and antilipid peroxidation properties and protects against the deleterious effects of free radicals . Several studies have also demonstrated that diosmin has several positive effects on hyperglycemia, hypertension and hyperlipidemia . Though diosmin seems to possess a multitude of biological activities to improve factors associated with diabetic complications, there is no comprehensible evidence relating to its protective role in DR. ...
We investigate diosmin for its effect on the ARPE-19 human retinal pigment epithelial cells exposed to high glucose, a model of diabetic retinopathy (DR). After incubation for 4 days with a normal (5 mmol/L) concentration of D-glucose, ARPE-19 cells were exposed separately to normal or high concentrations of D-glucose (30 mmol/L) with or without diosmin at different concentrations (0.1, 1, 10 μg/mL) for another 48 h. Next, we assessed cell viability, reactive oxygen species (ROS) generation and antioxidant enzyme activities. In order to examine the underlying molecular mechanisms, we meanwhile analyzed the expressions of Bax, Bcl-2, total and phosphorylated JNK and p38 mitogen-activated protein kinase (MAPK). Diosmin dose dependently enhanced cell viability following high glucose treatment in ARPE-19 cells. The activities of superoxide dismutase and glutathione peroxidase, as well as the levels of reduced glutathione were decreased, while it was observed that levels of ROS in high glucose cultured ARPE-19 cells increased. High glucose also disturbed Bax and Bcl-2 expression, interrupted Bcl-2/Bax balance, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by diosmin. Furthermore, diosmin could abrogate high glucose-induced apoptosis as well as JNK and P38 MAPK phosphorylation in ARPE-19 cells. Our results suggest that treatment ARPE-19 cells with diosmin halts hyperglycemia-mediated oxidative damage and thus this compound may be a candidate for preventing the visual impairment caused by DR.
... In recent years, flavonoids, derived from plants, have attracted broad attention for a wide range of biological functions such as antioxidant (Boudkhili et al., 2015;Sait et al., 2015), antitumor (Guo, 2013;Radhika, Ghoshal, & Chatterjee, 2012), immunological (Ciftci et al., 2015;Liu, Zhao, Ma, Ding, & Su, 2012), antimicrobial (Dzoyem, Hamamoto, Ngameni, Ngadjui, & Sekimizu, 2013;Liu et al., 2010), and antihyperlipidemic (Srinivasan & Pari, 2013;Zhang, Wu, Ma, Cheng, & Liu, 2015) activities. However, there was almost no attention paid to the flavonoids from C. fascicularis. ...
Ultrasonic-assisted extraction of flavonoids from Camellia fascicularis leaves was optimized using response surface methodology. The optimal extracting conditions of flavonoids were determined to be the ratio of liquid to raw material of 60 mL/g, ethanol concentration of 40%, extraction temperature of 72.3°C, and extraction time of 1.6 h, which contributed to the highest flavonoids yield of 4.765%. The crude flavonoids were purified through an AB-8 macroporous adsorption resin column, eluted with ethanol concentration of 40%, and purified flavonoids were obtained. In vitro antioxidant assay demonstrated that purified flavonoids showed significant antioxidant capacities in a concentration-dependent manner for scavenging hydroxyl radical, superoxide anion radical, 2,2-diphenyl-1-picrylhydrazyl radical, and azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical. Overall, ultrasonic-assisted extraction was found to be an effective method of extracting flavonoids from C. fascicularis leaves, which might be explored as potential natural antioxidant.
... For this purpose, innumerable polyphenolic molecules present in various food commodities irrespective of plant or animal origin are incessantly being exploited to assess their therapeutic potential in precluding and/or controlling diabetes. 84 Phenolic acids known to be secondary metabolites are predominantly found in several fruits, vegetables and spices. Various epidemiological investigations have illustrated the positive relationship among the utilization of phenolic rich diet and prevention of diabetes. ...
Eugenol, a phytogenic bioactive component is frequently found in diversified herbal plants possessing well-defined functional attributes. Prominent sources of eugenol are clove, cinnamon, tulsi and pepper. Various extraction methods have been practiced globally for the extraction of eugenol and other nutraceutics from plants. The most extensively employed approaches in this regard include solvent extraction, hydro-distillation, microwave-assisted extraction, supercritical carbon dioxide extraction and ultrasound-based extraction. Eugenol has been approved to encompass numerous beneficial aspects against a capacious spectrum of life threatening indispositions including oxidative stress, inflammation, hyperglycemia, elevated cholesterol level, neural disorders and cancer. In addition, eugenol has also shown strong potential as an antimicrobial agent against wide ranges of pathogenic and spoilage causing microorganisms. Predominantly, the principle mechanistic approaches associated with the therapeutic potential of eugenol include its free radical scavenging activity, hindrance of reactive oxygen species' generation, preventing the production of reactive nitrogen species, enhancement of cyto-antioxidant potential and disruption of microbial DNA & proteins. Consequently, this article is an attempt to elucidate the general properties, sources, extraction methods, therapeutic role and associated mechanisms of eugenol.
... In addition to the antioxidative activity, diosmin demonstrates also the protective effect in diabetes. It counteracts the oxidative stress in the plasma, liver and kidneys of diabetic rats, lowers glucose and glycated hemoglobin levels in plasma and shows protective activity against diabetic neuropathy in rats . As for now, there is only one in vitro study describing the effect of diosmin on sugar-induced cataract formation in goat lenses . ...
Diabetic cataractogenesis is a complex process connected with hyperglycemia and oxidative stress. Free radicals induce many unfavorable changes in the activity of the antioxidative enzymes and may also lead to oxidative damage. Since diosmin, a plant-derived flavonoid, reveals antioxidative activity, the aim of the study was to investigate if this substance may counteract the oxidative stress in the lenses of diabetic rats.
The study was conducted on the male Wistar rats with streptozotocin-induced type 1 diabetes. After the administration of diosmin at the doses of 50 and 100mg/kg for 4 weeks the oxidative stress markers in the lenses of these rats were evaluated. Tested markers included: activity of superoxide dismutase, catalase and glutathione peroxidase, as well as levels of total and soluble protein, level of glutathione, vitamin C, advanced oxidation protein products and malonyldialdehyde.
The obtained results indicate that the administration of diosmin to the diabetic rats counteracted the unfavorable changes induced by diabetes in the lenses.
It can be assumed that diosmin may be a promising compound in prevention or delaying the cataract formation during diabetes.
... In studies with rats, orally treatment of diosmin for 45 days significantly lowered plasma glucose level, increased the activities of hepatic key enzymes such as hexokinase and glucose-6-phosphate dehydrogenase (G6PD) in addition to decreasing glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FDPase) in streptozotocin (STZ)-nicotinamide treated rats exhibiting its antihypeglycemic activities . Studies from the same author claimed that, diosmin lowered plasma glucose and increased plasma insulin levels in diabetic rats by ameliorating the oxidative stress induced by STZ-nicotinamide and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), GPx, and reduced glutathione (GST), vitamin C, vitamin E and reduced glutathione were increased while lipid peroxidation was reduced in liver and kidney of diabetic rats upon treatment with diosmin . In recent study, treatment with diosmin at doses of 50 and 100 mg/kg bw for 1 month ameliorated hyperglycemia and oxidative stress . ...
Natural food products have been used for combating human diseases for thousands of years. Naturally occurring flavonoids including flavones, flavonols, flavanones, flavonols, isoflavones and anthocyanidins have been proposed as effective supplements for management and prevention of diabetes and its long-term complications based on in vitro and animal models.
To summarize the roles of dietary flavonoids in diabetes management and their molecular mechanisms.
Tremendous studies have found that flavonoids originated from foods could improve glucose metabolism, lipid profile, regulating the hormones and enzymes in human body, further protecting human being from diseases like obesity, diabetes and their complications.
In the current review, we summarize recent progress in understanding the biological action, mechanism and therapeutic potential of the dietary flavonoids and its subsequent clinical outcomes in the field of drug discovery in management of diabetes mellitus.
... Natural cholesterol-lowering compounds have been considered as functional food candidates for preventing atherosclerosis, hypertension and hyperdyslipidaemia (Srinivasan & Pari, 2013;Wu et al., 2013). Increasingly, plant extracts, recognised as food materials, are being developed as functional foods because of their safety and lower development costs. ...
... The activity of PL is affected by food constituents such as citrus flavonoid (Srinivasan & Pari, 2013), litchi flower-water extracts (Wu et al., 2013), lignin (Zhang, Xiao, Yang, Wang, & Li, 2014a) and dietary fibres (Isaksson, Lundquist, & Ihse, 1982;Lairon et al., 1985), suggesting that the higher intake of dietary fibres may not only reduce caloric density but may be also related to digestibility of fat. The hypocholesterolemic and hypotriacylglyceroldaemic effects of fibres, including pectin, wheat bran and cellulose, have been repeatedly observed in laboratory animals (Vahouny et al., 1980), but the capacity of wheat bran, a mainly insoluble fibre, to reduce absorption of cholesterol and triglycerides was marginal. ...
... High glucose levels in diabetes cause complications to develop. Heart disease and stroke, kidney disease, eye disease, periodontal disease, foot problems, skin disorders, diabetic neuropathy and nerve problems are among serious complications of diabetes . This study shows that the PSFH group experienced a stronger antihyperglycemic effect than the PSFL or PSFM groups. ...
The production of many edible and medicinal mushrooms has been steadily increasing, because of several of their physiological effects. In the present study, we investigated the antihyperglycemic activity of large exopolysaccharide molecules (PSF), which are produced in the fermented broth of ferula mushroom Pleurotus ferulae, on streptozotocin-induced diabetic rats. All experimental rats were divided into 6 groups consist of 8 rats. The diabetic rats were fed a diet containing PSF for 6 weeks at a dose of 30 mg (PSFL-group), 90 mg (PSFM-group), or 250 mg/kg body weight (PSFH-group) daily, respectively. The fasting blood glucose level of the PSFH-group was the lowest among all 3 PSF-fed groups. Insulin levels increased and HbA1c levels decreased significantly for the three PSF-fed groups in comparison with negative control group during period of breeding. The PSFH-group's low-density lipoprotein cholesterol and triglyceride levels were lower than those of other groups. A dose-dependent effect revealed that the exopolysaccharide of P. ferulae might mitigate hyperglycemia at the highest dose of 250 mg/kg body weight.
... The antioxidant activity of these bioactive molecules is well assessed (Atrooz, 2009;Bocco et al., 1998;Chen, Yuan, & Liu, 2010;Cook & Samman, 1996;Manners, 2007;Patil, Jayaprakasha, Murthy, & Vikram, 2009;Pernice et al., 2009). Carotenoids and flavonoids have been implicated in the protection against cancer, prevention of serious human health disorders such as heart and cardiovascular diseases, macular degeneration, cataracts, osteoporosis, hypertension and hyperlipidaemia (Gattuso et al., 2007;Rao & Rao, 2007;Srinivasan & Pani, 2013). Coumarins have also been demonstrated to exert many pharmacological and toxicological activities (Kleiner et al., 2008;Middleton, Kandaswami, & Theoharides, 2000;Murray, Mendey, & Brown, 1982;Row, Brown, Stachulski, & Lennard, 2006), possessing antibacterial (Kayser & Kolodziej, 1999), antiplatelet aggregation, anti-HIV (Wu et al., 2001) and intestinal anti-inflammatory (Luchini et al., 2008) properties. ...
... The pursuit of novel therapies targeting the residual risk is focused on preventing the increase of LDL concentration and favouring the increase of HDL (deGoma & Rader, 2011). Some natural compounds found in the human diet have been shown to possess therapeutic and pharmacologic properties, in particular, the daily consumption of citrus fruit juice has been shown to positively influence plasma lipid levels and reduce the risk of coronary heart disease (Gorinstein et al., 2004;Srinivasan & Pani, 2013). Hypolipidaemic effects can be correlated to several components of citrus juice, such as flavonoids (naringin and hesperidin), pectins, and ascorbic acid, which have a high antioxidant potential and interfere with cholesterol metabolism (Chen, Ma, Liang, Peng, & Zuo, 2011;Chinapongtitiwat, Jongaroontaprangsee, Chiewchan, & Devahastin, 2013;Gorinstein et al., 2005;Monforte et al., 1995). ...
... Other nutraceutical and functional food ingredients can exert a role in controlling lipid metabolism (Kwok, Li, Cheng, et al. 2013;Srinivasan & Pari 2013), but further trials are needed to corroborate the experimental results. ...
... Diabetes mellitus poses a major health problem on both clinical and social plan, not only for the high number of patients, but also for the onset of serious invaliding complications that frequently appear  . It is a prototypical, growing, costly chronic non-communicable disease causing increasing morbidity and mortality worldwide, often disproportionately hurting the poor and young subpopulations in developing countries  . ...
To investigate the effect of carvone on dearrangement in glycoprotein levels in the streptozotocin(STZ)-induced diabetic model.
Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w). The levels of glycoproteins were altered in experimental diabetes mellitus. Carvone were administered to diabetic rats intragastrically at 25, 50, 100 mg/kg bw for 30 d. The effects of carvone on plasma glucose, insulin, plasma and tissue glycoproteins were studied.
Oral administration of carvone (50 mg/kg b.w) for 30 d, dose dependently improved the glycemic status in STZ-induced diabetic rats. The levels of plasma glucose were decreased with significant increase of plasma insulin level. The altered levels of plasma and tissue glycoprotein components were restored to near normal.
The present findings suggest that carvone can potentially ameliorate glycoprotein components abnormalities in addition to its antihyperglycemic effect in experimental diabetes. In light of these advantageous results, it is advisable to broaden the scale of use of carvone in a trial to alleviate the adverse effects of diabetes.
This study examined the antiangiogenic capacity of diosmin in vitro and their interactions with certain important receptors related to cancer and infectious diseases via molecular docking. Diosmin, a naturally occurring flavone glycoside, largely found in citrus fruits, exhibits potentially antiangiogenic properties especially interacting with both VEGF and VEGFR. Treatment with certain doses of diosmin caused a reduction with a ratio of 22–68% on VEGF levels as compared to non-treated control groups. Western blotting and real-time PCR results demonstrated that protein expression of VEGF was downregulated in a dose- and time-dependent manner. On the other hand, we aimed to check the possible interaction of diosmin with VEGF, VEGFR, HER, PR, ER, and Omp-a, receptor proteins. According to our molecular docking results, diosmin effectively binds these receptors and probably this could be one of the possible reasons for its anti-angiogenic and anti-microbial properties.
Flavonoids are naturally occurring compounds widely distributed in the Citrus genus. These natural compounds have many health benefits, mainly for metabolic and cardiovascular diseases. In fact, some these compounds are components of drug products with approved indications for peripheral vascular insufficiency and hemorrhoids. However, information on pharmacological effects of these compounds remains disperse and there is scarce comprehensive analysis of whole data and evidence. These kinds of evidence analyses could be necessary in drug design and the development of novel and innovate drug products in diabetes and hypertension. We aimed to systematically search for evidence on the efficacy of citroflavonoids in diabetes and hypertension in in vivo models. We searched four literature databases based on a PICO strategy. After database curation, twenty-nine articles were retrieved to analyze experimental data. There was high heterogeneity in both outcomes and methodology. Naringenin and hesperetin derivates were the most studied citroflavonoids in both experimental models. More investigation is still needed to determine its potential for drug design and development.
Flavonoids are phytochemicals that are well known for their beneficial pharmacological properties. Diosmin is a flavone glycoside derived from hesperidin, a flavanone abundantly found in citrus fruits. Daflon is an oral phlebotonic flavonoid combination containing diosmin and hesperidin (9:1) that is commonly used for the management of blood vessel disorders. After oral administration, diosmin is converted to diosmetin, which is subsequently absorbed and esterified into glucuronide conjugates that are excreted in the urine. Pharmacological effects of diosmin have been investigated in several in vitro and in vivo studies, and it was found to possess anti-inflammatory, antioxidant, antidiabetic, antihyperlipidemic, and antifibrotic effects in different disease models. Diosmin also demonstrated multiple desirable properties in several clinical studies. Moreover, toxicological studies showed that diosmin has a favorable safety profile. Accordingly, diosmin is a potential effective and safe treatment for many diseases. However, diosmin exhibits inhibitory effects on different metabolic enzymes. This encourages the investigation of its potential therapeutic effect and safety in different diseases in clinical trials, while taking potential interactions into consideration.
Platelets exert an essential role in vascular inflammation and thrombosis. Flavonoids are natural compounds employed for the clinical management of vascular disorders preventing capillary permeability, working as phlebotonics and improving the blood rheology, although their mechanism of action remains partially unknown. The effects of quercetin, rutin, diosmetin and diosmin were investigated in platelet activation utilizing blood from healthy and non-treated volunteers. The arrangement of the different activation states of platelets and GPIIb/IIIa receptor occupation was computed by flow cytometry working with calcium ionophore as pro-aggregant to provoke platelet activation and aggregation. The flavonoids studied demonstrated relevant antiplatelet activity through the blocked of GPIIb/IIIa receptors, the suppression of the platelet activation, as well as the pro-aggregate effect of calcium ionophore. Therefore, whichever of the active ingredients examined could be beneficious in the prevention of cardiovascular disease and this article also contributes to elucidate a new mechanism of action for these drugs.
Commonly flavonoids are the natural components found in vegetables, spices and colored fruits. Flavonoids include a large group of polyphenolic compounds, namely flavones, flavanols, flavonols, flavanones, isoflavones and anthocyanidins, which have been proposed as effective supplements for the management of diabetes and associated disorders. The aim of present review was to highlight various classes of flavonoids, their structure – activity relationships, bioavailability, and mechanisms involved in the management of diabetes and associated complications. The relevant research and review articles were collected from online (Pubmed, Sciencedirect, Scopus, Google, andWeb of science) and offline sources (books and journals from library). A total of 245 articles published between 1996 to 2018 were reviewed, and 232 articles were included in present review. Article being related with flavonoids and diabetes is the major criterion for inclusion in this compilation. Flavonoids regulate the redox status and prevent damage caused by oxidative stress and possess anti-oxidant activity. Flavonoids are a wide group of compounds including quercetin, kaempferol, luteolin, apigenin, genistein, glycitein, eriodictyol, hesperidin, catechin, gallocatechin, pelargonidin, and cyanidin. Type 2 diabetes mellitus is associated with insulin resistance, β-cell dysfunction, inflammation, altered lipid metabolism and increased oxidative stress. It can affect many metabolic processes may cause serious complications such as retinopathy, cardiovascular disease and nephropathy. Flavonoids produce antidiabetic effect through suppressing α-amylase activities, attenuating insulin resistance and promoting pancreatic β-cells proliferation. Several reports including in-vitro and in-vivo studies on flavonoids confirmed their major role in maintaining metabolic pathways during type 2 diabetes mellitus treatment.
Objective: The research aimed to determine the effect of ethanolic extract of Scaevola taccada (Gaertn.) Roxb leaves in hyperlipidemic rats WITH Cholesterol and triglyceride parameter. Methods: The research used 30 samples divided into 6 groups: group I (negative control) was given Sodium Carboxymethyl cellulose of 1% w/v , group II (positive control) was given simvastatin of 1.023 mg/kg Body weight, Group III was given gemfibrozil 167.60kg/Body Weight, group IV, V and VI were respectively given ethanolic extract of Scaevola taccada (Gaertn) Roxb with the doses of 700 mg/kg body weight 900 mg/kg body weight, and 1100 mg/kg body weight. The sample was fed a high-fat diet during treatment and induced pure cholesterol for 28 days, the provision of dosage form was done orally once a day for 14 days and the measurement of rat cholesterol and triglycerides, level was done on day 0, 29, and 43. The research data were processed statistically by one way ANOVA test followed by Post Hoc Bonferroni test. Results: The result showed that the positive control group had no significant effect compared on ethanol extract Scaevola taccada (Gaertn.) Roxb. group (p> 0,5). Conclusion: The conclusion is the ethanolic extract of Scaevola taccada (Gaertn.) Roxb. leaves had an activity in reducing cholesterol and triglyceride level in rat hyperlipidemia and with an effective dose of 1100 mg /kg body weight Peer Review History: Received: 19 September 2020; Revised: 15 October; Accepted: 26 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Marwa A. A. Fayed, University of Sadat City, Egypt, firstname.lastname@example.org Dr. Rashad Mohammed Musleh Alnamer, University of Thamar, Yemen, email@example.com Comments of reviewer(s): Similar Articles: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC ACTIVITY OF DRACAENA CINNABARI BALF. RESIN ETHANOLIC EXTRACT OF SOQATRA ISLAND IN EXPERIMENTAL ANIMALS HYPOGLYCEMIC AND LIPID LOWERING EFFECT OF AQUEOUS FRESH LEAF EXTRACT OF CHROMOLAENA ODORATA (LINN) IN ALBINO WISTAR RATS FED DIFFERENT CONCENTRATIONS OF CHOLESTEROL ENRICHED DIET ESTIMATION OF ANTI-INFLAMMATORY ACTIVITY AS WELL AS APOPTOTIC ACTIVITY OF ETHANOLIC EXTRACTS OF CROCUS SATIVUS
Non-alcoholic steatohepatitis (NASH) is becoming of increasing significance due to its growing global prevalence and risk of progression to end-stage liver disease. This study was carried out to investigate the potential anti-inflammatory, insulin sensitizing, and antifibrotic effects of diosmin in an experimental model of NASH induced in rats using high-fat diet (HFD) and 30 mg/kg streptozotocin (STZ). Diosmin was administered orally at dose of 100 mg/kg for 8 weeks. Stained tissue sections were examined for histopathological signs of NASH, collagen deposition, and alpha smooth muscle actin (α-SMA) expression. In addition, insulin resistance, dyslipidemia, inflammation, and fibrosis markers were assessed. HFD/STZ successfully induced different NASH features such as insulin resistance seen by elevated fasting blood glucose levels and homeostasis model assessment for insulin resistance. Moreover, induced rats demonstrated dyslipidemia, a significant elevation in tumor necrosis factor alpha (TNF-α) and interleukin-6 levels, and an imbalance in the oxidative status of the liver. Those events altogether precipitated initiation of liver fibrosis as confirmed by elevated transforming growth factor beta (TGF-β) levels. Treatment with diosmin demonstrated multiple beneficial effects as it significantly ameliorated histopathological NASH findings, lowered TNF-α, interleukin-6, and malondialdehyde levels, improved lipid and glucose metabolism, and lowered hepatic TGF-β, α-SMA, and collagen content compared to untreated rats. The present study represents a drug repositioning scenario as diosmin is widely used for management of blood vessel disorders and is known to be well tolerated. This encourages the extension of our study to the clinical setting to explore diosmin effects in NASH patients.
The development of drugs possessing anti-diabetic activities is a long pursued goal in drug discovery. It has been shown that deregulated insulin mediated signaling, oxidative stress, obesity, and β-cell dysfunction are the main factors responsible for the disease. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can effectively treat diabetes by targeting different pathways has re-bloomed. Current anti-diabetic therapy is based on synthetic drugs that very often have side effects. For this reason, there is an instantaneous need to develop or search new alternatives. Recently, more attention is being paid to the study of natural products. Their huge advantage is that they can be ingested in everyday diet. Here, we discuss various causes, putative targets, and treatment strategies, mechanistic aspects as well as structural features with a particular focus on naturally occurring flavonoids as promising starting points for anti-diabetic led development.
Hyperlipidemia is currently rising at an alarming rate in human populations around the world, and new innovative ways of alleviating hyperlipidemia are needed. The effects of Jerusalem artichoke inulin on hyperlipidemia and the intestinal microflora in mice fed high-fat diet (HFD) were investigated. Inulin-treated HFD-fed hyperlipidemic mice had decreased serum lipid hepatic triglyceride (TG), hepatic total cholesterol (TC) concentrations and atherogenic index (AI). The inulin treatment increased hepatic superoxide dismutase (SOD) activity and decreased hepatic malondialdehyde (MDA) concentration. Histological analysis of liver revealed a decrease in abundance of lipid droplets in inulin-treated HFD-fed hyperlipidemic mice. Illumina high-throughput sequencing technology was used to analyze the bacterial community structure of the intestinal contents of mice. Analysis showed that the inulin treatment improved intestinal microflora; in particular, it significantly increased the number of Bifidobacterium in the intestine of HFD-fed mice. Inulin is therefore potentially potent functional food for preventing and treating hyperlipidemia.
This review was undertaken because of the lack of a comprehensive review on the compositions of secondary metabolites, extracts and volatiles of Ziziphora species and of the biological activities of these materials. The Lamiaceae or Labiatae family comprises a large number of flowering plants of widespread distribution, which have been classified into some 236 genera and 6900–7200 species. The genus Ziziphora is one of the well-known genera of this large family of plants and its species are of prime importance in different fields of pharmaceutical, chemical, medicinal, traditional and folk medicines. This review is concerned with characterization of chemical profiles of essential oils, extracts and volatiles, along with relevant biological and phytochemical properties of a wide spectrum of plants in this genus over the 46-year period, 1970–2016. These reports demonstrate the significant impact of these herbal and medicinal plants for the treatment of a variety of diseases and as effective alternative options for chemical drugs which sometimes have unpleasant side effects.
A simple green method to synthesize silver nanoparticles (AgNPs) is described where diosmin acts as reducing and capping agent. Formation of diosmin capped silver nanoparticles (Dios-AgNPs) was characterized using UV–vis spectroscopy, X- ray diffraction, TEM, Raman imaging and FTIR analysis. Investigations on the biosensing of Dios-AgNPs among various amino acids showed excellent response towards cysteine. Further a SPR based fiber optic sensor for cysteine was fabricated and its sensitivity, selectivity and limit of detection were investigated and reported. The fiber optic sensor was developed by coating a thin film of silver over the unclad core of the fiber and then coated with Dios-AgNPs. The sensor has advantages of low cost of production, fast response, high selectivity and sensitivity. The sensor can be used for online monitoring and remote sensing applications.
This investigation aimed to phytochemically characterize Ziziphora clinopodioides Lam. from 18 populations in XinJiang, China. Volatile components such as essential oils were analyzed using gas chromatography (GC) and GC-mass spectrometry, the contents of the total phenolic (TPC), flavonoid (TFC), triterpenoid (TTC), free amino acid (TFAAC) and polysaccharide (TPSC) were measured by visible spectrophotometry and the levels of caffeic acid, rosmarinic acid, diosmin, linarin, and pulegone were detected by high-performance liquid chromatography (HPLC). Next, the principal component analysis (PCA) and cluster analysis (CA) methods were used to analyze the genetic diversity of the Z. clinopodioides Lam. germplasm resources from XinJiang province according to the major chemical composition. According to the research, 6 principle components were extracted from the essential oils using PCA and the cumulative contribution rate reached 85.196%. According to CA, both the oils and 10 specific compositions of 18 samples could be classified into 3 clusters and the classification results were broadly consistent with the regions. The results of this research will provide a reliable basis for resource distributions and quality evaluations of Z. clinopodioides Lam.
Enhanced dopaminergic activity in rodents has been shown to lead to locomotor hyperactivity. MK-801, an NMDA (N-methyl-D-aspartate) receptor antagonist, indirectly activates dopaminergic activity in humans and rodents, and has the ability to induce locomotor hyperactivity. Abnormalities in locomotor activity are a prominent feature in the positive symptoms of schizophrenia. We showed here that the citrus flavonoid 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) has a protective effect on hyperactivity induced by MK-801 in the Y-maze test and open field test. These results suggest that HMF has the ability to relieve MK-801-induced schizophrenia positive symptom-like behavior.
Licorice, one of the oldest and most common herbal medicines, is used as a natural sweetener and flavoring agent in food products. This study aimed to investigate the inhibitory activity of flavonoids against α-glycosidase and protein tyrosine phosphatase 1B (PTP1B). Macroporous resins were used to isolate total flavonoids from licorice extract; the obtained total flavonoid content was >80%. The extracted flavonoids were then identified by HPLC-MS/MS, and 18 compounds were isolated. These compounds were further evaluated to determine α-glycosidase and PTP1B inhibitory activities. A total of 12 compounds demonstrated stronger activity than acarbose (IC50 = 5.42 ± 0.10 µg/mL); the compound 18 yielded higher IC50 (15.62 ± 0.20 µM) than NaVO4 (positive control; IC50 = 29.10 ± 0.20 µM). These results suggested that flavonoids from licorice are potential functional food ingredients that can be used to prevent and treat type 2 diabetes mellitus.
Flavonoids composition of Chinese bayberry (Myrica rubra Sieb. et Zucc.) pulp extracts was characterized by LC-ESI-Q-TOF-MS and quantification of flavonoids in nine bayberry cultivars was carried out by HPLC. As a result, five flavonoids, i.e. cyanidin-3-O-glucoside (C-3-Glu), myricetin-3-O-rhamnoside (M-3-Rha), quercetin-3-O-galactoside (Q-3-Gal), quercetin-3-O-glucoside (Q-3-Glu), and quercetin-3-O-rhamnoside (Q-3-Rha) were identified and quantified. The glucose consumption activities of nine bayberry cultivars varied significantly among cultivars and they were well correlated with their total phenolics, total flavonoids contents, and DPPH scavenging activities. In addition, C-3-Glu and three quercetin-3-O-glycosides (Q-3-Glys, i.e. Q-3-Gal, Q-3-Glu, and Q-3-Rha), but not M-3-Rha, showed significant enhancement of glucose consumption in HepG2 cells. There were significant correlations between the glucose consumption activity with the contents of C-3-Glu and the sum of three Q-3-Glys, respectively. These results showed that bayberry cultivars with high content of C-3-Glu and Q-3-Glys may have great potential as hypoglycemic foods.
The ability of thymol to attenuate the altered lipid metabolism by inhibiting tachycardia, altered electrocardiogram, apoptosis and cardiac hypertrophy in isoproterenol induced myocardial infarcted rats was evaluated. Rats were pre-and co-treated with thymol (7.5 mg/kg) for a period of 7 days. Isoproterenol (100 mg/kg) was injected subcutaneously into rats at an interval of 24 h for two days (6th and 7th day) to induce myocardial infarction. Isoproterenol induced rats showed increased levels of serum cardiac troponins, heart weight, left ventricular hypertrophy, elevated ST segments and tachycardia with increased levels of serum and heart lipids, alterations in the levels/activities of lipoproteins and lipid marker enzymes. Furthermore, isoproterenol induced myocardial infarcted rats showed a decrease in the expression of myocardial B-cell leukemia/lymphoma-2 (bcl-2) gene and an increase in the expression of myocardial bcl-2 associated-x (bax)-gene. Thymol pre-and co-treatment showed significant protective effects on all the biochemical parameters and molecular mechanisms studied. The in vitro studies confirmed its potent free radical scavenging effect. Thus, thymol attenuates the altered lipid metabolism by its antitachycardial, antihypertrophic, anti-apoptotic and antihyperlipidemic effects in isoproterenol induced myocardial infarcted rats.
Several factors may be responsible for the high prevalence of atherosclerosis in diabetes mellitus, including alterations in reverse cholesterol transport. In the present study, the activity of plasma lecithin: cholesterol acyltransferase (LCAT) and the cholesteryl ester transfer rate, and concentrations of lipids and lipoproteins were measured in 11 patients with insulin-dependent diabetes mellitus (type 1), 42 patients with non-insulin-dependent diabetes mellitus (type 2) and compared with those in age-matched control groups (Control 1, n = 14; and Control 11, n = 29, respectively). No statistically significant differences were observed in plasma total cholesterol, triglyceride, ester cholesterol or very low density lipoprotein (VLDL)-cholesterol concentrations between the diabetic and control groups. High density lipoprotein (HDL)- and HDL2-cholesterol levels were significantly lower in the diabetic patients. Plasma free cholesterol and low density lipoprotein (LDL)-cholesterol concentrations were higher in the type 2 diabetics than in the control subjects. LCAT activity was significantly lower in both groups of diabetic patients than in the control groups. The mass of cholesteryl ester transferred from HDL to VLDL + LDL was significantly greater in the diabetic groups than in the controls. In conclusion, the decrease in LCAT activity and the increase in cholesteryl ester transfer observed with both type 1 and type 2 diabetics could affect the reverse cholesterol transport of HDL and contribute to the development of atherosclerosis in diabetes.
Tumour necrosis factor-α (TNF-α) plays a pivotal role in cellular insulin resistance and can induce insulin resistance in mouse FL83B hepatocytes. Caffeic acid and cinnamic acid were found to improve glucose uptake in TNF-α-treated insulin-resistant mouse FL83B hepatocytes. The mechanism of glucose metabolism by caffeic acid and cinnamic acid was further investigated. The result from Western blot analysis revealed that caffeic acid and cinnamic acid increased expression of glycogen synthase, whereas the expression of glycogen synthase kinase and phosphorylation of glycogen synthase at Ser641 in insulin-resistant mouse hepatocytes was decreased. Caffeic acid and cinnamic acid suppressed the expression of hepatic nuclear factor-4 in TNF-α-treated mouse FL83B hepatocytes. The activity of phosphoenolpyruvate carboxykinase was also inhibited. Thus, caffeic acid and cinnamic acid ameliorated glucose metabolism by promoting glycogenesis and inhibiting gluconeogenesis in TNF-α-treated insulin-resistant mouse hepatocytes.
The effects of mate tea (MT) supplementation on LDL oxidisability and oxidative stress biomarkers in normolipidaemic and hyperlipidaemic volunteers after 60days of ingestion were investigated. A total of 60 volunteers, of whom 18 were hyperlipidaemic and 42 were normolipidaemic, ingested 200ml of MT (12.5mg/ml) per day. The oxidative stress was evaluated by means of comet assay analysis, serum total antioxidant status (TAS), lipid peroxidation products evaluated by thiobarbituric acid reactive substances (TBARS) in serum, enzymatic activity of the erythrocytes Cu–Zn superoxide dismutase (Cu–Zn SOD) and glutathione peroxidase (GSH-Px), and susceptibility to copper-induced in vitro oxidation of LDL was monitored by diene conjugates. It was observed that hyperlipidaemia caused an increase in lipid peroxidation products (P
In India, Adenanthera pavonina is traditionally used in the treatment of diabetes mellitus and lipid disorders. In the present study, the antihyperglycaemic and lipid lowering effect of Adenanthera pavonina seed aqueous extract (APSAE) was evaluated using streptozotocin induced diabetes in rats. Streptozotocin was given at the dose of 55 mg/kg, i.p. After induction of diabetes, APSAE was administered for 30 days p. o. and simultaneously different biochemical parameters like plasma glucose, HbA1c, serum triglyceride, cholesterol, LDL-cholesterol and HDL-cholesterol were estimated. Diabetic control showed significant increase (P < 0.01) in plasma glucose, serum triglyceride, cholesterol, LDL-cholesterol and significant decrease (P < 0.01) in serum HDL-cholesterol and HbA1c. Treatment with APSAE showed significant reduction (P < 0.01) in plasma glucose when compared with diabetic control. The elevated levels of serum triglyceride and cholesterol levels were significantly reduced (P < 0.01) by APSAE. APSAE treatment for 30 days showed significant decrease in serum LDL-cholesterol (P < 0.01) and significant increase in serum HDL cholesterol level (P < 0.01). Moreover, diabetic control there was significant decrease in HbA1c which was significantly increased (P < 0.05) by treatment with APSAE. Hence, from the result obtained in the present study it can be confirmed that Adenanthera pavonina has the potential to treat diabetes condition and associated lipid disorders.
A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL) level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT) plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.
Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme that catalyzes the esterification of free cholesterol in plasma lipoproteins and plays a critical role in high-density lipoprotein (HDL) metabolism. Deficiency leads to accumulation of nascent preβ-HDL due to impaired maturation of HDL particles, whereas enhanced expression is associated with the formation of large, apoE-rich HDL(1) particles. In addition to its function in HDL metabolism, LCAT was believed to be an important driving force behind macrophage reverse cholesterol transport (RCT) and, therefore, has been a subject of great interest in cardiovascular research since its discovery in 1962. Although half a century has passed, the importance of LCAT for atheroprotection is still under intense debate. This review provides a comprehensive overview of the insights that have been gained in the past 50 years on the biochemistry of LCAT, the role of LCAT in lipoprotein metabolism and the pathogenesis of atherosclerosis in animal models, and its impact on cardiovascular disease in humans.
Epidemiological studies have shown an inverse relationship between dietary flavonoid intakes and cardiovascular diseases. Citrus fruits are the main winter fruits consumed in the Mediterranean diet, so they are the main source of dietary flavonoids. The possible beneficial effects are due, not only to the high amounts of vitamins and minerals, but also to the antioxidant properties of their flavonoids. Dietary flavonoids may help to supplement the body antioxidant defences against free radicals. These compounds’ possible beneficial effects are due to their antioxidant activity, which is related to the development of atherosclerosis and cancer, and to anti-inflammatory and antimicrobial activity. The present review summarizes the existing bibliography on biological and pharmacological studies of Citrus flavonoids, both in vitro and in vivo.
Santalum album Linn (Santalaceae), commonly known as Sandalwood is used traditionally for its antihyperlipidemic and diuretic activity.
This study investigated the antihyperglycemic and antihyperlipidemic effect of long-term oral administration of the Santalum album pet ether fraction in streptozotocin-induced diabetic rats.
Diabetes was induced by a single intraperitoneal injection of streptozotocin at 70 mg/kg body weight. Rats were treated with Santalum album pet ether fraction orally at a dose of 10 µg/kg body weight twice daily for 60 days. Metformin (30 mg/kg body weight) was used as positive control. Lipid profile and glycated hemoglobin were estimated. HPLC profiling of Santalum album pet ether fraction was carried out.
Treatment of diabetic rats for 60 days demonstrated reduction in blood glucose level by 140 mg/dl. Metformin treated group showed a decrease in blood glucose by 70 mg/dl, as against an increase in diabetic control group by 125 mg/dl. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 22, 31 and 44%, respectively, in treated diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) increased by 46%. In case of metformin, the values were 11, 29 and 15% respectively, while HDL increased by 7%. Significant improvement in atherogenic index from 267 to 139% was observed in treated rats.
Santalum album pet ether fraction has potential antihyperlipidemic activity that can help in overcoming insulin resistance.
Cardiovascular disease (CVD) risk in type 2 diabetes (T2DM) is only partially reduced by intensive glycemic control. Diabetic dyslipidemia is suggested to be an additional important contributor to CVD risk in T2DM. Multiple lipid lowering medications effectively reduce fasting LDL cholesterol and triglycerides concentrations and several of them routinely reduce CVD risk. However, in contemporary Western societies the vasculature is commonly exposed to prolonged postprandial hyperlipidemia. Metabolism of these postprandial carbohydrates and lipids yields multiple proatherogenic products. Even a transient increase in these factors may worsen vascular function and induces impaired endothelial dependent vasodilatation, a predictor of atherosclerosis and future cardiovascular events. There is a recent increased appreciation for the role of gut-derived incretin hormones in controlling the postprandial metabolic milieu. Incretin-based medications have been developed and are now used to control postprandial hyperglycemia in T2DM. Recent data indicate that these medications may also have profound effects on postprandial lipid metabolism and may favorably influence several cardiovascular functions. This review discusses (1) the postprandial state with special emphasis on postprandial lipid metabolism and its role in endothelial dysfunction and cardiovascular risk, (2) the ability of incretins to modulate postprandial hyperlipidemia and (3) the potential of incretin-based therapeutic strategies to improve vascular function and reduce CVD risk.
The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain.
We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene.
The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group.
Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.)
A simple and rapid mixed-phase method for the quantitative assay of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and a procedure for the efficient reactivation of Mg-ATP-inactivated microsomal HMG-CoA reductase by potato acid phosphatase are described. The mixed-phase assay entails the direct addition of the acidified, deproteinized incubation mixture to a toluene-based scintillation fluor. The enzymatic reaction product [3H]-mevalonolactone partitions into the toluene while unreacted 3H-labeled HMG-CoA substrate remains in the aqueous phase and is not detected on scintillation counting. The accuracy and reproducibility of this method are compared to a thin-layer chromatographic assay for HMG-CoA reductase. Microsomal and solubilized HMG-CoA reductase inactivated by incubation with Mg-ATP is reactivated by purified potato acid phosphatase. Under appropriate conditions quantitative reactivation of HMG-CoA reductase is achieved, indicating that endogenous inhibitory and activating proteins regulate HMG-CoA reductase via a kinase-phosphatase system.
Development of the lipase gene family spans the change in science that witnessed the birth of contemporary techniques of molecular biology. Amino acid sequencing of enzymes gave way to cDNA cloning and gene organization, augmented by in vitro expression systems and crystallization. This review traces the origins and highlights the functional significance of the lipase gene family, overlaid on the background of this technical revolution. The gene family initially consisted of three mammalian lipases [pancreatic lipase (PL), lipoprotein lipase, and hepatic lipase] based on amino acid sequence similarity and gene organization. Family size increased when several proteins were subsequently added based on amino acid homology, including PL-related proteins 1 and 2, phosphatidylserine phospholipase A1, and endothelial lipase. The physiological function of each of the members is discussed as well as the region responsible for lipase properties such as enzymatic activity, substrate binding, heparin binding, and cofactor interaction.
Crystallization of several lipase gene family members established that the family belongs to a superfamily of enzymes, which includes esterases and thioesterases. This superfamily is related by tertiary structure, rather than amino acid sequence, and represents one of the most populous families found in nature.
Thiazolidinediones lower lipids, but it is unclear whether this is essential for their insulin-sensitizing action. We investigated relationships between lipid-lowering and insulin-sensitizing actions of a thiazolidinedione. Normal rats were pretreated with or without Pioglitazone (Pio, 3 mg/kg.d) for 2 wk. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp with elevation of free fatty acids (FFA) by Intralipid/heparin infusion over 6 h. In untreated rats insulin sensitivity decreased by 46% over 3-6 h of elevated FFA, whereas it remained normal but with a 50% increase in FFA clearance in Pio-treated rats. After matching plasma FFA, insulin sensitivity was still partially (30%) protected in Pio-treated rats, substantially by maintaining insulin suppressibility of hepatic glucose output. This was associated with lower hepatic long-chain acyl-coenzyme A. Plasma adiponectin was increased 2-fold in Pio-treated rats and was negatively correlated with hepatic glucose output (r2 = 0.70, P < 0.001) and liver long-chain acyl-coenzyme A (r2 = 0.39, P < 0.005). Pio-induced muscle insulin sensitization was largely diminished after matching plasma FFA elevation, but insulin-stimulated protein kinase B phosphorylation was protected. We conclude that thiazolidinediones can protect against lipid-induced insulin resistance with a significant component (mainly liver) of the protective effect not requiring lipid lowering. This may be related to chronic elevation of adiponectin by thiazolidinediones.
The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic clamps in 56 insulin sensitive (IS; mean +/- SD: GDR 15.8 +/- 2.0 mg. kg(-1). min(-1), fasting blood glucose [FBG] 4.7 +/- 0.3 mmol/l, BMI 26 +/- 5), 46 insulin resistant (IR; GDR 10.2 +/- 1.9, FBG 4.9 +/- 0.5, BMI 29 +/- 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 +/- 2.8, FBG 10.8 +/- 3.7, BMI 30 +/- 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size (r = -0.40) and an increase in large VLDL particle concentrations (r = -0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = -0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = -0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = -0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides; a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS versus diabetes) in LDL cholesterol; and a decrease in large cardioprotective HDL combined with an increase in the small HDL subclass such that there was no net significant difference in HDL cholesterol. We conclude that 1) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR; 2) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance; and 3) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NMR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS.
The liver exchanges high fluxes of glucose and free fatty acids (FFA) and is one main site of their reciprocal regulation. Acute exposure to hyperglycemia and hyperinsulinemia has been shown to reduce splanchnic beta-oxidation in healthy humans. We investigated whether a spontaneous condition of chronic mild hyperglycemia and hyperinsulinemia affects liver FFA uptake. Hepatic FFA influx rate constant (LKi) was measured after a 12-15-h fast in 10 patients with impaired glucose tolerance (IGT) and eight control subjects using positron emission tomography in combination with the long-chain FFA analog 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Compared with controls, IGT patients had higher serum insulin, glucose, and triglyceride levels (1.71 +/- 0.24 vs. 0.59 +/- 0.06 mmol/liter, P < 0.001), lower high-density lipoprotein (1.04 +/- 0.11 vs. 1.42 +/- 0.13 mmol/liter, P < 0.05), and similar FFA levels (0.59 +/- 0.06 vs. 0.56 +/- 0.05 mmol/liter(-1), P = not significant). LKi was significantly reduced in IGT (0.288 +/- 0.014 min(-1)) compared with control subjects (0.341 +/- 0.014 min(-1), P < 0.02). LKi was negatively correlated with plasma glucose (r = 0.51, P < 0.03), glycosylated hemoglobin (r = 0.55, P < 0.02), and blood lactate levels (r = 0.52, P < 0.03). We conclude that, in IGT patients, the ability of the liver to extract FFA from the circulation appears to be impaired. The reciprocal relationship between hepatic FFA extraction and glucose/lactate flux may derive from intrahepatic substrate competition.
The focus of this review is to explain the clinical significance of laboratory markers that are not used routinely, as well as standard laboratory tests (triglycerides, cholesterol, HDL, and LDL) to evaluate cardiovascular disease risk. Cardiovascular disease is the number one killer in the United States. According to national statistics, there are over 40 million people (men and women) that suffer with symptoms of heart disease. The current medical interventions in cases of advanced cardiovascular disease are Percutaneous Transluminal Coronary Angioplasty (PCTA) and Coronary Bypass Graft (CABG).The number of performed PCTA and CABG procedures can be drastically reduced if clinically-significant preventive risk markers are used coupled with appropriately designed therapeutics. The clinical significance of the following risk markers will be discussed in this review: Homocysteine, Lipoprotein (a), Fibrinogen, Lipid Peroxide. Anti-oxidative LDL antibody. Trialvceride, Total Cholesterol, LDL, VLDL and HOL.
Type 2 diabetes mellitus (T2DM) being a worldwide challenge to public health. The aim of this study was to examine the effect of esculetin, a major compound present in the herbal plant of Matricaria chamomilla L., on the key enzymes of carbohydrate metabolism in streptozotocin (STZ) induced diabetic rats. At first, the rats were induced intraperitonial injection of STZ (40 mg/kg bw) to attain diabetes and were then treated with different concentrations of esculetin (10, 20 and 40 mg/kg bw) for 45 days. The diabetic rats had elevated levels of plasma glucose and glycated haemoglobin (HbA1c) and decreased plasma insulin and haemoglobin (Hb) levels. Food intake, water intake and oral glucose tolerance test were also measured. Activities of carbohydrate metabolic enzymes such as glucose-6-phosphatase, fructose 1,6-bisphosphatase increased and glucokinase, glucose-6-phosphate dehydrogenase decreased significantly. Oral administration of esculetin significantly decreased the levels of plasma glucose, HbA1c and increased the levels of Hb and insulin. The activities of the key enzymes such as glucokinase and glucose-6-phosphate dehydrogenase had significantly increased whereas, glucose-6-phosphatase and fructose-1,6-bisphosphatase had significantly decreased. Further, protection against body weight loss of diabetic rats was observed. Among the three doses, 40 mg/kg bw of esculetin exerted a more pronounced antihyperglycemic effect against STZ-induced diabetic rats.
Elevated cholesterol and triacylglycerol levels are known risk factors for cardiovascular diseases. A number of animal studies have indicated that the consumption of oyster mushrooms (Pleurotus ostreatus) can positively influence the lipid profile. The present intervention study for the first time investigated the cholesterol lowering properties of an oyster mushroom diet in humans. A total of 20 subjects (9 male, 11 female; 20–34years) were randomized to take either one portion of soup containing 30g dried oyster mushrooms or a tomato soup as a placebo on a daily basis for 21days. Standardized blood concentrations of lipid parameters and oxidized low density lipoprotein were measured at the baseline (t0) and after 21days (t21). Treatment with oyster mushroom soup decreased triacylglycerol concentrations (−0.44mmol/L; p=0.015) and oxidized low density lipoprotein levels (−7.2U/mL; p=0.013) significantly, and showed a significant tendency in lowering total cholesterol values (−0.47mmol/L; p=0.059). No effects on low density lipoprotein and high density lipoprotein levels were found. The beneficial effects of oyster mushroom on blood serum parameters may be attributed to the presence of linoleic acid, ergosterol and ergosta-derivatives which showed notable activity in oxygen radical absorbance capacity and cyclooxygenase inhibition assays in vitro.
The aim of this study was to determine the effects of Ajuga iva aqueous extract on lecithin : cholesterol acyltransferase (LCAT) activity and amount and composition of high-density lipoprotein (HDL)(2) and (HDL)(3), in streptozotocin (STZ)-induced diabetic rats.
Diabetes was induced in male Wistar rats by intraperitoneal injection of STZ (60 mg/kg body weight). Diabetic rats (n = 12) were divided into two groups. The diabetic control group (D) received a 20% casein diet and the diabetic treated group received the same diet supplemented with A. iva aqueous extract (0.5 g/100 g diet) (DAi), for 4 weeks.
Total cholesterol and HDL(3) -C were respectively decreased by 32% and 55% in the DAi group compared with the D group, whereas HDL(2)-C was increased by 30%. The amounts of HDL(2) and HDL(3), which were the sum of apolipoproteins, unesterified cholesterol (UC), cholesteryl esters (CEs), triacylglycerols (TGs) and phospholipids (PLs), showed no significant difference. A. iva treatment increased LCAT by 33% and its cofactor-activator, apolipoprotein A-I, by 58%. HDL(3)-PL (enzyme substrate) and HDL(3)-UC (acyl group acceptor) were respectively decreased by 70% and 57%, whereas HDL(2)-CE (product of LCAT reaction) was enhanced by 30%.
In STZ-induced diabetic rats, A. iva improves reverse cholesterol transport by enhancing LCAT activity, leading to anti-atherogenic effects.
A method is described for the routine determination of free fatty acids (FFA) in plasma. The extraction medium used contains chloroform-heptane-methanol mixture with a phosphate buffer. This extraction mixture gives a sufficient extraction of FFA from serum and contamination with interfering agents is avoided. The copper soaps of FFA are determined colorimetrically with diphenylcarbazide. The recovery of free fatty acids is 100.4%. The standard deviation of double determinations is 0.013 mmoles per litre. The reference range calculated from 50 normal persons of varying age is 0.100 to 0.660 mmoles per litre.
This article reviews recent major efforts towards understanding the importance of carbohydrate chains for the physiological functioning of lecithin-cholesterol acyltransferase (LCAT), the plasma enzyme which esterifies cholesterol. The assembly of oligosaccharide chains in protein backbones is the most extensive of all the post-translational modifications, and can play a crucial role in protein folding, oligomer assembly and secretion, in regulating biological activity, as well as in clearance of glycoproteins from the bloodstream. Here, we describe modifications in LCAT-linked carbohydrate structures, arising from site-directed mutagenesis or from use of drugs and specific enzymes, which modify either the structure or the assembly of LCAT glycans, and evaluate how these help define their involvement in and importance to enzyme secretion, stability and activity.
Oxidative stress has been suggested as a contributory factor in development and complication of diabetes. The aim of the study was to evaluate the effect of diosmin (DS) in oxidative stress in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats by measuring the lipid peroxidation (LPO) as well as the ameliorative properties. Experimental diabetes was induced by a single intraperitoneal (i.p) injection of STZ (45 mg/kg body weight (b.w.)) dissolved in 0.1 mol/L citrate buffer (pH 4.5), 15 min after the i.p administration of NA (110 mg/kg b.w.). Diabetic rats exhibited increased plasma glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with DS (100mg/kg/day) for a period of 45 days showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that DS has potential ameliorative effects in addition to its antidiabetic effect in type 2 diabetic rats.
We took advantage of the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create a new experimental diabetic syndrome in adult rats that appears closer to NIDDM than other available animal models with regard to insulin responsiveness to glucose and sulfonylureas. Among the various dosages of nicotinamide tested in 3-month-old Wistar rats (100-350 mg/kg body wt), the dosage of 230 mg/kg, given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded a maximum of animals with moderate and stable nonfasting hyperglycemia (155 +/- 3 vs. 121 +/- 3 mg/dl in controls; P < 0.05) and 40% preservation of pancreatic insulin stores. We also evaluated beta-cell function both in vitro and in vivo 4-9 weeks after inducing diabetes. In the isolated perfused pancreas, insulin response to glucose elevation (5-11 mmol/l) was clearly present, although significantly reduced with respect to controls (P < 0.01). Moreover, the insulin response to tolbutamide (0.19 mmol/l) was similar to that observed in normal pancreases. Perfused pancreases from diabetic animals also exhibited a striking hypersensitivity to arginine infusion (7 mmol/l). In rats administered STZ plus nicotinamide, intravenous glucose tolerance tests revealed clear abnormalities in glucose tolerance and insulin responsiveness, which were interestingly reversed by tolbutamide administration (40 mg/kg i.v.). In conclusion, this novel NIDDM syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM in that it has a significant response to glucose (although abnormal in kinetics) and preserved sensitivity to tolbutamide, may provide a particularly advantageous tool for pharmacological investigations of new insulinotropic agents.
Diabetes mellitus is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. The present study was carried out to evaluate the effects of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) alone and in combination on alterations in lipids, lipoproteins and enzymes involved in lipid metabolism in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. A significant (p<0.05) increase in the concentrations of plasma and tissue (liver and kidney) lipids (cholesterol, triglycerides (TGs), free fatty acids (FFAs) and phospholipids (PLs)) and low density and very low-density lipoproteins (LDL and VLDL), and a decrease in the concentration of high-density lipoproteins (HDL) were noticed in STZ administered diabetic rats. In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly (p<0.05) in the liver and kidney whereas the activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly (p<0.05) in the plasma of diabetic rats. Combined administration of CGA (5mg/kg b.w.) and THC (80mg/kg b.w.) for 45 days remarkably reduced the STZ-induced changes in lipids, lipoproteins and lipid metabolising enzymes when compared to the effects of CGA or THC alone in diabetic rats. These results indicate that combination of THC and CGA can potentially ameliorate lipid abnormalities in experimental type 2 diabetes.
The purpose of this study was to investigate the effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Diosmin was administered to streptozotocin-induced (45 mg/kg b.w) diabetic rats at different doses (25, 50, 100 mg/kg b.w) for 45 days to assess its effect on fasting plasma glucose, insulin, glycosylated hemoglobin, hemoglobin and carbohydrate metabolic enzymes, it was found that plasma glucose was significantly reduced in a dose-dependent manner when compared to the diabetic control. In addition, oral administration of diosmin (100mg/kg b.w) significantly decreased glycosylated hemoglobin and increased hemoglobin and plasma insulin. The activities of the hepatic key enzymes such as hexokinase and glucose-6-phosphate dehydrogenase were significantly increased whereas, glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly decreased. Furthermore, protection against body weight loss of diabetic animals was also observed. These results showed that diosmin has potential antihyperglycemic activity in streptozotocin-nicotinamide-induced diabetic rats.
We estimated the number of people worldwide with diabetes for the years 2010 and 2030.
Studies from 91 countries were used to calculate age- and sex-specific diabetes prevalences, which were applied to national population estimates, to determine national diabetes prevalences for all 216 countries for 2010 and 2030. Studies were identified using Medline, and contact with all national and regional International Diabetes Federation offices. Studies were included if diabetes prevalence was assessed using a population-based methodology, and was based on World Health Organization or American Diabetes Association diagnostic criteria for at least three separate age-groups within the 20-79 year range. Self-report or registry data were used if blood glucose assessment was not available.
The world prevalence of diabetes among adults (aged 20-79 years) will be 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7%, and 439 million adults by 2030. Between 2010 and 2030, there will be a 69% increase in numbers of adults with diabetes in developing countries and a 20% increase in developed countries.
These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries.
Diosmetin (3',5,7-trihydroxy-4'-methoxyflavone) is the aglycone of the flavonoid glycoside diosmin (3',5,7-trihydroxy-4'-methoxyflavone-7-ramnoglucoside). Diosmin is hydrolyzed by enzymes of intestinal micro flora before absorption of its aglycone diosmetin. A specific, sensitive, precise, accurate and robust HPLC assay for the simultaneous determination of diosmin and diosmetin in human plasma was developed and validated. Plasma samples were incubated with beta-glucuronidase/sulphatase. The analytes were isolated by liquid-liquid extraction with tert-butyl methyl ether at pH 2, and separated on a C(18) reversed-phase column using a mixture of methanol/1% formic acid (58:42, v/v) at a flow rate of 0.5ml/min. APCI in the positive ion mode and multiple reaction monitoring (MRM) method was employed. The selected transitions for diosmin, diosmetin and the internal standard (7-ethoxycoumarin) at m/z were: 609.0-->463.0, 301.2-->286.1 and 191, respectively. A good linearity was found in the range of 0.25-500ng/ml (R(2)>0.992) for both compounds. The intra-batch assay precision (CV) for diosmin and diosmetin ranged from 1.5% to 11.2% and from 2.8% to 12.5%, respectively, and the inter-batch precision were from 5.2% to 11.5% and 8.5% to 9.8%, respectively. The accuracy was well within the acceptable range the accuracies (from -2.7% to 4.2% and -1.6% to 3.5% for diosmin and diosmetin, respectively). The mean recoveries of diosmin, diosmetin and the internal standard were 87.5%, 89.2% and 67.2%. Stability studies showed that diosmin and diosmetin were stable in different conditions. Finally, the method was successfully applied to the pharmacokinetic study of diosmin in healthy volunteers following a single oral administration (Daflon).
This paper describes a new microchromatographic method on Bio-Rex 70 ion-exchanger, which enables the isolation and quantitation of the minor components hemoglobin AIa+b and hemoglobin AIc. The method relies on the equilibration of the resin in a polyphosphate buffer with a pH closer to the pKa of the carboxylic group of the resin, and on the adjustment of the sample pH at 5. This induces linear pH and ionic strength gradient during the elution of the hemoglobin components. The method is little affected by temperature between 20 and 30 degrees C, by the presence of the aldimine Schiff base, and is not expected to be greatly influenced by moderate fluctuations in pH and ionic strength of the buffers used. There was good correlation between the values obtained by the new micromethod and four procedures currently used, namely high-performance liquid chromatography (r = 0.96), and Trivelli Bio-Rex 70 macromethod (r = 0.99), bioaffinity chromatography (r = 0.98), and Isolab hemoglobin AI kit (r = 0.91). The method is reproducible, the interassay and the intra-assay correlation coefficients did not exceed 4.2%. The mean value for hemoglobin AIc was 4.6 +/- 0.35% for eleven non-diabetics and 8.9 +/- 2.6% for twenty-one diabetics.
Plasma lipid, lipoprotein, and apolipoprotein levels were measured in 55 insulin-dependent diabetics (20 males and 35 females) before and after 2–3 wk of intensive insulin therapy in a metabolic unit.
At the time of discharge from the metabolic unit the levels of total, low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol as well as triglycerides, VLDL triglycerides, and apolipoprotein B (Apo B) were significantly decreased. Conversely, the levels of high-density lipoprotein (HDL) cholesterol, and apolipoprotein A1 (Apo A1) were significantly increased.
The data were further analyzed after subdividing the patients into two subgroups: (1) patients admitted in poor glycemic control (HbA1c > 11%) and (2) patients admitted in fair control (HbA1c < 11%). In the group admitted in poor control the changes in lipid and lipoprotein levels were similar to the ones found in the group of patients as a whole, while in patients admitted in fair control only the levels of total and VLDL triglycerides showed significant changes with control.
Patients' sex appeared to influence the magnitude of changes observed in HDL cholesterol and Apo A1, levels. In males a significant increase in both HDL cholesterol and Apo A1 was achieved after glycemic control either in the whole group or in the subgroup admitted in poor control. In the subgroup admitted in fair control HDL cholesterol levels rose but no significant change was observed in the Apo A1 levels. In females no significant change was observed with improved control in HDL cholesterol and Apo A1, either in the whole group or in the group admitted in fair control. A small but significant increase was detected in the HDL cholesterol levels of the female patients admitted in poor control, but no change was observed in the Apo A1 levels.
In conclusion, in insulin-dependent diabetics, normalization in plasma lipid, lipoprotein, and apolipoprotein levels was obtained after intensive insulin therapy.
Plasma lecithin:cholesterol acyltransferase (LCAT) has been measured by an enzymatic method. We did not observe any significant sex variations, but age variations were found. In females, LCAT activities are stable up to 40 years (60 mumol . 1.1 . h-1 at the 50th centile). Also, from 50 years the median increased progressively to 76 mumol . 1-1 . h-1. In males, the activity increased from 52 to 71 mumol . 1-1 . h-1 at the 50th centile in two age groups (15-20 years and 50 years). The effect of some xenobiotics on LCAT activity was studied. We observed an increase in activity of 33% in males when the daily alcoholic beverage consumption ranged from 0 to more than 0.5 litre of wine or beer. LCAT activity increased in children who were treated with hypolipidemic drugs (fenofibrate, Lipanthyl). In boys, the mean enzyme activity increased to 35% (p less than 0.05). The increase was greater in girls (75%, p less than 0.01). Treatment with anticonvulsant drugs gave a decrease in LCAT activity of 32-46%.