Hypocholesterolemic Effect of Blackcurrant (Ribes nigrum) Extract in Healthy Female Subjects: A Pilot Study.

Blackcurrant extract (BCE) ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can prevent lipid abnormalities in healthy individuals. Lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined the effects of BCE administered for 29 days on serum lipids in young healthy women. Blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in the serum were separated using a gel-permeation high-performance liquid chromatography method to measure the triacylglycerol and cholesterol levels in lipoproteins. There were no effects on lipids on day 4 of BCE intake, but the total cholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL) cholesterol, small VLDL cholesterol, and large low-density lipoprotein cholesterol were significantly decreased. These results suggest that the daily intake of BCE has a hypocholesterolemic effect in healthy women, and that it is effective in preventing atherosclerosis.

The Role of Essential Oils and Their Main Compounds in the Management of Cardiovascular Disease Risk Factors.

Cardiovascular diseases (CVDs) are a global health burden that greatly impact patient quality of life and account for a huge number of deaths worldwide. Despite current therapies, several side effects have been reported that compromise patient adherence; thus, affecting therapeutic benefits. In this context, plant metabolites, namely volatile extracts and compounds, have emerged as promising therapeutic agents. Indeed, these compounds, in addition to having beneficial bioactivities, are generally more amenable and present less side effects, allowing better patient tolerance. The present review is an updated compilation of the studies carried out in the last 20 years on the beneficial potential of essential oils, and their compounds, against major risk factors of CVDs. Overall, these metabolites show beneficial potential through a direct effect on these risk factors, namely hypertension, dyslipidemia and diabetes, or by acting on related targets, or exerting general cellular protection. In general, monoterpenic compounds are the most studied regarding hypotensive and anti-dyslipidemic/antidiabetic properties, whereas phenylpropanoids are very effective at avoiding platelet aggregation. Despite the number of studies performed, clinical trials are sparse and several aspects related to essential oil's features, namely volatility and chemical variability, need to be considered in order to guarantee their efficacy in a clinical setting.

Lipid Profile and Vascular Remodelling in Young Dyslipidemic Subjects Treated with Nutraceuticals Derived from Red Yeast Rice.

BACKGROUND AND AIMS: A relevant role is emerging for functional foods in cardiovascular prevention. The aim of this study was to assess the effect of a nutraceutical multitargeted approach on lipid profile and inflammatory markers along with vascular remodelling in a cohort of dyslipidemic subjects without history of cardiovascular (CV) disease. METHODS AND RESULTS: We enrolled 25 subjects (mean age 48.2 years) with low to moderate CV risk profile and total cholesterol (TC) levels between 150 and 250 mg/dl. The patients were assigned to receive for one year a tablet/die of a nutraceutical combination containing red yeast rice (RYR) extract (Monacolin 3 mg/tablet) and coenzyme Q10 (30 mg/tablet). Treatment with the nutraceutical compounds led to a significant reduction of TC (from 227 to 201 mg/dl, p < 0.001), LDL-c (from 150 to 130 mg/dl, p = 0.001), triglycerides (from 121 to 109 mg/dl, p = 0.013), non-HDL-cholesterol (from 168 to 141 mg/dl, p < 0.001), hs-CRP (from 1.74 to 1.20 mg/l, p = 0.015), and osteoprotegerin (from 1488 to 1328 pg/ml, p = 0.045). Levels of HDL-c, Lp(a), glucose, liver enzyme, CPK, or creatinine did not change over time. An ultrasound study was performed to assess changes in mean carotid intima-media thickness (IMT) and maximum IMT (M-MAX) as well as modification in local carotid stiffness by means of determining the carotid compliance coefficient (CC) and distensibility coefficient (DC). At the end of the treatment, we observed small but significant reductions in both mean-IMT (from 0.62 to 0.57 mm, p = 0.022) and M-MAX (from 0.79 to 0.73 mm, p = 0.002), and an improvement in carotid elasticity (DC from 22.4 to 24.3 × 10-3/kPa, p = 0.006 and CC from 0.77 to 0.85 mm2/kPa, p = 0.019). CONCLUSIONS: A long-term treatment with a combination of RYR and coenzyme Q10 showed lipid-lowering activity along with a reduction of inflammatory mediators and an improvement of vascular properties in young subjects with a low-to-moderate CV risk profile.

Effects of Danhong injection on dyslipidemia and cholesterol metabolism in high-fat diets fed rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI) is a Chinese medical injection applied to the clinical treatment of cardiovascular diseases that has anti-inflammatory, antiplatelet aggregation and antithrombotic effects. This study aimed to explore the effects of DHI on dyslipidemia and cholesterol metabolism in high-fat diet-fed rats. METHODS: Sprague Dawley (SD) rats were randomly divided into six groups: normal group (Normal); hyperlipidemia model group (Model); DHI-treated groups at doses of 1.0 mL/kg, 2.0 mL/kg, 4.0 mL/kg; and simvastatin positive control group (2.0 mg/kg). The hypolipidemic effects of DHI were evaluated by measuring serum lipid levels, hepatic function and oxidative stress, respectively. And pathological changes in liver tissues were determined using hematoxylin-eosin (H&E) and oil red O staining. Moreover, the mRNA and protein expression levels of cholesterol metabolism related genes were detected by real-time PCR (RT-PCR) and Western blot. RESULTS: Compared with the Model group, DHI treatment markedly decreased the liver index and improved the pathological morphology of liver tissues. DHI treatment dose-dependently decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and free fatty acids (FFA) in serum or liver tissues (P < 0.01 or P < 0.05), and increased the high-density lipoprotein cholesterol (HDL-C) and tripeptide glutathione (GSH) (P < 0.01 or P < 0.05). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in the DHI-treated groups (P < 0.01 or P < 0.05), while the alanine transaminase (ALT) and aspartate transaminase (AST) were decreased (P < 0.01 or P < 0.05). Furthermore, the expression levels of LDL receptor (LDLR), cholesterol 7-α-hydroxylase (CYP7A1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor α (PPARα) were dose-dependently upregulated in the DHI-treated groups, whereas the expression of sterol regulatory element-binding protein-2 (SREBP-2) was downregulated. CONCLUSIONS: Our study demonstrated that DHI markedly ameliorated hyperlipidemia rats by regulating serum lipid levels, inhibiting hepatic lipid accumulation and steatosis, improving hepatic dysfunction, and reducing oxidative stress. The potential mechanism was also tentatively investigated and may be related to the promotion of bile acid synthesis via activation of the PPARα-LXRα-CYP7A1 pathway. Therefore, DHI could be regarded as a potential hypolipidemic drug for the treatment of hyperlipidemia.

An update on vascular calcification and potential therapeutics.

Pathological calcification is a major cause of cardiovascular morbidities primarily in population with chronic kidney disease (CKD), end stage renal diseases (ERSD) and metabolic disorders. Investigators have accepted the fact that vascular calcification is not a passive process but a highly complex, cell mediated, active process in patients with cardiovascular disease (CVD) resulting from, metabolic insults of bone fragility, diabetes, hypertension, dyslipidemia and atherosclerosis. Over the years, studies have revealed various mechanisms of vascular calcification like induction of bone formation, apoptosis, alteration in Ca-P balance and loss of inhibition. Novel clinical studies targeting cellular mechanisms of calcification provide promising and potential avenues for drug development. The interventions include phosphate binders, sodium thiosulphate, vitamin K, calcimimetics, vitamin D, bisphosphonates, Myoinositol hexaphosphate (IP6), Denosumab and TNAP inhibitors. Concurrently investigators are also working towards reversing or curing pathological calcification. This review focuses on the relationship of vascular calcification to clinical diseases, regulators and factors causing calcification including genetics which have been identified. At present, there is lack of any significant preventive measures for calcifications and hence this review explores further possibilities for drug development and treatment modalities.

Vildagliptin, a dipeptidyl peptidase-4 inhibitor, reduces betel-nut induced carcinogenesis in female mice.

AIM: Betel-nut, a popular masticatory among Southeast Asian populations is a class I carcinogen, previously associated with dyslipidemia and aberrant lipid metabolism, and is reported to be used more frequently by females, than males. This study investigates the potential of repurposing the anti-diabetic drug, vildagliptin, a dipeptidyl peptidase-4 inhibitor, for alleviating the oncogenic condition in female Swiss Albino mice administered an aqueous extract of betel-nut (AEBN) orally (2 mg ml-1) for 24 weeks. MAIN METHODS: Tissues were investigated by histopathological, immunohistochemical and apoptosis assays. Biochemical analyses of oxidative stress markers and lipid profile were performed using different tissues and sera. The expressions of different proteins involved in lipid metabolism and oncogenic pathways were evaluated by Western blotting. KEY FINDINGS: AEBN induced carcinogenesis primarily in the liver by significantly impairing AMPK signaling, inducing oxidative stress, activating Akt/mTOR signaling, increasing Ki-67 immunoreactivity and cyclin D1 expression, and significantly diminishing apoptosis. Co-administration of AEBN with vildagliptin (10 mg kg-1 body weight) for 8 weeks reduced liver dysplasia, and significantly decreased free palmitic acid, increased free oleic acid, normalized lipid profile, decreased oxidative stress, cyclin D1 expression, Ki-67 immunoreactivity, and Bcl2 expression, and increased the ratio of apoptotic/non-apoptotic cells. Mechanistically, vildagliptin elicited these physiological and molecular alterations by restoring normal AMPK signaling and reducing the cellular expressions of FASN and HMGCR, restoring AMPK-dependent phosphorylation of p53 at Ser-15 and reducing Akt/mTOR signaling. SIGNIFICANCE: These results indicate that vildagliptin may alleviate betel-nut induced carcinogenesis in the liver of female mice.

Matcha Improves Metabolic Imbalance-Induced Cognitive Dysfunction.

This study was conducted to assess the protective effect of extract of match (EM) on high-fat diet- (HFD-) induced cognitive deficits in male C57BL/6 mice. It was found that EM improved glucose tolerance status by measuring OGTT and IPGTT with HFD-induced mice. EM protected behavioral and memory dysfunction in Y-maze, passive avoidance, and Morris water maze tests. Consumption of EM reduced fat mass, dyslipidemia, and inflammation in adipose tissue. Also, EM ameliorated hepatic and cerebral antioxidant systems. EM improved the cerebral cholinergic system by regulating ACh contents and expression of AChE and ChAT. Also, EM restored mitochondrial function in liver and brain tissue. EM attenuated hepatic inflammatory effect, lipid synthesis, and cholesterol metabolism by regulating the protein expression of TNF-α, TNFR1, p-IRS-1, p-JNK, IL-1ß, iNOS, COX-2, HMGCR, PPARγ, and FAS. Finally, EM regulated cognitive function and neuroinflammation in the whole brain, hippocampus, and cerebral cortex by regulating the protein expression of p-JNK, p-Akt, p-tau, Aß, BDNF, IDE, COX-2, and IL-1ß. These findings suggest that EM might be a potential source of functional food to improve metabolic disorder-associated cognitive dysfunction.

Modulation of mitochondria and NADPH oxidase function by the nitrate-nitrite-NO pathway in metabolic disease with focus on type 2 diabetes.

Mitochondria play fundamental role in maintaining cellular metabolic homeostasis, and metabolic disorders including type 2 diabetes (T2D) have been associated with mitochondrial dysfunction. Pathophysiological mechanisms are coupled to increased production of reactive oxygen species and oxidative stress, together with reduced bioactivity/signaling of nitric oxide (NO). Novel strategies restoring these abnormalities may have therapeutic potential in order to prevent or even treat T2D and associated cardiovascular and renal co-morbidities. A diet rich in green leafy vegetables, which contains high concentrations of inorganic nitrate, has been shown to reduce the risk of T2D. To this regard research has shown that in addition to the classical NO synthase (NOS) dependent pathway, nitrate from our diet can work as an alternative precursor for NO and other bioactive nitrogen oxide species via serial reductions of nitrate (i.e. nitrate-nitrite-NO pathway). This non-conventional pathway may act as an efficient back-up system during various pathological conditions when the endogenous NOS system is compromised (e.g. acidemia, hypoxia, ischemia, aging, oxidative stress). A number of experimental studies have demonstrated protective effects of nitrate supplementation in models of obesity, metabolic syndrome and T2D. Recently, attention has been directed towards the effects of nitrate/nitrite on mitochondrial functions including beiging/browning of white adipose tissue, PGC-1α and SIRT3 dependent AMPK activation, GLUT4 translocation and mitochondrial fusion-dependent improvements in glucose homeostasis, as well as dampening of NADPH oxidase activity. In this review, we examine recent research related to the effects of bioactive nitrogen oxide species on mitochondrial function with emphasis on T2D.

Promising therapeutic use of Baccharis trimera (less.) DC. as a natural hepatoprotective agent against hepatic lesions that are caused by multiple risk factors.

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC is a perennial subshrub, popularly known as "carqueja," that belongs to the Asteraceae family. Ethnobotanical studies indicate that this species is used for the treatment of diabetes and digestive and liver diseases. However, studies that sought to validate its popular use were conducted using ethanolic extracts of the plant, which does not reflect the ethnomedicinal use of this species in humans. AIM OF THE STUDY: Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the liver that can progress to cirrhosis and hepatocellular carcinoma. Because of the severity of this disease, less toxic and more effective therapeutic agents need to be developed. B. trimera may be a promising therapeutic alternative, but its activity against multiple risk factors for liver disease (e.g., smoking, dyslipidemia, and diabetes mellitus) has not been studied. The present study investigated the effects of an ethnomedicinal form of a B. trimera preparation in a rat model of NAFLD that is associated with multiple risk factors. MATERIAL AND METHODS: Phytochemical analysis of the ethanolic soluble fraction of B. trimera extract was performed using ultra-performance liquid chromatography coupled to high-resolution mass spectrometry. Streptozotocin was used to induce diabetes in male Wistar rats. The rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day, 5 days/week, for 4 weeks). In the last 2 weeks, the animals were orally treated with vehicle (negative control group), B. trimera extract (30, 100, and 300 mg/kg), or insulin + simvastatin. One group of rats that was not exposed to these risk factors was also evaluated. Blood was collected for glucose, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) analysis. The liver and feces were collected for lipid quantification. The liver was additionally processed for histopathological analysis. RESULTS: The model successfully induced NAFLD and increased levels of glucose, AST, and ALT in the negative control group. Treatment with the B. trimera extract (30 and 100 mg/kg) and insulin + simvastatin decreased hepatic and fecal lipids. In contrast to insulin + simvastatin treatment, all three doses of B. trimera effectively reduced AST and ALT levels. CONCLUSION: B. trimera may be promising as a hepatoprotective agent against hepatic lesions that are caused by multiple risk factors.

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells.

Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.

Tissue lipocalin-2 in psoriasis: is it a marker of metabolic disturbance or a possible marker of therapeutic efficacy after narrow band ultraviolet B?

Background: Lipocalin-2 (LCN2) is an adipokine related to insulin resistance and metabolic syndrome (MetS) in addition to its role in innate immunity and apoptosis.Objective: To estimate LCN2 tissue levels (lesional and non-lesional) in psoriasis. To assess the metabolic status of patients and to detect any possible associations between LCN2 and MetS. To evaluate the effect of narrow-band ultraviolet B (NBUVB) on tissue LCN2 in psoriasis.Methods: This case-control study was conducted on 25 psoriatic patients and 25 healthy controls. Dyslipidemia and MetS have been evaluated. Tissue LCN2 was estimated using ELISA technique before and after treatment with NBUVB.Results: Tissue LCN2 was significantly higher in psoriasis, with no significant difference as regards dyslipidemia or metabolic disturbance in these patients. Both lesional and non-lesional LCN2 and PASI score dropped significantly after NBUVB. No significant correlations have been detected between tissue LCN2 and disease extent or PASI score. Significant positive correlations were detected regarding tissue LCN2 levels between lesional and non-lesional samples before and after treatment.Conclusions: Psoriatic patients were at higher risk of metabolic disorders. LCN2 was not related to metabolic disturbances in our patients. NBUVB might exert its therapeutic effect in psoriasis through reduction of tissue LCN2.

Antihypertensive and antidiabetic activities of Erythrina senegalensis DC (Fabaceae) stem bark aqueous extract on diabetic hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina senegalensis is traditionally used in Cameroon for its relaxing and hypoglycemic properties in the treatment of cardiovascular diseases and diabetes. AIM OF THE STUDY: High blood pressure and diabetes mellitus are frequently linked. These pathologies represent major risk factors for cardiovascular and renal diseases. The present study was designed to evaluate the antidiabetic and antihypertensive activity of the stem bark of Erythrina senegalensis aqueous extract in male hypertensive diabetic rats (HDR). MATERIALS AND METHODS: Hypertension and diabetes were induced by oral administration of sucrose (15%) and ethanol (40°) at doses of 1.5 g/kg and 5 g/kg respectively for 30 days, followed by an intravenous injection of streptozotocin (STZ; 40 mg/kg). A control group of 5 rats received distilled water (10 mL/kg) followed by intravenous injection of 0.9% NaCl (1 mL/100 g). HDR were divided into 4 groups of 5 rats each according to their blood glucose level and continued to receive ethanol in association with: distilled water (10 mL/kg); group I, metformin (200 mg/kg)+nifedipine (10 mg/kg); group II, plant extract (100 and 200 mg/kg) group IV and V, respectively for 28 days. At the end of the treatment, hemodynamic parameters were recorded by the direct method. Animals were sacrificed; blood and organs (aorta, heart, liver, and kidneys) were collected for biochemical and histological analysis. Phytochemistry and HPLC-DAD-HRESI-MS were used to determine the major compounds of the extract. RESULTS: The administration of sucrose, alcohol, and STZ resulted in a significant increase in blood glucose, hemodynamic parameters, and body weight loss. A significant decrease in pancreatic islets size, nitrite, GSH, SOD and catalase activity was observed in HDR. There was also a significant increase in serum triglycerides, total cholesterol, creatinine, bilirubin, and transaminases activity in HDR. The aqueous extract of E. senegalensis, as well as the metformin + nifedipine combination, significantly improved all these parameters. HPLC coupled to both diode array and mass spectrometry detectors revealed the presence of 15 compounds and 11 of them were identified. CONCLUSION: These results suggest that the aqueous extract of E. senegalensis possess antihypertensive, hypoglycemic, hypolipidemic, cardiomodulator and antioxidant properties involved in the improvement of the metabolic disorders found in HDR. This may be due at least in part to the presence of Erysenegalensein (D, O, N, E), Warangalone, senegalensin and 6,8-diprenylgenistein identified in the extract.

Oxylipins in triglyceride-rich lipoproteins of dyslipidemic subjects promote endothelial inflammation following a high fat meal.

Elevated triglyceride-rich lipoproteins (TGRL) in circulation is a risk factor for atherosclerosis. TGRL from subjects consuming a high saturated fat test meal elicited a variable inflammatory response in TNFα-stimulated endothelial cells (EC) that correlated strongly with the polyunsaturated fatty acid (PUFA) content. This study investigates how the relative abundance of oxygenated metabolites of PUFA, oxylipins, is altered in TGRL postprandially, and how these changes promote endothelial inflammation. Human aortic EC were stimulated with TNFα and treated with TGRL, isolated from subjects' plasma at fasting and 3.5 hrs postprandial to a test meal high in saturated fat. Endothelial VCAM-1 surface expression stimulated by TNFα provided a readout for atherogenic inflammation. Concentrations of esterified and non-esterified fatty acids and oxylipins in TGRL were quantified by mass spectrometry. Dyslipidemic subjects produced TGRL that increased endothelial VCAM-1 expression by ≥35%, and exhibited impaired fasting lipogenesis activity and a shift in soluble epoxide hydrolase and lipoxygenase activity. Pro-atherogenic TGRL were enriched in eicosapentaenoic acid metabolites and depleted in esterified C18-PUFA-derived diols. Abundance of these metabolites was strongly predictive of VCAM-1 expression. We conclude the altered metabolism in dyslipidemic subjects produces TGRL with a unique oxylipin signature that promotes a pro-atherogenic endothelial phenotype.

Xiexin Tang ameliorates dyslipidemia in high-fat diet-induced obese rats via elevating gut microbiota-derived short chain fatty acids production and adjusting energy metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal medicine has been taken as a new and effective approach to treat many chronic diseases. Xiexin Tang (XXT), a compound recipe composed of Dahuang (Rheum palmatum L.), Huangqin (Scutellaria baicalensis Georgi) and Huanglian (Coptis chinensis Franch.), has been reported to have hypoglycemic and hypolipidemic effects, but its mechanism remains unclear. Our previous study found that Xiexin Tang markedly ameliorated the composition of the gut microbiota, especially for some short chain fatty acids (SCFAs) producing bacteria, and then notably increased SCFAs production. However, the mechanism of XXT on the fermentation of gut bacteria and further improvement of obesity is not yet clear. AIM OF THE STUDY: This study aimed to unravel the molecular mechanism of XXT on the amelioration of obesity. MATERIALS AND METHODS: Here, high-fat diet-induced obese rat model was established to investigate the intervention efficacy following oral administration of XXT. Additionally, the expressions of key enzymes of gut microbe-derived SCFAs biosynthesis and key targets in the signaling pathway of energy metabolism were investigated by ELISA and qPCR analysis. RESULTS: Results showed that XXT could notably correct lipid metabolism disorders, alleviate systematic inflammation, improve insulin sensitivity and reduce fat accumulation. Additionally, XXT could increase gut microbiota-derived SCFAs-producing capacity by enhancing mRNA levels and activities of SCFA-synthetic key enzymes such as acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD), butyryl-CoA: acetate CoA transferase (BUT) and butyrate kinase (BUK), which markedly decreased the adenosine triphosphate (ATP) contents, elevated adenosine diphosphate (ADP) and adenosine monophosphate (AMP) levels and further lowered the energy charge (EC) in obese rats via activating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/uncoupling protein-2 (UCP-2) signaling pathway. What's more, XXT could notably ameliorate dyslipidemia via increasing the gene expression of 5'-AMP-activated protein kinase (AMPK) and blocking mammalian target of rapamycin (mTOR) signaling pathway. CONCLUSIONS: Taken together, our data provided a novel insight into the role of XXT in losing weight from energy metabolism regulation, which unraveled the molecular mechanism of XXT on the alleviation of dyslipidemia and fat heterotopic accumulation. The study provided useful information for XXT in clinical application to treat obesity.

Effects of a New Combination of Medical Food on Endothelial Function and Lipid Profile in Dyslipidemic Subjects: A Pilot Randomized Trial.

Nutritional approaches to improve dyslipidemias have been recently developed, but evidences on different medical foods are often incomplete. The main aim of our study was to evaluate the effects on endothelial function, lipid profile, and glucose metabolism of two different combinations of nutraceuticals, first one containing Bergavit (200 mg Citrus bergamia), Omega-3 (400 mg), Crominex 3+ (10 mcg trivalent chromium), and red yeast rice (100 mg; 5 mg monacolin K) and second one containing red yeast rice (200 mg; 3 mg monacolin K), Berberine (500 mg), Astaxanthin (0.5 mg), folic acid (200 mcg), Coenzyme Q10 (2 mg), and Policosanol (10 mg). Fifty subjects affected by dyslipidemia not requiring statin treatment were enrolled in this randomized, blind, controlled trial and submitted to blood sampling for lipid and glucose profiles and instrumental evaluation of endothelial function before and after 6 weeks of treatment with nutraceuticals. Both nutraceutical combinations improved the lipid profile; the nutraceutical containing 5 mg of monacolin K, 200 mg of the extract Citrus bergamia, 400 mg of Omega-3, and 10 mcg of trivalent chromium entailed a significant improvement of endothelial function with enhanced cholesterol lowering effect. In conclusion, this study confirms the positive effect of functional food on lipid profile and endothelial function in absence of major undesirable effects.

Cardiovascular complications and related risk factors underlying opium consumption.

Opium is considered as the second most abused addictive compound in worldwide. It seems that one of the causes for common consumption of opium in many countries is a traditional belief, even among medical personnel, through which opium might have advantageous influences on cardiovascular events and be beneficial in controlling hypertension, dyslipidemia, and diabetes. According to several investigations, it is thought that opium not only has no beneficial effects on cardiovascular events, but it might have deleterious influences on these settings. As a result, people need to be trained with regard to the adverse effects of opium on cardiovascular events. In this review, we try to go through the understanding of the effects of opium cardiovascular disorders and related complications such as blood pressure, blood sugar, lipid circumstances, and finally atherosclerosis.

Role of Borage Seed Oil and Fish Oil with or without Turmeric and Alpha- Tocopherol in Prevention of Cardiovascular Disease and Fatty Liver in Rats.

The aim of the present research was to Study the prevention of dyslipidemia, oxidative stress, inflammation and fatty liver as risk factors for cardiovascular disease via intervention by borage oil (B) and fish oil (F) with or without turmeric (T) and alpha-tocopherols (TC). Fatty acids were assessed in both oils while curcuminoids were determined in turmeric. Rats were divided into; first group fed on balanced diet and designated as normal control (NC), second fed on dyslipidemic and steatohepatitis (DS) inducer diet which represented the DS control group and groups 3-6 fed on DS inducer diet with daily oral administration of B, B+T+TC, F and F+T+TC; respectively for 5 weeks. Liver fat and plasma lipid profile, oxidative stress and inflammatory biomarker and liver and heart histopathology were assessed. Results showed gamma linolenic to be 21.01% in B. F contained eicosapentaenoic as 22.768% and docosahexaenoic acid as 13.574%.Total curcuminoids were 4.63 mg/g turmeric. The DS control group showed significant dyslipidemia, elevated malondialdehyde (MDA), tumor necrosis factor-alpha and liver fat with significant reduction in total antioxidant capacity (TAC) compared to NC. The different treatments produced significant improvement in all the parameters and histopathology. F was superior to B in ameliorating liver histopathological changes while B was more efficient in elevating TAC. B was more promising in improving lipid profile and liver fat compared to B + T + TC, while the latter was superior in improving MDA and liver histopathology. Fish oil was more efficient than F+TC+T except for TAC and high density lipoprotein cholesterol which were more improved on addition of TC and T. Conclusion: Borage and fish oil with or without antioxidants protect from cardiovascular and fatty liver diseases with variable degrees.

The adiponectin promoter activator NP-1 induces high levels of circulating TNFα and weight loss in obese (fa/fa) Zucker rats.

Chronic NP-1 administration reduces body weight and hepatic steatosis despite induction of tolerance in adiponectin gene transcription with respect to the acute actions of this drug. This study explored the hypothesis that NP-1 could exert these effects through mechanisms independent of adiponectin. To this aim, we took advantage of the Zucker (fa/fa) rat model, which exhibits obesity, fatty liver and elevated leptin and adiponectin levels. Body weight and food intake were reduced after chronic NP-1 treatment. Plasma TNFα concentrations were elevated but no increase in adiponectin was found. Even so, NP-1 ameliorated fatty liver and corrected dyslipidemia by mechanisms probably associated with reduced feeding, transcription of Cpt1 and down-regulation of Hmgcr-CoA expression. In brown fat tissue NP-1 increased Dnmt1 (inhibitor of Adipoq) while it reduced Ucp1 expression and heat production, which excludes thermogenesis as a mechanism of the NP-1 slimming effect. The anti-obesity action of chronic NP-1 administration might be mediated by TNFα, which is known to have anorectic actions in the hypothalamus and to regulate both Dmnt1 and Ucp1 expression in adipose tissues. This finding opens up the possibility of using NP-1-mediated TNFα-induced weight loss as an innovative treatment of complicated obesity under strict pharmacologic control.

Maternal Consumption of Low-Isoflavone Soy Protein Isolate Confers the Increased Predisposition to Alcoholic Liver Injury in Adult Rat Offspring.

Offspring of female rats fed either a casein (CAS) diet or a low-isoflavone soy protein isolate (SPI) diet were compared in an animal model of chronic ethanol consumption to investigate whether maternal diet regulates the adaptive responses of offspring to postnatal ethanol exposure and potentially affects the development of liver disease in later life. Female rats were fed either a CAS or an SPI diet before mating, and during pregnancy and lactation. Male offspring from the same litter were pair-fed either a control or ethanol diet for six weeks (CAS/CON, CAS/EtOH, SPI/CON, and SPI/EtOH groups). Serum aminotransferase activities and hepatic inflammatory indicators were higher in the SPI/EtOH group than in the CAS/EtOH group. Ethanol consumption increased serum homocysteine levels, hepatic S-adenosylmethionine:S-adenosylhomocysteine ratio, and hepatic endoplasmic reticulum stress only in offspring of SPI-fed female rats. Total and high-density lipoprotein (HDL) cholesterol levels and mRNA levels of hepatic genes involved in HDL cholesterol assembly were reduced in the SPI group in response to ethanol consumption. In conclusion, offspring of SPI-fed female rats were more susceptible to the later development of alcoholic liver disease than offspring of CAS-fed female rats. Furthermore, maternal SPI consumption altered one-carbon metabolism and cholesterol metabolism of offspring fed an ethanol diet.

Aged Oolong Tea Reduces High-Fat Diet-Induced Fat Accumulation and Dyslipidemia by Regulating the AMPK/ACC Signaling Pathway.

While oolong tea (OT) has been shown to induce weight loss and reduce fat accumulation, the mechanisms remain poorly defined, especially for aged OT. In this study, five groups of mice (n = 9/group) were used including a normal diet with vehicle treatment, and a high-fat diet (HFD) with vehicle or the water extracts from aged OTs (EAOTs, three different storage years) by oral gavage at 1000 mg/kg·BW for 6 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The morphology of hepatocytes and adipocytes was analyzed by being stained with hematoxylin and eosin. The levels of p-AMPK, p-ACC (and non-phosphorylated versions), CPT-1 and FAS were determined by Western blotting and immunohistochemistry. EAOTs decreased HFD-induced body weight, fat accumulation, serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol, while enhancing the serum high-density lipoprotein cholesterol level. At the same time, EAOTs clearly alleviated fatty liver and reduced the size of adipocytes in the epididymal fat, especially in the 2006 group. Most importantly, EAOTs increased the phosphorylation of AMPK and ACC, and up-regulated the expression of CPT-1 but down-regulated the expression of fatty acid synthase, TNF-α and iNOS. Thus, EAOTs may inhibit obesity by up-regulating energy expenditure and fatty acid oxidation while inhibiting fatty acid synthesis and inflammation.