Multizonal observational study conducted by clinical practitioners on Repatha® use in patients with hyperlipidemia (ZERBINI): Colombian results.

BACKGROUND: Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia. METHODS: Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia. RESULTS: This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5-183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0-95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10-12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported. CONCLUSIONS: Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported.

Methanolic extract of S. securidaca flowers, leaves, and seeds' antihyperlipidemic effects on high fat diet-induced hyperlipidemia in Wistar rats.

Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.

GlucoMedix®, an extract of Stevia rebaudiana and Uncaria tomentosa, reduces hyperglycemia, hyperlipidemia, and hypertension in rat models without toxicity: a treatment for metabolic syndrome.

BACKGROUND: The objective of this in vivo study is to evaluate in five rat models the pharmacologic effects and toxicity of a commercial hydro-alcoholic extract, GlucoMedix®, derived from Stevia rebaudiana and the pentacyclic chemotype of Uncaria Tomentosa (Willd.) DC, for use as a treatment for metabolic syndrome. The extract contains phytochemicals of Stevia (e.g., steviol glycosides) and Uncaria (e.g., pentacyclic oxindole alkaloids, but lacks tetracyclic oxindole alkaloids). METHODS: The pharmacologic assessments in three rat models include reductions in chemically induced hyperglycemia, hyperlipidemia (cholesterol and triglycerides), and hypertension, all of which are comorbidities of metabolic syndrome. Acute toxicity and 28-day subacute toxicity were assessed in rat models at doses higher than those used in the efficacy models. RESULTS: The acute oral toxicity was evaluated in Holtzman rats and the extract did not produce acute toxic effects or lethality, with the LD50 > 5000 mg/kg (extract wet weight). Furthermore, subacute oral toxicity was evaluated in rats for 28 days at daily doses as high as 2000 mg/kg without toxicity or abnormal clinical chemistry or hematological effects. Daily oral doses of 250 - 1000 mg/kg were used to evaluate the treatment effects in hyperglycemic (alloxan-induced and glibenclamide-controlled), hyperlipidemic (cholesterol-induced and atorvastatin-controlled), and hypertensive (L-NAME-induced and enalapril-controlled) rat models. Alloxan-induced hyperglycemia was reduced in a dose-dependent manner within 28 days or less. Cholesterol-induced hyperlipidemic rats exhibited dose-dependent reductions in cholesterol and triglycerides at 21 days. Furthermore, GlucoMedix® produced a dose-dependent decrease in systolic and diastolic arterial blood pressure in L-NAME-induced hypertensive rats at 28 days. CONCLUSIONS: The five in vivo rat models revealed that the all-natural phytotherapy GlucoMedix® is a safe and effective treatment for hyperglycemia, hyperlipidemia, and hypertension. This extract is expected to affect multiple comorbidities of metabolic syndrome, without any acute or subacute oral toxicity in humans. Although multiple prescription drugs are well known for the treatment of individual comorbidities of metabolic syndrome, no drug monotherapy concurrently treats all three comorbidities.

New Therapies for Primary Hyperlipidemia.

Primary hyperlipidemias include a heterogeneous set of monogenic and polygenic conditions characterized by a strong family aggregation, severe forms of hypercholesterolemia and/or hypertriglyceridemia, appearance early on life, and a high risk of cardiovascular events and/or recurrent pancreatitis. In real life, a small proportion of the primary hyperlipidemia cases is recognized and treated properly. Our goal is to present an update of current and upcoming therapies for patients with primary hyperlipidemia. Recently, new lipid-lowering medications have obtained authorization from the U.S. Food and Drug Administration and the European Medicines Agency. These drugs target metabolic pathways, including (adenosine 5'-triphosphates)-citrate lyase (bempedoic acid), proprotein convertase subtilisin/kexin 9 (inclisiran), apolipoprotein CIII (volanesorsen), and angiopoietin-like 3 (volanesorsen), that have additive effects with the actions of the currently available therapies (i.e., statins, ezetimibe or fibrates). We discuss the potential clinical indications for the novel medications. To conclude, the addition of these new medications to the therapeutic options for primary hyperlipidemia patients may increase the likelihood of achieving the treatment targets. Also, it could be a safer alternative for patients with side effects for the currently available drugs.

Antioxidant compounds from Annona crassiflora fruit peel reduce lipid levels and oxidative damage and maintain the glutathione defense in hepatic tissue of Triton WR-1339-induced hyperlipidemic mice.

Dyslipidemia is a risk factor for the pathogenesis of several diseases, such as obesity, hypertension, atherosclerosis and cardiovascular diseases. In addition to interfering with serum concentrations of cholesterol and triglycerides, hyperlipidemia is involved in oxidative stress increase and reduction of the endogenous antioxidant defenses. The fruit peel of Annona crassiflora crude extract (CEAc) and its polyphenols-rich fraction (PFAc) were investigated against hypertriglyceridemia, hypercholesterolemia and hepatic oxidative stress in Triton WR-1339-induced hyperlipidemic mice. Lipid parameters in serum, feces and liver, as well as hepatic oxidative status, and enzymatic and non-enzymatic antioxidant defense systems were analyzed. Pre-treatment with CEAc for 12 days decreased hepatic triglycerides and total cholesterol, and similar to PFAc, increased the high-density lipoprotein level. There were reductions in lipid peroxidation and protein carbonylation, as well as restoration of the glutathione defense system and total thiol content in the liver of the hyperlipidemic mice treated with PFAc. The fruit peel of A. crassiflora, a promising natural source of bioactive molecules, showed a potential lipid-lowering action and hepatoprotective activities triggered by reduction of oxidative damage and maintenance of the enzymatic and non-enzymatic antioxidant systems impaired by the hyperlipidemic state.

Tucumã (Astrocaryum aculeatum) prevents memory loss and oxidative imbalance in the brain of rats with hyperlipidemia.

Hyperlipidemia generates deposition of lipids, inflammation, and oxidative damage in cells and tissues, including those of the brain. Tucumã (Astrocaryum aculeatum) fruits contain bioactive compounds with antioxidant and anti-inflammatory effects. We evaluated the action of Tucumã extract on memory and brain cortex redox balance in hyperlipidemic rats. For 30 days, Wistar rats received Tucumã extract (250 mg/kg). Then, hyperlipidemia was induced by intraperitoneal administration of Poloxamer-407. Twenty-four hours later, the object recognition index was measured. The animals were euthanized for sample collection 36 hr postinduction. Hyperlipidemic animals showed memory loss and an imbalance between reactive species and intrinsic antioxidants. We found that Tucumã prevented memory loss and protein and lipid oxidative damage and prompted a better antioxidant response in the cerebral cortex of rats with hyperlipidemia. These findings suggest a neuroprotective effect and nutraceutical potential of Tucumã. PRACTICAL APPLICATIONS: In the present work, we demonstrated that induced hyperlipidemia in rats caused memory loss and redox unbalance, both factors prevented by the administration of Tucumã (Astrocaryum aculeatum) extract. Two aims were fulfilled with these results. The first was to show that hyperlipidemia affected brain function through oxidative damage and concerned basic research. The second was to offer a therapy that prevented this harm and could be applied in the clinic. Tucumã has ethnopharmacological importance through the consumption of fruits or the administration of extracts and oils by a population that was shown to enjoy improved health and longevity. Here, we show evidence that Tucumã contributes to the maintenance of brain health by preventing memory loss and oxidative damage, a nutraceutical supplement that may aid the prevention of vascular, inflammatory, and brain diseases.

Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution.

AIMS: The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution. MAIN METHODS: 24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140 days. After this period, animals were randomly allocated into four groups (n = 6): Control (C), C + Pterostilbene (PT), Sucrose (S), and S + PT. Pterostilbene (40 mg/kg) was given orally for 45 consecutive days. KEY FINDINGS: Pterostilbene did not influence morphometric and nutritional parameters. The insulin sensitivity index TyG was elevated in the C + PT group (p < 0.01) and reduced in S + PT group (p < 0.05). Basal glucose levels were lower in the S + PT group (p < 0.05), and the glycemic response was improved with PT treatment in glucose provocative tests. Conversely, rats from the C + PT group showed impaired glucose disposal during those tests. Lipid profile was partially improved by PT treatment. Hepatic oxidative stress in the S group was improved after PT treatment. In the C group, PT reduced SOD activity, glutathione levels, and increased catalase activity. Collagen content was reduced by PT treatment. SIGNIFICANCE: PT effects depends on the type of diet the animals were submitted. In rats fed with sucrose-solution, PT confirmed its positive effects, improving glucose and lipid profile, and acting as a potent antioxidant. The effects of PT on rats that consumed a normal diet were very discrete or even undesirable. We suggest caution with indiscriminate consume of natural compounds by healthy subjects.

Lipotoxicity-associated inflammation is prevented by guarana (Paullinia cupana) in a model of hyperlipidemia.

Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.

Effect of Statin Therapy on Age-Associated Changes in Physical Function Among Men With and Without HIV in the Multicenter AIDS Cohort Study.

BACKGROUND: The longer-term risks of statins on physical function among people with HIV are unclear. METHODS: Longitudinal analysis of Multicenter AIDS Cohort Study men between 40 and 75 years of age with ≥2 measures of gait speed or grip strength. Generalized estimating equations with interaction terms between (1) statin use and age and (2) HIV serostatus, age, and statin use were considered to evaluate associations between statin use and physical function. Models were adjusted for demographics and cardiovascular risk factors. RESULTS: Among 2021 men (1048 with HIV), baseline median age was 52 (interquartile range 46-58) years; 636 were consistent, 398 intermittent, and 987 never statin users. There was a significant interaction between age, statin, and HIV serostatus for gait speed. Among people with HIV, for every 5-year age increase, gait speed (m/s) decline was marginally greater among consistent versus never statin users {-0.008 [95% confidence interval (CI) -0.017 to -0.00007]; P = 0.048}, with more notable differences between intermittent and never users [-0.017 (95% CI -0.027 to -0.008); P < 0.001]. Similar results were observed among men without HIV. Significant differences in grip strength (kg) decline were seen between intermittent and never users [-0.53 (95% CI -0.98 to -0.07); P = 0.024] and differences between consistent and never users [-0.28 (95% CI -0.63 to 0.06); P = 0.11] were not statistically significant. CONCLUSIONS: Among men with and without HIV, intermittent statin users had more pronounced declines in physical function compared with consistent and never users. Consistent statin use does not seem to have a major impact on physical function in men with or without HIV.

Ameliorating effect of Malva Neglecta on hyperglycemia and hyperlipidemia in diabetic rats

The plant, Malva neglecta wallr., is widely consumed for medicinal and nutritional purposes. The current study was carried out to assess the hypoglycemic and antihyperlipidemic potential of aqueous methanolic extract of M. neglecta. Chemical evaluation of the extract was performed by high pressure liquid chromatography. Oral glucose tolerance test (OGTT) was done in diabetic rats pre-exposed to 250, 500 and 750 mg/kg plant extract via the oral route. For hypoglycemic and biochemical study, the same therapy was administered to alloxan induced diabetic rats for 14 days. The standard control group received Glibenclamide (5 mg/kg). Ferulic acid, p-coumaric acid and other phenolic acids were detected and estimated in the extract. Administration of the plant extract significantly reduced blood glucose level in diabetic rats subjected to OGTT. The plant extract lowered the fasting blood glucose and alpha amylase, and prevented the damage to pancreas. It also corrected dyslipidemia in diabetic animals following 14 days therapy. Hence, this experimental study establishes the fact that M. neglecta exhibited significant antidiabetic and antihyperlipidemic activities in alloxan induced diabetic rats.

Valores de riesgo vascular de indicadores metabólicos en adolescentes y ancianos de La Habana / Vascular Risk Values of Metabolic Indicators in Adolescents and Elderlies from Havana

Introducción: Durante el ciclo de vida de los individuos son imprescindibles intervenciones para detectar y reducir el riesgo y las complicaciones de las enfermedades crónicas. Objetivo: Determinar la prevalencia de valores de riesgo vascular de los principales indicadores del metabolismo glucídico y lipídico en adolescentes y ancianos de La Habana. Métodos: Se realizó un estudio transversal en una muestra conformada por adolescentes (469 de 12-16 años) aparentemente sanos y ancianos (395 de 65-100 años) sin diagnóstico de enfermedades asociadas a la alteración marcada del estado nutricional y metabólico. Ambas poblaciones fueron evaluadas para glucosa, triglicéridos, colesterol total, colesterol de lipoproteinas de alta densidad y colesterol de lipoproteínas de baja densidad, séricos, mediante métodos enzimáticos convencionales. Se usaron rangos de riesgo referentes. Los resultados se analizaron mediante estadística descriptiva. Resultados: En los adolescentes evaluados, los triglicéridos (35,6 por ciento) y el colesterol total (23,9 por ciento) mostraron las mayores frecuencias de valores de riesgo. En las hembras ambos marcadores se mantuvieron como los más elevados en ese orden, mientras que, en los varones, la glucosa (25,5 por ciento) secundó a los triglicéridos como indicadores más alterados. En ancianos, al colesterol de lipoproteínas de baja densidad (58,2 por ciento) y al colesterol total (48,6 por ciento) correspondieron las mayores frecuencias de cifras de riesgo, patrón que se repitió en cada sexo. Los valores promedio de los indicadores fueron marcadamente superiores en ancianos que, en adolescentes, excepto para glucosa y colesterol de lipoproteínas de alta densidad. Conclusiones: Los resultados obtenidos muestran una elevada prevalencia de valores de riesgo vascular de varios indicadores metabólicos evaluados en adolescentes y ancianos, lo que sugiere la necesidad de monitorear los indicadores analizados e implementar intervenciones modificadoras de sus valores hacia la reducción del riesgo asociado, desde etapas tempranas, como las previas a la adolescencia(AU)

Introduction: During the life cycle of individuals, interventions are essential to detect and reduce the risk and complications of chronic diseases. Objective: To determine the prevalence of vascular risk values of the main indicators of carbohydrate and lipid metabolism in adolescents and elderlies in Havana. Methods: A cross-sectional study was carried out with a sample made up of apparently healthy adolescents (469; aged 12-16 years) and elderlies (395 aged 65-100 years) without a diagnosis of diseases associated with marked alteration of nutritional and metabolic status. Both populations were evaluated regarding serum glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol using conventional enzymatic methods. Reference risk ranges were used. The results were analyzed using descriptive statistics. Results: In the evaluated adolescents, triglycerides (35.6 percent) and total cholesterol (23.9 percent) showed the highest frequencies of risk values. In females, both markers remained the highest in that aspect; while in males, glucose (25.5 percent) accounted second after triglycerides as the most altered indicators. In the elderlies, low-density lipoprotein cholesterol (58.2 percent) and total cholesterol (48.6 percent) corresponded to the highest frequencies of risk values, a pattern that was repeated in each sex. The average values of the indicators were markedly higher in the elderlies than in adolescents, except for glucose and high-density lipoprotein cholesterol. Conclusions: The results obtained show high prevalence of vascular risk values of several metabolic indicators evaluated in adolescents and elderlies, which suggests the need to monitor the analyzed indicators and implement interventions to modify such values, in view of reducing the associated risk, from stages early, such as the pre-adolescence stage(AU)

Purine Metabolism in Platelets and Heart Cells of Hyperlipidemic Rats.

PURPOSE: Hyperlipidemia, characterized by an increase in circulating lipid levels, doubles the chance of developing cardiovascular diseases. It prompts inflammation, immune activation, and oxidative stress in the bloodstream and organs of rats. Thus, we theorized that the metabolism of purines, an immunomodulatory mechanism, is altered in cells involved in the development of cardiovascular diseases. METHODS: Therefore, we induced acute hyperlipidemia in Wistar rats with Poloxamer-407 and euthanized the animals 36 h later. The leucocyte differential, the rate of purine metabolism on the surface of platelets and heart cells, and markers of oxidative stress in the heart tissue were evaluated. These parameters were also assessed in animals pretreated for 30 days with curcumin and/or rutin. RESULTS: Hyperlipidemia increased the hydrolyses of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in platelets. In heart cells, the metabolism of ATP and adenosine (ADO) were increased, while ADP hydrolysis was reduced. Additionally, lipid damage and antioxidant defenses were increased in heart homogenates. Hyperlipidemic rats also exhibited a reduced percentage of eosinophils and lymphocytes. CONCLUSION: Together, these findings are indicative of an increased risk of developing cardiovascular diseases in hyperlipidemic rats. The pretreatments with antioxidants reverted some of the changes prompted by hyperlipidemia preventing detrimental changes in the cells and tissues. Graphical Abstract.

Impact of multi-micronutrient supplementation on lipidemia of children and adolescents.

BACKGROUND: Micronutrient supplementation has been extensively explored as a strategy to improve health and reduce risk of chronic diseases. Fat-soluble vitamins like A and E with their antioxidant properties and mechanistic interactions with lipoproteins, have potentially a key impact on lipid metabolism and lipidemia. OBJECTIVE: The impact of micronutrients on lipid metabolism requires further investigation including characterization of plasma lipidome following supplementation and any cause-effect on circulating lipids. DESIGN: In this study, we elucidate the effect and associations of a multi-micronutrient intervention in Brazilian children and teens with lipoprotein alterations and lipid metabolism. RESULTS: Our analysis suggests a combination of short and long-term impact of supplementation on lipid metabolism, potentially mediated primarily by α-tocopherol (vitamin E) and retinol (vitamin A). Among the lipid classes, levels of phospholipids, lysophospholipids, and cholesterol esters were impacted the most along with differential incorporation of stearic, palmitic, oleic and arachidonic acids. Integrated analysis with proteomic data suggested potential links to supplementation-mediated alterations in protein levels of phospholipases and pyruvate dehydrogenase kinase 1 (PDK1). CONCLUSIONS: Associations between the observed differences in lipidemia, total triglyceride, and VLDL-cholesterol levels suggest that micronutrients may play a role in reducing these risk factors for cardiovascular disease in children. This would require further investigation.

Anti-hyperlipidemic effects of Campomanesia xanthocarpa aqueous extract and its modulation on oxidative stress and genomic instability in Wistar rats.

The use of natural products from herbs may be a therapeutic option in dyslipidemia treatment. Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae) leaves have been used to decrease cholesterol levels. However, studies to determine activities of this plant on triglycerides metabolism have received little attention. The aim of this study was to examine anti-hyperlipidemic effects of a C. xanthocarpa aqueous leaf extract (CxAE) and assess protective actions against oxidative stress and DNA damage. The tyloxapol-induced hyperlipidemia model was used in Wistar rats. Rats were treated orally with CxAE either 250 or 500 mg/kg/day for 7 days prior to tyloxapol administration. Biochemical parameters, oxidative stress levels, and genomic instability were assessed in several tissues. CxAE decreased cholesterol and triglyceride levels in serum and hepatic and renal DNA damage in tyloxapol-treated rats. There was no marked effect on the micronucleus frequency in bone marrow. The extract increased catalase activity and decreased glutathione S-transferase activity in kidney tissue. CxAE showed anti-hyperlipidemic effects, improved oxidative parameters, and protected DNA against damage induced by tyloxapol-induced hyperlipidemia, suggesting C. xanthocarpa leaves may be useful in preventing dyslipidemias.Abbreviations: ALP: Alkaline phosphatase; ALT: Aspartate aminotransferase; ANOVA: Analysis of variance; AST: Aspartate aminotransferase; Ator: Atorvastatin; CAT: Catalase; Chol: Cholesterol; CxAE: Campomanesia xanthocarpa aqueous extract; GST: Glutathione S-transferase; HDL: High density cholesterol; i.p.: Intraperitoneal; NCE: Normochromatic erythrocyte; PBS: Phosphate buffer solution; PCE: Polychromatic erythrocyte; ROS: Reactive oxygen species; SD: Standard deviation; SOD: Superoxide dismutase; T: Tyloxapol; TBARS: Thiobarbituric acid reacting substances; TG: Triglyceride.

Biotechnological Production of Statins: Metabolic Aspects and Genetic Approaches.

Statins are drugs used for people with abnormal lipid levels (hyperlipidemia) and are among the best-selling medications in the United States. Thus, the aspects related to the production of these drugs are of extreme importance for the pharmaceutical industry. Herein, we provide a non-exhaustive review of fungal species used to produce statin and highlighted the major factors affecting the efficacy of this process. The current biotechnological approaches and the advances of a metabolic engineer to improve statins production are also emphasized. The biotechnological production of the main statins (lovastatin, pravastatin and simvastatin) uses different species of filamentous fungi, for example Aspergillus terreus. The statins production is influenced by different types of nutrients available in the medium such as the carbon and nitrogen sources, and several researches have focused their efforts to find the optimal cultivation conditions. Enzymes belonging to Lov class, play essential roles in statin production and have been targeted to genetic manipulations in order to improve the efficiency for Lovastatin and Simvastatin production. For instance, Escherichia coli strains expressing the LovD have been successfully used for lovastatin production. Other examples include the use of iRNA targeting LovF of A. terreus. Therefore, fungi are important allies in the fight against hyperlipidemias. Although many studies have been conducted, investigations on bioprocess optimization (using both native or genetic- modified strains) still necessary.

Effect of Hydro-alcoholic Extract from Prosopis Farcta Leaves on Liver Injury Caused by High-fat Diet in Rats / Efecto del extracto hidro-alcohólico de las hojas de Prosopis Farcta en la lesión hepática causada en ratas por una dieta rica en grasas

ABSTRACT Objective: To determine the hepatoprotective and antioxidant effects of hydro-alcoholic extract of Prosopis farcta (P farcta) leaves on high fat diet-fed (HFDF) rats. Methods: In this experimental study, 40 male Wistar rats were divided into four groups - group 1: normal control group; group 2: untreated control group, fed a high-fat diet; group 3: hyperlipidaemic + P farcta (500 mg/kg orally per day); and group 4: hyperlipidaemic + simvastatin (1.0 mg/kg). All groups were treated for 30 days. Liver enzymes, levels of total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein, blood urea nitrogen and creatinine, antioxidant enzyme activity, lipid peroxidation and liver histopathology were assessed. Results: Prosopis farcta extract reduced the elevated levels of total cholesterol, triglycerides, LDL and body weight. Catalase and superoxide dismutase activity were reduced in the HFDF animals, whose levels were increased statistically significantly by extract of P farcta leaves. The statistically significant increases in liver malondialdehyde in HFDF rats were reduced after treatment with P farcta. Histopathological findings also revealed positive effects of the extract. Conclusion: These results indicate the lipid-lowering and antioxidative activity of extract of P farcta leaves.

RESUMEN Objetivo: Determinar los efectos hepatoprotectores y antioxidantes del extracto hidroalcohólico de las hojas de Prosopis farcta (P farcta) en ratas alimentadas con dieta rica en grasas (ADRG). Métodos: En este estudio experimental, 40 ratas macho Wistar se dividieron en cuatro grupos - Grupo 1: Grupo de control normal; Grupo 2: Grupo de control no tratado, alimentado con una dieta alta en grasas; Grupo 3: hiperlipidémico + P farcta (500 mg/kg por vía oral por día); y Grupo 4: hiperlipidémico + simvastatina (1.0 mg/kg). Todos los grupos fueron tratados durante 30 días. Se evaluaron las enzimas hepáticas, los niveles de colesterol total, los triglicéridos, la lipoproteína de baja densidad (LBD), la lipoproteína de alta densidad (LAD), el nitrógeno ureico y la creatinina en sangre, la actividad enzimática antioxidante, la peroxidación lipídica, y la histopatología hepática. Resultados: El extracto de Prosopis farcta redujo los niveles elevados de colesterol total, los triglicéridos, la LBD, y el peso corporal. La actividad de la catalasa y el superóxido dismutasa se redujo en los animales ADRG, cuyos niveles se incrementaron estadísticamente en grado significativo mediante el extracto de hoja de P farcta. Los aumentos estadísticamente significativos en el malondialdehído hepático en ratas ADRG, disminuyeron después del tratamiento con P farcta. Los hallazgos histopatológicos también revelaron efectos positivos del extracto. Conclusión: Estos resultados indican la actividad de reducción de lípidos y la actividad anti-oxidantes del extracto de las hojas de P farcta.

Morus nigra L: revisão sistematizada das propriedades botânicas, fitoquímicas e farmacológicas / Morus nigra L: systematized review of botanical, phytochemical and pharmacological properties / Morus nigra L: revisión sistematizada de las propiedades botánicas, fitoquímicas y farmacológicas

Morus nigra é uma espécie vegetal popularmente conhecida por Amora negra. Esta espécie amplamente cultivada na Ásia e nas regiões sul e sudeste do Brasil, possui importância econômica devido a sua ampla utilização na alimentação e confeitaria, sendo também utilizada na medicina popular como anti-inflamatório, diurético, antitussígeno, anti-hemorrágico, para o tratamento do climatério e de doenças hepáticas e renais. Diversos estudos têm sido conduzidos a respeito das atividades farmacológicas da Morus nigra. Neste trabalho de revisão narrativa da literatura foram explorados estudos nas bases de dados acerca da atividade hipolipemiante e de outras atividades farmacológicas dos compostos fenólicos, estilbenos, flavonoide, isoprenilados, cumarinas, cromonas e xantonas da Morus nigra, para verificar sua capacidade de diminuição dos níveis de colesterol total, triglicerídeos, LDL e ainda, aumento dos níveis de HDL, como também outras propriedades antioxidantes, anticarcinogênica, antimutagênica. Desse modo, conclui-se a necessidade da realização de mais estudos com Morus nigra e principalmente mais ensaios clínicos que avaliem a segurança e eficácia na utilização desta planta(AU)

Morus nigra is a plant species popularly known as blackberry. This species, widely cultivated in Asia and in the south and southeast regions of Brazil, is economically important due to its wide use in food and confectionery. It is also used in folk medicine as anti-inflammatory, diuretic, antitussive, anti-hemorrhagic, for treatment climacteric and liver and kidney diseases. Several studies have been conducted regarding the pharmacological activities of Morus nigra. In this work of narrative review of the literature we explored studies in the databases on the lipid-lowering activity and other pharmacological activities of the phenolic, stilbenos, flavonoids, isoprenylates, coumarins, cromones and xanthones compounds of Morus nigra, to verify their capacity to decrease levels of total cholesterol, triglycerides, LDL and also, increased levels of HDL, as well as other antioxidant properties, anticarcinogenic, antimutagenic. Thus, it is concluded that further studies are needed with Morus nigra and, in particular, more clinical trials evaluating the safety and efficacy of this plant(AU)

Morus nigra es una especie vegetal popularmente conocida por Amora negra. Esta especie ampliamente cultivada en Asia y en las regiones sur y sudeste de Brasil, tiene una importancia económica debido a su amplia utilización en la alimentación y la confitería, siendo utilizada en la medicina popular como anti-inflamatorio, diurético, antitusígeno, anti-hemorrágico, para el tratamiento del climaterio y de las enfermedades hepáticas y renales. Se han realizado varios estudios sobre las actividades farmacológicas de Morus nigra. En este trabajo de revisión narrativa de la literatura se exploraron estudios en las bases de datos acerca de la actividad hipolipemiante y de otras actividades farmacológicas de los compuestos fenólicos, estilbenos, flavonoide, isoprenilados, cumarinas, cromonas y xantonas de Morus nigra, para verificar su capacidad de disminución de los niveles de colesterol total, triglicéridos, LDL y aún, aumento de los niveles de HDL, así como otras propiedades antioxidantes, anticarcinogénicas, antimutagénicas. De este modo, se concluye la necesidad de realizar más estudios con Morus nigra y principalmente más ensayos clínicos que evalúen la seguridad y eficacia en la utilización de esta planta(AU)

The Chemical Composition and Metabolic Effects of Attalea phalerata Nut Oil in Hyperlipidemic Rats Induced by a High-Fructose Diet.

The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was to identify and quantify the nut oil fatty acids from Attalea phalerata and investigate their metabolic effects in rats with hyperlipidemia induced by a diet rich in fructose. Oleic and lauric acids were the major compounds found in the A. phalerata nut oil (APNO). Hyperlipidemic rats treated with APNO showed a reduction in the total serum cholesterol similar to those treated with simvastatin, an increased body temperature by 1 °C, and a reduction in the body weight gain and mesenteric depot of white adipose tissue compared to the hyperlipidemic controls rats. There was an increase in the relative liver weight of rats treated with APNO, without, however, any change in the serum markers of hepatic toxicity. In addition, there was an increase in the moisture and lipid content of the feces of the rats treated with APNO compared to the controls. Together, these results suggest that APNO has potential use in health foods and nutritional supplements to control hypercholesterolemia and obesity.

Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study.

AIM: Although statins are considered a cornerstone for the treatment of high cholesterol levels due to their powerful cholesterol-lowering effects, response to drug administration is still one of the main pitfalls of statin treatment. So far, the reasons underlying this undesired outcome are still poorly understood, but recently, various studies have suggested that miRNAs may be involved. Therefore, we aimed at evaluating the effect of short-term low-dose treatment with 2 statins on miRNAs expression in patients with hypercholesterolemia. METHODS: A total of 40 hypercholesterolemic (HC) subjects following 1 month of atorvastatin (10 mg/day; n = 20) or simvastatin (10 mg/day; n = 20) were included. Multiple available boinformatic algorithms (TargetScan, miRanda, DianaLab, MicroCosm and PicTar) were employed to select miRNAs regulating genes involved in cholesterol metabolism and statin response. Differential miRNAs expression was determined in peripheral cells using the miScript® miRNA PCR Array platform. Pathways involving differentially expressed miRNAs were explored using the Ingenuity Pathway Analysis software. RESULTS: Atorvastatin repressed miR-29a-3p, miR-29b-3p, miR-300, miR-33a-5p, miR-33b-5p and miR-454-3p in HC subjects. On the contrary, simvastatin did not show any effect on miRNAs expression. Network analysis indicated that atorvastatin-modulated miRNAs regulate key cholesterol genes (ABCA1, HMGCR, INSIG1, LDLR, LPL, SCAP and SREBF1). Further subgroups analyses showed that miR-106b-5p, miR-17-3p and miR-590-5p were repressed in HC subjects within the lower quartile of atorvastatin response (lower LDL-C reduction), while the expression of miR-106b-5p, miR-17-3p and miR-183-5p was higher in the upper quartile of simvastatin response (higher LDL-C reduction) (p < 0.05). CONCLUSION: We show that a miRNAs-mediated epigenetic mechanism is differentially affected by statins therapy in vivo, which could be implicated in the variable response to these drugs. Further studies are necessary to disclose their particular role in the cholesterol-reduction response to statins.