Lowering Properties Research Articles

Phytosterol Profiling of Apiaceae Family Seeds Spices Using GC-MS.

Phytosterols are nutritionally vital phytoconstituent owing to their cholesterol (low-density plasma lipoprotein-cholesterol, LDL-C)-lowering, anti-inflammatory, and antioxidant properties. Among the widely used spices and herbs, the seeds spices of the Apiaceae family represented the healthiest fatty acid profile. Thus, to explore the other health-beneficial lipids, the present study was aimed to analyze the phytosterol profile of eight seed spices of the Apiaceae family, utilizing gas chromatography (GC)-mass spectrometry (MS). The sterols contents calculated on an oil (mg/100 g of oil) and spice weight (mg/100 g spices; dry weight) basis varied significantly among the seed spices (p < 0.05; Turkey HSD). The β-sitosterol and stigmasterol were the most dominating sterols among the studied spices, together accounted for 40.3 (Ajwain) to 69.8% (celery) of total sterols in the seed oil. Among the studied spices, the oil extracted from caraway seeds showed the highest total sterols (602.2 mg/100 g of oil). Interestingly, based on spice weight, fennel seeds also showed the similar highest number of total sterols (134.2 mg/100 g in fennel and 133.3 mg/100 g in caraway), owing to the high contents of oil (25.9%) in fennel seeds. Overall, celery, caraway, fennel, and anise seeds oil are rich sources of health-beneficial phytosterols.

Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia

Evidence associates cardiovascular risk factors with unfavorable systemic and neuro-inflammation and cognitive decline in the elderly. Cardiovascular therapeutics (e.g., statins and anti-hypertensives) possess immune-modulatory functions in parallel to their cholesterol- or blood pressure (BP)-lowering properties. How their ability to modify immune responses affects cognitive function is unknown. Here, we examined the effect of chronic hypercholesterolemia on inflammation and memory function in Apolipoprotein E (ApoE) knockout mice and normocholesterolemic wild-type mice. Chronic hypercholesterolemia that was accompanied by moderate blood pressure elevations associated with apparent immune system activation characterized by increases in circulating pro-inflammatory Ly6Chi monocytes in ApoE-/- mice. The persistent low-grade immune activation that is associated with chronic hypercholesterolemia facilitates the infiltration of pro-inflammatory Ly6Chi monocytes into the brain of aged ApoE-/- but not wild-type mice, and links to memory dysfunction. Therapeutic cholesterol-lowering through simvastatin reduced systemic and neuro-inflammation, and the occurrence of memory deficits in aged ApoE-/- mice with chronic hypercholesterolemia. BP-lowering therapy alone (i.e., hydralazine) attenuated some neuro-inflammatory signatures but not the occurrence of memory deficits. Our study suggests a link between chronic hypercholesterolemia, myeloid cell activation and neuro-inflammation with memory impairment and encourages cholesterol-lowering therapy as safe strategy to control hypercholesterolemia-associated memory decline during ageing.

Swertisin, a novel SGLT2 inhibitor, with improved glucose homeostasis for effective diabetes therapy

Failing pancreas and subsequent loss of pancreatic β cells worsen diabetic conditions which are further alleviated by the mounting up of glucose levels. Inhibition of sodium glucose cotransporter 2 (SGLT2) in the kidney responsible for glucose reabsorption strikingly reduces blood glucose levels. Bioactive swertisin showed a promising glucose-lowering effect. Hence, we aimed to mechanistically dissect the glucose lowering property of swertisin. A systematic in silico, in vitro, and in vivo approach was directed for target analysis of swertisin. Molecular docking was performed with Swertisn-hSGLT2 complex. Glucose uptake assay and protein expression for SGLT2 and regulatory proteins were performed under swertisin effect. Various physiological and metabolic parameters were evaluated in STZ induced BALB/c mice using swertisin treatment. SGLT2 expression was evaluated in the kidney tissue of mice. Swertisn-hSGLT2 molecularly docked complex showed similar binding energy compared to the Canagliflozin-hSGLT2 complex. Swertisin inhibited glucose uptake and decreased expression of SGLT2 in HEK293 cells. Swertisin does not affect GLUT mediated glucose transport. Swertisin treated diabetic mice demonstrated remarkable improvement in overall glucose homeostasis. Reduced expression of SGLT2 was found in kidney tissue along with reduced PKC expression which is one of the key regulators of SGLT2. Our study explored SGLT2 as a selective target of swertisin for its swift glucose-lowering action which not only inhibits SGLT2 but also reduces its expression in diabetic condition. Thus, the potential property of swertisin as a glucose-lowering agent is remarkable which points towards the likelihood of a wider avenue of diabetes therapy.

Effects of Momordica Charantia (Karela/bitterguord) in Type 2 Diabetic Patients Taking Allopathic Drugs: A pilot study

Background Momordica charantia is evolving as supplementary therapy in type 2 diabetes mellitus. Animal studies reveal its anti-diabetic and lipid lowering property. However, clinical studies with human subjects are very few.&#x0D; Objective To find out the effects of Momordica charantia supplements on glycemic and lipid profile among type 2 diabetes mellitus patients taking allopathic drugs.&#x0D; Method A comparative study was conducted in internal medicine department of B P Koirala Institute of Health Sciences, Dharan from July 2015 to May 2016 after ethical clearance. Twenty two uncomplicated type-2 diabetes mellitus patients were enrolled. Group A patients were supplemented with allopathic drug (oral anti-diabetic agents) only and Group B with add on treatment of 200 ml juice of Momordica charantia along with allopathic drug daily for ninety days. Fasting, post prandial blood sugar and lipid profile levels were compared between baseline and ninety days post supplementation. Data was collected and entry was done in Statistical Packages for Social Services version 20.0, using independent t test with p &lt; 0.05.&#x0D; Result Add on treatment with 200 ml of Momordica charantia along with anti-diabetic drug daily significantly reduced fasting (p= &lt; 0.0001) and post prandial blood sugar (p=&lt; 0.0001). Treatment with anti-diabetic drugs only reduced fasting (p = 0.0008) and post-prandial blood sugar but the reduction was not significant ((p =0.0001). There was improvement in lipid profile by both anti-diabetic drugs alone and Momordica charantia along with anti-diabetic drug, but it was not significant.&#x0D; Conclusion Add on treatment with 200 ml/day juice of Momordica charantia is effective in glycaemic control in type-2 diabetes mellitus patients as compared to the allopathic treatment alone.

Presence of antioxidants and nitric-oxide precursors in Mimosa pudica extract

Blood pressure lowering effect of Mimosa pudica induced by dieresis was reported earlier. As a diuretic it enhances urine outflow, decreases plasma volume, venous return; and thereby, reduce blood pressure. Besides the diuretic agent, some other blood pressure lowering substance may also be present in Mimosa pudica. Present study was undertaken to reveal the presence of antioxidants and nitrite in Mimosa pudica extract, which may help to reduce blood pressure. Methanolic extract of Mimosa pudica (using 80% methanol) was lyophilised to obtain dried Mimosa pudica Extract (MPE). For Total phenolic content estimation Folin’s method and for estimation of flavonoids, Aluminium chloride method were followed. The radical scavenging and superoxide anion radical scavenging activity were measured following standardised methods. Nitrite content of MPE at different dilutions (10-100 µl in methanol) was measured following standardised procedure keeping sodium nitrite as the standard. Present study noted presence of favonoids and phenolic compounds and also noted antioxidant property in the aforesaid extract that exhibited DPPH+ and superoxide scavenging activities. Besides that, this study also revealed formation of nitrites in the extract of Mimosa pudica in a dose dependent manner. Nitrite is the precursor of nitric oxide (NO). NO is a potent vasodilator that decreases blood pressure. Present study indicated the presence of both antioxidants and nitrites in Mimosa pudica extract; both of which have blood pressure lowering properties indicating it as a blood pressure lowering agent; and helpful in the maintenance of vascular health.

Red Yeast Rice: Lipid Lowering Properties and Safety Considerations

Red yeast rice is a traditional Chinese culinary and medicinal herbal ingredient. The use of red yeast rice dates as far back as the reign of the Tang Dynasty (approximately 800 ad). Over the past several centuries, red yeast rice has been used to improve the digestive process, lower cholesterol, and enhance blood circulation. Over the past few years, red yeast rice has been proffered as an alternative to statin therapy for patients with dyslipidemia. The safety and side-effect profile of red yeast rice product use is not well established.

AM833, a Long Acting Amylin Analogue Induces Hypocalcemia in Young Rats via a Calcitonin Receptor Mediated Mechanism

Abstract Amylin is a peptide hormone that is co-secreted with insulin from pancreatic β-cells. It is member of the calcitonin family and activates amylin receptors (AMYRs) in the calcitonin receptor (CTR) family. During recent years, several AMYR agonists have been in clinical development for treatment of diabetes and obesity. In contrast to pramlintide, which is a short acting amylin analogue approved for use in combination with meal-time insulin in patients with diabetes, the more recent development candidates have been dual acting analogues activating both the CTR and the AMYRs. In rodents the CTR plays a significant role in calcium homeostasis, while in humans this has been associated with little long-term effect on the plasma calcium levels (Ganong, 1993; Longo et al., 2011); Rodents are usually chosen as first choice pre-clinical models for in vivo testing and introducing acute and profound hypocalcaemia can lead to general neurological and neuromuscular disturbances, which can be challenging in clinical development programs. AM833 (NNC0174-0833) is a long acting acylated dual acting amylin analogue activating both CTR and AMYRs. When combined with the long acting GLP-1 analogue semaglutide for weight management, both preclinical studies in rat models of obesity and clinical trials in humans with obesity have demonstrated significant weight loss potential. In young rats aged 7–9 weeks, single sc dose of 3–300 nmol/kg AM833 induced a reduction of total and ionized calcium of 40–50% from baseline with lowest level around 12 hours after dosing. A similar response was seen after administration of salmon calcitonin which also activates both CTR and AMYRs. Tachyphylaxis was introduced, with no effect on calcium found after sub chronic daily treatment for 2 weeks. Age played a key role in the sensitivity to calcium lowering with almost no effect found in 11 months old rats. When administering AM1213 (NNC0174-1213), a selective AMYR agonist with little activation of the CTR, no or little calcium lowering of around 10% was seen. These data indicated that the calcium lowering properties are CTR mediated. The induction of hypercalcemia was a rodent specific phenomenon as no calcium lowering outside of normal range was seen in young dogs and rabbits. Clinical data confirmed that CTR induced calcium lowering was not human relevant, but these data showed that understanding physiology and pharmacology in the animal models of investigation as well as human translational relevance is of outmost importance in the progress of an early development program.

Sex Differences in Blood Pressure Variability in response to Sodium and Potassium Diets

It is well established that Americans consume more salt than recommended by the Dietary Guidelines for Americans. High sodium diets have been shown to increase blood pressure (BP) while dietary potassium is known for its BP lowering properties. Elevated BP variability (BPV), as indicated by spontaneous fluctuations in BP, is associated with cardiovascular morbidity and mortality. Although no recommendations exist for targeting elevated BPV, understanding how different dietary components affect BPV could be important to reduce CVD. Limited literature from rodent and human studies suggests a relation between a high sodium diet and an increased BPV. Additionally, mechanisms regulating BP between men and women differ which may lead to the hypothesis that BPV differs as well. Thus, the interactive effects of dietary sodium and potassium on BPV in humans are unknown as well as whether potential sex differences exist. The purpose of this study was to compare BP and BPV responses to varying dietary levels of sodium and potassium in salt-resistant, healthy, normotensive young adults. Twenty women (27±1 yrs. old; SBP: 112±3 mmHg; DBP: 71±1 mmHg; BMI: 24.1±0.7 kg/m2) and 17 men (26±1 yrs. old; SBP: 117±3 mmHg; DBP: 75±2 mmHg; BMI: 24.4±0.7 kg/m2) completed 7 days each of the following diets: moderate potassium/low sodium diet (65 mmol potassium/50 mmol sodium; MK/LS), a moderate potassium/high sodium diet (65 mmol potassium/300 mmol sodium; MK/HS) and a high potassium/high sodium (120 mmol potassium/300 mmol sodium; HK/HS) in random order. BP and BPV were calculated from 24 h ambulatory BP monitoring on day 6 of each diet. Average Real Variability (ARV) was used as an index of BPV. A mixed-model ANOVA was performed with a Tukey post hoc test with diet as a within subject factor and sex as a between subject factor to determine whether differences existed between men and women on each diet. For 24 h SBP, the main effect of sex was significant (p=0.01) and the sex*diet interaction was significant (p=0.03) such that men had a higher 24 h SBP than women on the HK/HS diet (117±2 mmHg vs 112±1 mmHg, p=0.02). On the MK/LS and MK/HS diets, 24 h SBP was not different between men and women (p>0.05). For 24 h DBP, the main effect of diet was significant (p=0.009) such that 24 h DBP was higher on the MK/LS diet vs HK/HS diet (69±1 mmHg vs 67±1 mmHg, p=0.01) and higher on MK/LS diet compared to MK/HS diet regardless of sex (69±1 mmHg vs 68±1 mm Hg, p=0.02). For 24 h SBP ARV, the main effects of diet and sex and the interaction of sex*diet were not significant (all p>0.05). For 24 h DBP ARV, the main effect of sex was significant (p=0.006) such that men had higher variability regardless of diet (9±0.2 mmHg vs 7±0.2 mm Hg). Our results suggest that in the context of a high sodium diet, potassium may help lower BP in women but not in men. In addition, men tended to have a higher BPV compared to women regardless of the diet. Future studies are warranted to further study the differential response of men and women to the effectiveness of dietary interventions for reducing CVD risk.

Medical management of resistant hypertension: the role of sodium-glucose cotransporter 2 inhibitors (SGLT2i).

Controlling hypertension to the desired target is commonly unsuccessful and requires multi-drug regimen, which can lead to undesirable side effects. Resistant hypertension (RH) is more cumbersome to deal with and has robust morbidity and mortality burden even with current multiple medical options. Herein, we review the literature for the potential role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a treatment option for hypertension and RH. With more recent randomized controlled trials (RCTs), SGLT2i have gained more recognition for their renal and cardiovascular protection as well as mortality benefit that are believed to be medication class-related effects. Multiple RCTs have evaluated blood pressure (BP) lowering properties of SGLT2i, as a primary or secondary end point, in diabetic and nondiabetic patients, yet trials are scarce in studying SGLT2i as first-line antihypertensives, or as add-on agents for treating RH. Finding the right medical therapy in treating hypertension, especially RH, is commonly onerous when it comes to achieving BP targets, avoiding medication side effects, and aiming for the best outcomes. Utilizing existing drugs like SGLT2i or exploring other novel agents with more RCTs for these purposes will be beneficial. The addition of SGLT2i to the therapeutic armamentarium in patients with RH should be considered as a target for upcoming RCTs.

Supplemental Berberine in a High-Fat Diet Reduces Adiposity and Cardiac Dysfunction in Offspring of Mouse Dams with Gestational Diabetes Mellitus

There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams. Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35%kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45%kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10%kcal fat, 35%kcal sucrose), HF (45%kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45%kcal fat, 17.5% sucrose diet) containing BBR (160mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis. In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P<0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; ∼150%) (P<0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P<0.05). In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.

Development, Validation and Application of a UHPLC-MS Method for the Quantification of Chios Mastic Gum Triterpenoids in Human Plasma

AbstractChios mastic gum is the resinous secretion obtained from the barks of the shrub Pistacia lentiscus var. Chia, which is endemic to the Greek island of Chios. Since antiquity, Chios mastic gum has found several uses as a phytotherapeutic remedy, primarily for the treatment of gastrointestinal disorders while recently, Chios mastic gum was also recognized by EMA as an herbal medicinal product with specific indications. Chios mastic gumʼs biological properties are attributed to triterpenes which comprise the major chemical group (approx. 70%) and notably isomasticadienonic acid and masticadienonic acid. However, due to their structural characteristics, the isolation thereof in high yield and purity is challenging and since they are not commercially available, pharmacological studies aiming to assess their biological properties are limited. In the present work, masticʼs phytochemical investigation by UPLC-HRMS is followed by the isolation and characterization of isomasticadienonic acid and masticadienonic acid to be used as analytical standards for their accurate and reliable quantification in human plasma. A UHPLC-tQ-MS method that was developed and validated (in terms of specificity, linearity, limit of quantification, accuracy and precision), for the direct quantification of the targeted compounds in the low ng/mL range of concentration, was subsequently implemented on plasma samples of healthy volunteers thus demonstrating its fitness for purpose. The results presented herein might provide insight to the understanding of this traditional natural product consumed notably for its anti-inflammatory, antioxidant and lipid lowering properties. Moreover, this method might serve as a starting point for any study aiming to monitor bioactive triterpenes in biological fluids.

A COMPREHENSIVE REVIEW ON MANAGEMENT OF TYPE 2 DIABETES THROUGH PROBIOTICS

In the recent time, people are often biased to decide an appropriate medicine to recover a chronic disease. This critical biasness is occurred due to use of some commercial drugs, which have prominent side effects. Probiotics is a promising approach for the upcoming eras. Probiotics are the live microbial food additives which give health beneficiary effects beyond basic nutrition upon consumption in adequate amount. In the recent time, consumption of probiotics based foods are increased and probiotics based foods like yoghurt is one of the best stratagies to overcome diabetes. Yoghurt is a potential source of probiotic lactobacilli. Dahi is a home made variant of yogurt. Dahi has been considered as a functional food due to its several health benefits i.e. antidiabetic, antidiarreal, anticarcinogenic, cholesterol lowering and antiatherogenic properties. In this review management of type 2 diabetes through probiotics are critically discussed.

Activity of Saponin in the parts of the medicinal plant Abutilon indicum

In different aspects of life, plants form a vast field of uses such as furniture, ornaments, decoration, stationary, buildings and others. Among those uses of plants are the medical ones because of the vast varieties of plant types, the low cost and the wide range of safety when use them. Mallow family includes small trees diversity of different parts like herbs, shrubs and flowering plants. Considering the chemical structure, it confines huge range of compounds like vitamins, alkaloids, saponin glycosides, proteins, carbohydrates, flavonoids and others. Because the Abutilon indicum has reported to have analgesic, antioxidant, laxative, anthelmintic and diuretic properties, it was chosen to be the topic of study in this review. Of these mentioned compounds saponin comes on priority and it was extracted from different plants beside abutilon such as sugar beet, soymilk, strawberry, plum and chickpea. The defense system of plants bases on saponin as it forms the attack line against pathogens. Saponin can be found in percentage about 30% in the leaves of Abutilon indium and it is seen to have cholesterol and glucose lowering properties beside antitumor ones. The study about the pharmacological properties of A. Indicum in Iraq area was recommended by the author to establish its effects against chronic diseases depending different doses in experimental animals.

Evinacumab — an ANGPTL3 inhibitor; a new drug in the treatment of lipid disorders. Review on the literature and clinical studies

Angiopoietin-like proteins (ANGPTL) are a family of several proteins, of which ANGPTL3, 4 and 8 are involved in lipid metabolism. These proteins, discovered relatively recently, regulate the availability of triglycerides for the heart, skeletal muscles and white and brown adipose tissue depending on the nutritional status of the body, thus contributing to the maintenance of energy homeostasis. ANGPTL3, 4 and 8 gene mutations are associated with a significant reduction in plasma lipid levels, which translates to a reduction in the risk of ischaemic heart disease and diabetes type 2. It was shown that blood levels of ANGPTL3, 4, 5 and 8 may change in various disease states, such as obesity or diabetes type 2, and thus may constitute biomarkers of the cardiovascular risk. Evinacumab, being a fully humanized anti-ANGPTL3 antibody, February, 11 th , 2021, as Evkeeza® preparation, has been registered by the US Food and Drug Administration for the treatment of homozygous familial hypercholesterolaemia. In clinical trials, evinacumab was characterized by a high lipid-lowering efficacy in patients with homozygous and heterozygous familial hypercholesterolaemia, as well as treatment-resistant hypercholesterolaemia and hypertriglyceridaemia. Another drug that reduces ANGPTL3 activity are antisense oligonucleotides targeting Angptl3 mRNA (ANGPTL3 ASO) which were also characterized by lipid lowering properties in clinical trials.

Biological application of canadine in the medicine for their lipid lowering properties and inhibitory effect on platelet aggregation: data analysis of various scientific research works

Biological application of canadine in the medicine for their lipid lowering properties and inhibitory effect on platelet aggregation: data analysis of various scientific research works

Nutraceuticals for the treatment of sarcopenia in chronic liver disease.

Sarcopenia, defined as loss of muscle mass, strength and function, is associated with adverse clinical outcomes in patients with cirrhosis. Despite improved understanding of the multifaceted pathogenesis, there are few established therapies to treat or prevent muscle loss in this population. This narrative review examines the available literature investigating the role of nutraceuticals for the prevention or treatment of muscle wasting in chronic liver disease. A comprehensive search or Medline and PubMED databases was conducted. Reference lists were screened to identify additional articles. A number of nutritional supplements and vitamins target the specific metabolic derangements that contribute to sarcopenia in cirrhosis including altered amino acid metabolism, hyperammonaemia and inflammation. Branched chain amino acid (BCAA) supplementation has proposed anabolic effects through dual pathways of enhanced ammonia clearance and stimulation of muscle protein synthesis. l-carnitine also has multimodal effects on muscle and shows promise as a therapy for muscle loss through anti-inflammatory, antioxidant and ammonia lowering properties. Other nutraceuticals including l-ornithine l-aspartate, omega-3 polyunsaturated fatty acids and zinc and vitamin D supplementation, may similarly have positive effects on muscle homeostasis, however further evidence to support their use in cirrhotic populations is required. Nutraceuticals offer a promising and likely safe adjunct to standard care for sarcopenia in cirrhosis. While there is most evidence to support the use of BCAA and l-carnitine supplementation, further well-designed clinical trials are needed to elucidate their efficacy as a therapy for muscle loss in this population.

Hypolipaemic nutraceutics: red yeast rice and Armolipid, berberine and bergamot.

Increased serum cholesterol levels constitute one of the main risk factors for cardiovascular diseases. Statins are a major method for reducing the levels which also lower the risk of cardiovascular events. However, these valuable drugs cannot be used in all patients who need them due to contraindications and intolerance. In such cases, help can be sought from nutraceutics that reduce the serum cholesterol concentration. Since there are numerous products of this type available at drugstores, registered as supplements, there seems to be a need to demonstrate their effectiveness in preventing cardiovascular diseases induced by atherosclerosis. In literature, increasingly more attention is drawn to red yeast rice, Armolipid, berberine and bergamot. This article presents knowledge about these nutraceutics based on clinical studies and expert statements relating to their use. The results of clinical studies and metaanalyses have shown that nutraceutics with cholesterol lowering properties, red yeast rice and Armolipid are the most favourable for reducing cardiovascular events. However, the evidence of benefits of berberine and bergamot is not so conclusive. Red yeast rice products and Armolipid may be used as an alternative treatment in statin intolerant patients, especially in combination with ezetimibe. These nutraceutics can be also considered, as an adjunct to diet therapy in primary prevention of cardiovascular diseases in patients with mild and moderate hypercholesterolaemia. The opinion of experts on berberine and bergamot is ambiguous.

Abstract 15205: MANP: A Novel ANP Analog for Hypertension Associated With Obesity and Metabolic Syndrome

Introduction: Atrial natriuretic peptide (ANP) plays an important role in blood pressure (BP) regulation via the second messenger cGMP. ANP also induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA). MANP is a new Mayo Clinic designed ANP analog consisting of the native ANP with a novel 12-amino-acid C-terminus extension. In experimental models, MANP is more potent than ANP in reducing BP and inducing natriuresis. These actions are mediated by the activation of the pGC-A receptor and generation of cGMP. To date, the BP pressure lowering, cGMP generating and lipolytic actions of MANP remain unexplored along with its safety and tolerability in subjects with hypertension (HTN) associated with metabolic disease. Hypothesis: In subjects with HTN, obesity and metabolic syndrome (MS), MANP administration is safe, well tolerated, activates cGMP and exerts BP lowering and lipolytic properties. Methods: Double-blind, placebo-control clinical trial in 22 subjects (17 receiving MANP) with HTN, obesity and MS involving a single subcutaneous (SQ) injection of MANP (2.5 μg/Kg) or placebo. Subjects were monitored and cardiovascular, cGMP and metabolic parameters were collected during 24 hours after the injection. Results: In all subjects, MANP was safe and well-tolerated with no serious adverse side effects. MANP increased mean cGMP plasma levels after 30 minutes (delta: 4.8 ± 2.0 pmol/mL, p=0.02) and 1 hour (delta: 2.9 ±1.3 pmol/mL, p=0.03) when compared to baseline. Six hours after MANP injection systolic BP decreased by 5.7 ± 2.9 mmHg (p=0.06) whereas subjects receiving placebo had no decrease in blood pressure values compared to baseline. During fasting period, one hour after the administration of MANP, NEFA plasma levels increased by 108.2 ± 37.4 μM (p=0.01). Conclusions: In subjects with HTN, obesity and MS, SQ MANP is safe, well tolerated and activates the pGC-A receptor as measured by a significant increase in the second messenger cGMP. Subjects receiving MANP showed a borderline significant decrease in systolic BP and a significant increase in NEFA circulating levels supporting anti-hypertensive and lipolytic properties. Our findings support MANP as a potential novel therapy for HTN associated with metabolic disease.

Novel Sulfonamide-Based Analogs of Metformin Exert Promising Anti-Coagulant Effects without Compromising Glucose-Lowering Activity.

Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 µmol/L for comp. 6 at 0.3 µmol/mL versus 11.4 ± 0.7 µmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not affect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin.

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE - EXECUTIVE SUMMARY.

Introduction: COVID-19 is now a global pandemic affecting millions of people Patients on dialysis are at an increased risk to COVID-19 infection due to their exposure in the health care setting Strategies for infection control and prevention are also being implemented in the dialysis units because of the increased risk of virus transmission within the unit Objective: Describe the different measures and strategies done to mitigate the spread of COVID-19 outbreak in a hospital based dialysis centre Methods: Review of the epidemic course with contact tracing was done from March 14 to May 14, 2020 in the dialysis unit of a tertiary hospital Results: Of 167 haemodialysis patients, 20 were considered COVID-19 suspects Eight tested positive-2 were traced to be exposed with the first confirmed case, 2 were handled by a COVID-19 infected healthcare worker (HCW) who was asymptomatic at time of contact while 2 asymptomatic patients tested positive during mass screening Two of 67 HCWs tested positive were exposed to patients Key interventions during the course of the outbreak included: mass testing of patients and HCWs after identifying 6 patients and 2 HCWs infected with COVID-19 using nasopharyngeal/oropharyngeal swabs by RT-PCR;dialysis of COVID-19 confirmed and suspected cases in isolation rooms separate from the dialysis unit (instead of cohorting);provision of adequate protective personal equipment for HCWs and surgical masks for all patients, environmental disinfection especially in the waiting area with strict social distancing and screening for signs and symptoms at the entrance of the unit Conclusion: Infection control strategies are needed to manage the spread of COVID-19 in dialysis centres These infection prevention measures should be implemented at the first indication of transmission in the area and should be maintained for the duration of the pandemic and until the area show no more reports of transmission