Antiatherogenic Effects Research Articles

Ipragliflozin and sitagliptin differentially affect lipid and apolipoprotein profiles in type 2 diabetes: the SUCRE study

BackgroundSGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters.MethodsThis is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20–74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120–399 mg/dL (1.35–4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment.ResultsIpragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin.ConclusionsWhile ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.

A REVIEW OF KOMBUCHA ANTIOXIDANT EFFECTS ON ATHEROSCLEROSIS IN PRECLINICAL STUDIES

Background Atherosclerosis is the leading cause of death among cardiovascular diseases in Indonesia, in which death is possible if uncontrolled. The prevalence of the disease may be prevented by consuming foods or drinks containing high levels of antioxidant such as kombucha. Exploration of kombucha properties as an antioxidant that will improve atherosclerosis could be obtained from preclinical studies. Objective To discuss the antioxidant effect of kombucha on atherosclerosis in preclinical studies. Method This study is a narrative review with literatures from 2013 to 2022. Result Kombucha is an antioxidant-rich beverage made from enzymes generated by the SCOBY bacteria, which are fermented in sweet tea for 7-14 days to achieve optimal quantities of polyphenols. In addition to the antioxidants in the blood, the effect will lower the levels of LDL, VLDL, triglycerides, and total cholesterol in the blood. Moreover, it can increase HDL in blood and inhibit lesion forming in the aorta. Conclusion Polyphenol in kombucha tea has an antiatherogenic effect that may prevent atherosclerosis in preclinical studies. Keywords: antioxidant, atherosclerosis, kombucha, polyphenol

Therapeutic Potential of Malaysian Stingless Bee Propolis Extract Targeting Macrophages in Atherogenesis: A Review

Propolis is a sticky substance that originates from the collection of plant saps and resins by stingless bees. The bees blend this material with pollen and wax flakes, and their salivary fluids combine with the mixture to produce a potent compound that contains various chemical constituents, such as flavonoids and phenolic compounds. Numerous studies have revealed that propolis from stingless bees displays anti-inflammatory, antioxidant, immunomodulatory, and cardioprotective properties. Geniotrigona thoracica is one of the Malaysian stingless bee species, and propolis from this species is composed of a wide array of biochemical compounds and antioxidant properties that may have an anti-atherogenic effect. This review highlights the possible role of propolis from the Malaysian stingless bee G. thoracica as a macrophage-targeted therapeutic in atherogenesis, as macrophage-derived foam cell formation is integral to the development of atherosclerosis. The review first describes the characteristics, chemical content, and antioxidant properties of propolis from G. thoracica. It then discusses the pathogenesis of atherosclerosis, with a focus on macrophage-derived foam cell formation. Subsequently, the anti-atherosclerotic effects of propolis from G. thoracica are presented, and recent studies on the anti-atherosclerotic effects of propolis from honeybees worldwide are summarized for comparison. Finally, future perspectives are emphasized, highlighting the knowledge gaps that need to be investigated by researchers in this field.

Expression of pro- and anti-inflammatory cytokines during anti-proprotein convertase subtilisin/kexin type 9 therapy in patients with statin-resistant familial hypercholesterolemia.

Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.

Comparing Similarity And Difference between Two Local Anesthetics, Lidocaine And Procaine

Amide type lidocaine and lipid type procaine are important anesthetics. In fact, they not only solve the problem of overused opioids, but also stimulate the invention of local anesthetic operations, which both declines the time of surgery and limits the possible damage of general anesthetics to patients’ bodies. But these two anesthetics also have their different target diseases, mechanisms, and side effects. For example, lidocaine is not only used for analgesic in dental and skin surgery operations, but also maintain the welfare of patients, who stay in the hospital waiting for recovery, by limiting the pain they could feel from their chronic illness. Actually, procaine has antiatherogenic effects, also multiple target sites which could provide some protection for the old while using. Besides, based on the fact that these chemicals come from different groups, amide type and lipid type, their mechanisms causing anesthetic effects could also be different, which would be introduced in the following context.

Salusin-α and salusin-β as new biological markers in cardiovascular diseases: literature review

Despite significant advances in medicine, cardiovascular disease continues to be the leading cause of death worldwide. An important task in cardiology is the search and study of new cardiovascular biological markers. In recent years, salusins have attracted the interest of scientists. Salusins are endogenous biologically active peptides, which were first identified in 2003. Thus far, studies have demonstrated that salusin-α and salusin-β play important roles in vascular remodeling, inflammation, hypertension, and atherosclerotic processes. Salusin-α exhibits an antiatherogenic effect, whereas salusin-β plays a proatherogenic role. Despite the diverse biological, physiological, and pathophysiological aspects of salusins, the exact mechanism of their cardiovascular effects is not fully known. Further in-depth studies of the role of salusins in cardiovascular diseases are required. The regulation of the concentration and expression of salusin-α and salusin-β may prove to be a promising strategy for the treatment of patients with cardiac diseases.

The effects of IGF-1 and IGFBP-2 treatments on the atherosclerosis in the aorta and the coronary arteries of the high cholesterol diet-fed rabbits

Several studies have demonstrated suppression of aortic atherosclerosis by insulin like growth factor-1 (IGF-1) in hypercholesterolemic rabbits. Though a recent study has reported that IGF-1 exerts anti-atherogenic effects in coronary arteries, the mechanisms of IGF-1 in coronary arteries need to be further verified. Studies about insulin like growth factor binding protein-2 (IGFBP-2) in atherosclerosis are rarely. The objective of this study is to examine the effects of IGF-1 and IGFBP-2 on the atherosclerosis development in the aorta and coronary arteries of the high-cholesterol diet (HCD)-fed rabbits. New Zealand white rabbits were fed either normal chow (n = 5) or a diet containing 1.0 % cholesterol (n = 18) for 12 weeks. Cholesterol-fed rabbits were given IGF-1 or IGFBP-2 or saline intravenously (each n = 6) for 10 weeks. The results revealed that IGF-1 decreased total cholesterol (TC) and low-density lipoprotein (LDL) levels (p < 0.05), whereas IGFBP-2 did not. IGF-1 significantly attenuated atherosclerotic lesions and reduced accumulated macrophages within the coronary artery plaques, whereas IGFBP-2 deteriorated these changes. Moreover, IGF-1 reduced serum platelet-activating factor acetylhydrolase levels, C reactive protein (CRP), and inhibited the protein expression levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). IGFBP-2 elevated serum 8-hydroxy-2′-deoxyguanosine levels, CRP, and promoted the protein expression levels of TNF-α and IL-6. In conclusion, IGF-1 can substantially suppress plaque formation in coronary arteries with a marked inhibition of macrophage accumulation likely via its anti-inflammatory properties, whereas IGFBP-2 plays an opposite effect on atherosclerosis. The present study highlighted a theoretical basis for pharmacological treatment of atherosclerosis.

Anti-atherogenic and Synergistic Effect of Decosapentanoic Acid/Linoleic Acid Fatty Acids via Janus Kinase [JAK] Mediate Inhibition of HMG-CoA Reductase in Rats Fed High Fat Diet

Anti-atherogenic and Synergistic Effect of Decosapentanoic Acid/Linoleic Acid Fatty Acids via Janus Kinase [JAK] Mediate Inhibition of HMG-CoA Reductase in Rats Fed High Fat Diet

Macrophage-targeted ultrasound nanobubbles for highly efficient sonodynamic therapy of atherosclerotic plaques by modulating M1-to-M2 polarization

Background and aimsSonodynamic therapy (SDT) is a new approach for the treatment of atherosclerosis (AS), yet the poor targeting ability of sonosensitizers limits its therapeutic efficacy. Herein, we reported a plaque-targeted nanoplatform modified with macrophage type A scavenger receptor (SR-A)-targeted peptide (designated as SR-A-Ce6NB) to augment the efficacy of low-intensity pulsed ultrasound (LIPUS)-mediated SDT of atherosclerotic plaque. MethodsSR-A-Ce6NB was fabricated by thin hydration method and biotin-avidin system, and its physicochemical properties, biocompatibility and plaque-targeting ability were investigated. RAW 264.7 cells were used for in vitro experimental studies. Male 6-week-old apolipoprotein E-deficient mice were fed a high-fat diet for 16 weeks to induce aortic atherosclerotic plaques. Plaque-bearing mice were randomly allocated into five groups (n = 6): control group, Ce6 + LIPUS group, Ce6NB + LIPUS group, SR-A-Ce6NB + LIPUS group and atorvastatin group. After treatment in each group, the aortic artery was harvested for Oil red O, H&E, Masson's trichrome staining, immunohistochemical and immunofluorescent staining. ResultsSR-A-Ce6NB with high stability and excellent biocompatibility was successfully fabricated. SR-A-Ce6NB could actively target activated macrophages and selectively accumulate in the plaque. SR-A-Ce6NB could be triggered by LIPUS and had a more potent sonodynamic effect than free Ce6 to potentiate SDT. SR-A-Ce6NB-mediated SDT enhanced the anti-atherogenic effect via modulating M1-to-M2 macrophage polarization and had an earlier onset of action on plaque than the statin-mediated effect. No apparent side effect was observed after intravenous SR-A-Ce6NB injection and LIPUS exposure. ConclusionsMacrophage-targeted nanoplatform SR-A-Ce6NB-mediated SDT provides a safe, effective and preferable anti-atherogenic therapy by mediating M1-to-M2 macrophage polarization.

The benefits of GLP1 receptors in cardiovascular diseases.

Glucagon like peptide-1 (GLP-1) receptor agonists are well established drugs for the treatment of type 2 diabetes (T2D). In addition to glycemic control, GLP-1 receptor agonists have beneficial other effects. They act by binding to GLP-1 receptors, which are widely distributed in the body, including cardiomyocytes and blood vessels. The aim of this article is to provide a comprehensive review of GLP-1 receptor agonists impact on cardiovascular outcomes and risk reduction. In the last decade, several cardiovascular outcomes trials (CVOT) have been conducted in order to explore cardiovascular benefit of GLP-1 receptor agonists. CVOTs primarily proved cardiovascular safety and tolerability of different GLP-1 receptor agonists, but also showed cardiovascular benefit of specific drugs. CVOTs have shown that GLP-1 receptor agonists reduce MACE in patients with T2D compared to placebo. In addition, they have positive impact on several cardiovascular risk factors such as obesity by promoting weight loss, blood pressure and blood lipid levels. Also, they stimulate the endothelium to produce nitric oxide, reduce oxidative stress, and have antiatherogenic and antiinflammatory effects. Studies have shown their positive impact on kidney outcomes in patients with T2D compared to placebo. The results of previous trials are encouraging in terms of multiple positive effects of GLP-1 receptor agonists. However, further research is needed to understand their full potential and all details of their mechanism of action, which will enable to expand the therapeutic indications and to determine their optimal use in clinical practice.

The effects of incretin mimetics on the level of the microbial metabolite trimethylamine-N-oxide, a marker of cardiovascular risk in type 2 diabetic patients

Background. The purpose was to investigate the effect of therapy with glucagon-like peptide-1 receptor agonists (GLP-1ra) on the serum concentration of trimethylamine-N-­oxide (TMAO), an intestinal microbiome metabolite, in patients with type 2 diabetes mellitus (T2DM) in relation to clinical and laboratory indicators and parameters of body composition. Materials and methods. Thirty-three T2DM patients (17 women and 16 men) were examined aged 31 to 72 years who had unsatisfactory control of carbohydrate metabolism (HbA1c &gt; 7.4 %) against the background of previous glucose-lowering therapy (metformin, sulfonylurea derivatives, insulin, gliflozin) and were administered GLP-1ra. Before the start of treatment and after 6 months of therapy, parameters of anthropometry, body composition were measured (using the bioelectrical impedance analysis with the Tanita analyzer); blood glucose and glycated hemoglobin, TMAO concentration, blood lipids were assessed. Results. Patients diagnosed with Т2DM had HbA1c &gt; 7.4 %; 91 % had general obesity (body mass index 34.7 ± 6.6 kg/m2), 100 % had abdominal obesity (waist circumference 118.00 ± 11.24 cm, Med ± SD). In 72 % of cases, there was a history of cardiovascular complications (myocardial infarction, stroke, coronary and peripheral atherosclerosis, arterial stenosis). Under the influence of a 6-month administration of GLP1ra, there was a decrease in the degree of total and abdominal obesity, a significant drop in the percentage of fat and the level of visceral fat, which was accompanied by an increase in hydration, a reduction in triglyceridemia and the concentration of very-low-density lipoprotein cholesterol (VLDL-C). A significant decrease in the level of TMAO microbial metabolite in the blood serum was recorded, which may reflect the antiatherogenic effect of GLP1ra, associated with the control of cholesterol and bile acid metabolism, the stimulation of VLDL-C receptors, and the effect on the secretion of insulin, glucagon, ghrelin, leptin, incretins. Conclusions. A study on the clinical effects of the incretin mimetic (GLP-1ra) in patients with T2DM confirmed its positive impact on glucose metabolism and blood lipids. At the same time, during GLP-1ra therapy, an improvement of some compositional and lipid indicators (visceral fat, triglycerides, VLDL-C) was recorded with a simultaneous decrease in the concentration of TMAO toxic metabolite.

Inhibition of EphA2 protects against atherosclerosis by synergizing with statins to mitigate macrophage inflammation

Statins are highly prevalent in patients with coronary artery disease. Statins exert their anti-inflammatory effects on the vascular wall and circulating levels of pro-inflammatory cytokines. However, increasing attention revealed the exacerbation of macrophage inflammation induced by statins, and a clear mechanistic explanation of whether the detrimental effects of statins on macrophage inflammatory phenotypes outweigh the beneficial effects is has not yet been established. Here, RNA-sequencing and RT-qPCR analyses demonstrated that statins significantly upregulated EphA2, Nlrp3, IL-1β and TNF-α expression in macrophages. Mechanistically, we found that atorvastatin reduced KLF4 binding to the EphA2 promoter using KLF4-chromatin immunoprecipitation, suppressed HDAC11-mediated deacetylation and subsequently led to enhanced EphA2 transcription. The 4D-label-free proteomics analysis further confirmed the upregulated EphA2 and inflammatory signals. Furthermore, the proinflammatory effect of atorvastatin was neutralized by an addition of recombinant Fc-ephrinA1, a selective Eph receptor tyrosine kinase inhibitor (ALW-II-41–27) or EphA2-silencing adenovirus (siEphA2). In vivo, EphA2 was identified a proatherogenic factor and apoE-/- mice placed on a high-fat diet following gastric gavage with atorvastatin exhibited a consistent elevation in EphA2 expression. We further observed that the transfection with siEphA2 in atorvastatin-treated mice significantly attenuated atherosclerotic plaque formation and abrogated statin-orchestrated macrophages proinflammatory genes expression as compared to that in atorvastatin alone. Increased plaque stability index was also observed following the addition of siEphA2, as evidenced by increased collagen and smooth muscle content and diminished lipid accumulation and macrophage infiltration. The data suggest that blockage of EphA2 provides an additional therapeutic benefit for further improving the anti-atherogenic effects of statins.

Neuroprotective potential of gliflozins

Gliflozins are a relatively new class of oral antihyperglycemic drugs that are increasingly being introduced into routine practice in the treatment of patients with type 2 diabetes mellitus (DM2). The hypoglycemic effect of gliflozins is associated with the stimulation of glucosuria, however, in addition to a pronounced hypoglycemic effect and high safety, these drugs also have many pleiotropic properties, due to the presence of many direct and indirect points of application. The purpose of this paper is to provide an overview of the currently best studied neuroprotective effects of this class of drugs. As materials in the course of the work, studies of foreign colleagues published in the period 2008–2022 were used. Analysis of the works showed that the neuroprotective effect of gliflozins is associated with many different mechanisms. Thus, gliflozins realize an anti-inflammatory effect by activating the M2 subpopulation of macrophages, reducing pro-inflammatory neurotransmitters (related primarily to the inflammasome). In addition, by reducing the activity of the mTOR signaling pathway, the drugs reduce the amount of beta-amyloid and improve neurotransmission. A group of works also showed the antiacetylcholinesterase effect of gliflozins, not to mention the decrease in the intensity of non-enzymatic protein glycation and insulin resistance. All of the above mechanisms provide an anti-inflammatory, anti-atherogenic effect, improve cognitive abilities in patients, reduce the frequency of hemorrhagic stroke, and can also potentially improve prognosis in patients with Alzheimer’s disease (AD). The effects described above were obtained during preclinical trials and many experimental studies, and some effects have already demonstrated their consistency in prospective clinical trials. However, the data obtained are still insufficient to form clear indications for this class of drugs in neurology, so the topic requires further study and clinical trials.

Effect of Flavonoids on MCP-1 Expression in Human Coronary Artery Endothelial Cells and Impact on MCP-1-Dependent Migration of Human Monocytes.

The monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (CC motif) ligand 2 (CCL2), is involved in the formation, progression, and destabilization of atheromatous plaques. Flavonoids, found in fruits and vegetables, have been associated with various health-promoting properties, including antioxidant, anti-inflammatory, and cardioprotective effects. In the present study, the flavonoids quercetin, kaempferol, and luteolin, but not cannflavin A, were shown to substantially inhibit interleukin (IL)-1β-induced MCP-1 mRNA and protein expression in human coronary artery endothelial cells (HCAEC). At the functional level, conditioned medium (CM) from IL-1β-stimulated HCAEC caused an increase in the migration of THP-1 monocytes compared with CM from unstimulated HCAEC. However, this induction was suppressed when IL-1β-treated HCAEC were coincubated with quercetin, kaempferol, or luteolin. The functional importance of MCP-1 in IL-1β-induced monocyte migration was supported by experiments showing that neutralization of MCP-1 in the CM of IL-1β-treated HCAEC led to a significant inhibition of migration. In addition, a concentration-dependent induction of monocyte migration in the presence of recombinant MCP-1 was demonstrated. Collectively, the flavonoids quercetin, kaempferol, and luteolin were found to exert potential antiatherogenic effects in HCAEC, challenging further studies with these compounds.

Role of Vitamins in Cardiovascular Health: Know Your Facts - Part 1.

Cardiovascular (CV) disease (CVD) is a major cause of morbidity and mortality world-wide, thus it is important to adopt preventive interventions. Observational data demonstrating CV benefits of vitamin supplements, advanced by self-proclaimed experts have resulted in ~50% of Americans reporting the use of multivitamins for health promotion; this practice has led to a multi-billion-dollar business of the multivitamin-industry. However, the data on the extensive use of multivitamins show no consistent benefit for CVD prevention or all-cause mortality, while the use of certain vitamins might prove harmful. Thus, the focus of this two-part review is on the attributes or concerns about specific vitamins on CVD. In Part 1, the CV effects of specific vitamins are discussed, indicating the need for further supportive evidence of potential benefits. Vitamin A preserves CV homeostasis as it participates in many biologic functions, including atherosclerosis. However, supplementation could potentially be harmful. Betacarotene, a pro-vitamin A, conveys pro-oxidant actions that may mitigate any other benefits. Folic acid alone and certain B-vitamins (e.g., B1/B2/B6/B12) may reduce CVD, heart failure, and/or stroke, while niacin might increase mortality. Vitamin C has antioxidant and cardioprotective effects. Vitamin D may confer CV protection, but all the data are not in agreement. Combined vitamin E and C have antiatherogenic effects but clinical evidence is inconsistent. Vitamin K seems neutral. Thus, there are individual vitamin actions with favorable CV impact (certain B-vitamins and vitamins C and D), but other vitamins (β-carotene, niacin) may potentially have deleterious effects, which also holds true for high doses of fat-soluble vitamins (A/D/E/K).

Role of Vitamins in Cardiovascular Health: Know Your Facts-Part 2.

Cardiovascular disease (CVD) is a major cause of morbidity/mortality world-wide, hence preventive interventions are crucial. Observational data showing beneficial CV effects of vitamin supplements, promoted by self-proclaimed experts, have led to ~50% of Americans using multivitamins; this practice has culminated into a multi-billion-dollar business. However, robust evidence is lacking, and certain vitamins might incur harm. This two-part review focuses on the attributes or concerns about specific vitamin consumption on CVD. The evidence for indiscriminate use of multivitamins indicates no consistent CVD benefit. Specific vitamins and/or combinations are suggested, but further supportive evidence is needed. Data presented in Part 1 indicated that folic acid and certain B-vitamins may decrease stroke, whereas niacin might raise mortality; beta-carotene mediates pro-oxidant effects, which may abate the benefits from other vitamins. In Part 2, data favor the anti-oxidant effects of vitamin C and the anti-atherogenic effects of vitamins C and E, but clinical evidence is inconsistent. Vitamin D may provide CV protection, but data are conflicting. Vitamin K appears neutral. Thus, there are favorable CV effects of individual vitamins (C/D), but randomized/controlled data are lacking. An important caveat regards the potential toxicity of increased doses of fat-soluble vitamins (A/D/E/K). As emphasized in Part 1, vitamins might benefit subjects who are antioxidant-deficient or exposed to high levels of oxidative-stress (e.g., diabetics, smokers, and elderly), stressing the importance of targeting certain subgroups for optimal results. Finally, by promoting CV-healthy balanced-diets, we could acquire essential vitamins and nutrients and use supplements only for specific indications.

Help sought for gout sufferers: A historical look at the treatment of gout in the New Kingdom of Granada

IntroductionDuring the colonial period, despite scarce knowledge and resources, doctors and apothecaries developed medical prescriptions mainly of vegetable origin for the management of multiple diseases, including gout. ObjectiveTo contextualise and describe the use of medical prescription in the early 19th century in the New Kingdom of Granada for the treatment of gout. Material and methodsA documentary search of medical prescription was carried out in the Cipriano Rodríguez Santamaría Historical Archive of the Octavio Arizmendi Posada Library of the University of La Sabana. Subsequently, an open literature review was carried out in the ScienceDirect, ClinicalKey, and Scielo databases in English and Spanish. ResultsPistacia lentiscus, the basis of the recipe described, has a high content of terpenes, tannins, flavonoids, and coumarins, which generate anti-inflammatory, antimicrobial, antioxidant, antibiotic, antiviral, and anti-atherogenic effects, among others. ConclusionMastic, one of the components of these recipes, possesses anti-inflammatory and antioxidant properties, which could explain its relative efficacy in the treatment of gout in the 19th century.

The Prophylactic Effect of Eucheuma spinosum on Total Blood Cholesterol Levels in Rattus norvegicus Dexamethasone-Induced

Hyperlipidemia is one of the main risk factors for heart disease caused by the formation of atherosclerosis. Eucheuma spinosum contains a natural antioxidant flavonoid, which has an antiatherogenic effect that can inhibit the formation of cholesterol in the liver so that it can prevent the development of atherosclerosis. This study aims to determine the effect of prophylactic administration of Eucheuma spinosum on the total cholesterol levels of Rattus novergicus induced by dexamethasone. This study was an experimental design with a post-test-only control group design. This study would use 24 white male Rattus norvegicus divided into three groups; a negative control group (K-) without treatment, a positive control group (K+) induced dexamethasone 8 mg/Kg BW on day 14 until day 20, treatment group (KP) given Eucheuma spinosum extract 200 mg/Kg BW on day 8 until day 20 as Prophylactic and on day 14 until day 20 induced dexamethasone 8 mg/Kg BW. After completing the treatment period, all groups were terminated and taken total calculation of cholesterol levels through the aorta of rats. Data was analyzed statistically computerized. The results of the study of total cholesterol levels that used Kruskal-Wallis test showed differences between groups (p&lt;0.001). There was a decrease in total cholesterol levels in the treatment group (p&lt;0.024) compared with the positive control group. The administration of Eucheuma spinosum extract as a prophylactic dose of 200 mg/Kg BW for 14 days could reduce the total cholesterol level of Rattus norvegicus induced by dexamethasone compared to those not given Eucheuma spinosum extract.

Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway

ABSTRACT Low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density lipoprotein cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogenic effects, but the underlying molecular mechanisms remain poorly understood. Therefore, we studied the effects of DMY on LDLR and PCSK9. The results showed DMY promoted LDLR protein and mRNA expression and increased LDL uptake in HepG2 cells. DMY inhibited intracellular PCSK9 protein and mRNA expression. And it also significantly reduced PCSK9 levels in the cell culture medium. Furthermore, DMY inhibited the expression of PCSK9 through the liver nuclear transcription factor 1 A (HNF1A) and increased the protein expression of LDLR. Taken together, our results support the idea that DMY regulates LDL-c metabolism through PCSK9/LDLR signaling. This study reveals the potential mechanism of DMY’s anti-atherogenic effect and provides a theoretical basis for dietary DMY supplementation.

Impaired Reverse Cholesterol Transport is Associated with Changes in Fatty Acid Profile in Children and Adolescents with Abdominal Obesity

BackgroundAbdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. ObjectivesOur aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. MethodsSeventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. ResultsThe obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). ConclusionsChildren and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.