Folic acid and plasma lipids: Interactions and effect of folate supplementation.

Dyslipidaemia and hyperhomocysteinemia are known risk factors for cardiovascular disease. While it is evident that optimization of plasma lipid is associated with low risk of cardiovascular disease in the general population, it is not yet fully clear whether reduction of homocysteinemia is associated with an improvement in risk in all subjects. The aim of our narrative review is to highlight eventual effects of folate supplementation on LDL-C levels, LDL-C oxidation and atherosclerosis-related complications. A comprehensive literature search was done in electronic database, including PubMed, Web of Science, Cochrane, and Scopus from inception up to January 2024. Based on the available evidence, epidemiological data, pathophysiological observations and meta-analyses of randomized clinical trials suggest that folic acid supplementation may modestly but significantly improve plasma lipid levels, lipid atherogenicity, and atherosclerosis-related early vascular damage, and that folic acid supplementation may significantly reduce the risk of cerebrovascular disease. Considering the low-cost and high safety profile of folic acid, its long-term supplementation could be considered for dyslypidaemic patients in secondary prevention for cardiovascular disease.

Treatment of dyslipidemia in acute coronary syndrome.

Despite numerous improvements in the management of acute coronary syndrome(ACS), it is a major cause of mortality in India. Lipids play a critical role in pathogenesis of ACS and reduction of lipid parameters plays a pivotal role in secondary prevention. High total cholesterol and high low-density lipoprotein(LDL) are the major lipid abnormalities globally as well as in Indians. Among all the lipid parameters, LDL is the primary target of lipid-lowering therapies across the globe. High-dose statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bempedoic acid are recommended therapies for LDL reduction in ACS patients. Statins have pleiotropic effects on the modulation of thrombogenesis, endothelial dysfunction, and myocardial protection. Multiple randomised controlled trials and meta-analyses have shown that the use of high-dose statin has significant benefits in ACS. LDL reduction goal is < 55 mg/dl or at least 50 % reduction from the baseline regardless of age or gender. Non-fasting LDL should be measured soon after the ACS as it varies minimally with food intake. The first line of therapy after ACS is to advise lifestyle modifications, combination therapy including high-dose statin with ezetimibe, and evaluation after 4-6 weeks of the index event. If the goal is not achieved then PCSK 9 inhibitors or Bempedoic acid should be used in combination with statins and ezetimibe to reduce recurrent ischaemic events. Despite the proven effect of these lipid-lowering therapies, undertreatment is still a big hurdle across the globe. Prohibitive costs, adverse effects, medication non-adherence, variation in health practice in different countries, and clinical inertia to prescribe this medication by physicians are the main reasons for the undertreatment.

The Impact of an 8-Week Supplementation with Fermented and Non-Fermented Aronia Berry Pulp on Cardiovascular Risk Factors in Individuals with Type 2 Diabetes.

Aronia berries contain antioxidants that may be health-promoting, e.g., demonstrated positive effects on hypertension and dyslipidaemia. There is a close link between cardiovascular diseases and hypertension and dyslipidaemia, and cardiovascular events are the leading cause of death among subjects with type 2 diabetes (T2D). Thus, we investigated the effect of an 8-week supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE), and placebo on cardiovascular risk factors. Snack bars were produced containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-crossover design. We examined the effects of aronia extracts on blood pressure, adiponectin, and high-sensitive C-reactive protein, and found no effects. After supplementation with placebo, there were significantly higher blood concentrations of total cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total cholesterol and LDL-cholesterol than the AE group. Furthermore, we observed an increase in HDL-cholesterol in the FAE group and an increase in triglyceride in the AE group. Thus, we assume that the raisins may have increased the participants' cholesterol levels, with both AE and FAE having the potential to prevent this increase.

Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia.

BACKGROUND: Evidence from preclinical studies has found a correlation between the development of type 2 diabetes (T2D) and vitamin D deficiency. However, evidence from randomized controlled trials (RCTs) revealed inconclusive results on vitamin D supplementation. We explored the effect of vitamin D on inflammation and dyslipidemia in T2D. METHODS: We comprehensively searched for RCTs evaluating the effect of vitamin D in T2D on PubMed. Data were analyzed using Review Manager 5.3 and reports, such as standardized mean difference (SMD) and 95% confidence intervals (CI) at a 5% significant level using a random effect model. RESULTS: This study revealed a significant reduction in tumor necrosis factor-alpha (TNF-α) SMD = (-0.51, 95%CI (-0.93, -0.09); p = 0.02), high sensitivity C-reactive protein (hs-CRP) SMD = (-1.06, 95%CI (-1.67, -0.45); p < 0.05) in vitamin D compared to placebo. Additionally, interleukin-6 (IL-6) exhibited a marginal effect SMD = (-0.52, 95%CI (-1.05, 0.01), p = 0.05). Furthermore, a significant reduction in the level of triglycerides SMD = (-0.65, 95%CI (-1.11, -0.18), p < 0.05) was observed, concomitant to a significantly increased high-density lipoprotein (HDL) level SMD = (0.53, 95%CI (0.08, 0.98), p = 0.02). However, no statistically significant changes were observed in total cholesterols SMD = (-0.16, 95%CI (-0.57, 0.24), p = 0.43) and low-density lipoprotein (LDL) SMD = (-0.06, 95%CI (-0.37, 0.24), p = 0.67). CONCLUSIONS: These findings suggest that vitamin D supplementation may be beneficial in ameliorating inflammation and dyslipidemia in T2D patients.

Flash'O real-world evidence programme - Attitude and practices toward the use of omega-3 FA by physicians from Middle East Countries.

The Flash'O project was designed to provide insights into the current use of prescription omega-3 and their perceived benefits by physicians in real-world clinical practice, in Russia, Saudi Arabia, Thailand, and Gulf countries, and to determine the adherence of physicians to dyslipidemia management guidelines. The present study focuses on Flash'O's process and results in Middle East countries. A total of 338 physicians and specialists completed the online questionnaire. Most responding physicians were male (91.7%), general practitioners (42.6%) with more than 5 years of seniority (80.4%) and saw more than 50 patients a week (71.5%). Most surveyed physicians (64.2%) reported using guidelines in their daily practice for the management of their patients with dyslipidemia. They mostly followed national guidelines (68.6%). American or European ones were less commonly used. Responding physicians thought that omega-3 supplementation could be more beneficial in all types of dyslipidemia, except high non- hight density lipoproteins, and for patients suffering from obesity, type 2 diabetes mellitus, acute coronary syndrome with ST-segment elevation myocardial infarction and high cardiovascular diseases risk (score ≥ 5% and < 10%), but less beneficial in chronic kidney disease. Respondents recommended omega-3 to their patients mainly after statin treatment in patients with dyslipidemia and for the treatment of dyslipidemia. This survey confirmed that omega-3 fatty acids are at the heart of the cardiovascular medical strategy.

Myrtle Berries Seeds Prevent Dyslipidemia, Inflammation, and Excessive Cardiac Reactive Oxygen Species Production in Response to High-Fat Diet-Induced Obesity.

Anthocyanins are the major polyphenols in myrtle berries seeds aqueous extract (MBSAE). This study investigates the protective potentials of MBSAE against obesity lipotoxicity and inflammation induced by a high-fat diet (HFD). It also describes the underlying mechanisms involved in its protective effects, with special attention to myocardial reactive oxygen species (ROS) production. Male Wistar rats were fed HFD for 6 weeks to induce obesity. MBSAE (100 mg/kg, b.w., p.o.) was orally administered to HFD-fed rats. Anti-obesity effects were triggered by the inhibitory action of the MBSAE against the weights of the body, its relative heart and the total abdominal fat. Treatment with MBSAE also restored the lipid profile to baseline compared with the HFD rats and lowered also the white blood cells count, including neutrophils, lymphocytes, and basophils number as well as cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1ß) levels in the rats serum, thus improving the tissue inflammatory status associated with obesity. Exposure of rats to HFD during 6 weeks induces a myocardial oxidative stress as assessed by deleterious effects on lipoperoxidation state, antioxidant enzyme (SOD, CAT, and GPx) activities as well as sulfhydryl groups and GSH rates. Of importance, our study shows also that HFD provokes a heart ROS (H2O2, OH•, and O2•-) overload. Of interest, all these oxidative heart disturbances were clearly ended by MBSAE treatment. Therefore, consumption of MBSAE as a natural extract may be a potential therapeutic strategy to treat obesity-associated diseases.

16-Hydroxy-ent-halima-5(10),13-dien-15,16-olide from Polyalthia longifolia targets adipogenesis by inhibiting mitotic clonal expansion and ameliorates dyslipidemia.

Obesity-related metabolic disorders are increasing at an alarming rate worldwide. The FDA has approved many molecules for weight loss therapy; most of them act on the gut level by inhibiting lipid uptake or on the central nervous system by controlling appetite. Limitations and drawbacks have propelled the search for new pharmacophores exhibiting favourable metabolic alteration at adipocytes, and natural products have always been there to prove their worth. In our efforts, we have identified 16-hydroxy-ent-halima-5(10),13-dien-15,16-olide (PLH), a halimane diterpene isolated from Polyalthia longifolia, demonstrating anti-adipogenic and anti-dyslipidemic activity. It inhibited adipogenesis in 3T3-L1 preadipocyte and C3H10T1/2 mesenchymal stem cell lines. Furthermore, it decreased set of adipogenic markers at transcript and protein levels. Cell cycle studies indicated that PLH halts the mitotic clonal expansion. Mechanistic studies shows that PLH activate Wnt/ß-catenin signaling pathway to inhibit the adipogenesis. The study suggested that PLH inhibited adipogenesis during the early phase of differentiation by targeting mitotic clonal expansion and arresting the cell cycle in the G1 phase of the cell cycle. It improved the dyslipidemic condition in HFD-fed hamsters by decreasing the body weight, fat mass, eWAT weight and improving the serum lipid profile. Overall, PLH has been found as a potential drug candidate and a pharmacophore for combating metabolic disorders including obesity and dyslipidemia.

Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.

Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.

Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association.

Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations for lifestyle therapies to manage dyslipidemia. This Clinical Perspective provides an update with a focus on nutrition interventions for the three most common dyslipidemias in adults: 1) low-density lipoprotein cholesterol (LDL-C) elevation; 2) triglyceride (TG) elevation, including severe hypertriglyceridemia with chylomicronemia; and 3) combined dyslipidemia, with elevations in both LDL-C and TG levels. Lowering LDL-C and non-high-density lipoprotein cholesterol are the primary objectives for reducing ASCVD risk. With severe TG elevation (≥500 mg/dL), the primary objective is to prevent pancreatitis and ASCVD risk reduction is secondary. Nutrition interventions that lower LDL-C levels include reducing cholesterol-raising fatty acids and dietary cholesterol, as well as increasing intakes of unsaturated fatty acids, plant proteins, viscous fibers, and reducing adiposity for patients with overweight or obesity. Selected dietary supplements may be employed as dietary adjuncts. Nutrition interventions for all patients with elevated TG levels include restricting intakes of alcohol, added sugars, and refined starches. Additional lifestyle factors that reduce TG levels are participating in daily physical activity and reducing adiposity in patients with overweight or obesity. For patients with severe hypertriglyceridemia, an individualized approach is essential. Nutrition interventions for addressing concurrent elevations in LDL-C and TG include a combination of the strategies described for lowering LDL-C and TG. A multidisciplinary approach is recommended to facilitate success in making and sustaining dietary changes and the assistance of a registered dietitian nutritionist is highly recommended.

[Update lipidology : Evidence-based treatment of dyslipidemia]. / Update Lipidologie : Evidenzbasierte Behandlung von Fettstoffwechselstörungen.

The treatment of elevated plasma lipid levels plays an important role in prevention of atherosclerosis. Lowering of low-density lipoprotein (LDL) cholesterol with statins and if required with additional ezetimibe, bempedoic acid and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is of utmost importance. While lifestyle modification can strongly influence the cardiovascular risk, it only plays a minor role in lowering LDL cholesterol values. The overall (absolute) cardiovascular risk determines if and in what intensity lipid-lowering treatment should be implemented. Based on new results from interventional studies the LDL cholesterol target values have been reduced in recent years. Thus, in patients with a very high risk (for example patients with established atherosclerotic disease) an LDL cholesterol level of < 55 mg/dl (< 1.4 mmol/l, conversion mg/dl×0.02586=mmol/l) and at least a 50% reduction from baseline should be strived for. With respect to elevated triglyceride levels, either alone or simultaneously with elevated LDL cholesterol levels, the treatment goals are less clearly defined, despite the fact that elevated triglyceride levels are causally linked to atherosclerotic events. Lifestyle modifications can significantly reduce triglyceride levels and are often more effective than specific triglyceride-lowering medications, such as fibrates and omega­3 fatty acids. New lipid-lowering drugs for the treatment of patients with severely elevated triglyceride levels and elevated lipoprotein(a) levels are being developed but their clinical benefits still have to be confirmed in endpoint studies.

Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Digeda-4 decoction and its disassembled prescriptions improve dyslipidemia and apoptosis by regulating AMPK/SIRT1 pathway on tyloxapol-induced nonalcoholic fatty liver disease in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and the leading cause of chronic liver disease worldwide. Digeda-4 decoction (DGD-4) is a commonly prescribed Mongolian herbal drug for treating acute and chronic liver injury and fatty liver. However, the mechanisms underlying the improvement of dislipidemia and liver injury via treatment with DGD-4 remain unclear. Disassembling a prescription is an effective approach to studying the effects and mechanisms underlying Mongolian medicine prescriptions. By disassembling a prescription, it is feasible to discover effective combinations of individual herbs to optimize a given prescription. Accordingly, we disassembled DGD-4 into two groups: the single Lomatogonium rotatum (L.) Fries ex Nym (LR) (DGD-1) and non-LR (DGD-3). AIM OF THIS STUDY: To study whether DGD-4 and its disassembled prescriptions have protective effects against tyloxapol (TY)-induced NAFLD and to explore the underlying mechanisms of action and compatibility of prescriptions. MATERIAL AND METHODS: NAFLD mice were developed by TY induction. Biochemical horizontal analyses, enzyme-linked immunosorbent assay, and liver histological staining were performed to explore the protective effects of DGD-4 and its disassembled prescriptions DGD-3 and DGD-1. Furthermore, we performed immunohistochemical analyses and Western blotting to further explore the expression of target proteins. RESULTS: DGD-4 and its disassembled prescriptions could inhibit TY-induced dislipidemia and liver injury. In addition, DGD-4 and its disassembled prescriptions increased the levels of p-AMPKα and p-ACC, but decreased the levels of SREBP1c, SCD-1, SREBP-2, and HMGCS1 proteins. The activation of lipid metabolic pathways SIRT1, PGC-1α, and PPARα improved lipid accumulation in the liver. Moreover, DGD-4 could inhibit hepatocyte apoptosis and treat TY-induced liver injury by upregulating the Bcl-2 expression, downregulating the expression of Bax, caspase-3, caspase-8, and the ratio of Bax/Bcl-2, and positively regulating the imbalance of oxidative stress (OxS) markers (such as superoxide dismutase [SOD], catalase [CAT], malondialdehyde [MDA], and myeloperoxidase [MPO]). DGD-1 was superior to DGD-3 in regulating lipid synthesis-related proteins such as SREBP1c, SCD-1, SREBP-2, and HMGCS1. DGD-3 significantly affected the expression of lipid metabolic proteins SIRT1, PGC-1α, PPARα, apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, and the regulation of Bax/Bcl-2 ratio. However, DGD-1 showed no regulatory effects on Bax and Bcl-2 proteins. CONCLUSION: This study demonstrates the protective effects of DGD-4 in the TY-induced NAFLD mice through a mechanism involving improvement of dyslipidemia and apoptosis by regulating the AMPK/SIRT1 pathway. Although the Monarch drug DGD-1 reduces lipid accumulation and DGD-3 inhibits apoptosis and protects the liver from injury, DGD-4 can be more effective overall as a therapy when compared to DGD-1 and DGD-3.

The anti-dyslipidemia property of saffron petal hydroalcoholicextract in cardiovascular patients: A double-blinded randomized clinical trial.

BACKGROUND AND AIMS: Dyslipidemia is one of the most important risk factors of cardiovascular diseases (CVDs). Despite developments in pharmacological treatments for dyslipidemia there are several challenges. Recently some herbs highly considered to control dyslipidemia due to their low toxicity and high potency. In this study we investigated the effects of saffron petals on the lipid profile of dyslipidemia patients as well as several other biochemical blood factors. METHODS: In this double blind, placebo controlled, clinical trial, we used systematic random sampling to divide 40 patients with at least two abnormalities in the following factors: (high-density lipoproteins (HDL) ≤40, low-density lipoproteins (LDL) ≥130, triglycerides (TG) ≥200, total cholesterol (Cho) ≥200), into 2 groups of 21 ones. At the end of the intervention period, serum lipid factors, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, creatinin (CR) and fasting blood sugar (FBS) were measured and statistically compared with their values just before the intervention. RESULTS: We found that the saffron petal pills markedly (P < 0.001) decreased the serum lipid levels of patients (TG, Cho and LDL) in the intervention group (113.81 ± 12.93, 56.52 ± 4.68 and 48.28 ± 3.70) as compared to the placebo group (18.42 ± 15.79, 4.57 ± 4.40 and 7.38 ± 3.54). Also, comparing the mean value of differences in two groups before and after the intervention showed significant reduction in TG (113.81 ± 26), Cho (56.53 ± 0.30) and LDL (48.28 ± 4.30) levels (P < 0.001). CONCLUSIONS: The saffron petal pills considerably reduced blood serum lipid profile and as well as urea and CR of dyslipidemia patients. So, this plant may be used as a potent phytomedicine for treatment and prevention of dyslipidemia and cardiovascular disorders. However, the results indicated that no statistical change was observed in the level of other biochemical blood factors such as ALT, AST, ALP and FBS.

Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia.

Gyejibongnyeong-hwan (GBH), a traditional Chinese medicine, is used in clinical practice to treat blood stasis in metabolic diseases. Herein, we examined the effects of GBH on dyslipidemia and investigated the underlying mechanisms by focusing on modulation of the gut microbiota-bile acid axis by GBH. We utilized a Western diet-induced dyslipidemia mouse model and divided animals into the following four groups (n = 5 each): the normal chow diet, vehicle control (WD), simvastatin (Sim, 10 mg/kg/day simvastatin; positive control), and GBH (GBH, 300 mg/kg/day) groups. The drugs were administered for 10 weeks, and morphological changes in the liver and aorta were analyzed. The mRNA expression of genes related to cholesterol metabolism, gut microbiota, and bile acid profiles were also evaluated. The GBH group showed significantly lower levels of total cholesterol, accumulation of lipids, and inflammatory markers in the liver and aorta of Western diet-fed mice. Low-density lipoprotein cholesterol levels were significantly lower in the GBH group than in the WD group (P < 0.001). The expression of cholesterol excretion-associated genes such as liver X receptor alpha and ATP-binding cassette subfamily G member 8, as well as the bile acid synthesis gene cholesterol 7 alpha-hydroxylase, which lowers cholesterol in circulation, was increased. Furthermore, GBH inhibited the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 signaling pathway through the interactions of gut microbiota with bile acids acting as FXR ligands, which included chenodeoxycholic acid and lithocholic acid. Overall, GBH improved dyslipidemia induced by a Western diet by modulating the gut microbiota-bile acid axis.

Formulation, and optimization of transdermal Atorvastatin Calcium-Loaded Ultra-flexible vesicles; ameliorates poloxamer 407-caused dyslipidemia.

Atorvastatin calcium (AC), a cholesterol-lowering medication, has limited oral bioavailability (14 %) and adverse impacts on the gastrointestinal tract (GIT), liver, and muscle. So, in an effort to improve the poor availability and overcome the hepatotoxicity complications attendant to peroral AC administration, transdermal transfersomal gel (AC-TFG) was developed as a convenient alternative delivery technique. The impact of utilizing an edge activator (EA) and varying the phosphatidylcholine (PC): EA molar ratio on the physico-chemical characteristics of the vesicles was optimized through a Quality by Design (QbD) strategy. The optimal transdermal AC-TFG was tested in an ex-vivo permeation study employing full-thickness rat skin, Franz cell experiments, an in-vivo pharmacokinetics and pharmacodynamics (PK/PD) evaluation, and a comparison to oral AC using poloxamer-induced dyslipidemic Wister rats. The optimized AC-loaded TF nanovesicles predicted by the 23-factorial design strategy had a good correlation with the measured vesicle diameter of 71.72 ± 1.159 nm, encapsulation efficiency of 89.13 ± 0.125 %, and cumulative drug release of 88.92 ± 3.78 % over 24 h. Ex-vivo data revealed that AC-TF outperformed a free drug in terms of permeation. The pharmacokinetic parameters of optimized AC-TFG demonstrated 2.5- and 13.3-fold significant improvements in bioavailability in comparison to oral AC suspension (AC-OS) and traditional gel (AC-TG), respectively. The transdermal vesicular technique preserved the antihyperlipidemic activity of AC-OS without increasing hepatic markers. Such enhancement was proven histologically by preventing the hepatocellular harm inflicted by statins. The results showed that the transdermal vesicular system is a safe alternative way to treat dyslipidemia with AC, especially when given over a long period of time.

Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia.

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with ß-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.

Medical Management of Dyslipidemia for Secondary Stroke Prevention: Narrative Review.

Dyslipidemia is a major risk factor for stroke, following hypertension, diabetes, and smoking, and is an important risk factor for the prevention and treatment of coronary artery disease and peripheral vascular disease, including stroke. Recent guidelines recommend considering low-density lipoprotein cholesterol (LDL-C)-lowering therapies, such as statins (preferably), ezetimibe, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to prevent the occurrence or recurrence of stroke, adhering to the "lower is better" approach. In this review, we examined the evidence supporting lipid-lowering medications like statins, ezetimibe, and PCSK9 inhibitors for secondary stroke prevention and dyslipidemia management in different stroke subtypes. Stroke guidelines advocate for administering the maximum tolerable dose of statins as the primary treatment and as soon as possible despite the potential for new-onset diabetes mellitus and possible muscle and liver toxicity due to their demonstrated benefits in secondary prevention of cardiovascular diseases and mortality reduction. When statin use is insufficient for LDL lowering, ezetimibe and PCSK9 inhibitors are recommended as complementary therapies. It is essential to establish lipid-lowering therapy goals based on the stroke subtype and the presence of comorbidities.

Erchen decoction to reduce oxidative stress in dyslipidemia phlegm-dampness retention syndrome mice: In vivo mechanism revealed by metabolomics (liquid chromatography-mass spectrometry).

OBJECTIVE: Erchen decoction, a traditional Chinese medicine formula, can reduce the level of oxidative stress for the treatment of dyslipidemia phlegm-dampness retention syndrome (DPDRS); however, studies have not elucidated the mechanism underlying its metabolic action. Here, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic techniques were utilized to characterize the in vivo effects of Erchen decoction in achieving reduction of oxidative stress levels and understand the potential metabolic mechanisms of action. METHODS: We constructed a DPDRS animal model using a multifactorial composite modeling approach, and Erchen decoction was administered by gavage. We employed LC-MS-based metabolomic techniques in combination with serum-associated factors, gene transcription, methylation detection, and hematoxylin and eosin staining. RESULTS: In this study, the constructed animal model of DPDRS had satisfactory quality. Erchen decoction treatment reduced the levels of low-density lipoprotein cholesterol, t total cholesterol and riglyceride; it improved the endothelial structure, increased levels of serum ß-nicotinamide adenine dinucleotide phosphate and glutathione concentrations, increased aortic phosphoserine aminotransferase and phosphoserine phosphatase gene expression levels, and decreased aortic phosphoglycerate dehydrogenase methylation level. A total of 64 differential metabolites were obtained using LC-MS assay, and 34 differential metabolic pathways were obtained after enrichment. CONCLUSIONS: Erchen decoction treatment of DPDRS mice reversed lipid indexes, improved vascular endothelial structure, increased serum and aortic anti-oxidative stress factor concentration and expression levels, and decreased methylation levels, thereby reducing oxidative stress and protecting vascular endothelium. Tricarboxylic acid cycle and metabolic pathways of serum glutamine, serine, tryptophan, pyrimidine, and pyruvate were the most relevant metabolic pathways involved in reducing oxidative stress levels by Erchen decoction during DPDRS treatment; especially, mitochondrial redox homeostasis maintenance in endothelial cells may be crucial. In this work, the therapeutic potential of Erchen decoction for reducing the oxidative stress level in DPDRS was demonstrated; however, its in-depth mechanism is worth further exploration.

Dose-Response Evaluation of Scopoletin, a Phytochemical, in a High-Fructose High-Fat Diet-Induced Dyslipidemia Model in Wistar Rats.

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II-VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III-VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial.

Ganoderma lucidum polysaccharides improve lipid metabolism against high-fat diet-induced dyslipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: As a kind of traditional medicinal fungi, Ganoderma lucidum has been employed as folk medicine in China against multiple metabolic diseases on account of its superior bioactivities. Recently, accumulated reports have investigated the protective effects of G. lucidum polysaccharides (GLP) on ameliorating dyslipidemia. However, the specific mechanism by which GLP improves dyslipidemia is not completely clear. AIMS OF THE STUDY: This study aimed to investigate the protective effects of GLP on high-fatdiet-induced hyperlipidemia and exploring its underlying mechanism. MATERIALS AND METHODS: The GLP was successfully obtained from G. lucidum mycelium. The mice were conducted with high-fatdiet to establish the hyperlipidemia model. Biochemical determination, histological analysis, immunofluorescence, western blot and real-time qPCR were used to assess the alterations in high-fatdiet-treated mice after the GLP intervention. RESULTS: It was found that GLP administration significantly decreased body weight gain and the excessive lipid levels, and partly alleviated tissue injury. Oxidative stress and inflammations were efficiently ameliorated after the treatment of GLP by activing Nrf2-Keap1 and inhibiting NF-κB signal pathways. GLP promoted cholesterol reverse transport by LXRα-ABCA1/ABCG1 signaling, increased the expressions of CYP7A1 and CYP27A1 responsible for bile acids production, accompanied by inhibition of intestinal FXR-FGF15 levels. Besides, multiple target proteins involved in lipid metabolism were also significantly modulated under the intervention of GLP. CONCLUSION: Taken together, our results suggested that GLP showed potential lipid-lowering effects and its possible mechanism was involved in improving oxidative stress and inflammation response, modulating bile acids synthesis and lipid regulatory factors, and promoting reverse cholesterol transport, thereby suggesting that GLP may possibly used as a dietary supplement or medication for the adjuvant therapy for hyperlipidemia.