Cardiovascular Protective Properties Research Articles

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

Dietary Polyphenols, Food Processing and Gut Microbiome: Recent Findings on Bioavailability, Bioactivity, and Gut Microbiome Interplay.

Polyphenols are organic chemical compounds naturally present in plants, renowned for their anti-inflammatory, antioxidant, immunomodulatory, anticancer, and cardiovascular protective properties. Their bioactivity and bioavailability can vary widely depending on the methods of food processing and interactions with the gut microbiome. These factors can induce changes in polyphenols, affecting their ability to achieve their intended health benefits. Thus, it is essential to develop and apply food processing methods that optimize polyphenol content while maintaining their bioactivity and bioavailability. This review aims to explore how various food processing techniques affect the quantity, bioactivity, and bioavailability of polyphenols, as well as their interactions with the gut microbiome, which may ultimately determine their health effects.

Trends of SGLT2 inhibitors among patients with and without cancer.

113 Background: While initial indications for SGLT2 inhibitors (SGLT2i) were for management of type 2 diabetes mellitus (DM), their use has broadened with cardiovascular and renal protective properties. Given limited studies in cancer patients, we evaluated the trends of SGLT2i usage in patients with or without cancer. Methods: This study is a retrospective cohort analysis that examined electronic medical records from a global health research network, TriNetX. Our study population included patients 18 and older having one of following diagnoses: heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), and cardiovascular disease (CVD) with DM. Cohorts were separated by cancer status, creating 8 study cohorts. The incidence of SGLT2i use was measured annually, defined as total new patients receiving an SGLT2i divided by total eligible patients for that year. Linear trend plots were created showing incidence percentage from 2016 to 2023 to compare trends in cancer patients and non-cancer patients. Results: Amongst all study cohorts, the observed yearly incidence of SGLT2i use was considerably lower from 2016 and 2019. Measured incidence did not exceed 2%, with no observable differences between cancer and non-cancer patients. From 2020 to 2023, the observed incidence dramatically increased year over year, doubling from the observed 2019 incidence for all groups. Differences in utilization between cancer non-cancer patient cohorts became visible from 2020 onward amongst patients with HFrEF, CKD, and DM with CVD. This is highlighted by differences in 2023 incidence percentages for HFrEF (13.1% Non-Cancer vs. 10.7% Cancer), CKD (10.0% Non-Cancer vs. 3.8% Cancer), and DM with CVD (7.6% Non-Cancer vs. 5.2% Cancer). Conclusions: Since 2020, there has been an uptick in SGLT2i usage across all patient cohorts, indicating increased adoption of this therapy in clinical practice. Observed incidence rates suggest that cancer patients were less likely to be prescribed SGLT2i compared to non-cancer patients. Further research is needed to understand the barriers of use and efficacy of SGLT2is in cancer patients. Yearly incidence percentage of SGLT2 inhibitor use for 8 study cohorts represented in each column; each row represents a year where incidence is reported. HFrEF HFpEF CKD CVD + DM Year Non-Cancer Cancer Non-Cancer Cancer Non-Cancer Cancer Non-Cancer Cancer 2016 0.27 0.32 0.28 0.41 0.31 0.37 0.88 0.8 2017 0.34 0.41 0.36 0.57 0.39 0.52 1.16 1.19 2018 0.45 0.53 0.41 0.5 0.46 0.49 1.28 1.14 2019 0.74 0.77 0.6 0.77 0.82 0.77 1.91 1.7 2020 1.55 1.31 0.83 1.02 1.52 1.04 2.77 2.07 2021 4.2 3.32 1.77 2.11 3.76 1.96 4.25 3.36 2022 8.85 7.02 4.04 3.84 7.3 2.89 5.99 4.36 2023 13.07 10.66 6.38 6.16 10 3.68 7.6 5.24 HFrEF= Heart Failure Reduced Ejection Fraction; HFpEF= Heart Failure Preserved Ejection Fraction; CKD= Chronic Kidney Disease; CVD + DM= Cardiovascular Disease with Diabetes Mellitus.

Cardiovascular Protective Properties of GLP-1 Receptor Agonists: More than Just Diabetic and Weight Loss Drugs.

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management.

Nutritional profile, bioactive properties and potential health benefits of buckwheat: A review

AbstractThe present review focuses on the physico‐chemical properties of buckwheat (BW) and shows that its incorporation makes food more nutritious. The bioactive substances included in BW, including vitamins, proteins, flavonoids, phenolic acids, dietary fibre, and fagopyrins are effective in treating chronic illnesses. It is also a rich source of protein of excellent quality as it contains balanced amino acids. Various bioactive compounds like phenolics, flavonoids including orientin, quercetin, rutin, vitexin, isovitexin and isoorientin, tannins and steroids help in providing therapeutic benefits. It has a number of beneficial impacts on health, including anti‐inflammatory, anti‐hemorrhagic, cardiovascular, antioxidant, and blood vessel protective properties. The food sector has experienced an increased interest in producing items based on BW, which boasts advantageous flavor profiles and technical attributes while offering health benefits and accommodating those with gluten sensitivity. BW is a beneficial ingredient for bread, rice, soup, cakes, noodles, cookies, and gluten‐free beer due to its functional properties. This review also emphasizes on the BW as a functional food in numerous industries including agriculture, food, pharmaceutical and as animal fodder. It provides researchers knowledge that could be useful for developing future plans, such as selecting BW as promising bioactive ingredients for functional foods.

Baicalein as a potential bioactive flavonoid: a concise overview

Baicalein (the aglycone of baicalin) is a trihydroxyflavone isolated from Scutellaria species, mainly Scutellaria baicalensis Georgi, which is used in Traditional Chinese Medicine to treat cold, hepatic and pulmonary diseases, insomnia, inflammation, hypertension, atherosclerosis, hyperlipidaemia, and dysentery. In scientific literature, baicalein has been extensively reported to exert in vitro and in vivo antioxidant and anti-inflammatory effects, as well as possessing anti-cancer, anti-microbial, immune-modulatory, metabolic, and cardiovascular protection properties. It may modulate a wide array of signaling pathways such as AMPK (5' adenosine monophosphate-activated protein kinase), PPAR-γ (Peroxisome proliferator-activated receptor gamma), Bcl-2 (B-cell lymphoma 2) and Bax (Bcl-2-associated X) proteins, CDKs (Cyclin-dependent kinases), MMP (metalloproteinases), SIRT1, NF-kB (nuclear factor kappa-light-chain-enhancer), EMT (epithelial–mesenchymal transition), TLRs (Toll-like receptors), CPT1 (carnitine palmitoyl transferase-1), and SREBP-1c (sterol regulation element binding response protein-1c). The present review is designed to focus on the potential bioactive activities of baicalein and/or baicalin.

Anti-Inflammatory Activities of (+)-Afzelechin against Lipopolysaccharide-Induced Inflammation.

In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.

Endothelial dysfunction in breast cancer survivors on aromatase inhibitors: changes over time

BackgroundBreast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal women, which includes approximately two-thirds of all women with breast cancer. AIs inhibit the peripheral conversion of androgens to estrogen by deactivation of the aromatase enzyme, leading to a reduction in serum estrogen level in postmenopausal women with ER+ breast carcinoma. Estrogen is known for its cardiovascular (CV) protective properties through a variety of mechanisms including vasodilation of blood vessels and inhibition of vascular injury resulting in the prevention of atherosclerosis. In clinical trials and prospective cohorts, the long-term use of AIs can increase the risk for hypertension and hyperlipidemia. Studies demonstrate mixed results as to the impact of AIs on actual CV events and overall survival.MethodsA single arm longitudinal study of 14 postmenopausal women with ER+ breast cancer prescribed adjuvant AIs at the University of Minnesota (UMN). Subjects with a history of known tobacco use, hypertension, hyperlipidemia, and diabetes were excluded to eliminate potential confounding factors. Participants underwent routine labs, blood pressure assessments, and vascular testing at baseline (prior to starting AIs) and at six months. Vascular assessment was performed using the EndoPAT 2000 and HDI/PulseWave CR-2000 Cardiovascular Profiling System and pulse contour analysis on two occasions as previously described. Vascular measurements were conducted by one trained vascular technician. Assessments were performed in triplicate, and the mean indices were used for analyses. All subjects were on an AI at the follow-up visit. The protocol was approved by the UMN Institutional Review Board and all participants were provided written informed consent. Baseline and follow-up characteristics were compared using Wilcoxon signed-rank tests. Analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).ResultsAfter six months of AI treatment, EndoPAT® ratio declined to a median 1.12 (Q1: 0.85, Q3: 1.86; p = 0.045; Figure 1) and median estradiol levels decreased to 2 pg/mL (Q1: 2, Q3: 3; p=0.052). There was no evidence of association between change in EndoPAT® and change in estradiol level (p = 0.91). There were no statistically significant changes in small or large arterial elasticity.ConclusionsWe hypothesize that long-term use of AI can lead to persistent endothelial dysfunction, and further investigation is necessary. In our study, patients were on AI for approximately 5-10 years. As a result, we do not have data on whether these changes, such as EndoPAT® ratio and the elasticity of small and large arterial, are reversible with discontinuation of AI. These findings set the stage for a larger study to more conclusively determine the association between AI exposure and cardiovascular outcomes. Further studies should evaluate for multivariate associations withmodifiable risk factors for CV disease.

Research Progress on Flavonoids in Traditional Chinese Medicine to Counteract Cardiotoxicity Associated with Anti-Tumor Drugs.

The development of anti-tumor drugs has notably enhanced the survival rates and quality of life for patients with malignant tumors. However, the side effects of these drugs, especially cardiotoxicity, significantly limit their clinical application. The cardiotoxicity associated with anti-tumor drugs has been a subject of extensive attention and research. Traditional to mitigate these side effects have included reducing drug dosages, shortening treatment duration, modifying administration methods, and opting for drugs with lower toxicity. However, either approach may potentially compromise the anti-tumor efficacy of the medications. Therefore, exploring other effective methods for anti-cardiotoxicity will be the focus of future research. The potential of traditional Chinese medicine (TCM) in managing cardiovascular diseases and cancer treatment has gained widespread recognition. TCM is valued for its minimal side effects, affordability, and accessibility, offering promising avenues in the prevention and treatment of cardiotoxicity caused by anti-tumor drugs. Among its constituents, flavonoids, which are present in many TCMs, are particularly notable. These monomeric compounds with distinct structural components have been shown to possess both cardiovascular protective properties and anti-tumor capabilities. In this discussion, we will delve into the classification of anti-tumor drugs and explore the underlying mechanisms of their associated cardiotoxicity. Additionally, we will examine flavonoids found in TCM and investigate their mechanisms of cardiovascular protection. This will include an analysis of how these natural compounds can mitigate the cardiac side effects of anti-tumor therapies while potentially enhancing overall patient health and treatment outcomes.

Fabrication of diosmin loaded food-grade bilayer nanoparticles with modified chitosan and soy peptides and antioxidant properties examination

Diosmin is a flavonoid derived from plants, possessing anti-inflammatory, antioxidant, antidiabetic, neuroprotective and cardiovascular protective properties. However, diosmin has low solubility in water, leading to low bioavailability. In this study, we constructed bilayer nanoparticles with trimethyl chitosan and soy peptides to improve the oral bioaccessibility and bioavailability of diosmin, and determined the characteristics and antioxidant properties of the diosmin-loaded nanoparticles. The results showed that the size of the nanoparticles was around 250 nm with the encapsulation efficiency higher than 97 %, and the nanoparticles were stable under regular conditions. In vitro digestion suggested the nanoparticles could protect diosmin from releasing in gastric digestion but promote the bioaccessibility of diosmin in intestine. Furthermore, the diosmin-loaded nanoparticles presented excellent antioxidant activities in vitro and significantly decreased the Lipopolysaccharides-induced brain Malondialdehyde (MDA) level by oral administration. Therefore, the reported nanoparticles may be an effective platform for improving the oral bioavailability of diosmin.

Schisandrol A, the Major Active Constitute in Schisandra chinensis: A Review of Its Preparation, Biological Activities, and Pharmacokinetics Analysis.

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage.

Astragaloside IV Alleviates Doxorubicin-Induced Cardiotoxicity by Inhibiting Cardiomyocyte Pyroptosis through the SIRT1/NLRP3 Pathway.

Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug used to treat a wide spectrum of tumors. However, its clinical application is limited due to cardiotoxic side effects. Astragaloside IV (AS IV), one of the major compounds present in aqueous extracts of Astragalus membranaceus, possesses potent cardiovascular protective properties, but the underlying molecular mechanisms are unclear. Thus, the aim of this study was to investigate the effect of AS IV on DOX-induced cardiotoxicity (DIC). Our findings revealed that DOX induced pyroptosis through the caspase-1/gasdermin D (GSDMD) and caspase-3/gasdermin E (GSDME) pathways. AS IV treatment significantly improved the cardiac function and alleviated myocardial injury in DOX-exposed mice by regulating intestinal flora and inhibiting pyroptosis; markedly suppressed the levels of cleaved caspase-1, N-GSDMD, cleaved caspase-3, and N-GSDME; and reversed DOX-induced downregulation of silent information regulator 1 (SIRT1) and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mice. The SIRT1 inhibitor EX527 significantly blocked the protective effects of AS IV. Collectively, our results suggest that AS IV protects against DIC by inhibiting pyroptosis through the SIRT1/NLRP3 pathway.

Glyceraldehyde derivatives inspired by empagliflozin as potential anti-heart failure agents independent of glucose-lowering effects

Sodium-glucose cotransporter 2 inhibitors are a class of glucose-lowering drugs known for robust cardiovascular protective properties. However, the side effects induced by Sodium-glucose cotransporter 2 inhibition limit application in cardiovascular medicine. Our prior research showed that thoughtful structural modifications can dissociate the anti-heart failure activity from glucose-lowering effects. Moreover, we showed that the glyceraldehyde derivative, JX22, developed by scaffold hopping from empagliflozin, exhibits a superior cardiomyocyte protective effect, albeit with increased cytotoxicity compared to empagliflozin. In the current study systematic structural modifications of JX22 were performed to enhance anti-heart failure efficacy and safety, while reducing glucose-lowering activity. Twenty glyceraldehyde-based derivatives were synthesized and compound 12 emerged as an optimal candidate by exhibiting an improved cytoprotective effect compared to JX22. Compound 12 significantly inhibited the activity of NHE1 on the myocardial membrane, thereby maintaining intracellular ion homeostasis. In vivo efficacy results demonstrated that compound 12 at 10 mg/kg significantly ameliorated cardiac dysfunction, myocardial fibrosis, and exercise tolerance in isoproterenol-induced heart failure mice without a glucose-lowering effect. Furthermore, compound 12 exhibited favorable safety profiles in single-dose toxicity and hERG inhibition tests, along with promising pharmacokinetic properties in mice. The current study not only underscores the potential of compound 12 for further investigation but also highlights the effectiveness of the scaffold hopping strategy.

Astragaloside IV mitigates hypoxia-induced cardiac hypertrophy through calpain-1-mediated mTOR activation

BackgroundAstragaloside IV (AsIV), a key functioning element of Astragalus membranaceus, has been recognized for its potential cardiovascular protective properties. However, there is a need to elucidate the impacts of AsIV on myocardial hypertrophy under hypoxia conditions and its root mechanisms. PurposeThis study scrutinized the influence of AsIV on cardiac injury under hypoxia, with particular emphasis on the role of calpain-1 (CAPN1) in mediating mTOR pathways. MethodsHypoxia-triggered cardiac hypertrophy was examined in vivo with CAPN1 knockout and wild-type C57BL/6 mice and in vitro with H9C2 cells. The impacts of AsIV, 3-methyladenine, and CAPN1 inhibition on hypertrophy, autophagy, apoptosis, [Ca2+]i, and CAPN1 and mTOR levels in cardiac tissues and H9C2 cells were investigated. ResultsBoth AsIV treatment and CAPN1 knockout mitigated hypoxia-induced cardiac hypertrophy, autophagy, and apoptosis in mice and H9C2 cells. Moreover, AsIV, 3-methyladenine, and CAPN1 inhibition augmented p-mTOR level but reduced [Ca2+]i and CAPN1 level. Additionally, lentivirus-mediated CAPN1 overexpression in H9C2 cells exacerbated myocardial hypertrophy, apoptosis, and p-mTOR inhibition under hypoxia. Specifically, AsIV treatment reversed the impacts of increased CAPN1 expression on cardiac injury and the inhibition of p-mTOR. ConclusionThese findings suggest that AsIV may alleviate cardiac hypertrophy under hypoxia by attenuating apoptosis and autophagy through CAPN1-mediated mTOR activation.

Analysis of Beneficial Effects of Flavonoids in Patients with Atherosclerosis Risk on Blood Pressure or Cholesterol during Random Controlled Trials: A Systematic Review and Meta-Analysis

Flavonoids are plant-secondary metabolites with cardiovascular protective properties. Few studies have examined specific flavonoid classes or pure flavonoids concerning some common cardiovascular risks. To obtain information in a systematic review to analyze in a meta-analysis, data were recovered regarding flavonoid intake in random controlled trials and atherosclerosis disease, related to risk factors such as blood pressure, total cholesterol (TC), and low-density lipoprotein cholesterol (LDLc). Our aim was to conduct a meta-analysis using the Scopus and PubMed databases without restrictions on the year of publication, extracting articles over the period 1–15 April 2023, searching for randomized controlled trials (RCTs) that investigated different types of flavonoids, measuring blood pressure and low-density cholesterol plasmatic concentration. This paper’s Prospero registration is CRD 42023414153. There were 19 RCTs: twelve RCTs were considered for blood pressure data analysis and fifteen RCTs for total cholesterol and LDL cholesterol data analysis. The meta-analysis showed no significant differences between placebo treatments and treatments with different flavonoids on blood pressure. However, there was a significant difference found in quantitative analysis for TC and LDLc. In conclusion, flavonoid consumption can be associated with a lower risk of LDLc and TC, and more RCTs are needed to specify the effect of more types of pure flavonoids in atherosclerotic patients.

Review on the Biological and Bioactive components of Cocoa (Theobroma Cacao). Insight on Food, Health and Nutrition

Cocoa (<i>Theobroma cacao</i>) is a well-known tropical plant extensively cultivated for its beans, which are the primary raw material for chocolate production. This article aims to comprehensively review and analyze the bioactive compounds present in cocoa and their corresponding biological activities, highlighting their potential implications for human health. A systematic literature review was conducted to gather relevant research articles and reviews related to the bioactive compounds of cocoa and their biological activities. The databases used for the search included PubMed, Scopus, and Google Scholar, with keywords such as "cocoa bioactive compounds," "flavonoids," "theobromine," "antioxidant activity," and "cardiovascular health" used for data retrieval. The analysis revealed that cocoa is rich in bioactive compounds, such as flavonoids (e.g., catechins, epicatechins), methylxanthines (e.g., theobromine, caffeine), and polyphenols. These bioactive compounds have been associated with various biological activities, including potent antioxidant effects, anti-inflammatory properties, and vasodilation, which may positively influence cardiovascular health. The consumption of cocoa and its bioactive compounds may offer several health benefits due to their antioxidant, anti-inflammatory, and cardiovascular-protective properties. However, further research is necessary to fully understand the mechanisms of action and to determine appropriate dosage recommendations for harnessing the potential health benefits of cocoa.

Research progress on the pharmacological activities of senkyunolides

Senkyunolides are a group of phthalide molecules that exist in Umbelliferae plants, with the highest abundance in Ligusticum chuanxiong Hort, a medicinal herb with therapeutic applications in various diseases such as coronary heart disease, migraine, and rheumatism. Modern research has highlighted the anti-inflammatory, analgesic, and cardiovascular-protective properties of senkyunolides. Recently, some novel effects, such as antibacterial, anti-osteoporosis, and anti-fibrosis, have been reported for senkyunolides, indicating their diverse biological activities. In addition, because of its high bioavailability and ability to cross the blood-brain barrier (BBB), particularly exemplified by senkyunolide I (SEI), holds promise for the treatment of brain diseases. Multiple signaling pathways have been related to the pharmacological activities of senkyunolides, such as the toll-like receptor 4/nuclear factor-kappa B (NF-κB) signaling, extracellular signal–regulated kinase (ERK) pathway, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) pathways. Here, we review the research progress on the pharmacokinetics and pharmacological effects of senkyunolides, which are promising candidates for future drug development and have significant clinical value in the treatment of various diseases. Graphical abstract: http://links.lww.com/AHM/A66.

Dietary ω3 Fatty Acids and Phytosterols in the Modulation of the HDL Lipidome: A Longitudinal Crossover Clinical Study.

High-density lipoproteins (HDLs) are complex particles composed of a wide range of lipids, proteins, hormones and vitamins that confer to the HDL particles multiple cardiovascular protective properties, mainly against the development of atherosclerosis. Among other factors, the HDL lipidome is affected by diet. We hypothesized that diet supplementation with ω3 (docosahexaenoic acid: DHA and eicosapentaenoic acid: EPA) and phytosterols (PhyS) would improve the HDL lipid profile. Overweight subjects (n = 20) were enrolled in a two-arm longitudinal crossover study. Milk (250 mL/day), supplemented with either ω3 (EPA + DHA, 375 mg) or PhyS (1.6 g), was administered to the volunteers over two consecutive 28-day intervention periods, followed by HDL lipidomic analysis. The comprehensive lipid pattern revealed that the HDL lipidome is diet-dependent. ω3-milk supplementation produced more changes than PhyS, mainly in cholesteryl esters (CEs). After ω3-milk intake, levels of DHA and EPA within phosphatylcholines, triglycerides and CE lipids in HDLs increased (p < 0.05). The correlation between lipid species showed that lipid changes occur in a coordinated manner. Finally, our analysis revealed that the HDL lipidome is also sex-dependent. The HDL lipidome is affected by diet and sex, and the 4 weeks of ω3 supplementation induced HDL enrichment with EPA and DHA.

The role of dietary polyphenols in the control of chronic noncommunicable diseases

AbstractNoncommunicable chronic diseases (NCDs) are among the leading causes of death and disability worldwide. The most common NCDs are cancer, obesity, cardiovascular diseases, and diabetes. Nowadays, they represent one of the greatest challenges health systems face worldwide. The increase in the consumption of polyphenol‐rich foods could contribute to the reduction of these pathologies, due to their antioxidant, anti‐inflammatory, anticancer, immunomodulatory, and cardiovascular protective properties, among others. This review aims to highlight some studies carried out in recent years to enhance the possible benefits of a diet rich in polyphenols in the prevention or treatment of NCDs.

Abstract 5251: Skeletonema marinoi algae extract and carotenoid fucoxanthin are endowed with potential chemopreventive and angiopreventive properties for prostate cancer

Abstract Background: Research and production of natural anti-oxidants is growing and is developed both in experimental laboratories and in nutraceuticals and pharmaceutical industries. Marine microorganisms represent underestimated sources of bioactive compounds endowed with anti-oxidant, anti-inflammatory, cardiovascular protective and anti-angiogenic properties, all beneficial effects on human health. Methods: Chemopreventive and anti-angiogenic activities of extracts from the marine coastal diatom Skeletonema marinoi (Sm) and carotenoid fucoxanthin, that is present in Sm, were evaluated in prostate cancer (PCa) and endothelial cell lines in in vitro. Morphogenesis assay was carried out to evaluate effects on HUVEC ability to form capillary-like structure on Matrigel. Gene expression analysis was performed by qPCR, measuring different inflammation and angiogenesis gene expression in cells treated with Sm extract and fucoxanthin. Membrane antibodies arrays were used to see alterations at protein level of pro- or anti-angiogenic factors. Results: Sm extract and fucoxanthin were able to decrease cell viability, in MTT and Crystal violet assays. Furthermore, we observed that fucoxanthin enhanced the effects of chemotherapeutic drugs, 5-Fluorouracil (5-FU) and cisplatin (Cis-Pt), two of the most commonly used anti-cancer drugs. Sm extract and fucoxanthin hindered vascular mimicry of PCa cells and also inhibited capillary structure formation in endothelial cells. Finally, Sm extract and fucoxanthin shown a down-regulation of inflammation and angiogenesis associated genes. Conclusions: Our study suggests promising potential chemopreventive and angiopreventive activities of Skeletonema marinoi extract and fucoxanthin for prostate cancer. Microalgae derived drugs can be a potential and relevant source of novel nutraceutical and preventive compounds, which can be considered as dietary supplements or in combination treatments in cancer prevention approaches. Citation Format: Adriana Albini, Luana Calabrone, Douglas M. Noonan, Marco Festa, Cinzia Ferrario, Valentina Carlini, Debora Macis, Luigi Pistelli, Christophe Brunet, Clementina Sansone. Skeletonema marinoi algae extract and carotenoid fucoxanthin are endowed with potential chemopreventive and angiopreventive properties for prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5251.