Cardiovascular Protective Effects Research Articles

Calycosin action against atherosclerosis: integrating network pharmacology and in-silico investigation

Atherosclerosis, caused by lipid deposit in the arterial wall for narrowing the arteries, is an increased risk factor of developing heart failure. Presently, clinical first-line drug therapy can be found with side effects, and thus new substitute medication should be developed needfully. Calycosin is one of the most bioactive products refined from natural plant, and it exerts promising cardiovascular protective effect. However, the pharmacological mechanisms of calycosin against atherosclerosis have not been elaborated. In this study, a systematic network pharmacology combined with molecular docking analysis was used to reveal the interaction activity and biological target in calycosin against atherosclerosis. We screened all preparative targets linked to calycosin and atherosclerosis from the available public databases. These results indicated total 409 putative targets in calycosin action, 71 of which were interacted with atherosclerosis. Further biological docking analysis suggested that calycosin displayed the powerful binding affinities with target proteins, including interleukin-6 (IL6) and mitogen-activated protein kinase 3 (MAPK3) MAPK3. Then enrichment findings revealed that calycosin action to treat atherosclerosis might be related to inhibition of inflammatory reaction and oxidative stress through modulating nucleolus transcription factor for improving lipid metabolism. In conclusion, the anti-atherosclerotic targets and molecular mechanisms in calycosin action were revealed systematically through preclinical evaluation. And calycosin may be a potential natural compound for the treatment of atherosclerosis.

Mixed messages? Exposure to reports about alcohol’s suggested cardiovascular effects and hazardous alcohol use: a cross-sectional study of patients in cardiology care

BackgroundHazardous alcohol use is a leading risk factor for disability and death, yet observational studies have also reported reduced cardiovascular disease mortality among regular, low-level drinkers. Such findings are refuted by more recent research, yet have received significant media coverage. We aimed to explore: (1) how patients with cardiovascular diseases access health information about moderate drinking and cardiovascular health; (2) the perceived messages these sources convey, and (3) associations with own level of alcohol use.MethodsWe conducted a cross-sectional survey of patients in cardiology services at three hospitals in Sweden. The study outcome was hazardous alcohol use, assessed using the AUDIT-C questionnaire and defined as ≥ 3 in women and ≥ 4 in men. The exposure was accessing information sources suggesting that moderate alcohol consumption can be good for the heart, as opposed to accessing information that alcohol is bad for the heart. Health information sources were described using descriptive statistics. Gender, age and education were adjusted for in multiple logistic regression analyses.ResultsA total of 330 (66.3%) of 498 patients (mean age 70.5 years, 65% males) who had heard that drinking moderately can affect the heart described being exposed to reports that moderate alcohol use can be good for the heart, and 108 (21.7%) met criteria for hazardous alcohol use. Health information sources included newspapers (32.9%), television (29.2%), healthcare staff (13.4%), friends/family (11.8%), social media (8.9%) and websites (3.7%). Participants indicated that most reports (77.9%) conveyed mixed messages about the cardiovascular effects of moderate drinking. Exposure to reports of healthy heart effects, or mixed messages about the cardiovascular effects of alcohol, was associated with increased odds of hazardous alcohol use (OR = 1.67, 95%CI = 1.02–2.74).ConclusionsThis study suggests that many patients in cardiology care access health information about alcohol from media sources, which convey mixed messages about the cardiovascular effects of alcohol. Exposure to reports that moderate drinking has protective cardiovascular effects, or mixed messages about the cardiovascular effects of alcohol, was associated with increased odds of hazardous alcohol use. Findings highlight a need for clear and consistent messages about the health effects of alcohol.

Alcohol and Binge Drinking Frequency and Hypertension: A National Cross-Sectional Study in the U.S.

The relationship between alcohol consumption and hypertension is multifaceted and a major public health concern. The association becomes even more complicated when hypertension is undiagnosed. This study investigates how alcohol consumption patterns are linked to measured, diagnosed, undiagnosed, and composite hypertension (any indications of hypertension from blood pressure readings, professional diagnosis, or reported medication use) in the United States. Data from the National Health and Nutrition Examination Survey 2015-2020, a nationally representative cross-sectional study, were analyzed in 2023-2024. The final analytic sample was 12,950 participants. Complex-survey weighted multivariable linear and logistic regression models estimated the effect of different alcohol consumption levels on hypertension. Descriptive findings show that those who consumed alcohol more than 3 times weekly exhibited the highest prevalence of measured (52.5%), undiagnosed (27.0%), and composite hypertension (69.4%) compared to other levels of alcohol drinking. Multivariable linear regression analysis indicated a notable elevation in systolic (4.8 unit) and diastolic (2.46 unit) blood pressure among individuals with frequent binge drinking episodes compared to individuals with infrequent drinking. Logistic regression models estimated that drinking over 3 times weekly increases the odds of measured, undiagnosed, and composite hypertension by 64%, 70%, and 54%, respectively, while frequent binge drinking episodes raise these odds by 82%, 65%, and 47%. Contrary to some studies suggesting moderate alcohol intake has protective cardiovascular effects, the findings did not corroborate a "J-shaped" curve. This underscores the importance of regular blood pressure monitoring among individuals with binge drinking episodes and emphasizes the need for public health interventions to mitigate alcohol consumption and its associated hypertension risks.

The Protective Role of Resilience on Cardiovascular Health in Young Adults Exposed to Adverse Childhood Experiences

Background: Adverse childhood experiences (ACEs) are strong emotional or physical stressors that occur during sensitive developmental periods and are associated with reduced cardiovascular health (CVH). Resilience, or the psychological capacity of individuals to cope with adversity, has been recently shown to have a positive influence on CVH. Despite the dose-dependent detrimental impact of ACEs on CVH, it is unknown whether resilience exerts a protective cardiovascular effect against early stress. Thus, the purpose of this study was to investigate the impact that resilience may have on CVH in young adults who experienced ACEs. Methods: Eighteen young and apparently healthy adults (22±3 yo) with a history of severe ACE exposure (≥4) participated in this study and provided self-reported data about resilience. CVH was assessed non-invasively through transcutaneous arterial tonometry to evaluate arterial stiffness (pulse-wave velocity, PWV), myocardial oxygen demand (Systolic Pressure Time Index, SPTI), myocardial oxygen supply (Diastolic Pressure Time Index, DPTI) and myocardial perfusion (Subendocardial Viability Ratio, SEVR). Circulating biomarkers related to CVH were also evaluated (high-sensitive C-reactive protein, hsCRP). Results: Eleven participants reported high resilience (HR: resilience score≥95), while seven reported low resilience (LR: resilience score<95). Young adults with high resilience presented with a significantly lower myocardial oxygen demand (SPTI; HR: 1866±111 vs. LR: 2227±117mmHg·s/min, p=0.047) and higher myocardial perfusion (SEVR; HR: 168±13 vs.LR: 127 ±9% , p=0.034) than those with low resilience and a positive association between SEVR and resilience was identified ( r=0.492; p=0.045). No differences in myocardial oxygen supply ( p=0.225) or arterial stiffness ( p=0.614) were observed between groups. However, circulating hsCRP was also significantly lower in the HR group than the LR (0.89±0.3 vs. 2.96±1 mg/dL, p=0.041) and negatively associated with resilience ( r=-0.511; p=0.051). Conclusions: Our data suggests that, among young and apparently healthy adults exposed to childhood adversity, those who are psychologically more resilient exhibit higher myocardial perfusion and overall better CVH than those less resilient despite a history of severe ACEs. These findings suggest that resilience may protect, at least partially, against the early impact of ACEs on CVH. Future studies are thus warranted to further explore the relationship between resilience and CVH. Supported in part by the Child Health Research Institute at VCU. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hematopoietic Stem Cells as an Integrative Hub Linking Lifestyle to Cardiovascular Health

Hematopoietic Stem Cells as an Integrative Hub Linking Lifestyle to Cardiovascular Health

The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.

Arachidonic acid (AA) has three main metabolic pathways: the cycloxygenases (COXs) pathway, the lipoxygenases (LOXs) pathway, and the cytochrome P450s (CYPs) pathway. AA produces epoxyeicosatrienoic acids (EETs) through the CYPs pathway. EETs are very unstable in vivo and can be degraded in seconds to minutes. EETs have multiple degradation pathways, but are mainly degraded in the presence of soluble epoxide hydrolase (sEH). sEH is an enzyme of bifunctional nature, and current research focuses on the activity of its C-terminal epoxide hydrolase (sEH-H), which hydrolyzes the EETs to the corresponding inactive or low activity diol. Previous studies have reported that EETs have cardiovascular protective effects, and the activity of sEH-H plays a role by degrading EETs and inhibiting their protective effects. The activity of sEH-H plays a different role in different cells, such as inhibiting endothelial cell proliferation and migration, but promoting vascular smooth muscle cell proliferation and migration. Therefore, it is of interest whether the activity of sEH-H is involved in the initiation and progression of cardiovascular diseases by affecting the function of different cells through EETs.

Calorie restriction anti-hypertrophic effects are associated with improved mitochondrial content, blockage of Ca2+-induced mitochondrial damage, and lower reverse electron transport-mediated oxidative stress

Calorie restriction is a nutritional intervention that reproducibly protects against the maladaptive consequences of cardiovascular diseases. Pathological cardiac hypertrophy leads to cellular growth, dysfunction (with mitochondrial dysregulation), and oxidative stress. The mechanisms behind the cardiovascular protective effects of calorie restriction are still under investigation. In this study, we show that this dietetic intervention prevents cardiac protein elevation, avoids fetal gene reprogramming (atrial natriuretic peptide), and blocks the increase in heart weight per tibia length index (HW/TL) seen in isoproterenol-induced cardiac hypertrophy. Our findings suggest that calorie restriction inhibits cardiac pathological growth while also lowering mitochondrial reverse electron transport-induced hydrogen peroxide formation and improving mitochondrial content. Calorie restriction also attenuated the opening of the Ca2+-induced mitochondrial permeability transition pore. We also found that calorie restriction blocked the negative correlation of antioxidant enzymes (superoxide dimutase and glutatione peroxidase activity) and HW/TL, leading to the maintenance of protein sulphydryls and glutathione levels. Given the nature of isoproterenol-induced cardiac hypertrophy, we investigated whether calorie restriction could alter cardiac beta-adrenergic sensitivity. Using isolated rat hearts in a Langendorff system, we found that calorie restricted hearts have preserved beta-adrenergic signaling. In contrast, hypertrophic hearts (treated for seven days with isoproterenol) were insensitive to beta-adrenergic activation using isoproterenol (50 nM). Despite protecting against cardiac hypertrophy, calorie restriction did not alter the lack of responsiveness to isoproterenol in isolated hearts harvested from isoproterenol-treated rats. These results suggest (through a series of mitochondrial, oxidative stress, and cardiac hemodynamic studies) that calorie restriction possesses beneficial effects against hypertrophic cardiomyopathy.

Cardiovasculoprotective Effects of Estrogen and its Use as Hormonal Replacement Therapy

Epidemiologic studies have shown that the incidence of cardiovascular disease is closely related to gender. This is because endogenous estrogens have broad effects on the circulatory system, leading to the hypothesis that estrogens are cardiovascular protective, underlying their use as hormone replacement therapy (HRT) to reduce the incidence of cardiovascular disease. However, large prospective clinical trials (HERS and WHI) do not support this. This review aims to better understand the cardiovascularoprotective effects of estrogen and answer the question of whether estrogen can be used as hormonal replacement therapy in post-menopausal women to prevent cardiovascular events by incorporating data from the most recent prospective clinical trial, the KEEPS study. HERS and WHI reported no reduction in cardiovascular events in postmenopausal women using HRT, even showing an increased risk of thromboembolism. This study was criticized because participants had been menopausal for 12 years, so the KEEPS study was conducted with participants within three years of menopause, with the result that there was no significant reduction in the progression of atherosclerosis between the HRT group and the placebo group. The KEEPS study states that HRT is safe, and no thromboembolic events were found. Although endogenous estrogen has cardiovascular protective effects, estrogen hormone therapy cannot reduce cardiovascular events in postmenopausal women despite metabolic improvements and beneficial effects such as improvement of postmenopausal-related symptoms, maintaining bone density, and improving sexual function.

Omega-3 supplementation changes the physical properties of leukocytes but not erythrocytes in healthy individuals: An exploratory trial

n3-PUFA impact health in several ways, including cardiovascular protection and anti-inflammatory effects, but the underlying mechanisms are not fully understood. In this exploratory study involving 31 healthy subjects, we aimed to investigate the effects of 12 weeks of fish-oil supplementation (1500 mg EPA+DHA/day) on the physical properties of multiple blood cell types. We used deformability cytometry (DC) for all cell types and Laser-assisted Optical Rotational Red Cell Analysis (Lorrca) to assess red blood cell (RBC) deformability. We also investigated the correlation between changes in the physical properties of blood cells and changes in the Omega-3 Index (O3I), defined as the relative content of EPA+DHA in RBCs. Following supplementation, the mean±SD O3I increased from 5.3 %±1.5 % to 8.3 %±1.4 % (p < 0.001). No significant changes in RBC properties were found by both techniques. However, by DC we observed a consistent pattern of physical changes in lymphocytes, neutrophils and monocytes. Among these were significant increases in metrics correlated with the cells’ deformability resulting in less stiff cells. The results suggest that leukocytes become softer and have an increased ability to deform under induced short-term physical stress such as hydrodynamic force in the circulation. These changes could impact immune function since softer leukocytes can potentially circulate more easily and could facilitate a more rapid response to systemic inflammation or infection. In conclusion, fish-oil supplementation modulates some physical properties of leukocyte-subfractions, potentially enhancing their biological function. Further studies are warranted to explore the impact of n3-PUFA on blood cell biology, particularly in disease states associated with leukocyte dysregulation.

Cardiovascular Protective Effect of Garcinia dulcis Flower Acetone Extract in 2-Kidney-1-Clip Hypertensive Rats.

Morelloflavone and camboginol are bioactive compounds purified from Garcinia dulcis (GD), which has anti-inflammatory and antihypertensive properties. The objective of this study was to examine the cardiovascular protective effect of GD flower acetone extract in 2-kidney-1-clip (2K1C) hypertensive rats. Male Wistar rats underwent 2K1C or sham operation (SO) and were housed for 4 weeks. Each group of rats, then, was further divided into 2 subgroups receiving oral administration of either 50 mg/kg BW GD extract or corn oil (vehicle) daily for 4 weeks. Noninvasive blood pressure (BP) and body weight were measured weekly throughout the study. Subsequently, the invasive measurement of arterial BP and the heart rate were determined in all anesthetized rats. The baroreceptor reflex sensitivity (BRS) was investigated by injection of either phenylephrine or sodium nitroprusside for bradycardia or tachycardia response, respectively. Histological examination of the heart and thoracic aorta was also performed in order to investigate the general morphology and the tumor necrosis factor alpha (TNF-α) expression. We found that the GD flower extract significantly diminished the BP and restored the impaired BRS. Moreover, it also decreased the TNF-α expression in the cardiac muscle and thoracic aorta of 2K1C when compared to the SO group. Taken together, our data showed that GD flower extract exhibits the cardiovascular protective effect in the 2K1C hypertensive rats.

Effects of wolfberry (Lycium barbarum) consumption on the human plasma lipidome and its association with cardiovascular disease risk factors: a randomized controlled trial of middle-aged and older adults.

Long-term wolfberry intake as part of a healthy dietary pattern was recognized to have beneficial vascular outcomes. Characterization of the plasma lipidome may further provide comprehensive insights into pathways underlying these cardiovascular protective effects. We analyzed the plasma lipidome of subjects who adhered to a healthy dietary pattern either with or without wolfberry and investigated the associations between the plasma lipidomic profile and cardiovascular health-related indicators. In this 16-week, parallel design, randomized controlled trial, middle-aged and older adults (n = 41) were provided dietary counseling and assigned to either consume or not consume 15 g of wolfberry daily. At baseline and post-intervention, plasma lipidomics was assayed, and its relationships with classical CVD risk factors, vascular health, oxidant burden, carotenoids status, body composition, and anthropometry were examined. From the plasma lipidome, 427 lipid species from 26 sub-classes were quantified. In the wolfberry and control groups, significant changes were prominent for 27 and 42 lipid species, respectively (P < 0.05 with > 0.2-fold change). Fold changes for seven lipid species were also markedly different between the two groups. Examining the relationships between the plasma lipidome and CVD-related risk factors, total cholesterol revealed a marked positive correlation with 13 ceramide species, while HDL-cholesterol which was notably increased with wolfberry consumption showed a positive correlation with 10 phosphatidylcholine species. Oxidant burden, as represented by plasma 8-isoprostanes, was also inversely associated with lipidomic triglycerides and ether-triglycerides (41 species) and directly associated with hexosylceramides (eight species) and sphingomyelins (six species). There were no differential associations with CVD risk detected between groups. Characteristic alterations to the plasma lipidome were observed with healthy dietary pattern adherence and wolfberry consumption. An examination of these fluctuations suggests potential biochemical mechanisms that may mediate the antioxidant and cardiovascular protective effects of healthy dietary pattern adherence and wolfberry intake. This study was registered at clinicaltrials.gov as NCT0353584.

Integration of transcriptome and metabolome reveals the accumulation of related metabolites and gene regulation networks during quinoa seed development.

Quinoa seeds are gluten- and cholesterol-free, contain all amino acids required by the human body, have a high protein content, provide endocrine regulation, protein supplementation, and cardiovascular protection effects. However, metabolite accumulation and transcriptional regulatory networks in quinoa seed development are not well understood. Four key stages of seed development in Dianli-3260 and Dianli-557 were thus analyzed and 849 metabolites were identified, among which sugars, amino acids, and lipids were key for developmental processes, and their accumulation showed a gradual decrease. Transcriptome analysis identified 40,345 genes, of which 20,917 were differential between the M and F phases, including 8279 and 12,638 up- and down-regulated genes, respectively. Grain development processes were mainly enriched in galactose metabolism, pentose and glucuronate interconversions, the biosynthesis of amino acids, and carbon metabolism pathways, in which raffinose, phosphoenolpyruvate, series and other metabolites are significantly enriched, gene-LOC110689372, Gene-LOC110710556 and gene-LOC110714584 are significantly expressed, and these metabolites and genes play an important role in carbohydrate metabolism, lipid and Amino acid synthesis of quinoa. This study provides a theoretical basis to expand our understanding of the molecular and metabolic development of quinoa grains.

The Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors for Patients with Sarcopenia or Frailty: Double Edged Sword?

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) show cardiovascular protective effects, regardless of the patient's history of diabetes mellitus (DM). SGLT2is suppressed cardiovascular adverse events in patients with type 2 DM, and furthermore, SGLT-2is reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF. Along with these research findings, SGLT-2is are recommended for patients with HF in the latest guidelines. Despite these benefits, the concern surrounding the increasing risk of body weight loss and other adverse events has not yet been resolved, especially for patients with sarcopenia or frailty. The DAPA-HF and DELIVER trials consistently showed the efficacy and safety of SGLT-2i for HF patients with frailty. However, the Rockwood frailty index that derived from a cumulative deficit model was employed for frailty assessment in these trials, which might not be suitable for the evaluation of physical frailty or sarcopenia alone. There is no fixed consensus on which evaluation tool to use or its cutoff value for the diagnosis and assessment of frailty in HF patients, or which patients can receive SGLT-2i safely. In this review, we summarize the methodology of frailty assessment and discuss the efficacy and safety of SGLT-2i for HF patients with sarcopenia or frailty.

The Effect of Anti-Tumor Necrosis Factor Therapy on The Plasma Atherogenic Index in Rheumatic Diseases.

Background: The risk of atherosclerosis is increased in individuals with rheumatological disease. The objective of this study is to examine the heightened susceptibility to atherosclerosis in persons afflicted with rheumatological disorders. This study aimed to assess the impact of anti-tumor necrosis factor (anti-TNF) medication on the plasma atherogenic index (PAI) in persons diagnosed with rheumatological disease. Methods: This study used a retrospective cross-sectional design to investigate a cohort of 136 patients with rheumatological disease who were undergoing anti-TNF therapy (Group 1), as well as a comparison group of 117 patients getting conventional therapy (Group 2). Measurements of PAI were conducted at the initial baseline and again at the sixth month of treatment. Results: Initially, there was no statistically significant disparity observed in PAI values between the two cohorts. After a period of 6 months, a notable reduction in PAI was identified in the group receiving anti-TNF medication (P = 0.01), while no significant alteration was detected in the group receiving conventional treatment. Conclusion: It provides findings showing that anti-TNF therapy can reduce the PAI in individuals with rheumatological disease. This may indicate a potential cardiovascular protective effect of anti-TNF therapy.

Proteomic analysis of extracellular vesicle cargoes mirror the cardioprotective effects of rivaroxaban in patients with venous thromboembolism.

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality worldwide. Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; yet, these remain poorly characterized. Extracellular vesicles (EVs) are considered proinflammatory messengers regulating a myriad of (patho)physiological processes and may be highly relevant to the pathophysiology of VTE. The effects of Rivaroxaban on circulating EVs in VTE patients remain unknown. We have established that differential EV biosignatures are found in patients with non-valvular atrial fibrillation anticoagulated with Rivaroxaban versus warfarin. Here, we investigated whether differential proteomic profiles of circulating EVs could also be found in patients with VTE. We performed comparative label-free quantitative proteomic profiling of enriched plasma EVs from VTE patients anticoagulated with either Rivaroxaban or warfarin using a tandem mass spectrometry approach. Of the 182 quantified proteins, six were found to be either exclusive to, or enriched in, Rivaroxaban-treated patients. Intriguingly, these proteins are involved in negative feedback regulation of inflammatory and coagulation pathways, suggesting that EV proteomic signatures may reflect both Rivaroxaban's anti-coagulatory and anti-inflammatory potential. These differences suggest Rivaroxaban may have pleiotropic effects, supporting the reports of its emerging anti-inflammatory and cardiovascular-protective characteristics relative to warfarin.

Renalase mediates macrophage-to-fibroblast crosstalk to attenuate pressure overload-induced pathological myocardial fibrosis.

A potential antifibrotic mechanism in pathological myocardial remodeling is the recruitment of beneficial functional subpopulations of macrophages or the transformation of their phenotype. Macrophages are required to activate molecular cascades that regulate fibroblast behavior. Identifying mediators that activate the antifibrotic macrophage phenotype is tantamount to identifying the button that retards pathological remodeling of the myocardium; however, relevant studies are inadequate. Circulating renalase (RNLS) is mainly of renal origin, and cardiac myocytes also secrete it autonomously. Our previous studies revealed that RNLS delivers cell signaling to exert multiple cardiovascular protective effects, including the improvement of myocardial ischemia, and heart failure. Here, we further investigated the potential mechanism by which macrophage phenotypic transformation is targeted by RNLS to mediate stress load-induced myocardial fibrosis. Mice subjected to transverse aortic constriction (TAC) were used as a model of myocardial fibrosis. The co-incubation of macrophages and cardiac fibroblasts was used to study intercellular signaling. The results showed that RNLS co-localized with macrophages and reduced protein expression after cardiac pressure overload. TAC mice exhibited improved cardiac function and alleviated left ventricular fibrosis when exogenous RNLS was administered. Flow sorting showed that RNLS is essential for macrophage polarization towards a restorative phenotype (M2-like), thereby inhibiting myofibroblast activation, as proven by both mouse RAW264.7 and bone marrow-derived macrophage models. Mechanistically, we found that activated protein kinase B is a major pathway by which RNLS promotes M2 polarization in macrophages. RNLS may serve as a prognostic biomarker and a potential clinical candidate for the treatment of myocardial fibrosis.

Benzoylaconine: Potential Therapeutic Agent for Cardiovascular Diseases From Fuzi

Modern pharmacological studies have elucidated the presence of aconitine (AC) alkaloids, polysaccharides, and saponins as the primary bioactive constituents of Fuzi. Among these, benzoylaconine, a pivotal active compound, demonstrates notable pharmacological properties including antitumor, anti‐inflammatory, and cardiovascular protective effects. In recent years, benzoylaconine has garnered significant attention in basic research on heart diseases, emerging as a focal point of investigation. This paper presents a comprehensive review of the pharmacological effects of benzoylaconine, alongside an overview of advancements in metabolic characterization. The objective is to furnish valuable insights that can serve as a cornerstone for further exploration, utilization, and advancement of benzoylaconine in pharmacological research.

Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.

The probability of cardiovascular events has been reported lower in rheumatoid arthritis (RA) patients treated with leflunomide. However, the anti-atherosclerotic and cardiovascular protective effects and metabolism of leflunomide are not explored. In this study, we assessed the potential benefits of leflunomide on atherosclerosis and revealed the underlying mechanism. ApoE-/- mice were fed a western diet (WD) alone or supplemented with leflunomide (20 mg/kg, oral gavage, once per day) for 12 weeks. Samples of the aorta, heart, liver, serum, and macrophages were collected. We found that leflunomide significantly reduced lesion size in both en-face aortas and aortic root in WD-fed ApoE-/- mice. Leflunomide also obviously improved dyslipidemia, reduced hepatic lipid content, and improved disorders of glucose and lipid metabolism in vivo. RNA-Seq results showed that leflunomide effectively regulated the genes' expression involved in the lipid metabolism pathway. Importantly, leflunomide significantly increased the phosphorylation levels of AMPKα and acetyl-CoA carboxylase (ACC) in vivo. Furthermore, leflunomide and its active metabolite teriflunomide suppressed lipid accumulation in free fatty acid (FFA)-induced AML12 cells and improved endothelial dysfunction in palmitic acid (PA)-induced HUVECs through activating AMPK signaling and inhibiting dihydroorotate dehydrogenase (DHODH) signaling pathway. We present evidence that leflunomide and teriflunomide ameliorate atherosclerosis by regulating lipid metabolism and endothelial dysfunction. Our findings suggest a promising use of antirheumatic small-molecule drugs leflunomide and teriflunomide for the treatment of atherosclerosis and related cardiovascular diseases (CVDs).

Bibliometric and visual analysis of global publications on kaempferol.

Kaempferol, a flavonoid found in numerous foods and medicinal plants, offers a range of health benefits such as anti-inflammatory, antioxidant, antiviral, anticancer, cardioprotective, and neuroprotective effects. Herein, a bibliometric and visual analysis of global publications on kaempferol was performed to map the evolution of frontiers and hotspots in the field. Using the search string TS = kaempferol, bibliometric data for this analysis was extracted from the Web of Science Core Collection database and analyzed using the VOSviewer, CiteSpace, and Scimago Graphica software. As a result, by February 26, 2024, 11,214 publications were identified, comprising articles (n = 10,746, 96%) and review articles (n = 468, 4%). Globally, the annual number of kaempferol publications surpassed 100 per year since 2000, exceeded 500 per year since 2018, and further crossed the threshold of 1,000 per year starting in 2022. The major contributing countries were China, the United States of America, and India, while the top three institutes of the citations of kaempferol were the Chinese Academy of Sciences, Consejo Superio de Investigaciones Cientficas, and Uniersidade do Porto. These publications were mainly published in agricultural and food chemistry journals, food chemistry, and phytochemistry. The keywords frequently mentioned include phenolic compounds, antioxidant activity, flavonoids, NF-kappa B, inflammation, bioactive compounds, etc. Anti-inflammation, anti-oxidation, and anti-cancer have consistently been the focus of kaempferol research, while cardiovascular protection, neuroprotection, antiviral, and anti-bacterial effects have emerged as recent highlights. The field of kaempferol research is thriving.

Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids.

Covering: up to June 2024Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from L-tyrosine, exhibiting significant pharmacological properties such as anti-microbial, anti-spasmodic, anti-cancer, cardiovascular protection, and analgesic effects. The industrial production of valuable BIAs relies on extraction from plants; however, challenges concerning their low concentration and efficiency hinder drug development. Hence, alternative approaches, including biosynthesis and chemoenzymatic synthesis, have been explored. Model species like Papaver somniferum and Coptis japonica have played a key role in unraveling the biosynthetic pathways of BIAs; however, many aspects, particularly modified steps like oxidation and methylation, remain unclear. Critical enzymes, e.g., CYP450s and methyltransferases, play a substantial role in BIA backbone formation and modification, which is essential for understanding the origin and adaptive evolution of these plant specialized metabolites. This review comprehensively analyzes the structural diversity of reported BIAs and their distribution in plant lineages. In addition, the progress in understanding biosynthesis, evolution, and catalytic mechanisms underlying BIA biosynthesis is summarized. Finally, we discuss the progress and challenges in metabolic engineering, providing valuable insights into BIA drug development and the sustainable utilization of BIA-producing plants.