Search Results (209)

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Studies have shown that sodium-glucose cotransporter type 2 (SGLT2) inhibitors not only help lower blood glucose levels but also offer cardioprotective effects, reduce the progression of heart failure, and may even slow the progression of aortic stenosis. The mechanisms of these beneficial properties are thought to involve multiple pathways, including reducing inflammation, oxidative stress, and improving cellular energy metabolism. Advancing knowledge about the mechanisms of action of these drugs and their effects on the course of the aforementioned diseases has become the subject of intensive clinical and scientific research. This publication aims to provide insight into the role of SGLT2 inhibitors in the context of diabetes mellitus, heart failure and acute coronary syndrome, through clinical analysis, mechanistic insights and comparison of the effects of these drugs. Full article

Microbial lipids are substances of high added value produced by single-cell organisms grown on simple substrates. These lipids, depending on the producing organism, may contain rare fatty acids, whose isolation and purification from non-microbial sources usually is an inefficient and costly procedure. Such fatty acids mostly include members of the omega-3 and omega-6 families of polyunsaturated fatty acids, which are credited with potential anticancer, anti-inflammatory, cardioprotective, and neuroprotective actions. However, their poor solubility in aqueous solutions often restricts their potential applications, as routes other than dietary consumption are unavailable. A promising approach for administering them is their conversion into alkali salts, mostly with lithium or potassium, which are water-soluble and bio-assimilable. In this article, all studies investigating the potential anticancer effects of alkali salts of fatty acids isolated from microorganisms were reviewed in an attempt to sum up existing knowledge and encourage further research. Full article

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), commonly known as flozins, have garnered attention not only for their glucose-lowering effects in type 2 diabetes mellitus (T2DM) but also for their cardioprotective properties. This review examines the mechanisms underlying the anti-fibrotic effects of SGLT2is, with a focus on key clinical trials and preclinical models. SGLT2is, mainly empagliflozin and dapagliflozin, have demonstrated significant reductions in heart failure-related hospitalizations, cardiovascular death, and fibrosis markers, independent of their glucose-lowering effects. The cardioprotective benefits appear to stem from direct actions on cardiac tissues, modulation of inflammatory responses, and improvements in metabolic parameters. In animal models of heart failure, SGLT2is were demonstrated to reduce cardiac fibrosis through mechanisms involving AMPK activation, reduced oxidative stress, and inhibition of pro-fibrotic pathways, not only through the inhibition of SGLT2 present on cardiac cells but also by targeting several other molecular targets. These findings confirm their efficacy in the treatment of heart failure and align with evidence from human trials, supporting the potential involvement of multiple pathways in mediating cardiac fibrosis. These results also provide a promising basis for clinical trials specifically targeting pathways shared with SGLT2is. Full article

: Legumes and their seeds (pulses) have various nutritional and health benefits and form an important part of a healthy diet. The present work reviews recent studies from the literature concerning the cardioprotective properties of legumes, particularly pulses, and summarizes their molecular basis. The literature was gathered from electronic databases, including ScienceDirect, PubMed, SCOPUS, Web of Knowledge, Sci Finder, and Web of Science, using the following terms: “legume seeds”, “pulses”, “beans”, “peas”, “broad beans”, “chickpea”, “lentils”, “cardiovascular system”, and “cardiovascular disease”, and their combinations. The abstracts of any identified articles were initially analyzed to confirm whether they met the inclusion criteria. Pulses may reduce the risk of cardiovascular diseases (CVDs) by various mechanisms, including altering plasma lipid composition (especially lowering total and LDL cholesterol), increasing satiety, reducing inflammation, and decreasing oxidative stress and blood pressure. It is, however, unclear whether pulses maintain their cardioprotective properties after processing, and more research is needed in this area. Full article

Background: Sepsis-induced cardiomyopathy (SIC) is a life-threatening cardiac complication of sepsis with limited therapeutic options. Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has demonstrated cardioprotective effects in heart failure, but its role in mitigating sepsis-related cardiac dysfunction remains unclear. Methods: A retrospective cohort analysis was conducted to assess the impact of pre-hospital dapagliflozin use on major adverse cardiovascular events (MACEs) and survival in patients with SIC. Additionally, a murine SIC model was established using cecal ligation and puncture (CLP) to evaluate the effects of dapagliflozin on cardiac function, histopathology, and biomarkers of myocardial injury. Transcriptomic and metabolomic profiling, combined with multi-omics integration, was employed to elucidate the molecular mechanisms underlying dapagliflozin’s cardioprotective effects. Results: In the clinical cohort, pre-hospital dapagliflozin use was associated with a significant reduction in the risk of MACE and improved survival outcomes. In the murine SIC model, dapagliflozin restored cardiac function, reduced biomarkers of myocardial injury, and alleviated histological damage. Multi-omics analysis revealed that dapagliflozin modulates inflammatory responses, enhances autophagy, and regulates metabolic pathways such as AMPK signaling and lipid metabolism. Key regulatory genes and metabolites were identified, providing mechanistic insights into the underlying actions of dapagliflozin. Conclusions: Dapagliflozin significantly improves cardiac outcomes in sepsis-induced cardiomyopathy through the multi-level regulation of inflammation, energy metabolism, and cellular survival pathways. These findings establish dapagliflozin as a promising therapeutic strategy for SIC, offering translational insights into the treatment of sepsis-induced cardiac dysfunction. Full article

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, driven by complex interactions among genetic, environmental, and lifestyle factors, with diet playing a pivotal role. Extra Virgin Olive Oil (EVOO), a cornerstone of the Mediterranean diet (MedDiet), is a plant-based fat that has garnered attention for its robust cardiovascular benefits, which are attributed to its unique composition of monounsaturated fatty acids (MUFAs), particularly oleic acid (OA); and bioactive polyphenols, such as Hydroxytyrosol (HT) and oleocanthal. These compounds collectively exert antioxidant, anti-inflammatory, vasodilatory, and lipid-modulating effects. Numerous clinical and preclinical studies have demonstrated that EVOO’s properties reduce major modifiable cardiovascular risk factors, including hypertension, dyslipidemia, obesity, and type 2 diabetes. EVOO also promotes endothelial function by increasing nitric oxide (NO) bioavailability, thus favoring vasodilation, lowering blood pressure (BP), and supporting vascular integrity. Furthermore, it modulates biomarkers of cardiovascular health, such as C-reactive protein, low-density lipoprotein (LDL) cholesterol, and NT-proBNP, aligning with improved hemostatic balance and reduced arterial vulnerability. Emerging evidence highlights its interaction with gut microbiota, further augmenting its cardioprotective effects. This review synthesizes current evidence, elucidating EVOO’s multifaceted mechanisms of action and therapeutic potential. Future directions emphasize the need for advanced extraction techniques, nutraceutical formulations, and personalized dietary recommendations to maximize its health benefits. EVOO represents a valuable addition to dietary strategies aimed at reducing the global burden of cardiovascular diseases. Full article

Sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have emerged as a class of agents relevant for managing diabetic nephropathy and cardiopathy. In a previous report, we noticed that these drugs share, with other drugs with “nephroprotective” effects, the ability to reduce the glomerular filtration rate (GFR), thus suggesting the kidney hemodynamic effect as a proxy for optimal drug dosage. We also noticed that all known nephroprotective drugs exert cardioprotective functions, suggesting the possibility of activities not mediated by the kidney. Finally, we observe that nephroprotective drugs can be grouped according to their effects on hemoglobin levels, thus suggesting their mechanism of action. While the primary mechanism of SGLT2i involves glycosuria and natriuria, growing evidence suggests broader therapeutic effects beyond hemodynamic modulation. Specifically, the evidence that SGLT2 can be expressed in several atypical regions under pathological conditions, supports the possibility that its inhibition has several extratubular effects. Evidence supports the hypothesis that SGLT2i influence mitochondrial function in various cell types affected by diabetes, particularly in the context of diabetic nephropathy. Notably, in SGLT2i-treated patients, the extent of albumin-creatinine ratio (ACR) reduction post-treatment may be correlated with mitochondrial staining intensity in glomerular endothelial cells. This implies that the anti-proteinuric effects of SGLT2i could involve direct actions on glomerular endothelial cell. Our investigation into the role of SGLT2 inhibitors (SGLT2i) in endothelial function suggests that the aberrant expression of SGLT2 in endothelial cells in T2DM would lead to intracellular accumulation of glucose; therefore, SGLT2i are the first type of endothelial protective drugs available today, with potential implications for ageing-related kidney disease. The review reveals two major novel findings: SGLT2 inhibitors are the first known class of endothelial-protective drugs, due to their ability to prevent glucose accumulation in endothelial cells where SGLT2 is aberrantly expressed in Type 2 Diabetes. Additionally, the research demonstrates that SGLT2 inhibitors share a GFR-reducing effect with other nephroprotective drugs, suggesting both a mechanism for optimal drug dosing and potential broader applications in ageing-related kidney disease through their effects on mitochondrial function and glomerular endothelial cells. Full article

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action. Full article

Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus, and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, and “dementia” in connection with “meroterpenoids”. Results: Meroterpenoids modulate different cell signaling pathways and exhibit different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition, and anti-inflammatory activities, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation. Full article

Schisandra chinensis Turcz. (Baill.) is a dioecious vine belonging to the Schisandraceae family. Its berries show beneficial activities, including cardioprotective, antioxidant, and anti-inflammatory. We examined the chemical content of S. chinensis berry extract and its antiplatelet potential in vitro. The antiplatelet activity assays included measurements of thrombus formation in full blood (with Total Thrombus-formation Analysis System) and platelet activation and adhesion. We also assessed the extract’s effect on coagulation times in human plasma and its cytotoxicity toward blood platelets based on extracellular lactate dehydrogenase activity. The most important constituents of the extract were dibenzocyclooctadiene lignans; schisandrin was the dominant compound. S. chinensis berry extract at the concentration of 50 μg/mL inhibited thrombus formation by approximately 15%. The adhesion of unstimulated and thrombin-activated blood platelets to collagen was inhibited by all used concentrations of the extract (0.5–50 μg/mL), while the adhesion of adenosine diphosphate (ADP)-activated platelets to fibrinogen was inhibited only by the concentrations of 10 and 50 μg/mL. The extract also inhibited the exposition of the active form of GPIIb/IIIa on the surface of platelets stimulated with 10 μM ADP (at 0.5–50 μg/mL) and 20 μM ADP (at 50 μg/mL). The exposition of P-selectin was inhibited only by the extract at the concentrations of 5–50 μg/mL in platelets stimulated with 10 μg/mL collagen. Moreover, the extract was not cytotoxic toward blood platelets. This indicates that S. chinensis berries hold promise as new antiplatelet agents, but more studies are needed to determine their mechanisms of action and in vivo efficiency. Full article

Quercetin, a flavonoid found in vegetables and fruits, has been extensively studied for its health benefits and disease management. Its role in the prevention of various pathogenesis has been well-documented, primarily through its ability to inhibit oxidative stress, inflammation, and enhance the endogenous antioxidant defense mechanisms. Electronic databases such as Google Scholar, Scopus, PubMed, Medline, and Web of Science were searched for information regarding quercetin and its role in various pathogeneses. The included literature comprised experimental studies, randomized controlled trials, and epidemiological studies related to quercetin, while editorials, case analyses, theses, and letters were excluded. It has been reported to have a wide range of health benefits including hepatoprotective, antidiabetic, anti-obesity, neuroprotective, cardioprotective, wound healing, antimicrobial, and immunomodulatory effects, achieved through the modulation of various biological activities. Additionally, numerous in vitro and in vivo studies have shown that quercetin’s efficacies in cancer management involve inhibiting cell signaling pathways, such as inflammation, cell cycle, and angiogenesis, activating cell signaling pathways including tumor suppressor genes, and inducing apoptosis. This review aims to provide a comprehensive understanding of the health benefits of quercetin in various pathogeneses. Additionally, this review outlines the sources of quercetin, nanoformulations, and its applications in health management, along with key findings from important clinical trial studies. Limited clinical data regarding quercetin’s safety and mechanism of action are available. It is important to conduct more clinical trials to gain a deeper understanding of the disease-preventive potential, mechanisms of action, safety, and optimal therapeutic dosages. Furthermore, more research based on nanoformulations should be performed to minimize/overcome the hindrance associated with bioavailability, rapid degradation, and toxicity. Full article

Background/Objectives: Septic cardiomyopathy (SCM) is a severe cardiac complication of sepsis, characterized by cardiac dysfunction with limited effective treatments. This study aimed to identify repurposable drugs for SCM by integrated multi-omics and network analyses. Methods: We generated a mouse model of SCM induced by lipopolysaccharide (LPS) and then obtained comprehensive metabolic and genetic data from SCM mouse hearts using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and RNA sequencing (RNA-seq). Using network proximity analysis, we screened for FDA-approved drugs that interact with SCM-associated pathways. Additionally, we tested the cardioprotective effects of two drug candidates in the SCM mouse model and explored their mechanism-of-action in H9c2 cells. Results: Network analysis identified 129 drugs associated with SCM, which were refined to 14 drug candidates based on strong network predictions, proven anti-infective effects, suitability for ICU use, and minimal side effects. Among them, acetaminophen and pyridoxal phosphate significantly improved cardiac function in SCM moues, as demonstrated by the increased ejection fraction (EF) and fractional shortening (FS), and the reduced levels of cardiac injury biomarkers: B-type natriuretic peptide (BNP) and cardiac troponin I (cTn-I). In vitro assays revealed that acetaminophen inhibited prostaglandin synthesis, reducing inflammation, while pyridoxal phosphate restored amino acid balance, supporting cellular function. These findings suggest that both drugs possess protective effects against SCM. Conclusions: This study provides a robust platform for drug repurposing in SCM, identifying acetaminophen and pyridoxal phosphate as promising candidates for clinical translation, with the potential to improve treatment outcomes in septic patients with cardiac complications. Full article

Background: Prostaglandins are naturally occurring local mediators that can participate in the modulation of the cardiovascular system through their interaction with Gs/Gi-coupled receptors in different tissues and cells, including platelets. Thrombin is one of the most important factors that regulates platelet reactivity and coagulation. Clinical trials have consistently shown that omega-3 fatty acid supplementation lowers the risk for cardiovascular mortality and morbidity. Since omega-3 fatty acids are the main precursors of PGE3 in vivo, it would be relevant to investigate the effects of PGE3 on Thrombin Receptor Activating Peptide (TRAP-6)-induced platelet reactivity to determine the receptors and possible mechanisms of action of these compounds. Methods: We have measured platelet aggregation, P-selectin expression, and vasodilator-stimulated phosphoprotein (VASP) phosphorylation to evaluate platelet reactivity induced by TRAP-6 to determine the effects of PGE3 on platelet function. Results: We assessed the ability of DG-041, a selective prostanoid EP3 receptor antagonist, and of ONO-AE3-208, a selective prostanoid EP4 receptor antagonist, to modify the effects of PGE3. PGE3 inhibited TRAP-6-induced platelet aggregation and activation. This inhibition was enhanced in the presence of a Gi-coupled EP3 receptor antagonist and abolished in the presence of a Gs-coupled EP4 receptor antagonist. The effects of PGE3 were directly related to changes in cAMP, assessed by VASP phosphorylation. Conclusions: The general effects of PGE3 on human platelet reactivity are the consequence of a balance between activatory and inhibitory effects at receptors that have contrary effects on adenylate cyclase. These results indicate a potential mechanism by which omega-3 fatty acids underlie cardioprotective effects. Full article

Resveratrol, a naturally occurring polyphenolic compound found in various plants, has been extensively studied for its broad spectrum of beneficial biological effects. These encompass its potent antioxidant properties, anti-inflammatory activities, anti-aging capabilities, cardioprotective functions, and neuroprotective potential. The diverse biological actions of resveratrol extend beyond these well-established properties. It also exerts a significant impact on metabolic processes and bioavailability, and critically, it demonstrates the ability to effectively traverse the blood–brain barrier. This capacity to penetrate the central nervous system renders resveratrol a promising therapeutic agent for the management of central nervous system malignancies, as it has been shown to inhibit tumor cell proliferation, induce apoptosis, and modulate key signaling cascades, such as PI3K/Akt, JAK/STAT, and NF-kB. The multifaceted nature of resveratrol’s biological effects, including its influence on diverse physiological processes, underscores its potential as a valuable therapeutic option for the treatment of central nervous system tumors. Full article