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Background: The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility. Objectives: This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility. Methods: A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package. Results: Twenty-one studies involving 203-208 animals treated with Dox and 271-276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger's test, and Begg's test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence. Conclusion: Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility. [ABSTRACT FROM AUTHOR]

One of the most vital processes of the body is the cardiovascular system's proper operation. Physiological processes in the heart are regulated by the balance of cardioprotective and pathological mechanisms. The insulin-like growth factor system (IGF system, IGF signaling pathway) plays a pivotal role in regulating growth and development of various cells and tissues. In myocardium, the IGF system provides cardioprotective effects as well as participates in pathological processes. This review summarizes recent data on the role of IGF signaling in cardioprotection and pathogenesis of various cardiovascular diseases, as well as analyzes severity of these effects in various scenarios. [ABSTRACT FROM AUTHOR]

This study investigated the cardioprotective effect of oleuropein against cisplatin-induced cardiac damage in terms of inflammatory, oxidative stress and cardiac parameters. In this study, 40 female Wistar albino rats were divided into four groups: control, cisplatin, oleuropein and cisplatin+oleuropein. To establish the experimental model, oleuropein (200 mg/kg) was administered for 14 days and cisplatin (7 mg/kg) was administered as a single dose on the seventh day. Cisplatin increased MDA cardiac parameters (CK, CK-MB and cTnI) and inflammatory cytokines (TNF-α, IL-1β and IL-6) in cardiac tissue and decreased GSH, GSH-Px and catalase levels. On the other hand, oleuropein improved cardiac parameters and decreased inflammatory cytokine and oxidative stress levels in cardiac tissue. [ABSTRACT FROM AUTHOR]

Coronary artery disease and myocardial infarction are major global health issues, with myocardial infarction becoming more common. In the current study, the cardioprotective effects of methanol extract from the aril of the Blighia sapida fruit were assessed in relation to certain cardiac function biomarkers, endogenous antioxidant activity, and the pathology of the heart in Wistar rats that had undergone isoprenaline-induced myocardial infarction. Phytochemical screening was according to methods described by Trease and Evans. The LD50 of the extract was calculated using Lorke's approach. The LD50 was calculated using nine (9) Wistar rats. For cardioprotective and antioxidant activities, six groups of seven Wistar rats each were formed from forty-two (42), which were divided at random. Group 1 were administered 1ml of normal saline daily, group 2 through 4 were pretreated with 250 mg/kg, 500 mg/kg, and 750 mg/kg of the extract, respectively, for 28 days. Group 5 were administered 85 mg/kg of isoprenaline on days 26 and 27, 24 hours apart to cause myocardial infarction. Group 6 served as the positive control (pretreated with 2 mg/kg carvedilol for 28 days). The plant contains bioactive substances like alkaloids, flavonoids, polyphenols, cardiac glycosides, cyanogenic glycosides, steroid glycosides, cardenolides, terpenes, and tannins. No mortality even at a dose of 5000mg/kg. Glutathione peroxidase, reduced glutathione, catalase, and superoxide dismutase all show considerable increases. Total troponin, troponin c, troponin I, creatine kinase, creatine kinase-MB, and myoglobin, significantly decreased when compared to the isoprenaline group. Additionally, there was a significant drop in the levels of some biochemical markers in the extract treated groups compared to the isoprenaline control. Total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and ALT, AST, and ALP significantly decreased. Histological analysis revealed some degree of cardiac modification and a notable improvement. According to the data, the extract contains modest antioxidant and cardioprotective characteristics.

Introduction: In contrast to the antihypertensive effect of esaxerenone, there is little evidence of its cardioprotective effect. We investigated the efficacy and safety of esaxerenone in patients with uncontrolled hypertension and left ventricular hypertrophy taking a renin-angiotensin system inhibitor (RASi) or calcium-channel blocker (CCB). Methods: This was a multicenter, open-label, exploratory study with a 24-week treatment period. Esaxerenone was orally administered at an initial dose of 2.5 mg/day (maximum dose: 5 mg/day). The primary endpoints were the change in morning home systolic blood pressure (BP)/diastolic BP and change and percentage change in left ventricular mass index (LVMI) from baseline to end of treatment (EOT). Key secondary endpoints included change from baseline in bedtime home and office BP, achievement rate of target BP, and safety. Results: In total, 60 patients were enrolled. Morning home systolic/diastolic BP was significantly decreased from baseline to EOT in the total population (− 11.5/ − 4.7 mmHg, p < 0.001) and in both the RASi and CCB subcohorts (all p < 0.01). Significant reductions in bedtime home and office BP were shown in the total population and both subcohorts. LVMI was also significantly decreased from baseline to EOT in the total population (− 9.9 g/m2, − 8.5%, both p < 0.001) and both subcohorts (all p < 0.05). The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 35.0% and 3.3%, respectively; most were mild or moderate. No new safety concerns were identified. Conclusion: Esaxerenone showed favorable antihypertensive and cardioprotective effects and safety in hypertensive patients with cardiac hypertrophy. Trial Registration: Japan Registry of Clinical Trials (jRCTs071190043). [ABSTRACT FROM AUTHOR]

The purpose of this research was to investigate the cardioprotective effects and pharmacokinetics of Dalbergia odorifera flavonoids. The cardioprotective effects were detected by hematoxylin‐eosin staining histopathological observations and the detection of myocardial enzymes by kits in serum, peroxidation and antioxidant levels and ATPase activities by kits in the homogenate supernatant, and antioxidant and apoptosis‐related protein expression in heart tissue by immunohistochemistry. The pharmacokinetics parameters of the flavonoids in rat plasma were investigated by ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry. Molecular docking of the compounds absorbed by the blood with specific proteins was carried out. D. odorifera flavonoids significantly reduced the levels of creatinine kinase, alanine transaminase, nitric oxide, and Hydrogen peroxide, elevated the levels of glutathione, superoxide dismutase, and ATPase, significantly reduced the pathological degree of heart tissue and had obvious anti‐myocardial ischemia efficacy. Nine out of the 17 flavonoids were detected in rat plasma. The peak concentration and the area under the plasma concentration‐time curve values of 3′‐O‐methylviolanone and sativanone were significantly higher than those of other ingredients. The peak time of most flavonoids (except for Genistein and Pruneion) was lower than 2 h, while the half‐life of elimination of the nine flavonoids ranged from 3.32 to 21.5 h. The molecular docking results showed that daidzein, dalbergin, formononetin, and genistein had the potential to bind to the target proteins. The results of the study provide an important basis for understanding the cardioprotective effects and clinical application of D. odorifera. [ABSTRACT FROM AUTHOR]

BackgroundThe cardioprotective effect of remote ischemia preconditioning in clinical studies is inconsistent with experimental results. Adaptation to high-altitude hypoxia has been reported to be cardioprotective in animal experiments. However, the clinical significance of the cardioprotective effect of high-altitude adaptation has not been demonstrated.MethodsA retrospective cohort study with propensity score matching was designed to compare the outcomes of cardiac surgery between highlanders and lowlanders in a tertiary teaching hospital. The data of adult cardiac surgical patients from January 2013 to December 2022, were collected for analysis. Patients with cardiopulmonary bypass and cardioplegia were divided into a low-altitude group (

Myocardial infarction (MI) triggers adverse ventricular remodeling (VR), cardiac fibrosis, and subsequent heart failure. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is postulated to play a significant role in VR processing via activation of the TLR4 inflammatory pathway. We hypothesized that an eNAMPT specific monoclonal antibody (mAb) could target and neutralize overexpressed eNAMPT post-MI and attenuate chronic cardiac inflammation and fibrosis. We investigated humanized ALT-100 and ALT-300 mAb with high eNAMPT-neutralizing capacity in an infarct rat model to test our hypothesis. ALT-300 was 99mTc-labeled to generate 99mTc-ALT-300 for imaging myocardial eNAMPT expression at 2 hours, 1 week, and 4 weeks post-IRI. The eNAMPT-neutralizing ALT-100 mAb (0.4 mg/kg) or saline was administered intraperitoneally at 1 hour and 24 hours post-reperfusion and twice a week for 4 weeks. Cardiac function changes were determined by echocardiography at 3 days and 4 weeks post-IRI. 99mTc-ALT-300 uptake was initially localized to the ischemic area at risk (IAR) of the left ventricle (LV) and subsequently extended to adjacent non-ischemic areas 2 hours to 4 weeks post-IRI. Radioactive uptake (%ID/g) of 99mTc-ALT-300 in the IAR increased from 1 week to 4 weeks (0.54 ± 0.16 vs. 0.78 ± 0.13, P

Abstract Background Myocardial protection is still a focus of ongoing research. Propofol is used widely during the induction of anaesthesia in cardiac surgery. So, this triggers us to investigate the cardioprotective effect of the propofol when added to the cardioplegia compared to systemic propofol by measuring the troponin T level. Methods This clinical randomized controlled trial was carried out on 150 patients operated for elective valvular heart surgery. Patients were assigned into three equal groups: Group 1: received propofol in the cardioplegia, Group 2: received propofol injection in the aortic line before and after the aortic cross-clamp, and Group 3 (control group): patients without propofol in the cardioplegia or aortic line. All patients were subjected to full medical histories, physical examinations, routine tests, and echocardiography. Cardiac troponin T was measured before surgery and 4 times postoperatively. Results In group 1, there was a significant improvement in troponin T level at the last reading compared with the control group (mean ± SD. of group 1 was 246.4 ± 131.4, mean ± SD. of group 3 was 317.0 ± 117.9, p = 0.031), denoting propofol's cardioprotective effect when added as a cardioplegia additive. In group 2, there was a significant improvement of troponin T level at the last reading compared with the group 1 and control group (mean ± SD. of group 2 was 202.54 ± 156.03, mean ± SD. of group 3 was 317.0 ± 117.9, p

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1.7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant omega-6/omega-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in both adult and pediatric populations. Furthermore, ALA has shown protective effects against hypertension, contributing to balancing blood pressure through customary diet. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardioprotective effects. [ABSTRACT FROM AUTHOR]

Background: Myocardial protection is still a focus of ongoing research. Propofol is used widely during the induction of anaesthesia in cardiac surgery. So, this triggers us to investigate the cardioprotective effect of the propofol when added to the cardioplegia compared to systemic propofol by measuring the troponin T level. Methods: This clinical randomized controlled trial was carried out on 150 patients operated for elective valvular heart surgery. Patients were assigned into three equal groups: Group 1: received propofol in the cardioplegia, Group 2: received propofol injection in the aortic line before and after the aortic cross-clamp, and Group 3 (control group): patients without propofol in the cardioplegia or aortic line. All patients were subjected to full medical histories, physical examinations, routine tests, and echocardiography. Cardiac troponin T was measured before surgery and 4 times postoperatively. Results: In group 1, there was a significant improvement in troponin T level at the last reading compared with the control group (mean ± SD. of group 1 was 246.4 ± 131.4, mean ± SD. of group 3 was 317.0 ± 117.9, p = 0.031), denoting propofol's cardioprotective effect when added as a cardioplegia additive. In group 2, there was a significant improvement of troponin T level at the last reading compared with the group 1 and control group (mean ± SD. of group 2 was 202.54 ± 156.03, mean ± SD. of group 3 was 317.0 ± 117.9, p < 0.001), denoting propofol's more cardioprotective effect when used systemically during cardiopulmonary bypass than when added as a cardioplegia additive. Conclusions: In valvular cardiac surgery, propofol has an additional cardioprotective effect and a superior cardiac outcome when administered systematically during cardiopulmonary bypass rather than added to cardioplegia. Trial registration: Pan African Clinical Trials Register PACTR201907764652028. Registered on 01 July 2019, retrospectively registered, https://pactr.samrc.ac.za/ TrialDisplay.aspx?TrialID = 5726. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine has been proven to be of great significance in cardioprotective effects. Clinopodium chinense (Lamiaceae) has unique advantages in the treatment and prevention of cardiovascular diseases. Tournefolic acid B (TAB) was proven to be a potent component against myocardial ischemia reperfusion injury (MIRI) from Clinopodium chinense (Lamiaceae). This article will attempt to establish a gram-scale synthesis method of TAB and discuss the structure-activity relationship of its analogs. The total synthesis of TAB was completed in 10 steps with an overall yield of 13%. In addition, analogs were synthesized, and their cardioprotective activity was evaluated on the hypoxia/reoxygenation of H9c2 cells. Amidation of the acid position is helpful to the activity, while methylation of phenolic hydroxyl groups greatly decreased the cardioprotective activity. The easily prepared azxepin analogs also showed cardioprotective activity. Most of the clogP values calculated by Molinspiration ranged from 2.5 to 5, which is in accordance with Lipinski's rule of 5. These findings represent a novel kind of cardioprotective agent that is worthy of further study. [ABSTRACT FROM AUTHOR]

Abstract Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but its clinical application is greatly limited because of the cardiotoxicity. Thus, exploration of effective therapies against DOX-induced cardiotoxicity is necessary. The aim of this study is to investigate the effects and possible mechanisms of Trametes Sanguinea Lyoyd fermented crude polysaccharide (TSLFACP) against DOX-induced cardiotoxicity. We investigated the protective effects of TSLFACP on myocardial injury and its possible mechanisms using two in vitro cells of DOX-treated cardiomyocytes H9C2 and embryonic myocardial cell line CCC-HEH-2 and a in vivo mouse model of DOX-induced myocardial injury. We found that TSLFACP could reverse DOX-induced toxicity in H9C2 and CCC-HEH-2 cells. Similarly, we found that when pretreatment with TSLFACP (200 mg/kg, i.g.) daily for 6 days, DOX-induced myocardial damage was attenuated, including the decrease in serum myocardial injury index, and the amelioration in cardiac histopathological morphology. Additionally, immunohistochemistry and western blotting were used to identify the underlying and possible signal pathways. We found that TSLFACP attenuated the expression of LC3-II, Beclin-1 and PRAP induced by DOX. In conclusion, our results demonstrated that TSLFACP could protect against DOX-induced cardiotoxicity by inhibiting autophagy and apoptosis.

Context Guanxin V (GX), a traditional Chinese medicine formula, is safe and effective in the treatment of coronary artery disease. However, its protective effect on myocardial ischaemia reperfusion injury (MIRI) is unclear.Objective To investigate the cardioprotective effect of GX on MIRI and explore the potential mechanism.Materials and methods Sprague-Dawley male rats were divided into Sham, MIRI and MIRI + GX groups. GX (6 g/kg) was administered to rats via intragastric administration for seven days before ischaemia reperfusion (IR) surgery. The infarct size, histopathology, serum enzyme activities, ultrastructure of the cardiac mitochondria were assessed. H9c2 cells were pre-treated with GX (0.5 mg/mL), and then exposed to hypoxia/reoxygenation (HR). The cell viability and LDH levels were measured. Network pharmacology was conducted to predict the potential mechanism. The related targets of GX were predicted using the TCMSP database, DrugBank database, etc. Finally, pharmacological experiments were used to validate the predicted results.Results In vivo, GX significantly reduced the myocardial infarct size from 56.33% to 17.18%, decreased the levels of AST (239.32 vs. 369.18 U/L), CK-MB (1324.61 vs. 2066.47 U/L) and LDH (1245.26 vs. 1969.62 U/L), and reduced mitochondrial damage. In vitro, GX significantly increased H9c2 cell viability (IC50 = 3.913 mg/mL) and inhibited the release of LDH (207.35 vs. 314.33). In addition, GX could maintain iron homeostasis and reduce oxidative stress level by regulating iron metabolism-associated proteins.Conclusions GX can attenuate MIRI via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.

β1-adrenergic receptor (β1-AR), a member in the family of G-protein-coupled receptors, is a transmembrane receptor of great significance in the heart. Physiologically, catecholamines activate β1-AR to initiate a positive chronotropic, inotropic, and dromotropic change. It is believed that β1-AR couples to Gs protein and transmits the signal through second messenger cAMP. However, increasing research shows that β1-AR can also bind with Gi protein in addition to Gs. When β1-AR-Gi is biasedly activated, cardioprotective effects are introduced by the activated cGMP-protein kinase G (PKG) pathway and the transactivation of epidermal growth factor receptor (EGFR) pathway. The discovery of β1-AR-Gi signaling makes us reconsider the selectivity of G protein with regard to β1-AR, which also provides new ideas for the treatment of heart diseases. This review summarizes the discovery of β1-AR-Gi pathway, including the evidence that supports β1-AR’s capability to couple Gi, details of the transduction process and functions of the β1-AR-Gi signaling pathway.

Dilated cardiomyopathy (DCM) is characterized by decreased systolic function and left or biventricular enlargement. There is no single specific medicine to delay the progression of DCM. Melatonin (Mel) plays a key role in many cardiovascular diseases by regulating cell damage, oxidative stress and other pathological processes,delaying myocardial remodeling and protecting cardiac function. There is a close relationship between DCM and Mel. It is confirmed that Mel plays an important role in delaying the progression of DCM.

Abstract Background The molecular mechanisms of protective effect of metformin (Met) on ischemic myocardium have not been fully understood. This study aims to evaluate the cardioprotective effect of metformin on myocardial ischemia–reperfusion injury (MIRI) in rat models at different time points using dynamic 18F-FDG micro-PET/CT imaging. Methods The I/R injury model in SD rats was established by ligation of left anterior descending coronary artery near the pulmonary arch root for 30 min. SD rats (n = 12) were randomly divided into 2 groups: Control group (n = 6) without any intervention and Met group (n = 6) with oral administration of metformin (50 mg/kg) twice a day. Gated 18F-FDG (40Mbq) micro-PET/CT imaging was performed for 10 min at different time points (day 1st, day 7th, day 14th and day 30th after operation). Volumes of interest were drawn to identify different myocardium regions (ischemia center, peri-ischemia area and remote area). Standardized uptake values (SUVs) (SUVmean and SUVmax) were analyzed to evaluate the FDG uptake activity, and then the center/remote ratio was calculated. In addition, the left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and LV ejection fraction (LVEF) were obtained. On the 30th day, all rats were scarified and myocardial ischemia was analyzed by HE staining and confirmed by pathology. Results In the Control group, the center/remote ratio showed no obvious change trend at each time point after reperfusion, while the LV EDV increased gradually over time, and they were significantly negatively correlated (r = − 0.507, p 0.05). On the 30th day, the center/remote ratio of the Met group was significantly higher than that of the Control group (0.81 ± 0.06 vs. 0.65 ± 0.09, p

Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but its clinical application is greatly limited because of the cardiotoxicity. Thus, exploration of effective therapies against DOX-induced cardiotoxicity is necessary. The aim of this study is to investigate the effects and possible mechanisms of Trametes Sanguinea Lyoyd fermented crude polysaccharide (TSLFACP) against DOX-induced cardiotoxicity. We investigated the protective effects of TSLFACP on myocardial injury and its possible mechanisms using two in vitro cells of DOX-treated cardiomyocytes H9C2 and embryonic myocardial cell line CCC-HEH-2 and a in vivo mouse model of DOX-induced myocardial injury. We found that TSLFACP could reverse DOX-induced toxicity in H9C2 and CCC-HEH-2 cells. Similarly, we found that when pretreatment with TSLFACP (200 mg/kg, i.g.) daily for 6 days, DOX-induced myocardial damage was attenuated, including the decrease in serum myocardial injury index, and the amelioration in cardiac histopathological morphology. Additionally, immunohistochemistry and western blotting were used to identify the underlying and possible signal pathways. We found that TSLFACP attenuated the expression of LC3-II, Beclin-1 and PRAP induced by DOX. In conclusion, our results demonstrated that TSLFACP could protect against DOX-induced cardiotoxicity by inhibiting autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, p < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, p < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, p > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, p < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, p < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect. [ABSTRACT FROM AUTHOR]

This Study aimed to characterise the phenolic compounds in Garcinia pedunculata extract and assess their potential antioxidant activity as well as its cardioprotective potential in isoproterenol-induced cardiac hypertrophy in an experimental animal model. In vitro antioxidant properties were determined using DPPH, ABTS, FRAP, PMD assays. In vitro lipid peroxidation experiment was also performed with heart tissues. Cardioprotective and cardiotoxicity effects were determined using the cell line studies. The cardioprotective effect of GP was assessed in a rat model of isoproterenol-(ISO-) induced cardiac hypertrophy by subcutaneous administration. Heart weight/tail length ratio and cardiac hypertrophy indicators were reduced after oral administration of GP. Additionally, GP reduced oxidative stress and heart inflammation brought on by ISO. In H9c2 cells, the antihypertrophic and anti-inflammatory effects of the extract of GP were seen in the presence of ISO, which were further supported by the in vivo observations. This study makes a compelling case for the possibility that supplementing with dried GP fruit can prevent heart hypertrophy by reducing oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1.7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant omega-6/omega-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in both adult and pediatric populations. Furthermore, ALA has shown protective effects against hypertension, contributing to balancing blood pressure through customary diet. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardioprotective effects.

Traditional Chinese medicine has been proven to be of great significance in cardioprotective effects. Clinopodium chinense (Lamiaceae) has unique advantages in the treatment and prevention of cardiovascular diseases. Tournefolic acid B (TAB) was proven to be a potent component against myocardial ischemia reperfusion injury (MIRI) from Clinopodium chinense (Lamiaceae). This article will attempt to establish a gram-scale synthesis method of TAB and discuss the structure-activity relationship of its analogs. The total synthesis of TAB was completed in 10 steps with an overall yield of 13%. In addition, analogs were synthesized, and their cardioprotective activity was evaluated on the hypoxia/reoxygenation of H9c2 cells. Amidation of the acid position is helpful to the activity, while methylation of phenolic hydroxyl groups greatly decreased the cardioprotective activity. The easily prepared azxepin analogs also showed cardioprotective activity. Most of the clogP values calculated by Molinspiration ranged from 2.5 to 5, which is in accordance with Lipinski’s rule of 5. These findings represent a novel kind of cardioprotective agent that is worthy of further study.

This Study aimed to characterise the phenolic compounds in Garcinia pedunculata extract and assess their potential antioxidant activity as well as its cardioprotective potential in isoproterenol-induced cardiac hypertrophy in an experimental animal model. In vitro antioxidant properties were determined using DPPH, ABTS, FRAP, PMD assays. In vitro lipid peroxidation experiment was also performed with heart tissues. Cardioprotective and cardiotoxicity effects were determined using the cell line studies. The cardioprotective effect of GP was assessed in a rat model of isoproterenol-(ISO-) induced cardiac hypertrophy by subcutaneous administration. Heart weight/tail length ratio and cardiac hypertrophy indicators were reduced after oral administration of GP. Additionally, GP reduced oxidative stress and heart inflammation brought on by ISO. In H9c2 cells, the antihypertrophic and anti-inflammatory effects of the extract of GP were seen in the presence of ISO, which were further supported by the in vivo observations. This study makes a compelling case for the possibility that supplementing with dried GP fruit can prevent heart hypertrophy by reducing oxidative stress and inflammation.

Pretreatment or treatment with anti-apoptotic, anti-inflammatory, or anti-oxidative approaches could be critical for attenuated the severity of myocardial ischemia/reperfusion (I/R) injury. Naringin, a natural flavonoid, plays important roles in inflammation-related diseases. Immature dry fruits of Citrus wilsonii Tanaka (Xiang Yuan) are rich in naringin that can be used as traditional Chinese medicine to treat inflammation-related symptoms. However, its roles in cardioprotective role remain unclear. This study aimed to isolate naringin from Citrus wilsonii Tanaka fruit and tested their cardioprotective effect. The dry fruits of Citrus wilsonii Tanaka were extracted with boiling water and then supernatants were freeze-dried to yield aqueous extract (ZQAE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, and then subjected to different chromatographic separation steps, and naringin was isolated in a high yield. The cardioprotective effects of the aqueous extract of ZQAE and naringin were investigated in a myocardial I/R rat model and to elucidate the mechanism underlying its cardioprotective effect. Our results indicated that 5-day ZQAE and naringin pretreatments both promoted histopathological changes and reduced myocardial enzymes (cTnl, CK-MB, CK and LDH) induced by I/R. Moreover, the 50 mg/kg and 100 mg/kg ZQAE dose pretreatments presented a significantly decreased infarct size as well as myocardial enzyme levels but also inhibited myocardial apoptosis (cleaved-caspase3 protein expression), the inflammatory response (IL-23, IL-6, and TNF-α) and oxidative stress (MDA and SOD). The cardioprotective effect of 5 mg/kg dose of naringin pretreatment is comparable with that of 5 mg/kg drug ditiazem pretreatment. Additionally, naringin pretreatment exhibited striking decreases in the apoptosis index and downregulation of the protein expression levels of cleaved-Caspase3, Bcl2 and Bax. Meanwhile, naringin downregulated HMGB1 expression and upregulated SIRT1 expression in the myocardium. These findings suggest that short-term pretreatments with ZQAE and naringin both protect against myocardial I/R injury by suppressing myocardial apoptosis, the inflammatory response, and oxidative stress. The cardioprotective effect of naringin involves SIRT1 activation and may interact with HMGB1 and inhibit the release of HMGB1. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanisms of protective effect of metformin (Met) on ischemic myocardium have not been fully understood. This study aims to evaluate the cardioprotective effect of metformin on myocardial ischemia-reperfusion injury (MIRI) in rat models at different time points using dynamic 18F-FDG micro-PET/CT imaging.Methods: The I/R injury model in SD rats was established by ligation of left anterior descending coronary artery near the pulmonary arch root for 30 min. SD rats (n = 12) were randomly divided into 2 groups: Control group (n = 6) without any intervention and Met group (n = 6) with oral administration of metformin (50 mg/kg) twice a day. Gated 18F-FDG (40Mbq) micro-PET/CT imaging was performed for 10 min at different time points (day 1st, day 7th, day 14th and day 30th after operation). Volumes of interest were drawn to identify different myocardium regions (ischemia center, peri-ischemia area and remote area). Standardized uptake values (SUVs) (SUVmean and SUVmax) were analyzed to evaluate the FDG uptake activity, and then the center/remote ratio was calculated. In addition, the left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and LV ejection fraction (LVEF) were obtained. On the 30th day, all rats were scarified and myocardial ischemia was analyzed by HE staining and confirmed by pathology.Results: In the Control group, the center/remote ratio showed no obvious change trend at each time point after reperfusion, while the LV EDV increased gradually over time, and they were significantly negatively correlated (r = - 0.507, p < 0.05). In the Met group, the center/remote ratio gradually increased with time, there was no significant correlation between center/remote ratio and LV EDV (r = - 0.078, p > 0.05). On the 30th day, the center/remote ratio of the Met group was significantly higher than that of the Control group (0.81 ± 0.06 vs. 0.65 ± 0.09, p < 0.05), while LV EDV in Met group was significantly lower than in Control group (358.21 ± 22.62 vs. 457.53 ± 29.91, p < 0.05). There was no significant difference of LVEF between Met group and Control group at different time points after reperfusion (p < 0.05). HE staining showed that the myocardial infarction and fibrosis in ischemic center area of the Control group was more serious than that of the Met group.Conclusions: Met could attenuate the severity of MIRI, delay and prevent the progress of LV remodeling. The cardioprotective progress could be dynamically assessed by 18F-FDG micro-PET/CT imaging. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to improve cardiovascular outcomes not only in patients with diabetes but also in those with heart failure, irrespective of diabetic status. However, the mechanisms underlying the cardioprotective effects of these newer anti-diabetic drugs remain to be fully elucidated. One exciting avenue that has been recently explored in both preclinical and clinical studies is the modulation of the cardiovascular autonomic nervous system. A reduction in sympathetic nervous system activity by SGLT2 inhibitors may potentially translate into a reduction in arrhythmic risk and sudden arrhythmic death, which may explain, at least partly, the cardioprotection shown in the cardiovascular outcome trials with different SGLT2 inhibitors. Although some of the data from the preclinical and clinical studies are promising, overall the findings can be contradictory. This highlights the need for more studies to address gaps in our knowledge of these novel drugs. The present review offers an in depth overview of the existing literature regarding the role of SGLT2 inhibitors in modulating cardiovascular autonomic function as one of the possible pathways of their cardioprotective effects. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is the result of reduced or stopped blood supply to a section of the myocardium. Regardless of its potential effectiveness in the treatment of several types of cancers, doxorubicin (DOX) capabilities are restricted because of its widespread cardiotoxic impact., Aim: In this study, the protective effect of zinc oxide nanoparticles against doxorubicin-induced myocardial infarction in rats is examined., Methods: Zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using X-ray diffraction, transmission electron microscope, and UV-Vis spectral analysis. A total cumulative dose of DOX (18 mg/kg body weight, i.p.) was injected once daily on days 2, 4, 6, 8, 10, and 12 (i.p.) to induce MI in rats. 24 rats were divided into 4 groups; control, MI, and MI treated with two doses of ZnO NPs (45 and 22.5 mg/kg)., Results: The treatment with ZnO NPs restored ST-segment near normal, ameliorated the changes in cardiac troponin T, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, total proteins, malondialdehyde, nitric oxide, reduced glutathione, and catalase.The histological investigation revealed that ZnO NPs treated group showed marked improvement in the examined cardiac muscle and liver in numerous sections.The lower dose of ZnO NPs (22.5 mg/kg) was significantly more effective than the higher dose (45 mg/kg)., Conclusion: The effect of ZnO NPs against doxorubicin-induced myocardial infarction in rats was assessed and the results revealed a successful cardioprotective potency through enhancing the antioxidant system and stimulating nitric oxide production in myocardial infarcted rats. This work implies that ZnO NPs could serve as promising agents for treating doxorubicin-induced cardiotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that there were no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Background: The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility., Objectives: This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility., Methods: A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package., Results: Twenty-one studies involving 203-208 animals treated with Dox and 271-276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger's test, and Begg's test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence., Conclusion: Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Chen and Wang.)

This study aimed to promote red pitaya fruit parts as alternate sources of nutraceuticals. The red pitaya of Chinese origin was determined for its in vitro efficacy, where the fruit extracts were evaluated based on the selected antioxidative properties, lipid-reducing capacity, and cytotoxicity. The betanin, total betacyanins, total anthocyanins, and DPPH radical scavenging activity of the red pitaya pulp and peel extracts were determined by spectrophotometric analyses. Cell culture assays were used to examine in vitro efficacy and cytotoxicity of the pitaya extracts. The result showed that red pitaya peel extract had a higher total betacyanins and total anthocyanins content than the pulp extract, but the peel extract had a lower DPPH radical scavenging effect than the pulp extract. The red pitaya extracts also had a protective effect in reducing oxidative stress, especially the peel extract. All fruit samples had a low anticancer potential except for betanin and anthocyanin standards. The protective effect of pitaya peel could be attributed to betacyanins and anthocyanins. Both pulp and peel extracts had a weak anticancer effect because these extracts contained polysaccharides and other phytochemicals that were not cytotoxic. As the peel extract of red pitaya was not cytotoxic, it is a potent source of betacyanins for reducing oxidative stress.

Infusion of allogeneic cardiosphere-derived cells (allo-CDCs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long-term effects of allo-CDCs have not been assessed. We performed a placebo-controlled pivotal study for long-term evaluation, as well as shorter-term mechanistic studies. Minipigs underwent 1.5-hour mid-left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo-CDCs or vehicle 30 minutes postreperfusion. Left ventriculography (LVG) demonstrated preserved ejection fraction (EF) and attenuation of LV remodeling in CDC-treated pigs. Pigs underwent cardiac magnetic resonance imaging (MRI) and LVG 1 hour and 8 weeks after therapy to evaluate efficacy. MRI showed improvement of EF and attenuation of LV remodeling immediately after allo-CDC infusion. In addition, allo-CDCs improved regional function and decreased hypertrophy 2 months post-treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo-CDC-treated pigs at 2 months. Allo-CDCs did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short-term experiments designed to probe mechanism revealed antiapoptotic effects of allo-CDCs on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. Allo-CDC infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.

Abstract The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction, the endothelium has numerous other complex roles involved in the maintenance of vascular homeostasis. Chronic exposure to cardiovascular risk factors and oxidative stress results in an imbalance in these functions, creating an environment that favors reduced vasodilation and a proinflammatory and prothrombic state. The involvement of endothelial dysfunction in all stages of the cardiovascular continuum makes it an important target for treatment. One of the major endothelial-derived factors involved in the maintenance of endothelial function is nitric oxide (NO). Angiotensin-converting enzyme (ACE) inhibitors increase NO production both directly and indirectly by preventing production of angiotensin II (which diminishes NO production) and inhibiting the degradation of bradykinin (which stimulates local release of NO). Among the ACE inhibitors, perindopril appears to have the greatest effects on bradykinin and has demonstrated efficacy in a number of markers of endothelial dysfunction including arterial stiffness and progression of atherosclerosis. There is also strong evidence supporting the use of perindopril-based therapy for the treatment of hypertension and for reducing the risk of cardiovascular morbidity and mortality in a wide range of patients across the cardiovascular continuum. Funding: The journal’s Rapid Service Fee was funded by Servier.

Background: Myocardial infarction (MI) is one of the most important causes of death worldwide. The effect of flunixin meglumine (FM) on MI is unknown. We investigated the protective effect of FM on the serum biochemical profile, malondialdehyde (MDA), and heart histology changes induced by isoproterenol (ISO) in adult male rats. Methods: Rats were randomly divided into four groups of six each as follows: Group 1, control. Group 2, was administered ISO subcutaneously at 85 mg/kg for 2 days. Group 3 was administered FM intraperitoneally at 2 mg/kg/d, for 3 days; and Group 4 was administered FM 2mg/kg/d intraperitoneally for 3 days and ISO 85mg/kg subcutaneously for two consecutive days. Blood samples were collected after anesthesia, 24h after the second ISO administration. The heart tissue was immediately removed for histopathological examination. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and serum MDA levels were measured on an autoanalyzer and spectrophotometer. Results: In Group 4 (FM+ISO) the levels of AST, LDH and MDA decreased compared with those for Group 2 (ISO) (P< 0.05). Histopathologic tests revealed that ISO induced myocardial injury in Group 3 rats, whereas the alterations of the heart architecture were improved by FM in Group 4 (FM+ISO). Conclusions: The results suggest that FM has a potential cardioprotective effect against an experimental model of MI in rats.

BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, p < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, p < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, p > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, p < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, p < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.

Background: Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition., Methods: Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning (IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl)., Results: The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group., Conclusion: The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Egashira et al.)

Background: The cardioprotective effect of remote ischemia preconditioning in clinical studies is inconsistent with experimental results. Adaptation to high-altitude hypoxia has been reported to be cardioprotective in animal experiments. However, the clinical significance of the cardioprotective effect of high-altitude adaptation has not been demonstrated., Methods: A retrospective cohort study with propensity score matching was designed to compare the outcomes of cardiac surgery between highlanders and lowlanders in a tertiary teaching hospital. The data of adult cardiac surgical patients from January 2013 to December 2022, were collected for analysis. Patients with cardiopulmonary bypass and cardioplegia were divided into a low-altitude group (<1,500 m) and a high-altitude group (≥1,500 m) based on the altitude of their place of residence., Results: Of 3,020 patients, the majority (87.5%) permanently lived in low-altitude regions [495 (435, 688) m], and there were 379 patients (12.5%) in the high-altitude group [2,552 (1,862, 3,478) m]. The 377 highlander patients were matched with lowlander patients at a ratio of 1:1. The high-altitude group exhibited a 44.5% reduction in the incidence of major adverse cardiovascular events (MACEs) compared with the low-altitude group (6.6% vs. 11.9%, P  = 0.017). The patients in the moderate high-altitude subgroup (2,500-3,500 m) had the lowest incidence (5.6%) of MACEs among the subgroups. The level of creatinine kinase muscle-brain isoenzymes on the first postoperative morning was lower in the high-altitude group than in the low-altitude group (66.5 [47.9, 89.0] U/L vs. 69.5 [49.3, 96.8] U/L, P  = 0.003)., Conclusions: High-altitude adaptation exhibits clinically significant cardioprotection in cardiac surgical patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DXC declared a shared affiliation with the author JL to the handling editor at the time of review., (© 2024 Lei, Liu, Ma, Lei, Zeng, Li, Huang, Lyu and Lei.)

Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the &quot;spider web&quot; mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of &quot;compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX&quot; and the four-dimensional spider web of &quot;compatibility-content-stability-protective effects against DOX-induced myocardial toxicity&quot; were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb&#95;1, astragaloside Ⅱ, cryptochlorogenic acid, and ginsenoside Rg&#95;2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-β-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.

Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin–APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA–APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA–APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA–APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA–APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA–apelin–APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF. [ABSTRACT FROM AUTHOR]

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In this study, through the combination of AB‐8 macroporous resin, Sephadex LH‐20 column chromatography and semi‐preparative HPLC, an antioxidant component was purified from the crude extract of Phellinus pini, thereby evaluating the cardioprotective effect of the fraction. As a result, total phenolic content of the 60% ethanol elution was increased by 4.8‐fold after one run treatment on Sephadex LH‐20 chromatography with gradient elution. After semi‐preparative HPLC separation, the first peak (PP‐S4‐1) showed that inhibition ratio of erythrocyte hemolysis was 91.9%, and inhibition ratio of lipid peroxidation was also increased by 87.6%, at 50 μg/ml (p <.01). Based on the results of ESI‐MS, 1HNMR, 13CNMR, and RP‐HPLC compared to many published results, PP‐S4‐1was identified as catechin (MW 290.015, C15H14O6). The results showed that PP‐S4‐1 pretreatment made cell viability increased, and the generation of reactive oxygen species (ROS) inhibited. Meanwhile, PP‐S4‐1 remarkably decreased the fluorescence intensity of Ca2+, and increased mitochondrial membrane potential (MMP; ΔΨm). In addition, PP‐S4‐1 could significantly inhibit the decrease of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) activity as well as the increase of MDA content in H9c2 cells induced by H2O2. Moreover, pretreatment with PP‐S4‐1 significantly improved the morphological changes and prevented H2O2‐induced DNA damage. Therefore, this study clarifies the ability of PP‐S4‐1 to treat H9c2 cell oxidative stress damage induced by H2O2 through its antioxidant effect. Practical applications: This research is not only helpful to elaborate the cardioprotective effect of Phellinus pini but also can contribute to the development of health foods or drug supplements for heart disease in the future. This is the first report dealing with phenolic component and cardioprotective activity of a medicinal mushroom P. pini belonging to the genus Phellinus. [ABSTRACT FROM AUTHOR]

Alcohol abuse is a risk factor for heart damage and deterioration of its inotropic function. Currently, there is no pathogenetic pharmacological treatment for alcohol-induced myocardial injury. Therefore, the study of drugs with cardioprotective action is of current interest. Our earlier studies of stress-induced heart damage showed that a new derivative of glutamic acid - glufimet - protects the myocardium's inotropic function and limits lipid peroxidation. Additionally, we found that it increases the activity of antioxidant enzymes and improves mitochondrial respiration. The purpose of our study was to assess the effect of glufimet on the heart after chronic alcohol intoxication (CAI). The comparison drug was mildronate, which possesses cardioprotective properties and is used to treat alcohol withdrawal. We conducted our study using female Wistar rats (10 months old, 280-320 g). CAI was simulated by replacing drinking water with a 10% ethanol solution sweetened with sucrose (50 g/L) over a period of 24 weeks. The day after the animals stopped ethanol solution drinking, the control group was injected intraperitoneally (i.p.) with a saline solution once a day for 14 days, while the experimental groups received glufimet (28.7 mg/kg) and the drug of comparison mildronate (50 mg/kg), respectively. After that, we studied the heart contractility by measuring volume load, adrenergic reactivity, and maximum isometric load. Under CAI, the control group showed significantly lower growth in left ventricular pressure (LVP), myocardium contraction rate, and relaxation rate during functional tests. Higher concentrations of LPO products (malondialdehyde) and low activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase), indicating a disturbance in mitochondrial respiration compared to the control group, were registered. While being treated with glufimet and mildronate, the animals demonstrated higher growth rates of myocardial contraction, myocardial relaxation, and LVP, compared to the control group. Mitochondrial functioning and activity of the antioxidant enzymes increased in the same group as well. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) triggers adverse ventricular remodeling (VR), cardiac fibrosis, and subsequent heart failure. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is postulated to play a significant role in VR processing via activation of the TLR4 inflammatory pathway. We hypothesized that an eNAMPT specific monoclonal antibody (mAb) could target and neutralize overexpressed eNAMPT post-MI and attenuate chronic cardiac inflammation and fibrosis. We investigated humanized ALT-100 and ALT-300 mAb with high eNAMPT-neutralizing capacity in an infarct rat model to test our hypothesis. ALT-300 was 99mTc-labeled to generate 99mTc-ALT-300 for imaging myocardial eNAMPT expression at 2 hours, 1 week, and 4 weeks post-IRI. The eNAMPT-neutralizing ALT-100 mAb (0.4 mg/kg) or saline was administered intraperitoneally at 1 hour and 24 hours post-reperfusion and twice a week for 4 weeks. Cardiac function changes were determined by echocardiography at 3 days and 4 weeks post-IRI. 99mTc-ALT-300 uptake was initially localized to the ischemic area at risk (IAR) of the left ventricle (LV) and subsequently extended to adjacent non-ischemic areas 2 hours to 4 weeks post-IRI. Radioactive uptake (%ID/g) of 99mTc-ALT-300 in the IAR increased from 1 week to 4 weeks (0.54 ± 0.16 vs. 0.78 ± 0.13, P < 0.01). Rats receiving ALT-100 mAb exhibited significantly improved myocardial histopathology and cardiac function at 4 weeks, with a significant reduction in the collagen volume fraction (%LV) compared to controls (21.5 ± 6.1% vs. 29.5 ± 9.9%, P < 0.05). Neutralization of the eNAMPT/TLR4 inflammatory cascade is a promising therapeutic strategy for MI by reducing chronic inflammation, fibrosis, and preserving cardiac function. [Display omitted] • Imaging of radiolabeled antibody reveals eNAMPT involving in ischemic injury. • Humanized eNAMPT-neutralizing mAb shows anti-fibrotic effects in infarcted hearts. • eNAMPT functions as a DAMP leading to post-infarct cardiac remodeling and heart failure. • eNAMPT/TLR4 inflammatory cascade drives post-infarct cardiac remodeling. • Anti-eNAMPT antibody theranostics provides diagnostic and therapeutic potential. [ABSTRACT FROM AUTHOR]

This investigation was aimed to explore the cardioprotective effect of Ramontchi fruits (Flacourtia indica; FI) in isoprenaline-administered Long-Evans rats. Administration of isoprenaline increased the total heart wet weight, MDA, NO, and APOP as well as ALT, AST, and CK-MB levels, which were normalized by FI fruits treatment. Moreover, expressions of antioxidant genes i.e., Nrf-2, HO-1, HO-2, SOD, catalase, and GPx were normalized by FI fruits in isoprenaline-induced rats. Besides, expression of inflammatory mediators i.e., IL-1, IL-6, TNF-α, TGF-β, iNOS, and NF-κB were also suppressed by FI fruits. The outcome of FI fruits treatment was noted as promising and comparable to the standard atenolol treatment. The enhanced biological activity shown by FI fruits may be due to its abundant polyphenolic compounds as determined by HPLC analysis. In conclusion, FI fruits may protect cardiac tissue in isoprenaline-administered rats by suppressing the oxidative stress and proinflammatory mediators and enhancing the antioxidant enzyme functions.

BackgroundDepression and coronary heart disease (CHD) often occur together in clinical practice. As a traditional Chinese medicine, Kai-Xin-San (KXS) has been widely used for the treatment of emotion-related disorders. In the present study, we aimed to explore whether KXS had both antidepressive effects and cardioprotective functions in a rat model of myocardial ischemia (MI) with depression.MethodsA total of 50 SD rats were randomly assigned into five groups as follows: normal control (control group), celiac injection of isopropyl adrenaline (ISO) (MI group), depression (depression group), MI+ depression (model group) and MI+ depression treated with intragastric administration of 370 mg/kg KXS (KXS group). MI was induced by subcutaneous injection of 85 mg/kg ISO. Depression was developed by a 7-week chronic mild stress (CMS) challenge. Behavioral test was conducted before and during the experiment. Echocardiography and biochemical analysis were carried out after 7 weeks of CMS challenge.ResultsAfter 7 weeks of experiment, depression-like behaviors were observed in all the groups except for control and KXS groups, and KXS treatment dramatically increased open-field test scores and sucrose consumption (P < 0.01 vs. model group). Echocardiography and biochemical analysis showed that KXS treatment could improve levels of ejection fraction (EF) and fractional shortening (FS), which were reduced by depression and ISO challenge. Meanwhile, KXS treatment significantly decreased the levels of creation kinase MB (CK-MB) and lactate dehydrogenase (LDH), which were increased in the model group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) were increased, while the malondialdehyde (MDA) activity was significantly decreased in the KXS group. Moreover, KXS treatment reduced the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in myocardial tissue compared with the model group.ConclusionsKXS had antidepressant-like activity and offered cardioprotective effects against ISO-induced myocardial infarction with depression.

The study aimed to investigate the nephroprotective and cardioprotective effects of ethanol extract of litchi leaf (LI) in two-kidney-one-clip (2K1C) rat model. HPLC analysis revealed the presence of several polyphenolic antioxidants in LI. Correspondingly, LI at 50–200 mg/kg reduced the level of oxidative stress markers (MDA, APOP, NO) and improved level of endogenous antioxidant enzymes (CAT, SOD) in 2K1C rats. Besides, LI caused significant improvements in kidney and heart functions in 2K1C rats by reducing the plasma level of uric acid and creatinine as well as CK-MB. Consistent with the biochemical findings, histopathological data further confirmed that LI is effective in decreasing heart and kidney injuries, oxidative stress and inflammation which ensued in 2K1C rats. Collectively, the outcomes suggest that the LI enriched in polyphenolic antioxidants may provide the protection against excessive oxidative stress, inflammation and tissue injury, thereby improving the kidney and heart function in 2K1C rats.

Abstract Background Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model. Methods We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17β-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings. Results The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium. Conclusion EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level.

Background: Depression and coronary heart disease (CHD) often occur together in clinical practice. As a traditional Chinese medicine, Kai-Xin-San (KXS) has been widely used for the treatment of emotion-related disorders. In the present study, we aimed to explore whether KXS had both antidepressive effects and cardioprotective functions in a rat model of myocardial ischemia (MI) with depression. Methods: A total of 50 SD rats were randomly assigned into five groups as follows: normal control (control group), celiac injection of isopropyl adrenaline (ISO) (MI group), depression (depression group), MI+ depression (model group) and MI+ depression treated with intragastric administration of 370 mg/kg KXS (KXS group). MI was induced by subcutaneous injection of 85 mg/kg ISO. Depression was developed by a 7-week chronic mild stress (CMS) challenge. Behavioral test was conducted before and during the experiment. Echocardiography and biochemical analysis were carried out after 7 weeks of CMS challenge. Results: After 7 weeks of experiment, depression-like behaviors were observed in all the groups except for control and KXS groups, and KXS treatment dramatically increased open-field test scores and sucrose consumption (P < 0.01 vs. model group). Echocardiography and biochemical analysis showed that KXS treatment could improve levels of ejection fraction (EF) and fractional shortening (FS), which were reduced by depression and ISO challenge. Meanwhile, KXS treatment significantly decreased the levels of creation kinase MB (CK-MB) and lactate dehydrogenase (LDH), which were increased in the model group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) were increased, while the malondialdehyde (MDA) activity was significantly decreased in the KXS group. Moreover, KXS treatment reduced the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in myocardial tissue compared with the model group. Conclusions: KXS had antidepressant-like activity and offered cardioprotective effects against ISO-induced myocardial infarction with depression. [ABSTRACT FROM AUTHOR]