Curdione Relieved Isoproterenol-Induced Myocardial Damage through Inhibiting Oxidative Stress and Apoptosis.

Isoproterenol (ISO) is widely used to treat bronchial asthma, cardiogenic or septic shock, complete atrioventricular block, and cardiac arrest. However, it can also cause myocardial damage owing to infarct-like necrosis. Curdione, an extract of the Chinese herb Rhizoma Curcumae, has a variety of pharmacological activities, including cardioprotective effects. In this study, we investigated the protective effects of curdione and its underlying mechanisms in an ISO-induced myocardial injury model. Our results showed that curdione attenuated ISO-induced H9c2 cell proliferation inhibition and lactic dehydrogenase (LDH) release. Curdione ameliorated morphological damage and reduced the ISO-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB) and LDH. Furthermore, curdione inhibited ISO-induced cell apoptosis, modulated the expression of Bcl-2 and Bax proteins, repealed the accumulation of ISO-induced reactive oxygen species (ROS), prevented mitochondrial dysfunction, and activated the Nrf2/SOD1/HO-1 signaling pathway. The above results show that curdione exerts a protective effect against ISO-induced myocardial damage by inhibiting apoptosis and oxidative stress, suggesting that curdione is a potential therapeutic strategy to prevent ISO-induced myocardial damage.

Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats.

ABSTRACT: Prolonged and intense stress can exceed the body's normal self-regulation and limited compensatory and repair capacity, resulting in pathological damage to the body. In this study, we established a rat stress myocardial injury (SMI) model to explore the protective effect of melatonin (MLT) on SMI and its possible mechanisms of action. Adult female Sprague Dawley (SD) rats were randomly divided into 5 groups: blank control group (NC), SMI group, MLT low-dose group, MLT medium-dose group, and MLT high-dose group, and 10 rats in each group were used to establish a SMI model by the water immersion restraint method. We observed the changes in body weight and tail vein glucose of each group. Serum levels of corticosterone (Cort), creatine kinase isoenzyme (CK-MB), and Troponin Ⅰ (Tn-Ⅰ) and activity of lactic acid dehydrogenase were measured by ELISA. Transcriptome sequencing was used to find differentially expressed genes in the control and model groups, and the results were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). HE staining was used to visualize the pathological changes in the heart tissue of each group, and Western blot was used to study the differences in protein expression in the cardiomyocytes of each group to further corroborate the results. The body weight growth rate of rats in the SMI group was significantly lower than that of the NC group ( P < 0.01), and the body weight growth rate of rats in the MLT high-dose group was significantly higher than that of the SMI group ( P < 0.05) with no significant difference compared with the NC group rats. The mean blood glucose of rats in the SMI group was significantly higher compared with the NC group ( P < 0.001), while the mean blood glucose of rats in the MLT administration groups was dose-dependently reduced compared with the SMI group. By RNA-seq and bioinformatics tools such as KEGG and Gene ontology, we found that the circadian clock-related genes Ciart , Arnt1 , Per1 , and Dbp were significantly downregulated in the SMI group during water immersion stress, and differentially expressed genes were enriched in the p38MAPK signaling pathway and p53 signaling pathway. Moreover, genes related to inflammation and apoptosis were differentially expressed. ELISA results showed that Cort, CK-MB, and Tn-Ⅰ levels were significantly higher in the SMI group compared with the NC group ( P < 0.01) and melatonin reduced the levels of Cort, CK-MB, and Tn-Ⅰ and decreased lactic acid dehydrogenase activity in rat serum. HE staining results showed that melatonin could attenuate stress-generated myocardial injury. Western blot showed that melatonin reduced the expression of p38MAPK, p53, Bax, and caspase-3 and increased the expression of Bcl-2 protein in rat heart. Melatonin can inhibit myocardial injury caused by water immersion, and its mechanism of action may be related to the regulation of the expression of circadian clock genes such as Ciart , Arnt1 , Per1 , and Dbp ; the inhibition of the expression of proapoptotic proteins such as p38MAPK, p53, Bax, and caspase-3; and the increase of the expression of Bcl-2 antiapoptotic protein.

Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats.

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

Biosynthesis of copper oxide nanoparticles and their potential synergistic effect on alloxan induced oxidative stress conditions during cardiac injury in Sprague-Dawley rats.

Cistus incanus leaf extract was used to biologically synthesize Copper oxide nanoparticles (CuO NPs). The characteristic UV-vis spectral band of CuO NPs found at 290 nm revealed the successful formation of CuO NPs. By the analysis of TEM and SEM, it is confirmed that the obtained CuO NPs were in spherical structure. By the analysis of Fourier transform infrared (FTIR) spectroscopy, it is evident that the absorption peak was situated at a position of about 480 cm-1 of wavenumber, which is typically considered as an extremely pure CuO NPs. The images of Transmission Electron Microscopy exhibited that the formed CuO NPs were in the size of about 15-25 nm and were relatively uniform in distribution. When related with the treatment of nanomaterials only, the synergistic interaction among CuO NPs and oxidative stress conditions considerably decreased the cardiac-related function catalogs, which includes pathological progressions of myocardium along with an obvious rise in the levels of creatine kinase-MB and cardiac troponin I. When compared to the void reaction of micro-CuO and cardiac operations in alloxan-injected rats, aggravation in the conditions of oxidative stress could be playing a significant part in the heart injury after dual exposing CuO NPs and alloxan. By these results, it is confirmed that the conditions of oxidative stress improved the contrary effects of CuO NPs to the heart, signifying that the utilization of nanomaterials in conditions of stress such as, in the delivery of drug, required to be cautiously monitored.

Nitric oxide plays a pivotal role in cardioprotection induced by pomegranate juice against myocardial ischemia and reperfusion.

Pomegranate juice (Pg) has demonstrated cardiovascular beneficial effects. The current research intends to investigate the roles of nitric oxide (NO) and antioxidants in Pg-induced cardioprotection against ischemia and reperfusion (I/R). Isolated hearts from anesthetized rats were subjected to 30-min global ischemia followed by 120-min reperfusion. The hearts in the test groups were treated with Pg, NG -nitro-L-arginine methyl ester (L-NAME) or both throughout the experiment. In Pg group, left ventricular developed pressure, rate of rise in left ventricular pressure (dp/dt max), and rate pressure product were 83%, 55%, and 127%, respectively, higher than those of the control group (p < 0.05). The infarct size declined to less than 40% (p < 0.0001), and biomarkers of myocardial damage including creatine kinase-MB, lactate dehydrogenase, and troponin-I, showed significant reductions (59%, 36%, and 94%, respectively) compared with the control. Furthermore, the indices of oxidative status including superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde showed significant improvement (2.4, 1.7, 1.9, and 2.4 fold, respectively). Most of these effects were mainly blocked by L-NAME. These results suggest potent cardioprotective effects for Pg against myocardial I/R injury. The current results suggest a key role for NO for this cardioprotection; however, other mechanisms seem to be also involved.

Preventive effect of hesperidin modulates inflammatory responses and antioxidant status following acute myocardial infarction through the expression of PPAR­Î³ and Bcl­2 in model mice.

Hesperetin is the main pharmacological ingredient of fruit of the citrus family, rutaceae. It is a flavanone, which has potent antioxidation and anti­inflammatory activities. The present study investigated the preventive effect of hesperidin in the modulation of acute myocardial infarction (AMI)­induced inflammatory responses and antioxidant status in a mouse model. The levels of creatine kinase­MB, tumor necrosis factor (TNF­α), interleukin (IL)­1ß, IL­6, monocyte chemoattractant protein 1 (MCP­1), intercellular adhesion molecule 1 (ICAM­1), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and caspase­3/9 were measured using ELISA kits. Western blot analysis analyzed p53 and B­cell lymphoma 2 (Bcl­2)­associated X protein/Bcl­2, and induced the expression of peroxisome proliferator­activated receptor­Î³ (PPAR­Î³). Hesperidin markedly decreased the myocardial infarction area, heart weight/body weight ratio and activity of creatine kinase­MB in AMI mice. Hesperidin treatment caused a significant decrease in the levels of TNF­α, IL­1ß, IL­6, MCP­1, ICAM­1, MDA, CAT, SOD and caspase­3/9 in mice with AMI. Hesperidin also significantly suppressed the protein expression levels of p53 and Bax/Bcl­2, and induced the expression of peroxisome proliferator­activated receptor­Î³ (PPAR­Î³) in mice with AMI. The preventive effect of hesperidin modulated the inflammatory response and antioxidant status following AMI through downregulation of the expression of PPAR­Î³ and Bcl­2 in the model mice.

Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK.

Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30[Formula: see text]mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30[Formula: see text]min and subsequent reperfusion for 3[Formula: see text]h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.

Effect of E-OJ-01 on Cardiac Conditioning in Young Exercising Adults: A Randomized Controlled Trial.

BACKGROUND AND AIM: Cardiac health is a determinant of athletic performance. A body of data suggests that in healthy young adults, an increase in maximal cardiac output leads to an increase in endurance. Terminalia arjuna (TA) has been studied for multiple benefits in cardiovascular health although its effects as a cardioprotective ergogenic aid require further exploration. The current trial was planned to study the effect of the proprietary TA extract (E-OJ-01) on the markers of cardiac conditioning in healthy young adults. STUDY QUESTION: No study has assessed the effect of TA extract on cardiac conditioning by improvement of left ventricular ejection fraction (LVEF) in young exercising individuals. STUDY DESIGN, MEASURES AND OUTCOMES: A randomized, double-blind, placebo-controlled, parallel group study was conducted to determine the efficacy and safety of E-OJ-01 for use as an ergogenic supplements in young exercising adults. This trial was registered at ClinicalTrials.gov (NCT02207101) and reported according to Consolidated Standards of Reporting Trials (CONSORT) requirements. Thirty-two healthy males, aged 18-40 years performing regular endurance exercise, were randomly assigned to 400 mg of E-OJ-01 or placebo for 56 days. LVEF, right and left ventricular Myocardial Performance Index, and Borg Rated Perceived Exertion (RPE) were assessed at baseline, day 28, and day 56; creatine kinase-MB and troponin-T were assessed at baseline and at day 56. RESULTS: As compared with placebo, 56 days of E-OJ-01 supplementation significantly improved the LVEF (P = 0.0001) and decreased the right ventricular Myocardial Performance Index (P = 0.001). The fatigue level captured by Borg Scale after completion of exercise showed a greater decrease in the E-OJ-01 group as compared with placebo. Creatine kinase-MB and troponin-T did not change significantly. CONCLUSIONS: TA (E-OJ-01) significantly increased cardiovascular efficiency and improved the cardiac conditioning in young healthy adults.

[Effect of prolonged propofol infusion on myocardial enzyme, mitochondrial cytochrome C and adenosine triphosphate in rabbits].

OBJECTIVE: To explore the effect of long-time propofol infusion on myocardial enzymes, mitochondrial cytochrome C and ATP in rabbits. 
 Methods: A total of 18 New Zealand rabbits were randomly divided into 3 groups: a control group, a propofol group and an intralipid group. The rabbits were continuously infused with 0.9% normal saline in the control group, 1% propofol in the propofol group, and 10% intralipid in the intralipid group, respectivey. The arterial blood was collected at 0, 8, 16 h and the end of experiment to examine creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the end, the myocardial mitochondria from myocardial tissues was separated by differential centrifugation, and mitochondrial cytochrome C content and adenosine triphosphate (ATP) levels were examined by high performance liquid chromatography.
 Results: Compared with the control group, the release of cytochrome C from mitochondria were increased in the propofol group and the intralipid group (both P<0.05), but there was no significant difference between them (P>0.05). There was also no significant difference in the ATP content of the mitochondria among the 3 groups (P>0.05). The levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group compared with that before the infusion (all P<0.05); compared with the control group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group (all P<0.05); compared with the intralipid group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group (all P>0.05); compared with the control group, the levels of CK-MB were obviously increased in the infusion of propofol for 24 h in the propofol group (P<0.05).
 Conclusion: The levels of serum CK increase after the infusion of propofol and intralipid for a long time, and the levels of CK-MB also elevate in the infusion of propofol. Propofol and intralipid can increase the release of myocardial mitochondrial cytochrome C, but they don't affect the ATP production in myocardial mitochondrial.

Epigallocatechin gallate exerts protective effects against myocardial ischemia/reperfusion injury through the PI3K/Akt pathway-mediated inhibition of apoptosis and the restoration of the autophagic flux.

Epigallocatechin gallate (EGCG), a polyphenol derived from green tea, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. In this study, the cardioprotective effects of EGCG on myocardial ischemia/reperfusion (I/R) injury in rats and the underlying mechanisms were investigated. A rat model of I/R injury was established by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. The levels of I/R-induced creatine kinase-MB (CK-MB) and the release of lactate dehydrogenase (LDH), as well as the infarct size, cardiomyocyte apoptosis and cardiac functional impairment were examined and compared. Western blot analysis was carried out to elucidate the potential molecular mechanisms of action of EGCG. The results revealed that EGCG post-conditioning significantly decreased the levels of CK-MB and the release of LDH, reduced the myocardial infarct size, decreased the apoptotic rate and partially preserved heart function. Furthermore, EGCG decreased the expression of cleaved caspase-3 concomitantly with the upregulation of PI3K, and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). It also inhibited I/R-induced overautophagy and promoted the clearance of autophagosomes, as evidenced by a decrease in the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, the downregulation of Beclin1, Atg5 and p62, and the upregulation of active cathepsin D. Additionally, we observed an increase in the phosphorylation levels of the mammalian target of rapamycin (mTOR) following treatment with EGCG. Taken together, the findings of this study demonstrate that, EGCG post-conditioning alleviates myocardial I/R injury by inhibiting apoptosis and restoring the autophagic flux, which is associated with several targets of the PI3K/Akt signaling pathway.

Synergistic cardioprotective effects of Danshensu and hydroxysafflor yellow A against myocardial ischemia-reperfusion injury are mediated through the Akt/Nrf2/HO-1 pathway.

In clinical practice, the traditional Chinese medicinal herbs, Radix Salvia Miltiorrhiza and Carthamus tinctorius L., are usually prescribed in combination due to their significant cardioprotective effects. However, the mechanisms responsible for these combined effects remain unknown. Thus, in this study, we investigated the mechanisms responsible for the combined effects of Danshensu (DSS) and hydroxysafflor yellow A (HSYA) by establishing a rat model of myocardial ischemia/reperfusion (MI/R), as well as a model of hypoxia/reoxygenation (H/R) using H9c2 cells. The combination index (CI) was calculated using the median-effect method. DSS and HSYA in combination led to a CI value of <1 as regards infarct size in vivo and cell viability in vitro. The rats with MI/R injury that were treated with DSS and/or HSYA were found to have significantly lower levels of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) and malondialdehyde (MDA), and a lower expressoin of 8-hydroxydeoxyguanosine (8-OHdG), and markedly enhanced superoxide dismutase (SOD) activity. Our in vitro experiments revealed that the cells treated with DSS and/or HSYA had a reduced lactate dehydrogenase (LDH) activity and a decreased percentage of cell apoptosis (increased Bcl-2/Bax ratio, decreased expression of cleaved caspase-3). DSS and HSYA increased the expression of heme oxygenase-1 (HO-1), the phosphorylation of Akt and the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the Akt inhibitor, LY294002, partially hampered the expression of Nrf2 and HO-1. The HO-1 inhibitor, zinc protoporphyrin IX (ZnPP­IX), did not decrease the expression of p-Akt and Nrf2, although it abolished the anti-apoptotic and antioxidant effects of DSS and HSYA. The findings of our study thus demonstrate that DSS and HSYA confer synergistic cardioprotective effects through the Akt/Nrf2/HO-1 signaling pathway, to certain extent, by enhancing the antioxidant defense system and exerting anti-apoptotic effects.

Paeonol and danshensu combination attenuates apoptosis in myocardial infarcted rats by inhibiting oxidative stress: Roles of Nrf2/HO-1 and PI3K/Akt pathway.

Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway.

Cardiac-protective effects and the possible mechanisms of alatamine during acute myocardial ischemia.

Alatamine is a constituent in the extract of a traditional herbal medicine Ramulus euonymi widely used for cardiac protection. However, its precise effects remain unclear. In the present study, we found that alatamine was able to reduce acute myocardial ischemia (AMI)-induced cardiac dysfunction in a rat model, as reflected by significantly restored electrocardiograms, M-mode echocardiograms, and left ventricular hemodynamics. Also, Nagar Olsen staining revealed that alatamine markedly reduced AMI-induced cardiac injury and cardiac myocyte apoptosis. TUNEL and caspase-3 activity assay showed that cardiac myocytes underwent significant apoptosis during AMI, and levels of LDH and CK-MB increased in the serum. However, such changes were significantly inhibited by pre-administration of alatamine. Furthermore, such anti-apoptotic effects of alatamine was also confirmed in a cardiac myocyte model of isoproterenol (ISO)-induced damage. Mechanistically, it was also found that alatamine improved the expression and activity of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA), which were inhibited during AMI, promoting contractility and relaxation. Meanwhile, alatamine decreased Bax and increased Bcl-2 expressions both in vivo and in vitro, therefore inhibiting cardiac myocyte apoptosis and preventing cardiac dysfunction caused by AMI at the cellular level. The present study revealed the beneficial role of alatamine in cardiac protection and highlighted it as a potential therapeutic reagent for reduction of AMI-induced cardiac injury.

Abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart.

BACKGROUND: Ischemic heart disease is the leading cause of death in postmenopausal women. The expression of caveolin, a membrane protein and a negative regulator of nitric oxide (NO), increases after menopause. The present study was designed to determine the effect of daidzein (DDZ), a phytoestrogen in attenuated cardioprotective effect of ischemic preconditioning (IPC) in ovariectomized rat heart. METHODS: Heart was isolated from ovariectomized rat and mounted on Langendorff's apparatus, subjected to 30 min ischemia and 120 min reperfusion. IPC was mediated by four cycles of 5 min ischemia and 5 min reperfusion. The infarct size was estimated using triphenyltetrazolium chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and creatine kinase MB (CK-MB) release to assess the degree of myocardial injury. The release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent. RESULTS: IPC-induced cardioprotection was significantly attenuated in ovariectomized rats as compared to normal rats, which was restored by treatment of DDZ, a caveolin inhibitor (0.2 mg/kg subcutaneously) for 1 week. However, this observed cardioprotection was significantly attenuated by perfusion of l-nitroarginine methyl ester, an endothelial nitric oxide synthase (eNOS) inhibitor (100 µM/L) and glibenclamide, an adenosine triphosphate-sensitive potassium ion channel blocker (10 µM/L) alone or in combination, noted in terms of increase in myocardial infarct size, release of LDH and CK-MB, and also decrease in the release of NO. CONCLUSION: Thus, it is suggested that DDZ restores the attenuated cardioprotective effect in ovariectomized rat heart, which may be due to downregulation of caveolin and subsequent increase in the activity of eNOS.

Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats.

Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities.

Antioxidative Role of Hatikana (Leea macrophylla Roxb.) Partially Improves the Hepatic Damage Induced by CCl4 in Wistar Albino Rats.

This research investigated the protective role of Leea macrophylla extract on CCl4-induced acute liver injury in rats. Different fractions of Leea macrophylla (Roxb.) crude extract were subjected to analysis for antioxidative effects. Rats were randomly divided into four groups as normal control, hepatic control, and reference control (silymarin) group and treatment group. Evaluations were made for the effects of the fractions on serum enzymes and biochemical parameters of CCl4-induced albino rat. Histopathological screening was also performed to evaluate the changes of liver tissue before and after treatment. Different fractions of Leea macrophylla showed very potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, FeCl3 reducing effect, superoxide scavenging effect, and iron chelating effect. Carbon tetrachloride induction increased the level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and other biochemical parameters such as lipid profiles, total protein, and CK-MB. In contrast, treatment of Leea macrophylla reduced the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities as well as biochemical parameters activities. L. macrophylla partially restored the lipid profiles, total protein, and CK-MB. Histopathology showed the treated liver towards restoration. Results evidenced that L. macrophylla can be prospective source of hepatic management in liver injury.

High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery.

Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde (MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including gp91(phox), p47(phox), p67(phox), and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction.

Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 µM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 µM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

[Protection effect of Yindan Xinnaotong capsule and main compositions compatibility on myocardial ischemia/reperfusion injury].

OBJECTIVE: To study the protected effect of Yindan Xinnaotong capsule (YDXNTC) and main components compatibility on myocardium ischemia/reperfusion injury. METHOD: Global ischemia/reperfusion was adopted to induce myocardial ischemia/reperfusion injury (MIRI) in isolated rat heart. Sprague-Dawley (SD) rats were divided into control, model, YDXNTC, Ginkgo biloba extract (GBE) group, ethanol extract of Salvia miltiorrhiza (SM-E) group, aqueous extract of Salvia miltiorrhiza (SM-H) group, mixed compatibility of other components in YDXNTC (MC), GBE and SM-E compatibility (GSEC), GBE and SM-H compatibility (GSHC), and SM-E and SM-H compatibility (SEHC). During the experiment, electrocardiogram was recorded to observe cardiac arrest time, heart resuscitation time, regaining normal rhythm time, the incidence and duration of arrhythmias (VT/VF). At the end of reperfusion, hearts were arrested and homogenated to assay the activity of superoxide dismutase (SOD), and the content of malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I. RESULT: (1) YDXNTC, SM-E, SM-H and MC elevated cardiac arrest time, also reduced rebeating time, restoring normal rhythm time as well as the duration of arrhythmia, but no remarkable impact on VT/VF occurrence. GBE was effective for incidence of VT/VF, also achieved good effect on shortening rebeating time, restoring normal rhythm time and arrhythmia duration. Likewise, obviously reduced rebeating time, restoring normal rhythm time and arrhythmia duration, and evaluated cardiac arrest time were also exhibited in compatibility groups except that no lengthened cardiac arrest time was detected in GSHC. And the incidence of VT/VF was decreased by GSEC. (2) YDXNT, ginkgo biloba extract (GBE), ethanol extract of salvia miltiorrhiza (SM-E), GBE and SM-E compatibility (GSEC), and SM-E and aqueous extract of salvia miltiorrhiza (SM-H) compatibility (SEHC) could improved SOD and decreased MDA level SM-H, mixed compatibility of other elements in YDXNTC (MC) and GBE and SM-H compatibility (GSHC) showed a role on MDA reduction. (3) LDH was declined by YDXNT and SM-H. CK-MB was reduced by GBE, SM-E, SM-H, and GSEC. (4) The release of cTnI was only inhibited by GSEC. CONCLUSION: YDXNTC, primary materials and main components compatibility has a certain protection effect on MIRI, its mechanism may be related to antioxidant and calcium overload reduction.

[Treating chronic persistent bronchial asthma children with abnormal myocardial enzyme spectrum by Yupingfeng powder: an efficacy observation].

OBJECTIVE: To observe the clinical efficacy of treating chronic persistent bronchial asthma (CPBA) children with abnormal myocardial enzyme spectrum (AMES) by Yupingfeng Powder (YP) combined routine therapy. METHODS: From January 2010 to December 2012, 156 CPBA children patients with AMES were randomly assigned to the treatment group (80 cases) and the control group (76 cases). All patients received routine treatment (inhaled corticosteroids and/or leukotriene regulator). Besides, those in the treatment group took YP. The treatment duration was 3 months. The scores of children asthma control test (C-ACT), pulmonary function (FEV,% and PEF%), myocardial enzyme spectrum were observed before and after treatment, and 3 months before and after treatment. The myocardial enzyme spectrum of 40 healthy children at the baby clinics during the same period were recruited as the control. RESULTS: Compared with the control group, creatine kinase isoenzyme (CK-MB), creatine kinase(CK), and lactate dehydrogenase (LDH) increased in the two treatment groups (P <0.01), but there was no statistical difference in AST (P >0.05). Compared with before treatment in the same group, CK-MB, CK, LDH, and AST decreased in the treatment group after treatment and 3 months after treatment (P <0.01). CK-MB, CK, LDH, and AST decreased in the control group 3 months after treatment (P <0.01, P <0.05).Compared with after treatment, CK decreased in the control group 3 months after treatment (P <0.01). C-ACT score, FEV(1),%, and PEF% all increased in the two groups after treatment and 3 months after treatment (P <0.01, P <0.05). Compared with after treatment in the same group, CK decreased in the control group 3 months after treatment (P <0. 01). Compared with the control group in the same period, post-treatment CK-MB and CK decreased (P <0. 01, P <0. 05), while post-treatment C-ACT score, FEV, %, and PEF% increased (P <0.05) in the treatment group (P <0.05). CONCLUSION: YP could strengthen specific and non-specific immunity of the organism, and improve clinical symptoms and the level of myocardial enzyme spectrum.