Atherosclerotic cardiovascular disease (ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice (RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.
Apoptosis ; drug effects ; Atherosclerosis ; pathology ; physiopathology ; prevention & control ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; pathology ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Endothelium, Vascular ; cytology ; drug effects ; physiology ; Humans ; Inflammation ; prevention & control ; Lipid Metabolism ; drug effects ; Oxidative Stress ; drug effects

With the increase in the rescue success rate of critically ill preterm infants and extremely preterm infants, the incidence rate of bronchopulmonary dysplasia (BPD) is increasing year by year. BPD has a high mortality rate and high possibility of sequelae, which greatly affects the quality of life of preterm infants and brings a heavy burden to their families, and so the treatment of BPD is of vital importance. At present, no consensus has been reached on the treatment measures for BPD. However, recent studies have shown that early application of caffeine can prevent BPD. With reference to the latest studies on the effect of caffeine in the prevention of BPD, this article reviews the mechanism of action of caffeine in reducing pulmonary inflammation, improving morphological abnormalities of lung injury, reducing oxidative stress injury, and improving pulmonary function.
Animals ; Bronchopulmonary Dysplasia ; genetics ; metabolism ; physiopathology ; prevention & control ; Caffeine ; administration & dosage ; Humans ; Infant, Premature ; growth & development ; metabolism ; Infant, Premature, Diseases ; genetics ; metabolism ; physiopathology ; prevention & control ; Oxidative Stress ; drug effects

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.
Acetaminophen ; adverse effects ; Alanine Transaminase ; metabolism ; Animals ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; metabolism ; Caspase 3 ; genetics ; metabolism ; Chemical and Drug Induced Liver Injury ; genetics ; metabolism ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Glutathione ; metabolism ; Humans ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Mitogen-Activated Protein Kinases ; chemistry ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Schisandra ; chemistry ; Signal Transduction ; drug effects

BACKGROUND/AIMS: Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone. METHODS: Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction. RESULTS: Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas gamma-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and gamma-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment. CONCLUSIONS: Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.
Animals ; Antioxidants/*pharmacology ; Ascorbic Acid/metabolism ; Bronchial Hyperreactivity/chemically induced/metabolism/*prevention & control ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoconstriction/drug effects ; Disease Models, Animal ; Female ; Flavonoids/*pharmacology ; Inhalation Exposure ; Lung/*drug effects/enzymology/physiopathology ; Malondialdehyde/metabolism ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/metabolism ; Oxidative Stress/*drug effects ; *Ozone ; Uric Acid/metabolism ; Vitamin A/metabolism ; alpha-Tocopherol/metabolism

The pelvis is one of the most likely affected areas of the human body in case of side impact, especially while people suffer from motor vehicle crashes. With the investigation of pelvis injury on side impact, the injury biomechanical behavior of pelvis can be found, and the data can help design the vehicle security devices to keep the safety of the occupants. In this study, a finite element (FE) model of an isolated human pelvis was used to study the pelvic dynamic response under different side impact conditions. Fracture threshold was established by applying lateral loads of 1000, 2000, 3000, 4000 and 5000 N, respectively, to the articular surface of the right acetabulum. It was observed that the smaller the lateral loads were, the smaller the von Mises stress and the displacement in the direction of impact were. It was also found that the failure threshold load was near 3000 N, based on the fact that the peak stress would not exceed the average compressive strength of the cortical bone. It could well be concluded that with better design of car-door and hip-pad so that the side impact force was brought down to 3000 N or lower, the pelvis would not be injured.
Accidents, Traffic ; Biomechanical Phenomena ; Computer Simulation ; Finite Element Analysis ; Fractures, Bone ; physiopathology ; prevention & control ; Humans ; Pelvis ; injuries ; Stress, Mechanical

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
Animals ; Anti-Arrhythmia Agents ; administration & dosage ; Antibiotics, Antineoplastic ; Carbazoles ; administration & dosage ; Cardiomyopathies ; chemically induced ; physiopathology ; prevention & control ; Doxorubicin ; Heart Rate ; drug effects ; Male ; Metoprolol ; administration & dosage ; Oxidative Stress ; drug effects ; Propanolamines ; administration & dosage ; Rabbits ; Treatment Outcome ; Ventricular Fibrillation ; chemically induced ; physiopathology ; prevention & control

Blood Glucose ; metabolism ; Diabetes Complications ; prevention & control ; Diabetes Mellitus, Type 1 ; blood ; metabolism ; physiopathology ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; physiopathology ; Dinoprost ; analogs & derivatives ; blood ; Glucose ; metabolism ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Oxidative Stress

OBJECTIVETo investigate the effects of luteolin (Chinese Traditional Medicine) on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats.

METHODSMale SD rats were randomly divided into a normal control group, a luteolin control group, a diabetic group, and diabetic groups orally administered with a low dose (10 mg/(kg x d)) or a high dose of luteolin (100 mg/ (kg x d)) for eight weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, myocardial collagen and reactive oxygen species (ROS) levels were assayed. The cardiac mitochondrial ROS level, superoxide dismutase (SOD) activity and the mitochondrial swelling were measured.

RESULTSTreatment with luteolin had no effect on the blood glucose but reduced the losing of body weight in diabetic rats. High dose of luteolin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure, and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial levels of ROS and collagen, the cardiac mitochondrial ROS level, and the mitochondrial swelling in diabetic rats were all markedly reduced by high dose of luteolin. Furthermore, high dose of luteolin significantly increased the mitochondrial SOD activity in diabetic rat hearts.

CONCLUSIONTreatment with luteolin for 8 weeks markedly improves the cardiac function, which may be related to reducing mitochondrial oxidative stress and mitochondrial swelling in diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; physiopathology ; Luteolin ; pharmacology ; Male ; Mitochondria, Heart ; metabolism ; Oxidative Stress ; physiology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Ventricular Dysfunction ; prevention & control

OBJECTIVETo determine whether auricularia auricular polysaccharide (AAP) protects heart against ischemia/reperfusion (1/ R) injury and its underlying mechanisms.

METHODSMale Sprague-Dawley rats, pretreated with AAP (50, 100, 200 mg/(kg x d), gastric perfusion) for 4 weeks, were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischemia for 30 min followed by 120 min of reperfusion and the left ventricular hemodynamic parameters were measured. Formazan, a product of 2, 3, 5-triphenyl-tetrazolium chloride (TTC), which is proportional to myocardial viability, was measured at 490 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury. The cardiac malondialdehyde (MDA), a product of lipid peroxidation, and superoxide dismutase (SOD) activity were determined after myocardial I/R.

RESULTSThe pretreatment with AAP at 50, 100, 200/(kg d) for 4 weeks before I/R increased myocardial formazan content, reduced LDH release, improved the recovery of the left ventficular developed pressure, maximal rise rate of left ventricular pressure, and rate pressure product (left ventricular developed pressure multiplied by heart rate) attenuated the decrease of coronary flow during reperfusion. The cardiac protective effect of high dose AAP was more potent than that of compound radix salviae miltiorrhizae (CRSM, 4 ml/(kg x d), gastric perfusion for 4 weeks). Pretreatment with AAP (100 mg/(kg x d)) markedly inhibited the increase of MDA level and the decrease of SOD activity induced by I/R in myocardium.

CONCLUSIONThe findings indicate that in the isolated rat heart, AAP protects myocardium against ischemia/reperfusion injury via enhancing the activity of SOD and reducing lipid peroxidation in heart.

Animals ; Basidiomycota ; chemistry ; Male ; Myocardial Ischemia ; pathology ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; prevention & control ; Oxidative Stress ; drug effects ; Polysaccharides ; isolation & purification ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats, and related mechanisms.

METHODSSprague-Dawley rats were randomly divided into six groups (n=6), sham-operation group, vehicle group, 3, 6, 12 and 24 h treatment group of L-serine. Focal cerebral ischemia was induced with the method of middle cerebral artery occlusion (MCAO) in rats, and reperfusion was emerged by removing the thread 2 h later. The treatment of L-serine (200 mg/kg ip) was begun at 3, 6, 12 and 24 h after MCAO respectively, and subsequently repeated once 12 h. The vehicle group was intraperitoneally injected with isodose normal saline. The neurological behavior score and cerebral infarction volume was measured 48 h after reperfusion. In addition, the contents of malondialdehyde (MDA), activity of superoxide dismetase (SOD), the levels of inflammatory cytokines (TNF-alpha, IL-6) and ultrastructure of neuron in brain tissue were investigated.

RESULTSCompared with the vehicle group, treatments with L-serine both 3 and 6 h after MCAO decreased the neurology deficit score and infarct volume. Only neurology deficit score had been reduced 12 h after MCAO, while no neuropmrotective effects had been observed during 24 h. Furthermore, L-serine elevated the content of SOD, decreased the level of MDA, TNF-alpha and IL-6 in ischemic brain tissue, and alleviated the injury of the neuronal ultrastructure.

CONCLUSIONL-serine exerted a time-dependent neuroprotective effect on the brain after MCAO in rat. This effect might be possibly mediated through following mechanisms: lessening oxidative stress and reducing the release of inflammatory cytokines.

Animals ; Brain Ischemia ; drug therapy ; pathology ; physiopathology ; Interleukin-6 ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Serine ; therapeutic use ; Superoxide Dismutase ; metabolism ; Time Factors ; Tumor Necrosis Factor-alpha ; metabolism