Red Ginseng Reduces Inflammatory Response via Suppression MAPK/P38 Signaling and p65 Nuclear Proteins Translocation in Rats and Raw 264.7 Macrophage.

Lipopolysaccharides (LPS) cause systemic inflammatory responses, which are characterized by high mortality and multiple signs, including metabolic disturbances, respiratory acidosis, hypotension, and vital organs disorder. Cytokines secretion and oxidative stress are the main features of the disease. Diagnosis and treatment of systemic inflammation (SI) remain a challenge. Korean Red Ginseng (RG) is one of medicinal herbs that showed a potent anti-oxidant effect. We aimed to study the protective effects of RG on systemic inflammatory response in rats and RAW 264.7 macrophage cells induced by LPS. The rats were treated with water and alcohol extracts of RG for four weeks to prevent the inflammatory response. The result showed that LPS toxin increased morbidity and mortality, and induced liver, kidney, and lung injuries manifested by deteriorated biomarkers. Hypotension, hypomagnesemia, acidosis, and oxidative stress were observed in septic rats. However, RG extracts attenuated liver, kidney, and lung enzymes and metabolites in treated groups via its anti-inflammatory and anti-oxidant properties. Furthermore, RG improved magnesium and blood pressure in the treated groups. RAW 264.7 macrophage cells exposed to LPS disturbance in translocation of p65 and MAPK/p38. Nevertheless, RG-pretreated cells did not significantly alter. In conclusion, RG reduced the rates of mortality and morbidity of treated rats - liver, kidney, and lung injuries were protected in the treated groups through the potentiation of anti-oxidant defense. RG was able to conserve mitochondrial function, inhibiting the activation of MAPK/p38 signaling and suppressing NF-κB p65 cytoplasm-nucleus transport. Further studies are needed to examine the effects on chronic conditions in animal models and human.

Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes.

The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001) compared to STZ (100%): 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001) in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%), total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%), and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%). There were also significant increases (p < 0.001) in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%), GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%), and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%). The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001) in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85%) together with increases (p < 0.01) in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145%) and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%). The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of ß-cells maintaining normal insulin and glucose levels.

Activation of glibenclamide-sensitive ATP-sensitive K+ channels during ß-adrenergically induced metabolic stress produces a substrate for atrial tachyarrhythmia.

BACKGROUND: Cardiac ATP-sensitive K(+) channels have been suggested to contribute to the adaptive physiological response to metabolic challenge after ß-adrenoceptor stimulation. However, an increased atrial K(+)-conductance might be expected to be proarrhythmic. We investigated the effect of ATP-sensitive K(+) channel blockade on the electrophysiological responses to ß-adrenoceptor-induced metabolic challenge in intact atria. METHODS AND RESULTS: Atrial electrograms were recorded from the left atrial epicardial surface of Langendorff-perfused rat hearts using a 5×5 electrode array. Atrial effective refractory period and conduction velocity were measured using an S(1)-S(2) protocol. The proportion of hearts in which atrial tachyarrhythmia was produced by burst-pacing was used as an index of atrial tachyarrhythmia-inducibility. Atrial nucleotide concentrations were measured by high performance liquid chromatography. Perfusion with ≥10(-9) mol/L of the ß-adrenoceptor agonist, isoproterenol (ISO), resulted in a concentration-dependent reduction of atrial effective refractory period and conduction velocity. The ISO-induced changes produced a proarrhythmic substrate such that atrial tachyarrhythmia could be induced by burst-pacing. Atrial [ATP] was significantly reduced by ISO (10(-6) mol/L). Perfusion with either of the ATP-sensitive K(+) channel blockers, glibenclamide (10(-5) mol/L) or tolbutamide (10(-3) mol/L), in the absence of ISO had no effect on basal atrial electrophysiology. On the other hand, the proarrhythmic substrate induced by 10(-6) mol/L ISO was abolished by either of the sulfonylureas, which prevented induction of atrial tachyarrhythmia. CONCLUSIONS: Atrial ATP-sensitive K(+) channels activate in response to ß-adrenergic metabolic stress in Langendorff-perfused rat hearts, resulting in a proarrhythmic substrate.

Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (P. ginseng) is one of the most widely used medicinal plants due to its wide spectrum of medicinal effects. Among the currently available Panax ginseng products, Korea red ginseng (KRG) has been shown to exhibit a variety of antioxidative and hepatoprotective action. AIM OF THE STUDY: Our aim was to investigate the effects of KRG and its primary ginsenosides (Rg3 and Rh2) on EtOH-induced injury to mouse hepatocytes (TIB-73). MATERIALS AND METHODS: We investigated the effects of KRG and its primary ginsenoside on EtOH-induced injury to TIB-73 cells and evaluated MAPKs signals as a possible mechanism of action. Hepatocytic injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), ROS and mitochondria membrane potential (MMP) level in TIB-73 cells. The levels of MAPK activation were analyzed by Western blots. RESULTS: The results showed that exposure of EtOH to TIB-73 cells led to cell death and membrane damage, accompanied by a decrease in cell viability, MMP, and Mg(2+) concentrations, but an increase in LDH, AST, ROS and MAPK activation. KRG and its primary ginsenosides reduced EtOH-induced generation of ROS and the activation of ERK and JNK, and increased Mg(2+) concentrations. CONCLUSION: These results suggest that KRG and its primary ginsenosides inhibit EtOH-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells.

Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload.

BACKGROUND: Although arterial hypertension and left ventricular hypertrophy are considered good epidemiological indicators of the risk of atrial fibrillation (AF) in patients, the link between elevated afterload and AF remains unclear. We investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats. METHODS AND RESULTS: Male Wistar rats (aged 3-4 weeks) were anesthetized and subjected to either partial stenosis of the ascending aorta (AoB) or sham operation (Sham). Experiments were performed on excised hearts 8, 14, and 20 weeks after surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5×5 electrode array. Cryosections of left atrial tissue were retained for histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed marked left atrial hypertrophy and fibrosis at 14 and 20 weeks postsurgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks postsurgery. The substrate for arrhythmia was associated with reduced vectorial conduction velocity and greater inhomogeneity in conduction but without changes in effective refractory period. Left atrial expression of the gap junction protein, connexin43, was markedly reduced in AoB compared with Sham hearts. CONCLUSIONS: Using a small-animal model, we demonstrate that elevated afterload in the absence of systemic hypertension results in increased inducibility of AF and left atrial remodeling involving fibrosis, altered atrial connexin43 expression, and marked conduction abnormalities.

Taurine prevents hypertension and increases exercise capacity in rats with fructose-induced hypertension.

BACKGROUND: Fructose-induced hypertension was used to test the hypothesis that taurine supplementation and/or exercise can prevent hypertension and increase exercise capacity. METHODS: Five groups of 15 Sprague-Dawley rats were allocated and designated as control, high fructose-fed (fructose), high fructose-fed plus exercise (FE), high fructose-fed plus 2% taurine supplement (FT) and high fructose-fed plus 2% taurine supplement and exercise (FET) groups. Noninvasive systolic blood pressure (SBP) was recorded weekly and invasive arterial blood pressure (ABP) was recorded at the end of the 4-week trial. Three consecutive swimming tests were performed in the selected rats from each group and the plasma biomarkers were measured in the remaining rats. RESULTS: Noninvasive SBP differed significantly (P < 0.001) from week 3, both noninvasive and invasive ABP increased significantly (P < 0.001), and exercise capacity significantly decreased (P < 0.001) in the fructose group compared with the control group. The individual effects of swimming and taurine supplementation were incapable of preventing the development of hypertension and SBP significantly (P < 0.001) increased in the FE and FT groups; exercise capacity in those groups remained similar to control. The combined effects of exercise and taurine alleviated hypertension and significantly increased exercise capacity in the FET group. Insulin resistance increased significantly and plasma nitric oxide (NO) decreased significantly in the F, FE, and FT groups. Both parameters remained similar to control values in the FET group with an increasing antioxidant activity. CONCLUSION: Taurine supplementation in combination with exercise prevents hypertension and increases exercise capacity by possibly antioxidation and maintaining NO concentrations.

The cardiovascular depression caused by bee venom in Sprague-Dawley rats associated with a decrease of developed pressure in the left ventricular and the ratio of ionized calcium/ionized magnesium.

Bee venom (BV) has been used in Oriental medicine to treat inflammatory diseases, such as tendonitis, bursitis, and rheumatoid arthritis, despite the sensitivity of the victims and toxicity of the venom. This study examined the mechanisms for the effects of BV on the cardiovascular system in rats. The arterial pressure and heart rate (HR) were measured in anesthetized rats. In addition, the left ventricular development pressure (LVDP) and total magnesium efflux ([Mg]e) in isolated perfused hearts, the vascular tonic responses in the isolated aorta, and the blood ionic and biochemical changes were determined simultaneously. In the anesthetized rats, the mean arterial pressure, systolic pressure, and pulse pressure were reduced by BV in a dose-dependent manner, even though the HR was increased. BV had no effects on the relaxation of phenylephrine- or KCl-induced contraction of the aortic rings. In the isolated hearts, BV generated a reversible decrease in the LVDP and velocity with changes in pressure, which were accompanied by increases in the HR and [Mg]e. BV increased the plasma ionized and total magnesium concentrations, and decreased the total magnesium level in the red blood cells. The ratio of ionized calcium/ionized magnesium was also decreased by the BV treatment. BV caused a detectable increase in blood creatine kinase, glutamic oxaloacetic transaminase, and lactic dehydrogenase, as well as a decrease in the blood total protein albumin and globulin levels. These results suggest that BV induces cardiovascular depression by decreasing the cardiac pressure and increasing the ionized magnesium concentration in the blood.