Kyu Hee Lim

Ginsenoside-Re ameliorates ischemia and reperfusion injury in the heart: a hemodynamics approach.

Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (±dp/dtmax). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-α (TNF-α) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-α level. Treatment of G-Re at 30 and 100 μM doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-α level. In this study, G-Re at 100 μM dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than 30 μM. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.

Cardioprotective potential of Korean Red Ginseng extract on isoproterenol-induced cardiac injury in rats

The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure (+dP/dtmax) and minimal rate of developed left ventricular pressure (−dP/dtmax), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

Assessment of antidiabetogenic potential of fermented soybean extracts in streptozotocin-induced diabetic rat

Most of the available drugs for the treatment of diabetes mellitus (DM) produce detrimental side effects, which has prompted an ongoing search for plant with the antidiabetic potential. The present study investigated the effect of soybean extracts fermented with Bacillus subtilis MORI, fermented soybean extracts (BTD-1) was investigated in streptozotocin (STZ)-induced diabetic rats. The possible effects of BTD-1 against hyperglycemia and free radical-mediated oxidative stress was investigated by assaying the plasma glucose level and the activity of enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). A significant increase in the levels of both plasma glucose and reactive oxygen species (ROS) was observed in the diabetic rats when compared to normal control group. After administration of BTD-1 (500 and 1000 mg/kg/day), the elevated plasma glucose level was significantly reduced while the plasma insulin level and the activities of SOD, GSH-Px, CAT and MDA were significantly increased. The results suggest that administration of BTD-1 can inhibit hyperglycemia and free radical-mediated oxidative stress. The administration of BTD-1 also inhibited the contractile response by norepinephrine (10(-10)-10(-5) M) in the presence of endothelium, and caused significant relaxation by carbachol (10(-8)-10(-5) M) in rat aorta. These findings indicate that BTD-1 improves vascular functions on STZ-induced diabetic rats. Therefore, subchronic administration of BTD-1 could prevent the functional changes in vascular reactivity in STZ-induced diabetic rats. The collective findings support that administration of BTD-1 may prevent some diabetes-related changes in vascular reactivity directly and/or indirectly due to its hypoglycaemic effect and inhibition of production of ROS.

Protective effects of red ginseng extract against vaginal herpes simplex virus infection

Numerous studies have suggested that Korean red ginseng (KRG) extract has various immune modulatory activities both in vivo and in vitro. In this study, we used a mouse model to examine the effects of orally administered KRG extract on immunity against herpes simplex virus (HSV). Balb/c mice were administered with 100, 200, and 400 mg/kg oral doses of KRG extract for 10 d and then vaginally infected with HSV. We found that KRG extract rendered recipients more resistant against HSV vaginal infection and further systemic infection, including decreased clinical severity, increased survival rate, and accelerated viral clearance. Such results appeared to be mediated by increased vaginal IFN-γ secretion. Moreover, increased mRNA expression of IFN-γ, granzyme B, and Fas-ligand was identified in the iliac lymph node and vaginal tracts of KRG extract treated groups (200 and 400 mg/kg). These results suggest that the activities of local natural killer cells were promoted by KRG extract consumption and that KRG may be an attractive immune stimulator for helping hosts overcome HSV infection.

Proteomic Analysis and Identification of Paracrine Factors in Mesenchymal Stem Cell-Conditioned Media under Hypoxia

Background/Aims: We previously showed that a hypoxic environment modulates the antiarrhythmic potential of mesenchymal stem cells. Methods: To investigate the mechanism by which secreted proteins contribute to the pathogenesis of antiarrhythmic potential in mesenchymal stem cells, we used two-dimensional electrophoresis combined with MALDI-TOF-MS to perform a proteomic analysis to compare the paracrine media produced by normoxic and hypoxic cells. Results: The proteomic analysis revealed that 66 protein spots out of a total of 231 matched spots indicated differential expression between the normoxic and hypoxic conditioned media of mesenchymal stem cells. Interestingly, two tropomyosin isoforms were dramatically increased in the hypoxic conditioned medium of mesenchymal stem cells. An increase in tropomyosin was confirmed using Western blot to analyze the conditioned media between normoxic and hypoxic cells. In a network analysis based on gene ontology (GO) Molecular Function by GeneMANIA analysis, most of the identified proteins were found to be involved in the regulation of heart processes. Conclusion: Our results show that hypoxia up-regulates tropomyosin and other secreted proteins which suggests that tropomyosin may be involved in regulating proarrhythmic and antiarrhythmic functions.

Korean Red Ginseng Induced Cardioprotection against Myocardial Ischemia in Guinea Pig

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/dtmax) and maximal rate of relaxation (-dP/dtmax). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

Red Ginseng (Panax ginseng) Decreases Isoproterenol-Induced Cardiac Injury via Antioxidant Properties in Porcine

Red ginseng (RG, Panax ginseng) has been shown to possess various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The present study was designed to evaluate the cardioprotective potential of RG against isoproterenol (ISO)-induced myocardial infarction (MI), by assessing electrocardiographic, hemodynamic, and biochemical parameters. Male porcines were orally administered with RG (250 and 500 mg/kg) or with vehicle for 9 days, with concurrent intraperitoneal injections of ISO (20 mg/kg) on the 8th and 9th day. RG significantly attenuated ISO-induced cardiac dysfunctions as evidenced by improved ventricular hemodynamic functions and reduced ST segment and QRS complex intervals. Also, RG significantly ameliorated myocardial injury parameters such as antioxidants. Malonaldialdehyde formation was also inhibited by RG. Based on the results, it is concluded that RG possesses significant cardioprotective potential through the inhibition of oxidative stress and may serve as an adjunct in the treatment and prophylaxis of MI.

Alterations in Cardiomyocyte Differentiation-Related Proteins in Rat Mesenchymal Stem Cells Exposed to Hypoxia.

Background/Aims: It is known that mesenchymal stem cells (MSCs) can have variable responses to hypoxic conditions and that hypoxia may specifically stimulate differentiation into osteogenic, chondrogenic, or adipogenic cells. Based on our previous study, we hypothesized that hypoxia may also induce MSC differentiation into cardiomyocytes and/or cells with comparable phenotypes. Methods: The differences in the proteomes were specifically investigated in bone marrow-derived rat MSCs (BM-rMSCs) under normoxic and hypoxic conditions using 2-DE combined with a MALDI-TOF-MS analysis and western blot analysis. In addition, genetic and/or proteomic interactions were assessed using a String network analysis. Results: Among the 35 markedly changed spots from a total of 393 matched spots, 24 were highly up-regulated and 11 were significantly down-regulated in hypoxic rMSCs based on a proteomic analysis. Although hypoxia failed to induce the direct differentiation of rMSCs into cardiomyocytes, several cardiomyocyte differentiation-related genes and proteins were significantly increased by hypoxic stress. Conclusion: We found that BM-rMSCs alter their expression of several cardiomyocyte differentiation-related genes and proteins under hypoxic conditions, and we examined the interactions between these genes and/or proteins, providing new insights for the applicability of MSCs preconditioned by hypoxic stimulation for use in cardiac diseases.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Gender-dimorphic effects of adipose-derived stromal vascular fractions on HUVECs exposed to oxidative stress

Stromal vascular fractions (SVFs) are a heterogeneous collection of cells within adipose tissue that are being studied for various clinical indications. In this study, we aimed to determine whether SVF transplantation into impaired tissues has differential effects on inflammatory and angiogenetic properties with regard to gender. As reactive oxygen species have been implicated in cardiovascular disease development, we investigated differences in gene and protein expression related to inflammation and angiogenesis in HUVECs co-cultured with adipose-derived SVFs from male (M group) and female (F group) individuals under oxidative stress conditions. The expression of several inflammatory (interleukin (IL)-33) and angiogenetic (platelet-derived growth factor (PDGF)) factors differed dramatically between male and female donors. Anti-inflammatory and pro-angiogenetic responses were observed in HUVECs co-cultured with SVFs under oxidative stress conditions, and these characteristics may exhibit partially differential effects according to gender. Using network analysis, we showed that co-culturing HUVECs with SVFs ameliorated pyroptosis/apoptosis via an increase in oxidative stress. Activation of caspase-1 and IL-1B was significantly altered in HUVECs co-cultured with SVFs from female donors. These findings regarding gender-dimorphic regulation of adipose-derived SVFs provide valuable information that can be used for evidence-based gender-specific clinical treatment of SVF transplantation for understanding of cardiovascular disease, allowing for the development of additional treatment.