[Show abstract][Hide abstract] ABSTRACT: Ginseng has been shown to be effective on cardiac dysfunction. Recent evidence has highlighted the mediation of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Thus, we are interested to investigate the role of PPAR δ in ginseng-induced modification of cardiac contractility. The isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats were applied to measure the actions of ginseng ex vivo and in vivo. In normal rats, ginseng enhanced cardiac contractility and hemodynamic dP/dt max significantly. Both actions were diminished by GSK0660 at a dose enough to block PPAR δ . However, ginseng failed to modify heart rate at the same dose, although it did produce a mild increase in blood pressure. Data of intracellular calcium level and Western blotting analysis showed that both the PPAR δ expression and troponin I phosphorylation were raised by ginseng in neonatal rat cardiomyocyte. Thus, we suggest that ginseng could enhance cardiac contractility through increased PPAR δ expression in cardiac cells.
[Show abstract][Hide abstract] ABSTRACT: Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma beta-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats).
In the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma beta-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of beta-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions.
Rhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid mu-receptors using cyprodime. An increase of plasma beta-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid mu-receptors.
Taken together, rhodiola-water extract improves hyperglycemia via an increase of beta-endorphin secretion from adrenal gland to activate opioid mu-receptors in STZ-diabetic rats.
Full-text · Article · Jan 2014 · BMC Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: Alternating hypothalamic-pituitary-adrenal axis mechanisms would lead to multiple organs dysfunction or failure. Herein, we attempt to assess whether hypothalamic inflammation and ischemic and oxidative damage that occurred during heatstroke (HS) can be affected by hyperbaric oxygen (HBO2) therapy in streptozotocin-induced diabetic rats.
In this study, anesthetized diabetic rats, immediately after the onset of HS, were divided into two major groups and given the normobaric air (21% O2 at 1.0 atmospheres absolute) or HBO2 (100% O2 at 2.0 atmospheres absolute). HS was induced by exposing the animals to heat stress (43°C). Another group of anesthetized diabetic rats was kept at normothermic state and used as controls.
The survival time values for the HBO2-treated HS-diabetic rats increased form the control values of 78-82 minutes to new values of 184-208 minutes. HBO2 therapy caused a reduction of HS-induced cellular ischemia (e.g., increased cellular levels of glutamate and lactate/pyruvate ratio), hypoxia (e.g., decreased cellular levels of PO2), inflammation (e.g., increased cellular levels of interleukin-1β, tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase), and oxidative damage (e.g., increased values of nitric oxide, 2,3-dihydroxybenzoic acid, glycerol, and neuronal damage score) in the hypothalamus of the diabetic rats.
Our results suggest that, in diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing heat-induced activated inflammation and ischemic and oxidative damage in the hypothalamus and other brain regions.
No preview · Article · Aug 2013 · Journal of the Formosan Medical Association
[Show abstract][Hide abstract] ABSTRACT: Musclin is a novel skeletal muscle-derived factor found in the signal sequence trap of mouse skeletal muscle cDNAs. Recently, it has been demonstrated that musclin is involved in the pathogenesis of spontaneously hypertensive rats (SHRs). However, it is known as a genetic hypertension model. In the present study, we aim to investigate the role of musclin in another animal model of hypertension and characterize the direct effect of musclin on vascular contraction. The results show that expression of musclin was increased in arterial tissues isolated from DOCA-salt induced hypertensive rats or the normal rats received repeated vasoconstriction with phenylephrine. Additionally, direct incubation with phenylephrine did not modify the expression of musclin in the in vitro studies. Also, the direct effect of musclin on the increase of intracellular calcium was observed in a concentration-dependent manner. These results provide the evidence to support that musclin is involved in hypertension. Thus, musclin is suitable to be considered as a novel target for treatment of hypertension.
[Show abstract][Hide abstract] ABSTRACT: The effect of allantoin, an active component of yam, on plasma glucose of streptozotocin-induced diabetic rats (STZ-diabetic rats) is investigated. Allantoin decreased plasma glucose levels in a dose-related manner, which was reduced by pretreatment with naloxone or naloxonazine. A concomitant increase in plasma β-endorphin, detected by enzyme-linked immunosorbent assay, was observed. Moreover, allantoin enhanced β-endorphin release from the isolated adrenal medulla of STZ-diabetic rat in a dose-related manner. However, its plasma glucose lowering action was reduced but not totally abolished by bilateral adrenalectomy. Furthermore, allantoin directly increased radioactive glucose uptake in isolated skeletal muscle, and repeated administration for 3 days increased GLUT4 mRNA and protein levels in muscle. This effect was markedly reduced in STZ-diabetic rats with bilateral adrenalectomy. This study suggests that allantoin increases GLUT4 gene expression in muscle by increasing β-endorphin secretion from the adrenal gland in STZ-diabetic rats.
No preview · Article · Nov 2010 · Journal of Agricultural and Food Chemistry
[Show abstract][Hide abstract] ABSTRACT: The present study was conducted to assess the effects of whole body cooling on multiorgan dysfunction that occurred during heatstroke in streptozotocin (STZ)-induced diabetic rats. The rats were randomly divided into four groups:  the normal control,  diabetic control,  diabetic heatstroke, and  diabetic heatstroke-whole body cooling (WBC). They were exposed to ambient temperature of 43 degrees C for exactly 58 min to induce heatstroke. When the diabetic heatstroke rats underwent heat stress, their survival time values were found to be 11-13 min. Immediately after the onset of heatstroke, resuscitation with body cooling greatly improved survival (221-257 min). Compared with the diabetic (STZ-treated) controls, the diabetic-heatstroke rats displayed higher levels of body temperature, intracranial pressure, serum nitric oxide metabolite, tumor necrosis factor-alpha and dihydroxybenzoic acid, blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and brain levels of local blood flow, and partial pressure of oxygen were all significantly lower during heatstroke. The cerebrovascular, renal, and hepatic dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis factor-alpha, and dihydroxybenzoic acid in the serum during heatstroke were significantly reduced by WBC. Although the serum interleukin-10 maintained at a negligible levels before heat stress, they were significantly elevated by WBC in diabetic-heatstroke rats. The data demonstrate that heatstroke-induced multiorgan dysfunction in streptozotocin-induced diabetic rats can be decreased by WBC.
Preview · Article · Feb 2009 · The Chinese journal of physiology
[Show abstract][Hide abstract] ABSTRACT: In heatstroke related symptoms in streptozotocin-induced diabetic rats (STZ-diabetic rats) exposed to a high temperature (43 degrees C) for 60 min, like that in normal rats, the high colon temperature and the decreases of mean arterial pressure, heart rate and cerebral blood flow were abolished by MK-801, the NMDA receptor antagonist. Also, striatal glutamate was markedly released in both animals by this exposure while the release was higher and the survival time was shorter in STZ-diabetic rats than in normal rats. After insulin treatment, like that by MK-801 pretreatment, the striatal glutamate and the incidence of heatstroke in STZ-diabetic rats were markedly reduced. Therefore, heatstroke was more easily induced via the elevated striatal glutamate in STZ-diabetic rats by high temperature exposure. Insulin treatment seems helpful in the prevention of heatstroke in STZ-diabetic rats.
No preview · Article · Oct 2003 · Neuroscience Letters
[Show abstract][Hide abstract] ABSTRACT: Oxygen-derived free radicals have been implicated in the development of myocardial injury during hypoxia/reperfusion. Antioxidants can effectively inhibit the formation of free radicals and ameliorate the myocardial damage which may occur during hypoxia/reperfusion. Trilinolein is a triacylglycerol recently purified from the traditional Chinese medicinal plant Panax pseudo-ginseng. It has linoleic-acid residues as the only type of fatty acid residue in all three esterified positions of the triacyglycerol. It has been proposed that decreased endogenous superoxide dismutase (SOD) activity may contribute to free radical-mediated reperfusion injury of the ischemic myocardium. In the present study, when isolated rat hearts were subjected to hypoxia for 10, 30, 60 and 90 min without normoxic perfusion, a significant decrease in Mn-SOD activity was shown throughout the period of hypoxia, whereas the Cu·Zn-SOD activity was increased at 10 and 30 min but was not different from the baseline at 60 and 90 min of hypoxia. In rat hearts pretreated with 10–7 mol/l trilinolein and subjected to 60 min of hypoxia without normoxic perfusion, Cu·Zn-SOD was augmented compared with baseline and compared with hearts subjected to 60 min of hypoxia without trilinolein, whereas Mn-SOD activity was still reduced compared with baseline, although less so than after 60 min of hypoxia without trilinolein. Pretreatment with trilinolein was associated with better preservation of left ventricular function during hypoxia and more rapid return to recovery during normoxic perfusion. This myocardial protective effect may be related to an antioxidant effect through potentiation of SOD, particularly Cu·Zn-SOD during hypoxia.
[Show abstract][Hide abstract] ABSTRACT: There ia abundant evidence for the premise that oxygen-derived free radicals (OFR) mediate ischemia/reperfusion injury to the myocardium. OFR scavengers such as Superoxide dismutase can effectively reduce damage through lipid peroxidation during ischemia/reperfusion. Enhanced chemiluminescence, which has been used to measure OFR, was used to measure the antioxidant activity of fatty acids (palmitic and linoleic acid) and triglycerides (triolein, tristearin) and natural plant antioxidants (magnolol, catechin, trilinolein). Trilinolein, which has recently been isolated from natural products, as well as the well-known water soluble analogue of vitamin E - Trolox, were used as control. During pretreatment with chemicals, at concentrations of 10−9 to 10−7 M, enhanced chemiluminescence of linoleic acid (C 18:2) showed a dose-responsive reduction of OFR with a maximal mean reduction of -31.9 % when compared to baseline. A saturated fatty acid such as palmitic acid (C 16:0) showed only relatively weak antioxidant activity at concentrations of 10−7 to 10−6 M with a maximum reduction of OFR of -15.2 % only. Control chemicals such as trilinolein and Trolox showed significant antioxidant activity. At concentrations between 10−6 and 10−10 M and trilinolein has the most potent antioxidant activity with a maximal mean reduction of OFR of -48.0%, whereas Trolox showed only -39.2 %. As for the natural plant antioxidants, only catechin showed potent antioxidant activity (-40 %). Polyunsaturated triglycerides such as triolein (oleic acid, C 18:1) also possess significant OFR scavenging effect (- 31.9 %) whilst saturated triglycerides such as tristearin (stearic acid, C 18:0) had only relatively weak antioxidant activity (- 15.2 %). Generally, the antioxidant activity of unsaturated compounds is stronger than saturated compounds; double-bond existence may partially explain this phenomenon.