A Comparison of Food-grade Folium mori Extract and 1-Deoxynojirimycin for Glycemic Control and Renal Function in Streptozotocin-induced Diabetic Rats

ABSTRACTFolium mori (桑葉 Sāng Yè, leaf of Morus alba L.; FM) is known to possess hypoglycemic effects, and 1-deoxynojirimycin (1-DNJ) has been proposed as an important functional compound in FM. However, the hypoglycemic activity of purified 1-DNJ has been rarely studied. It is also not known how FM and 1-DNJ affect the development of DM nephropathy. This study compared the antidiabetic effect of a commercial FM product with that of purified 1-DNJ in streptozotocin-induced diabetic rats. Seven days after induction, the diabetic rats were gavaged with FM (1, 3, 10, and 30mg/kg/day), 1-DNJ (30mg/kg/day), or vehicle (distilled deionized water; 2ml/kg/day) for 7days. All doses of FM ameliorated fasting and post-prandial blood glucose concomitantly with an increase in peripheral and pancreatic levels of insulin and improved homeostasis model assessment (HOMA-IR) in diabetic rats in a dose-dependent manner. Increased thiobarbituric acid reactive substances (TBARS) and nitrate/nitrite levels in the kidney, liver, and muscle of diabetic rats were reversed by all doses of FM. The renal function of the diabetic rats was normalized by all doses of FM, while blood pressure changes were reversed by FM at doses of 3mg/kg and above. Moreover, most of the above-mentioned parameters were improved by FM at doses of 3mg/kg and above to a similar extent as that of 1-DNJ. The results showed superior antidiabetic potential of the commercial FM product for glycemic control and protection against the development of diabetic nephropathy

Anti-Neuroinflammatory Effects of the Calcium Channel Blocker Nicardipine on Microglial Cells: Implications for Neuroprotection

Background/Objective Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved. Methodology/Principal Findings In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses. Treatment with nicardipine inhibited microglial cell migration. Nicardipine also significantly inhibited LPS plus IFN-γ-induced release of nitric oxide (NO), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, nicardipine also inhibited microglial activation by peptidoglycan, the major component of the Gram-positive bacterium cell wall. Notably, nicardipine also showed significant anti-neuroinflammatory effects on microglial activation in mice in vivo. Conclusion/Significance The present study is the first to report a novel inhibitory role of nicardipine on neuroinflammation and provides a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases

Effects of L-Amphetamine on the Central Neurons of the Snail

The effects of l-amphetamine on the spontaneous firing of central neurons of African snails (Achatina fulica Ferussac) were studied electrophysiologically. The effects of dopamine, noradrenaline, d- amphetamine, and methamphetamine on the central neurons also were tested. The l- and d- amphetamines (0.3 mM) elicited bursting firing of action potentials in the RP4 neuron of the snail, whereas dopamine (0.3 mM), noradrenaline (NE, 0.3 mM), and methamphetamine (2 mM) did not. The bursting firing of action potentials elicited by l-amphetamine was decreased if potassium-free solution, sodium-free solution, or solution containing oubain (0.1 mM), a sodium pump inhibitor, was perfused. The results suggested that l-amphetamine did, and methamphetamine did not, elicit a sodium-dependent bursting firing of action potentials of the neuron

Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats

Abstract In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R) injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules). The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ)-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau) which lead to decrease in cardiac output (CO) without changing total peripheral resistance (TPR). The phosphorylated Akt and glucose transporter 4 (GLUT 4) protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.</p

Sirt1 Activation by Post-ischemic Treatment With Lumbrokinase Protects Against Myocardial Ischemia-Reperfusion Injury

Lumbrokinase is used as an oral supplement to support and maintain healthy cardiovascular function, and to treat cardiovascular diseases in clinical for more than 10 years. Up until now, the mechanism of the cardioprotective effects of post-ischemic treatment with lumbrokinase has remained unclear. We therefore investigated the signaling pathways involved in the amelioration of myocardial ischemia-reperfusion (I-R) injury in rats treated with lumbrokinase 20 min after myocardial ischemia. Compared to vehicle-treated rats, post-ischemic treatment with lumbrokinase was associated with significant reductions in myocardial I-R-induced arrhythmias and myocardial damage, and an improvement in cardiac function. Moreover, lumbrokinase significantly upregulated levels of silent information regulator 1 (Sirt1). In addition, lumbrokinase significantly increased manganese-dependent superoxide dismutase expression, decreased Cleaved-Caspase-3 expression, and induced deacetylation of FoxO1. On the other hand, lumbrokinase also significantly downregulated levels of succinate dehydrogenase, cytochrome c oxidase, nuclear factor kappa B (NF-κB) and elevated levels of microtubule-associated protein light chain 3. Notably, the cardioprotective effects of lumbrokinase were abolished by administration of the specific Sirt1 inhibitor EX527. These findings demonstrate that post-ischemic treatment with lumbrokinase attenuates myocardial I-R injury through the activation of Sirt1 signaling, and thus enhances autophagic flux and reduces I-R-induced oxidative damage, inflammation and apoptosis

Mechanisms of Acupuncture Therapy in Ischemic Stroke Rehabilitation: A Literature Review of Basic Studies

Acupuncture is recommended by the World Health Organization (WHO) as an alternative and complementary strategy for stroke treatment and for improving stroke care. Clinical trial and meta-analysis findings have demonstrated the efficacy of acupuncture in improving balance function, reducing spasticity, and increasing muscle strength and general well-being post-stroke. The mechanisms underlying the beneficial effects of acupuncture in stroke rehabilitation remain unclear. The aim of this study was to conduct a literature review, summarize the current known mechanisms in ischemic stroke rehabilitation through acupuncture and electroacupuncture (EA) therapy, and to detail the frequently used acupoints implicated in these effects. The evidence in this review indicates that five major different mechanisms are involved in the beneficial effects of acupuncture/EA on ischemic stroke rehabilitation: (1) Promotion of neurogenesis and cell proliferation in the central nervous system (CNS); (2) Regulation of cerebral blood flow in the ischemic area; (3) Anti-apoptosis in the ischemic area; (4) Regulation of neurochemicals; and, (5) Improvement of impaired long-term potentiation (LTP) and memory after stroke. The most frequently used acupoints in basic studies include Baihui (GV20), Zusanli (ST36), Quchi (LI11), Shuigou (GV26), Dazhui (GV14), and Hegu (LI4). Our findings show that acupuncture exerts a beneficial effect on ischemic stroke through modulation of different mechanisms originating in the CNS

Role of Opioid Receptors Signaling in Remote Electrostimulation - Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts

<div><p>Aims</p><p>Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.</p><p>Methods & Results</p><p>Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.</p><p>Conclusion</p><p>The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.</p></div