Pai Feng Kao

Effect of trilinolein on the activity and gene expression of superoxide dismutase in cultured rat brain astrocytes

Stroke is one of the major causes of morbidity and mortality in recent. Oxygen free radicals produced during cerebral infarction increases the damage to neurons. Superoxide dismutase (SOD) is the endogenous antioxidant enzyme that can effectively scavenge superoxide radicals. Catechin is a hydrophilic antioxidant usually existed in tea, fruits and vegetables. In the cultured rat brain astrocytes (RBA), the activity of SOD (both Cu, Zn-SOD and Mn-SOD subtypes) was markedly increased by incubation with catechin at low concentration (0.1 microM) for 2 days (short-term) and 7 days (long-term). This stimulatory effect of catechin was not related to the incubating concentration. Similar changes were also observed in the gene expression of SOD in RBA. The increase in quantity of SOD-messenger RNA was remarkable and seemed to be more obvious than the other antioxidants such as vitamin E. This result shows that catechin is an effective antioxidant to increase the activity of SOD in RBA which would be beneficial to neurons subjected to oxygen free radical damage.

Effects of the angiotensin II type 1 receptor antagonist valsartan on the expression of superoxide dismutase in hypertensive patients

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro‐oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT1) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double‐blind, placebo‐controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD–mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration‐dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD‐mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down‐regulation of SOD‐mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT1 receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.

EFFECTS OF HESPERIDIN ON CYCLIC STRAIN-INDUCED ENDOTHELIN-1 RELEASE IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS

1 Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species and has been reported to have antihypotensive and vasodilator properties. However, the mechanism of action of hesperidin in the prevention and treatment of vascular diseases remains unclear. 2 The vascular endothelium can produce potent contracting factors, such as endothelin (ET)‐1, and endothelium‐derived relaxing factors, such as nitric oxide (NO). The aims of the present study were to test the hypothesis that hesperidin may alter strain‐induced ET‐1 secretion and NO production and to identify the putative underlying signalling pathways in human umbilical vein endothelial cells (HUVEC). 3 Hesperidin (10 and 100 mmol/L) inhibited strain‐induced ET‐1 secretion. Hesperidin also inhibited strain‐induced increases in the formation of reactive oxygen species and extracellular signal‐regulated kinase (ERK) phosphorylation. 4 Hesperidin treatment of HUVEC enhanced NO production, endothelial NO synthase (eNOS) activity and the phosphorylation of eNOS and Akt. Furthermore, hesperidin modulated strain‐induced ET‐1 release and suppressed ERK phosphorylation in part via the NO/protein kinase G pathway. 5 In summary, we have demonstrated that hesperidin inhibits strain‐induced ET‐1 secretion and enhances NO production in HUVEC.

Tetramethylpyrazine downregulates angiotensin II-induced endothelin-1 gene expression in vascular endothelial cells

1. Tetramethylpyrazine (TMP) is one of the active ingredients of the Chinese herb Ligusticum wallichii Franchat. It is well documented that TMP exerts a cardiovascular protective effect. The aims of the present study were to examine whether TMP alters angiotenisn (Ang) II‐induced endothelin (ET)‐1 gene expression and to identify the putative underlying signalling pathways in vascular endothelial cells.

Changes of Serum β-Endorphin by Programmed Exercise Training Are Correlated with Improvement of Clinical Symptoms and Quality of Life in Female Mitral Valve Prolapse Syndrome

Background: Mitral valve prolapse (MVP) is a common entity in female population. Although this is a minor disease, it may cause annoying symptoms that impair quality of life (QOL), and no established therapy for this problem. The aim of this study isto examine whether programmed exercise training by treadmill in female MVP syndrome would improve clinical symptoms and QOL. Methods: An interventional study of 39 females with MVP syndrome with treadmill exercise endurance training for 12 weeks. Every individual received training for 30 min a day, thrice a week for 12 weeks. Baseline and post-exercise at 12 weeks serum β-endorphins were measured. Symptom improvement was assessed by the MVP symptom checklist questionnaire and the Euro-QOL-5D was used to measure QOL improvement in these females. Results: The mean serum β-endorphin increased from 0.5 to 1.68 ng/ml (p = 0.001) in the exercise group (n = 18) after 12 weeks exercise, whereas the control group (n = 21) did not show any significant changes (0.44 vs. 0.43 ng/ml). Major symptoms of MVP such as chest pain, palpitation, fatigue were improved significantly by the assessment of MVP symptom checklist. The QOL of the exercised females also showed significant changes. Conclusions: Through programmed exercise training in these MVP females, the improvement of symptoms and QOL is parallel to the increase of serum β-endorphin. This result implicates that MVP females should initiate exercise to tackle this annoying problem.

Downregulation of Superoxide Dismutase Activity and Gene Expression in Cultured Rat Brain Astrocytes after Incubation with Vitamin C

Reactive oxygen species have been linked with neuropathological changes in the central nervous system. Epidemiological studies supported the beneficial effect of supplementation of antioxidants. Superoxide dismutase (SOD) is an endogenous enzyme which can scavenge reactive oxygen species. This study investigated the effect of supplementation with ascorbic acid (vitamin C) on the changes of SOD in cultured neurological cells. Rat brain astrocytes (RBA-1 cells) were incubated with vitamin C and divided into four groups: a control group (without vitamin C) and three treatment groups with vitamin C at 40, 80, and 160 µmol/l. After short-term (2 days) and long-term (7 days) incubation, SOD activity, SOD mRNA level by Northern blotting, and SOD protein amounts by Western blotting were measured. After 2 days of incubation, vitamin C resulted in a decrease in the activity of SOD in a concentration-dependent manner (Mn-SOD from 14.8 ± 1.2 to 13.2 ± 0.5 U/mg protein and Cu/Zn-SOD from 64.8 ± 1.2 to 51.7 ± 0.9 U/mg protein; p < 0.05), and vitamin C also attenuated the Cu/Zn-SOD mRNA level from 100 to 86.3 ± 6.7%; p < 0.01), whereas the protein amounts of these two SODs remained unchanged. After 7 days of incubation with vitamin C, the SOD activity of RBA-1 cells decreased significantly (Mn-SOD from 14.9 ± 0.3 to 11.8 ± 0.3 U/mg protein and Cu/Zn SOD from 61.8 ± 1.8 to 54.6 ± 0.9 U/mg protein; p < 0.01), and the mRNA level was also attenuated (Mn-SOD from 100 to 86.8 ± 8.7% and Cu/Zn-SOD from 100 to 84.7 ± 4.8%; p < 0.01). These results suggest that 2 and 7 days of incubation with relatively high concentrations of vitamin C may downregulate activity and gene expression of SOD in cultured RBA-1 cells.