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Cardiovascular diseases cause significant morbidity and mortality worldwide, incurring a major public health burden. Gastrodia elata Blume is a traditional Chinese herbal medicine that has been widely used to treat central nervous system and cardiovascular diseases. Gastrodin, as the major active component in Gastrodia elata Blume, can confer protection against cardiovascular diseases. In this review, we summarize the anti-inflammatory actions, anti-cardiac hypertrophy, anti-hypertension, anti-atherosclerosis, and angiogenic effects of gastrodin, as well as its protective effects on vascular cells and against myocardial ischemia-reperfusion injury. The medical potential of gastrodin in diabetes-related cardiovascular diseases is also discussed.
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Aim To observe the role of ERK signaling protein in morphine preconditioning reducing global ischemia-reperfusion injury in isolated rat hearts.Methods Adult male Sprague-Dawley rats were distributed into six groups (n =10 for each) using a random number table:control group (CON),ischemia-reperfusion group (I/R),ischemia preconditioning group (IPC),morphine preconditioning group at the concentration of 1 μmol · L-1 (MPC),ERK inhibitor PD98059 + MPC (MPD),and group of ERK inhibitor-PD98059 (PD).The isolated rat hearts were treated on a Langendorff perfusion apparatus system.The coronary effluent was collected at 15 min of equilibration (baseline),5 and 10 min of reperfusion for detection of the activity of LDH.Meanwhile,a water-filled balloon was inserted into the left ventricular for continuous LVDP measurement.The IS and AAR and IS/AAR ratios were observed by TTC.Western blot was used to examine the level of phosphorylated ERK in myocardium.Results As compared with the I/R group,MPC significantly decreased IS and IS/AAR ratio as well as LDH activities at 5 min and 10 min of reperfusion,but improved the LVDP at the end of reperfusion.Moreover,the phosphorylation level of ERK in myocardium was up-regulated by MPC.However,ERK inhibitor PD98059 could block the protective effects of MPC,as indicated by the increased IS and IS/AAR ratio,elevated LDH activity at the reperfusion of 5 and 10 min,and the suppressed LVDP at the end of reperfusion.Furthermore,the MPC-induced phosphorylation of ERK was also reversed by PD98059.Conclusion Morphine preconditioning may confer cardio-protection against the global ischemia-reperfusion injury in rat hearts through enhancing the phosphorylation of ERK.
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Aim To explore the role of PI3 K/Akt/Sirt1 pathway in cardioprotection of hydrogen sulfide ( H2 S ) postconditioning against ischemia/reperfusion ( I/R) injury. Methods Langendorff perfusion appa-ratus was used to build an isolated rat myocardial I/R model. Isolated rat hearts were subjected to 30 min global ischemia followed by 60 min reperfusion after 20 min of equilibrium. 60 male SD rats were randomly di-vided into 5 groups(n=12):control group(Control), ischemia/reperfusion group( I/R) , H2 S postcondition-ing group( H2 S) , inhibitor LY294002 group( LY) and H2 S with inhibitor group( H2 S+LY) . The left ventric-ular diastolic pressure ( LVEDP ) , the left ventricular developed pressure(LVDP), the maximum rate of in-crease or decrease of left ventricular pressure ( ± dp/dtmax ) were registered at the end of 20 min equilibri-um, 30 and 60 min of reperfusion separately. Triphe-nyl tetrazolium chloride( TTC) staining was used to de-termine the myocardial infarct size. The levels of Sirt1 and PGC-1 mRNA were tested using real-time PCR. The expressions of Sirt1 and PGC-1αwere detected with Western blot analysis. Immunohistochemical method was used to determine the location of Sirt1 . Results There were no differences in equilibrium hemodynamics observed between the experimental groups(P>0. 05). At the end of reperfusion, compared with I/R group, H2 S group had obviously ameliorated functional recov-ery and significantly decreased the myocardial infarct size(26. 9 ± 4. 9)% vs(48. 9 ± 5. 6)%(P <0. 05). Meanwhile, the expression of Sirt1 and PGC-1α in-creased significantly. However,LY294002 reversed the cardioprotective effects provided by hydrogen sulfide postconditioning and reduced the level of Sirt1 and PGC-1α, the percentage of Sirt1-positive nuclei. Con-clusion PI3 K/Akt/Sirt1 signaling pathway mediates the hydrogen sulfide postconditioning-induced protec-tion against I/R injury.
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Aim To investigate whether hydrogen sul-fide ( H2 S ) inhibits cardiomyocyte apoptosis induced by acute myocardial ischemia in isolated perfused rat heart. Methods The myocardial ischemia injury model was replicated with Langendorff isolated perfused rat heart, and the left anterior descending coronary ar-tery was ligated for 4 h. 40 male SD rats were divided into five groups randomly: sham group, ischemia group, and NaHS groups (5,10,20μmol·L-1). The segmental heart samples were used for HE staining. Cardiomyocyte apoptosis was detected with TUNEL as-say. The expressions of caspase-3 and Cyt-C in hearts were determined with Western blot analysis. Results Myocardial cells were found to show serious disorder and coagulated zonal necrosis under light microscope, the apoptotic rate of cardiomyocytes and the expression of caspase-3 and Cyt-C were significantly increased af-ter ischemia for 4h. Perfusion of NaHS resulted in more clear cell morphology and milder pathologic chan-ges of myocardiocytes according to the HE staining a-nalysis, and the significant decrease of expression of Cyt-C. After perfusion of 10,20 μmol·L-1 NaHS,the apoptotic rate of cardiomyocytes and the expression of caspase-3 were significantly decreased. Conclusion H2 S has certain protective effects on acute myocardial ischemic injury in isolated perfused rat heart via inhibi-ting cardiomyocyte apoptosis.
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La hipertensión es pobremente controlada en la mayoría de los pacientes. La tasa de control definida como una presión arterial sistólica (PAS) < 140 mmHg y presión arterial diastólica (PAD) < 90 mmHg, es menor a 20% en México. Este estudio que involucró 31 centros de investigación, realizado en condiciones reales, fue diseñado para establecer que 6.25 mg de hidroclorotiazida (HCTZ) dados una vez al día en combinación fija con 2.5 o 5 mg de fumarato de bisoprolol pueden contribuir a alcanzar las metas de control en pacientes con hipertensión sistémica grado I, II o III que fracasaron en un régimen antihipertensivo previo, y que estas combinaciones son más seguras que los fármacos por separado. Los resultados mostraron disminuciones significativas de la presión arterial sistólica y diastólica de 33.3 y 18.4 mmHg, respectivamente. La tasa de respuesta fue de 85.7% a las 32 semanas de tratamiento. Se observó disminución de la frecuencia cardiaca promedio de 10.8 latidos/minuto; la frecuencia cardiaca promedio final fue de 67.05 latidos/minuto. Los resultados de este estudio muestran que la combinación de bisoprolol en dosis de 2.5 o 5.0 mg con 6.25 mg de hidroclorotiazida al día, tiene efectos aditivos que resultan eficaces en el control de la presión arterial ya sea leve, moderada o severa; y que ayuda a pacientes hipertensos a alcanzar las metas de control en muy alto porcentaje y a corto plazo, sin afectación sobre otros sistemas, por lo que son seguros en pacientes hipertensos diabéticos y dislipidémicos, y que en conjunción con la regulación de la frecuencia cardiaca proveen cardioprotección a pacientes con alto riesgo cardiovascular. Las combinaciones fijas de antihipertensivos simplifican el régimen de dosis, mejoran el apego, el control de la hipertensión, disminuyen los efectos adversos dependientes de la dosis y reducen los costos como primera línea de tratamiento de la hipertensión.
Hypertension is poorly controlled in most patients. The control rate, defined as a systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg, is less than 20% in Mexico. This study involving 31 research centers, carried out under real conditions was designed to establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily in fixed combination with 2.5 mg or 5 mg of bisoprolol fumarate can contribute to achieve the control targets in patients with grade I, II or III systemic hypertension who failed to a previous antihypertensive regimen, and that these combinations are safer than the drugs alone. The results showed significant mean decreases in systolic and diastolic blood pressure of 33.3 mmHg and 18.4 mmHg respectively. The response rate was 85.7% at 32 weeks of treatment. There was a decrease in mean heart rate of 10.8 beats/min, final average heart rate was 67.05 beats per minute. The results of this study show that the combination of bisoprolol in doses of 2.5 or 5.0 mg to 6.25 mg of hydrochlorothiazide per day, has additive effects that are effective in controlling blood pressure, whether mild, moderate or severe, and that helps hypertensive patients to achieve the control goals at a very high percentage and in the short term, without affecting other systems so they are safe in hypertensive diabetic and dyslipidemic patients, and in conjunction with the heart rate regulation provides cardio-protection to patients at high cardiovascular risk. Fixed combinations of antihypertensive drugs simplify dosing regimen, improve adherence to treatment, hypertension control, decrease dose-dependent adverse effects and decrease costs as a first line treatment for hypertension.
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Discovery of a new drug is time consuming and laborious process. Natural products have long been a thriving source for the discovery of new drugs due to their chemical diversity and ability to act on various biological targets. The phytochemical exploration of indigeneous flora has contributed to some extent in this race for the discovery of new drugs. The traditional Indian systems of medicine has been a part of our lifestyle since ages and the classical texts like Ayurveda and Charak Samhita have served as materia medica for this purpose. This review focuses on the contributions made from India in the drug discovery and development process and provides future directions in the area.
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@#Objective To observe the protective effect of spironolactone on heart of hypertensive SD rats.Methods 30 male SD rats were randomly divided into the control group,hypertensive group(HS group),low spironolactone dose group(HSL group)and high spironolactone dose group(HSH group).The animals except the control group were treated with L-NAME 50 mg/kg/d.Then the animals of the HS group were fed with 1% sodium chloride water solution.Those of the HSL and HSH groups were treated same but the former added with spironolactone 20 mg/kg/d,the later added with spironolactone 100 mg/kg/d.8 weeks late,the animals were killed and hearts were taken out to observe following items:myocardial cross-sectional area,ratio of per-arteriolar fibrous area/arteriolar luminal area of arterioles,ratio of collagen area/total myocardial area,myocardial necrosis and inflammation.Results The myocardial cross-sectional areas in the HS group were significantly more than those in other 3 groups(P<0.01).Collagen ratios of the HS group were significantly higher than others(P<0.01).The ratios of arteriolar wall area versus luminal area in the HS group were significantly higher than those of control and HSH groups(P<0.01).Myocardial injuries in the HS group were more severe than those of other 3 groups.There were no differences between HSL and HSH groups.Conclusion Spironolactone has protective effect on heart of hypertensive SD rats.