The Role And Mechanism Of Of Rhodiola Active Ingredients Of Anti-ischemic Heart Disease

Objectives:Recently, we reported the unique effects of cerebral protection of the Chinese herbal medicine-Braintone (a formulation containing Radix Rhodiola, Folium Ginkgo, Radix Notoginseng and Rhizoma Ligustici Chuangxion), also known as Remembrance. In the present study, we tested the hypothesis that Braintone may extend cardioprotective effects on ischemic myocardium in Wistar rats. Salidroside, a potent adaptogen form Rhodiola rosea L, is intensively reported to increase resistance to various harmful stimuli. In the present study, we also tested the hypothesis that salidroside might extend its therapeutic benefits in protecting cardiomyocytes against ischemic insults.Materials and Methods:1. Animal model was created by ligating of left descending coronary artery. Mortality rate and infarct volume were assessed. In addition, capillary density, antioxidant enzymes, apoptosis modulators and VEGF, eNOS mRNA expression level were investigated to reveal the underlying mechanisms.2. Primary cultured neonatal rat cardiomyocytes were pretreated with salidroside for 12 h and subsequently exposed to oxygen-glucose deprivation (OGD) condition for another 8 h. Then cell viability and morphological alterations were detected to assess cardioprotective effects of salidroside. To further explore potential mechanism underlying, intracellular reactive oxygen species (ROS) generation, apoptosis and mitochondrial membrane potential (ΔΨm) were investigated.Reasults:1. Treatment with Braintone reduced mortality rate from 41.5% to 22.2% associate with notable diminished infarct volume (18.0%±3.0% vs 30.4%±9.0%). Braintone also acted as antioxidant agent for preserving the activities of Catalase (13.1±0.48U vs 9.71±0.44U in vehicle, P<0.01). Furthermore, Braintone dramatically boosted the expression levels of anti-apoptotic genes Bcl-2 and Bcl-xl (1.43-,2.30-fold, P<0.01) as compared to vehicle group and significantly down-regulated the expression level of pro-apoptotic genes Bax (0.84-fold, P<0.01) while slightly inhibited Caspase-9 and Caspase-3 signals. Moreover, higher mRNA expression levels of VEGF and eNOS were observed in Braintone group consisting with a remarkable raise of capillary density (46.0±13.3 vs 27.4±12.6, P<0.01) in myocardium.2. Pretreatment with salidroside notably ameliorated cell viability losses in a dose-dependant manner in parallel it alleviated morphologic injury detected under phase and electron microscopes. Mechanistically, diminished OGD-induced cardiomyocytes apoptosis was shown in salidroside-pretreated cardiomyocytes, in accordance with minimal ROS burst probed. Moreover, salidroside markedly upregulated the Bcl-2/Bax ratio and preservedΔΨm.Conclusion:The findings indicated that Braintone markedly attenuate myocardial damage induced by ischemic insults in vivo. Braintone may confer cardioprotection via scavenging free radicals, inhibiting cardiomyocytes apoptosis and promoting angiogenesis in ischemic region. Additionally, these findings suggest that salidroside protects cardiomyocytes against OGD-induced cell death probably via scavenging ROS, inhibiting apoptosis and restoring mitochondrial function. Salidroside therefore has potential to be a promising drug for preventing and treating myocardial ischemic diseases.