Abstract P110: Standardized Ginseng Extract Protects Rat Hearts From Ischemia and Reperfusion Injury via GR/PI3K/Akt/eNOS Signaling
Background: Ginseng (Panax ginseng C.A. Meyer) is a popular medicinal herb used in Chinese community for over 2000 years. Previous studies have confirmed the cardioprotective effects of ginseng. However, the mechanism for such protection remains unclear. In the present study, we investigated whether acute oral administration of a standardized ginseng extract (RSE) could protect rat heart against ischemia-reperfusion (I/R) injury and whether such protection was related to nitric oxide (NO) generation and glucocorticoid receptor (GR) signaling.
Methods: Rats were subjected to 30 min ischemia followed by 90 min reperfusion by occluding and reopening of left anterior descending coronary artery. RSE that was chemically standardized by HPLC fingerprint was orally given to rats 60 min before ischemia. Some rats also received GR inhibitor RU468 (30 mg/kg), endothelial NO synthase (eNOs) inhibitor L-NAME (30 mg/kg), PI3K inhibitor LY294002 (0.25 mg/kg), Akt inhibitor IV (4 mg/kg), or transcriptional inhibitor actinomycin D (ActD, 0.8 mg/kg).
Results: Compared with I/R control (10.2±2.1 %), RSE treatment significantly decreased infarct size (TTC staining method) of heart in a dose-dependent manner (0.3±0.3 % and 5.8±1.2 % for 80 and 40 mg/kg of RSE, respectively). RSE also induced a significant increase in serum NO level (10.7±0.7 microM vs. 6.5±0.9 microM) while a remarkable decrease in CK activity (1518±65 U/L vs. 916±55 U/L) and LDH level (178±31 U/L vs. 464±43 U/L). Western blotting analysis showed that I/R treatment induced significant decreases of total and phosphorylation form of GR, PI3K, Akt, and eNOS in heart tissue, but RSE significantly reversed the decreases of expression and activation of these proteins. In addition, the protection induced by RSE (80mg/kg, 0.3±0.3 %) was also abolished by the blockage of GR (11.4±3.8 %), PI3K (10.0±2.4 %), Akt (8.8±3.9 %), and eNOS (14.2±1.6 %). However, ActD (0.6±0.3 %) didn’t reverse the RSE-induced protection.
Conclusion: RSE affords acute cardioprotection to rat hearts subjected to I/R. This protection is related to NO production and requires the activation of GR through non-genomic pathway in which PI3K, Akt, and eNOS are sequentially activated. 1