title: Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.
abstract: Mechanisms for Panax ginseng's cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury.
authors.affiliation: State Key Laboratory for Quality Research of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Pei
authors.forename: Hou
authors.initials: H
authors.lastname: Shaozhen
authors.forename: Dong
authors.initials: D
authors.lastname: Gengting
authors.forename: Chen
authors.initials: C
authors.lastname: Tingbo
authors.forename: Liu
authors.initials: L
authors.lastname: Liang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Hua