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Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.

Pei L, Shaozhen H, Gengting D, Tingbo C, Liang L, Hua Z - Evid Based Complement Alternat Med (2013)

Bottom Line: RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE.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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Quality Research of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

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.

No MeSH data available.


Related in: MedlinePlus

Outline of experimental protocol to evaluate the effects of flutamide on cardioprotection of RSE against myocardial I/R injury in rats. Sham: sham operation group; IRI: I/R injury group with vehicle treatment; RSE, I/R injury with RSE 80 mg/kg treatment; RSE + Flu: I/R injury group with RSE 80 mg/kg + flutamide 10 mg/kg treatment. 6 time points include 0 min, 30 min, and 60 min after pretreatment; 15 min after ischemia; 30 min after ischemia; 90 min after reperfusion. Heart tissue and blood sample were collected, respectively (n: number of rats at each time point). ∗: heart and serum samples were collected for Western blot analysis, NO production and testosterone concentration assays. #: heart and serum samples were collected for TTC staining, CK and LDH activities determinations.
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fig2: Outline of experimental protocol to evaluate the effects of flutamide on cardioprotection of RSE against myocardial I/R injury in rats. Sham: sham operation group; IRI: I/R injury group with vehicle treatment; RSE, I/R injury with RSE 80 mg/kg treatment; RSE + Flu: I/R injury group with RSE 80 mg/kg + flutamide 10 mg/kg treatment. 6 time points include 0 min, 30 min, and 60 min after pretreatment; 15 min after ischemia; 30 min after ischemia; 90 min after reperfusion. Heart tissue and blood sample were collected, respectively (n: number of rats at each time point). ∗: heart and serum samples were collected for Western blot analysis, NO production and testosterone concentration assays. #: heart and serum samples were collected for TTC staining, CK and LDH activities determinations.

Mentions: Rats were randomly assigned to four experimental groups (shown in Figure 2), that is, Sham group (given vehicle by oral gavage at 60 min before sham surgery without I/R, n = 24), I/RI group (given saline by oral gavage at 60 min before I/R, n = 31), RSE group (given 80 mg/kg of RSE by oral gavage at 60 min before I/R, n = 29), and RSE + Flutamide group (given 80 mg/kg of RSE by oral gavage and 10 mg/kg of flutamide by subcutaneous injection at 60 min before I/R, resp., n = 31). Sham group rats were subjected to all the procedures except that the LAD ligation was not tightened. The vehicle or drugs were given 60 min before sham operation or I/R procedure, which was designated as time 0 min. In each group, 3~5 rats were sacrificed at the following time points: 30 min after drug treatment, 1 hr after drug treatment, 15 min after ischemia, 30 min after ischemia, and 90 min after reperfusion. At each time point, arterial blood samples were drawn from aorta immediately before animal sacrifice and then centrifuged at 1,000 g and 4°C for 15 min. All serum samples were stored at −80°C before the measurements of nitrate/nitrite, LDH, and CK. Heart was excised and weighed immediately. After collection of serum samples, 2 mL of 10% potassium chloride was injected via inferior vena cava to stop the heart in diastole, and the heart was excised for infarct size measurement by TTC staining or frozen in liquid nitrogen for Western blot analysis.


Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.

Pei L, Shaozhen H, Gengting D, Tingbo C, Liang L, Hua Z - Evid Based Complement Alternat Med (2013)

Outline of experimental protocol to evaluate the effects of flutamide on cardioprotection of RSE against myocardial I/R injury in rats. Sham: sham operation group; IRI: I/R injury group with vehicle treatment; RSE, I/R injury with RSE 80 mg/kg treatment; RSE + Flu: I/R injury group with RSE 80 mg/kg + flutamide 10 mg/kg treatment. 6 time points include 0 min, 30 min, and 60 min after pretreatment; 15 min after ischemia; 30 min after ischemia; 90 min after reperfusion. Heart tissue and blood sample were collected, respectively (n: number of rats at each time point). ∗: heart and serum samples were collected for Western blot analysis, NO production and testosterone concentration assays. #: heart and serum samples were collected for TTC staining, CK and LDH activities determinations.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824556&req=5

fig2: Outline of experimental protocol to evaluate the effects of flutamide on cardioprotection of RSE against myocardial I/R injury in rats. Sham: sham operation group; IRI: I/R injury group with vehicle treatment; RSE, I/R injury with RSE 80 mg/kg treatment; RSE + Flu: I/R injury group with RSE 80 mg/kg + flutamide 10 mg/kg treatment. 6 time points include 0 min, 30 min, and 60 min after pretreatment; 15 min after ischemia; 30 min after ischemia; 90 min after reperfusion. Heart tissue and blood sample were collected, respectively (n: number of rats at each time point). ∗: heart and serum samples were collected for Western blot analysis, NO production and testosterone concentration assays. #: heart and serum samples were collected for TTC staining, CK and LDH activities determinations.
Mentions: Rats were randomly assigned to four experimental groups (shown in Figure 2), that is, Sham group (given vehicle by oral gavage at 60 min before sham surgery without I/R, n = 24), I/RI group (given saline by oral gavage at 60 min before I/R, n = 31), RSE group (given 80 mg/kg of RSE by oral gavage at 60 min before I/R, n = 29), and RSE + Flutamide group (given 80 mg/kg of RSE by oral gavage and 10 mg/kg of flutamide by subcutaneous injection at 60 min before I/R, resp., n = 31). Sham group rats were subjected to all the procedures except that the LAD ligation was not tightened. The vehicle or drugs were given 60 min before sham operation or I/R procedure, which was designated as time 0 min. In each group, 3~5 rats were sacrificed at the following time points: 30 min after drug treatment, 1 hr after drug treatment, 15 min after ischemia, 30 min after ischemia, and 90 min after reperfusion. At each time point, arterial blood samples were drawn from aorta immediately before animal sacrifice and then centrifuged at 1,000 g and 4°C for 15 min. All serum samples were stored at −80°C before the measurements of nitrate/nitrite, LDH, and CK. Heart was excised and weighed immediately. After collection of serum samples, 2 mL of 10% potassium chloride was injected via inferior vena cava to stop the heart in diastole, and the heart was excised for infarct size measurement by TTC staining or frozen in liquid nitrogen for Western blot analysis.

Bottom Line: RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE.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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Quality Research of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

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.

No MeSH data available.


Related in: MedlinePlus