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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

Effects of RSE and flutamide on time course changes of serum NO production. The concentrations of NO in serum were determined by measuring serum nitrite and nitrate levels. Data are shown as mean ± S.E.M, n = 3~5/group at each time point. *P < 0.05, RSE group versus IRI group at the corresponding time point; #P < 0.05, RSE + Flu group versus RSE group at the corresponding time point.
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fig5: Effects of RSE and flutamide on time course changes of serum NO production. The concentrations of NO in serum were determined by measuring serum nitrite and nitrate levels. Data are shown as mean ± S.E.M, n = 3~5/group at each time point. *P < 0.05, RSE group versus IRI group at the corresponding time point; #P < 0.05, RSE + Flu group versus RSE group at the corresponding time point.

Mentions: During acute myocardial I/R injury, nitric oxide (NO) plays important physiological and pathological roles in a time-dependent mechanism. We found that oral administration of RSE significantly protected rat hearts against I/R, and this effect was abolished by joint administration of flutamide. We wondered whether this protective effect of RSE involves an NO-related mechanism that is somehow affected by flutamide. We first measured the NO level in the serum of rats that underwent sham surgery or I/R process without drug pretreatment. The result showed no significant difference in the serum level of NO between the sham group and the IRI group. However, pretreatment of RSE in rats that underwent I/R process resulted in a remarkable elevation of serum NO production. NO production increased after 30 min RSE administration and reached a peak at 15 min after ischemia (compared with IRI group, P < 0.05). Figure 5 illustrates these time-dependent changes in serum NO production during pretreatment and I/R period. In the RSE + Flutamide group, the levels of NO production were significantly lower than those in RSE group (P < 0.05 at 1 h after pretreatment and P < 0.05 at 15 min after ischemia), suggesting that flutamide did indeed suppress NO production stimulated by RSE treatment.


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)

Effects of RSE and flutamide on time course changes of serum NO production. The concentrations of NO in serum were determined by measuring serum nitrite and nitrate levels. Data are shown as mean ± S.E.M, n = 3~5/group at each time point. *P < 0.05, RSE group versus IRI group at the corresponding time point; #P < 0.05, RSE + Flu group versus RSE group at the corresponding time point.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Effects of RSE and flutamide on time course changes of serum NO production. The concentrations of NO in serum were determined by measuring serum nitrite and nitrate levels. Data are shown as mean ± S.E.M, n = 3~5/group at each time point. *P < 0.05, RSE group versus IRI group at the corresponding time point; #P < 0.05, RSE + Flu group versus RSE group at the corresponding time point.
Mentions: During acute myocardial I/R injury, nitric oxide (NO) plays important physiological and pathological roles in a time-dependent mechanism. We found that oral administration of RSE significantly protected rat hearts against I/R, and this effect was abolished by joint administration of flutamide. We wondered whether this protective effect of RSE involves an NO-related mechanism that is somehow affected by flutamide. We first measured the NO level in the serum of rats that underwent sham surgery or I/R process without drug pretreatment. The result showed no significant difference in the serum level of NO between the sham group and the IRI group. However, pretreatment of RSE in rats that underwent I/R process resulted in a remarkable elevation of serum NO production. NO production increased after 30 min RSE administration and reached a peak at 15 min after ischemia (compared with IRI group, P < 0.05). Figure 5 illustrates these time-dependent changes in serum NO production during pretreatment and I/R period. In the RSE + Flutamide group, the levels of NO production were significantly lower than those in RSE group (P < 0.05 at 1 h after pretreatment and P < 0.05 at 15 min after ischemia), suggesting that flutamide did indeed suppress NO production stimulated by RSE treatment.

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