Protective effects of Diosgenin against
myocardial injury induced by ischemia and reperfusion in rats
JP Chen*1,
J.Liu2, DM Wang3
SH Lin3 DP Yang3,
and TM Wong2
1. School of Chinese Medicine, the
University of Hong Kong,Hong Kong SAR, China
2. Department of Physiology, the
University of Hong Kong Hong Kong SAR, China
3. Zhongshan University Guangzhou, China 510089
Correspondence: Dr. JP Chen
School of
Chinese Medicine, the University of Hong Kong, Hong Kong SAR, China
Tel.: (852)
25890479, Fax No.: (852) 28725476
Email:
jianpingchen@hkucc.hku.hk
Diosgenin is a sapogenin derived from the root of wild yam (Dioscorea villosa). Structurally
it is similar to progesterone. It is a raw material for the synthesis of
16-dehydro pregnenolone acetate. It can also be used
for the synthesis of other steroids such as hydrocortisone, prednisone, norethindronum, fluocinolone and daxamethasone etc. Diosgenin has
been reported to possess estrogen actions in mammary gland (). Administration
of diosgenin at the dose levels of 20 and 40
milligrams/kilogram body weight for a period of 15 days increased DNA content
and number of ducts and induced appearance of terminal end buds, which
indicates growth of mammary epithelium (Ref). Diosgenin
further enhanced the effects of estrogen when co-administered. The observations
indicate estrogenic action of diosgenin. On the other
hand, it did not increase the mammary development scores, suggesting that it
does not have progesteronic action despite the
structural similarity.
Estrogen is believed to protect the heart against ischemic heart
diseases. Women are less
susceptible than men to ischemic heart diseases until they reach
menopause. As women enter menopause,
reduction in the production of estrogen, an ovarian hormone, is accompanied
by an increased incidence coronary vascular disease (Stampfer
et al 1991). We therefore hypothesize that diogenin
may protect the heart against injury induced by ischemic insults. In this study
we administered diosgenin systematically to female
rats for 15 days as previously described () and determined injury of the
isolated perfused heart in response to myocardial
ischemia and reperfusion. We also determined the contractile recovery. Results
showed that diogenine at 20 – 40 mg/kg body weight
protected the heart against ischemia-induced injury and improved contractile
recovery.
Materials and methods
Please write
the materials and methods together with Liu Jing
Results
The body weights of three groups of rats
2.1 Effect of diosgenin on
ischemia and reperfusion-induced myocardial infarction
The infarct size in the vehicle control group was 40%. Administration of
diosgenin at 20 and 40 mg/kg body weight reduced the
infarct size to 18 and 9%, respectively. The reductions were statistically
significantly.
Fig.1 Effect of diosgenin on myocardial infarction in the isolated perfused rat heart subjected to myocardial ischemia and
reperfusion
2.2 Effect of diosgenin on LDH release from the isolated perfused rat heart
The LDH release from the control group was 61.44. The LDH
release was significantly reduced in the groups treated with diosgenin (Table 1). Table 1
Table 1: effect of diosgenin on LDH release from the isolated perfused rat heart subjected to ischemia and reperfusion (±s )
Group |
Dosage |
n |
LDH(U/L) |
Control group |
1ml H2O |
8 |
61.44±8.56 |
Low dosage pretreatment group |
20mg/ kg |
8 |
40.51±3.85* |
High dosage pretreatment group |
40mg/ kg |
8 |
35.35±6.54* |
* P<0.05 vs. control
Use a bar chart instead of a table
2.3 Effect of diosgenin on contractile recovery and heart rate in the
isolated perfused rat heart subjected to ischemia and
reperfusion
Table 2: Effects of diosgenin on
contractile recovery in the isolated perfused rat heart
subjected to ischemia and reperfusion
The contractile
functions were determined at the end of 2 hr reperfusion
Group |
N |
+dp/dtmax |
-dp/dtmax |
LVDP |
Control group |
8 |
0.4313±0.1 |
0.377±0.05 |
0.541±0.05 |
Diosgenin 20 mg/kg BW |
8 |
0.5178±0.79 |
0.515±0.06* |
0.694±0.057 |
Diosgenin 40 mg/kg BW |
6 |
0.611±0.15 |
0.547±0.087* |
0.72±0.061* |
* P<0.05 vs. control group
Do you have the pretreatment values?
At the end of 2 hr reperfusion, the +dp/dtmax, -dp/dtmax and LVDP were greater in the treatment groups than in the sham control group (Table 2). However, significant difference was only observed in -dp/dtmax in both treatment groups and LVDP in the group receiving high dose of diosgenin. The observation indicated an improved contractile recovery after treatment with diosgenin for 15 days.
Fig.2 Effect of diosgenin on heart rate of isolated perfused
heart subjected to ischemia and reperfusion:
The heart rate was measured at the end of2
hr reperfusion.
I think the heart rate is higher in the
treatment groups. I suggest that the results should not be reported.
Discussion
The important observation in the present study was
that, after administration of diosgenin to the female
rats for 15 days at 2- and 40 mg/kg BW, the infarct size of- and release of LDH
from the isolated perfuse heart induced by myocardial ischemia and reperfusion
were significantly reduced, indicating a protective effect of diosgenin against injury induced by ischemia and
reperfusion. In support of the protective effect of diosgenin,
the contracilte recovery was also improved. A
previous study showed that diosgenin promoted on the
mammary gland growth, an effect similar to that of estrogen. The cardioprotective effect of diosgenin
observed in the present study also suggested that the effect might be similar
to that of estrogen. Further study is needed to determine whether it act at the
myocardium and via the classical estrogen receptor.
Hormone replacement therapy is used to menopausal women. Whether it is
beneficial is controversial. One of the factors affecting the outcome of
hormone replacement therapy is the undesirable effects of female sex hormones.
The finding that diosgenin has estrogen-like effect
in cardioprotection is encouraging. Further study
should be conducted with the hope to find agents that have the desirable cardioprotective effect of estrogen, but without the
undesirable effects.
Acknowledgement
References
1 王波,陳修.
抗心肌缺血藥實驗方法評述.
藥學通報,
1987 ; 22∶583~5
2 Kam KWL, Qi JS, Chen M and TM Wong. Estrogen reduces cardiac injury and expression of beta1-adrenoceptor upon ischemic insult in the rat heart. J Pharmacol Exp Ther 2004;309: 8-15
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