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 KongHong 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

 

Introduction

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

LDHU/L

Control group

1ml H2O

8

61.448.56

Low dosage pretreatment group

20mg/ kg

8

40.513.85*

High dosage pretreatment group

40mg/ kg

8

35.356.54*

* 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

0.43130.1

0.3770.05

0.5410.05

Diosgenin

20 mg/kg BW

8

0.51780.79

0.5150.06*

0.6940.057

Diosgenin

40 mg/kg BW

6

0.6110.15

0.5470.087*

0.720.061*

* P0.05 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 ; 225835

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 2004309: 8-15

 


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