PHYTOTHERAPY RESEARCH, VOL. 10,5 17-5 18 ( 1996)

SHORT COMMUNICATION Hypolipidaemic and Antiatherosclerotic Effects of Zingiber oflcinale in Cholesterol Fed Rabbits

Indu Sharma, Deepali Gusain and V. P. DMt* Department of Zoology, University of Rajasthan, Jaipur - 302004, India

Hyperlipidaemic rabbits when challenged with a 50% EtOH extract of Zingiber ofiinule showed a reduction in total cholesterol and serum LDL-cholesterol. A reduction in HDL ratio was seen in atherofed rabbits compared with controls which were restored when challenged with the Zingiber extract. An atherogenic index of 4.7 was brought down to 1.2 using plant products. The tissue lipid profiles of liver, heart and aorta showed similar changes to those noticed in serum lipids. Zingiber extract feeding increased the f a d excretion of cholesterol thus suggesting a modulation of absorption.

Keywords: hyperlipidaemia; atherosclerosis; LDL-cholesterol; Zingber officinale; plaque prevention.

INTRODUCTION

Several epidemiological studies have demonstrated an inverse relationship of high density lipoprotein cholesterol to the incidence of coronary heart disease (Miller and Miller, 1975; Gordon et al., 1977; Gordon, 1985; Castelli et al., 1986). The protective role of HDL - cholesterol in atherogenesis was shown in the Helsinki Heart Study (Frick et al., 1987) emphasizing that an 11% increase in HDL- cholesterol concentration can reduce myocardial infarction by 34%. With increased interest in the prevention of coronary heart disease and the recognition of the role of hyperlipoproteinaemia, it becomes desirable and important to reduce the plasma cholesterol concentration and retard the development of atheroma.

Lipid lowering and lesion regression of Zingiber ofici- nale (rhizome) has already been established as a constituent of Panchcole (an Ayurvedic formulation) (Sharma et al., 1990). The aim of the present study is to investigate the hypolipidaemic and lesion regressive activity of Zingiber oficinale in cholesterol fed rabbits.

MATERIALS AND METHODS

An ethanol extract (50%) of Zingiber oficinale (rhizome) was obtained through soxhelation, the yield was 22% of dry mass.

Adult healthy male rabbits of 1.5-1.75 kg body weight were maintained on control and atherogenic diets as specified in the experimental groups. In addition cholesterol powder along with coconut oil (400 mgkg b.wt) was fed to animals of groups 11-IV (Sharma et al., 1991). Each group comprised five rabbits group I: placebo treated controls (120 days); group 11: atherodiet (60 days); group 111: atherodiet (60 days): atherodiet withdrawn and animals were kept on control diet (days 61-120); group IV atherodiet (60 days);

Author to whom correspondence should be addressed.

treated with Zingiber extract (500 mgkg b.wt oral) from days 61-120. At the termination of experiments the animals were killed. Biochemical analyses of serum, tissues and faeces were done. Surface area studies of aorta were made as detailed earlier (Sharma et al., 1991).

RESULTS AND DISCUSSION

Dietary cholesterol and an atherogenic diet induced a 7-fold increase in the total serum cholesterol and a significant enhancement in the lipid parameters, together with high atherogenic indices and a reduced HDL ratio (Table 1). Natural recovery of atherofed animals showed 23.9% less cholesterol in the blood serum. Atherofed animals under a controlled diet when challenged with Zingiber extract (500 mgkg, b.wt) exhibited a blood serum cholesterol decrease of 79.7%, a net difference of 55.8%. Similar changes were noticed for LDL-cholesterol (natural low- ering, 32%; Zingiber feeding, 84.8%). An increased ratio of total cholesteroYphospholipid (C/P ratio) is attributed to a high incidence of atherosclerosis (Duff and Payne, 1950). Zingiber extract feeding reduced the C/P ratio by 24.7% (Table 1). The cholesterol, triglyceride and phospholipid content of liver and aorta were significantly higher in the atherodiet fed rabbits. Zingiber extract feeding (group IV) reduced this to near normal (Krause et al., 1979) (Table 2).

There are several mechanisms by which plant products may lower cholesterol, phospholipid and triglyceride levels. Increased removal of VLDL by peripheral tissues (Harris et al., 1984) and an increased excretion of bile in the faeces (Balasubramaniam et al., 1985) are examples. Faecal excretion of cholesterol and phospholipid was significantly enhanced after Zingiber extract feeding (Table 1) and is suggestive of the fact that modulation of absorption was affected. Evidence has shown that the fats digested and absorbed in the intestine are transported by chylomicrons. Dietary fats modulate and metabolize the chylomicrons to chylomicron remnants for ultimate removal by the liver

CCC 095 1-4 I 8X/96/0605 17-02 0 1996 by John Wiley & Sons, Ltd. Accepted (revised) 18 June 1995

518 I. SHARMA ET AL.

'IBble 1. Serum and faecal analysis of rabbits at the time of killing Group Total Triglyce- Photpho- VLDL Chol. LDL Chol.

cholesterol ride lipids (mgIdL1

I 100.026.0 52.022.0 120.024.0 10.4i2.0 41.6i3.8 II 710.0i6.5 342.822.8 371.5i3.7 68.6i2.6 481.4i1.5 111 540.0i4.5 284.924.1 296.5i2.6 56.9e0.8 327.1i1.8 %Deviation ( - 123.9 ( - 116.9 ( - 120.2 ( - 117.0 ( - )32.0 IV 143.8i 2.9' 133.32 2.7O 108.9i3.0' 26.620.1' 73.3k0.7' % Deviation ( - 179.7 ( - 161.1 ( - )70.1 ( - 161.2 ( - 184.8

% Deviation in groups 111, IV in comparison with group II. *p<0.001, highly significant, group IV compared with group 111.

HDL Atherogenic Faecal Faecal ratio index cholesterol phospholipid

92.3 1.08 41.421.2 19.920.8 29.9 3.44 66.523.1 30.4i0.4 40.62 2.46 75.1 23.7 39.1 i 1.1

(meld

53.3 1.88 154.0i 1.6. 54.221.01'

(Redgrave, 1970). Surface area studies showed that Table 2. Tissue bidemistry of liver and aorta at the h e of 32.7%-39.8% of the aortic wall was occupied by plaques in killing the atherofed animals (group 11). In contrast 13.5% plaque Group Totalcholesterol Triglyceride Phospholipid was noticed in Zingiber extract fed groups in the thoracic Liver Aorta Liver Aorta Liver Aorta

region Of the reflecting the prevention Of encroach- I 8.420.4 4.120.2 3.120.04 2.2550.1 5.151.3 4.220.5 ment of the aortic lumen (Davis et al., 1987) (Table 3).

(meld

II 30.7i0.5 14.121.3 5.021.2 5.0i1.2 12.01i1.1 6.920.9 Possible mechanisms for regressio~prevention of Plaque 111 25.420.2 11.220.2 5.10i0.9 4.820.9 11.7kO.9 6.820.8

i1.6+i.oa 5.620.1' 5.7i0.02 4.420.08 10.04ii.2 6.8io.2 could be (1). Zingiber extract feeding inhibited the influx of

Cholesterol esters present in the lesions are converted into free cholesterol and are transported by HDL to the liver for catabolism (Small, 1988). 6-Ginger01 a pungent principle increases the secretion of bile as one of its effects on

IV atherogenic lipoproteins (LDL and VLDL cholesterol). (2) ap<O.Ool, highly significant, group IV compared with group 111.

digestive tract functions (Yamahara et al., 1985) and thus is protectant in atheroma.

Table 3. Surface area studies of thoracic and abdominal aorta

I 50.74 2 1.6% 51.522.3% 49.25*1.6% 48.5=2.3%

II 83.1 2 0.7% 79.7~2.3% 16.87i0.7% 20.3 22.3%

111 77.7 20.53% 78.6+3.1% 22.420.4% 21.4i3.09%

IV 63.3 2 6.2% 58.9+1.5%' 36.7 26.2% 41.05 i 1.5%'

*p<0.001, highly significant, group IV compared with group 111.

Group Total wall area Lumen Thoracic Abdominal Thoracic Abdominal

(73.329.9 pm') (54.423.7 pm') (69.9i7.9 pm2) (50.762 1.4 pm')

(387.2213.5 Fm') (127.57213.5 pm') (78.12i1.2 pm') (31.5922.0 pm')

(315.2*35.6 pm') (68.764.8 pm') (90.9i.8 pm') ( 1 7 . 8 ~ 1.5 pm')

(110.6i32.3 pm') (38.323.5 pm') (57.6i9.2 pmZ) (28.5i7.0 pm')

Plaque

Nil Nil Thoracic Abdominal

39.8 i 1.9% 32.7 22.6% (186.32 14.0 pm') (52.927.9 pm')

23.6 2 1.8% 9.9i2.196 (96.82 18.5 pm') (8.7i 1.84 pm')

13.520.756' Nil (23.624.2 pm')

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