Phytomedicine, Vol. 6(3), pp.

181-185

Phytomedicine

Urban & Fischer Verlag 1999

http://www.urbanfischer.de/journals/phytomed

Salvadora persica L.: hypolipidemic activity on

experimental hypercholesterolemia in rat
E. M. Galati, M. T. Monforte, A. M. Forestieri, N. Miceli, A. Bade, and A. Trovato
Pharmaco-Biological Department, School of Pharmacy, Messina, Italy

Summary
Stems of Salvadora persica are widely used as tooth cleaning sticks in Arabic countries and decoctions
show hypocholesterolemic properties.
The effects of prolongcd administration of a lyophilized stem decoction of Salvadora persica were
evaluated in diet-induced rat hypercholesterolemia. The preparation was administered for 15 and 30
days (by gavage at a dose of 500 mg/kg in an aqueous vehicle in a volume of 0.5 ml/100 g b.w.). Cholesterol, HDL, LDL and triglyceride plasma levels were assayed. The results showed that the S. persica decoction significantly lowered cholesterol and LDL plasma levels in rats, proving to be more active at 30
days of treatment. The systemic administration of Triton results in a rise in plasma cholesterol and triglyceride levels. The results obtained show that S. persica decoction was inactive at 18 hr after treatment,
whereas at 27 hr, it was able to reduce cholesterol and LDL plasma levels. In all experiments HDL and
triglycerides were unchanged.
Key words: Salvadora persica L., hypocholesterolemic activity, cholesterol, HDL, LDL, triglycerides.

Introduction
Salvadora persica L. is a desert plant which grows from
north-western India to Africa.
Branches and roots of S. persica are widely used as a
tooth cleaning-stick (Abderahim and Jurner, 1983; Attar, 1979), but various other uses of this plant have
been reviewed (Watt, 1962).
There are many references in the literature on its use
in traditional medicine. Salvadora persica is used for
gonorrhoea, spleen disorders, boils, sores, gum disease
and stomachache (Boulos, 1983; Ayensu, 1979; Kokwaro, 1976). The wood, boiled in oil, constitutes a liniment used against contusions (Bellakhdar, 1978). The
bark is used against bites of poisonous animals (Bouquet, 1921). Leaves, roots, bark and flowers contain a
diuretic oil (Ducros, 1930; Ezmirly, 1979).
The leaves are used for cough, asthma, scurvy, rheumatism, as an antiinflammatory and antisyphilitic (Faroogi and Srivastava, 1968; Ezmirly, 1979; Boulos,
1983).

In order to confirm some of the locally reported medicinal properties of S. persica, we investigated a stem
decoction of this species for a number of biological effects. In previous works we observed that the decoction
of S. persica possessed significant protective action
against ethanol and stress-induced ulcers in rats (Galati et al., 1998) and we confirmed the antiulcer activity
of S. persica decoction by optical microscopy (Sanogo
et al., 1998). Moreover, a stem decoction of S. persica
showed hypoglycemic effects, in normal rats an increase in plasma immunoreactive insulin (IRI) and increased oral-glucose tolerance (Trovato et al., 1998).
This plant contains trimethylamine (Farooqi and Srivastava, 1968), related to urea alkaloids (Ray et al.,
1975; Robinson, 1983), sulphur (Cornu and Massot,
1975), organic sulphur compounds (Daxenbichler,
1991, Miller, 1973), ~-sitosterol (Awasthi and Mitra,
1964; Ezmirly et al., 1979), ascorbic acid (Faroogi and
Srivastava, 1968; Kapoor, 1990; Boulos, 1983; Etkin,
0944-7113/99/06/03-181 $ 12.00/0

182

E. M. Galati et al.

1981; Lewis and Elvin-Lewis, 1977; Oliver, 1960),

small amounts of saponins (Von Kampf, 1975; Ezmirly
et al., 1979) and lignan glycosides (Kamel et al., 1992).
Literature data show that some components of S.
persica such as ~-sitosterol and ascorbic acid, show hypocholesterolemic properties (Nagy et al., 1977; Malini and Vanithakumari, 1990).
Therefore it seemed of interest to evaluate the effects
of prolonged administration of a lyophilized decoction
of S. persica on rats with diet-induced hypercholesterolemIa.
In the present study the effects on triton-induced hypercholesterolemia were also recorded. Cholesterol,
HDL, LDL and triglyceride plasma levels were determined.

Materials and methods

Plant material

The stems of Salvadora persica L. were obtained from

Arabic commercial sources. The identity of the plant
was confirmed by bibliographic data (Farooqui and
Srivastava, 1968; Kapoor, 1990; Cronquist, 1981).
Voucher specimens are deposited at the Pharmaco-Biological Department at the University of Messina.
50 g of powdered stems of S. persica were boiled with
500 ml distilled water for 30 min. After filtration, the
decoction was lyophilized. The quantity of lyophilized
powder obtained from 100 g of drug was 9.6 g.
The lyophilized powder was administered, in the
morning, by gavage, at doses of 500 mg/kg, dissolved
in aqueous vehicle, in a volume of 0.5 ml/l00 g of body
weight.
The reproducibility of our experiments was guaranteed by a repetition of the experiment with a second decoction prepared independently from the first one and
the results were analogous.
Animals

Adult male Wistar rats (180-200 g) were used in all experiments. They were maintained in standardized conditions (temperature 22 2C; humidity 60% 4%,
natural lighting) and water was provided ad libitum.
The food intake and growth rates were monitored
during the treatment. The rats were divided into 8
groups of 10 animals each.
At the end of every treatment, the animals were fasted overnight. Blood was collected, in heparinized
tubes, from the carotid artery of rats under light diethyl-ether anaesthesia; the plasma was immediately
centrifuged and kept at -20C until assayed.
Total cholesterol (Allain et al., 1974), HDL (High
Density Lipoproteins), LDL (Low Density Lipoproteins) (Vikari, 1976; Izzo et al., 1981; Grillo et al.,

1981) and triglycerides (Wahlefeld, 1962) were assayed

with colorimetric and enzymatic methods (Boehringer
Mannheim Diagnostica).
Statistical analysis

Data are expressed as mean S.E, of 10 determinations. The results were statistically analyzed by
Student's t-test P < 0.05, versus control was taken as
significant.
Diet-induced hypercholesterolemia in rat

The animals of group I were kept on a standard diet (S.

Morini, Mill rat GLP), whereas the other groups of animals were fed with a hypercholesterolemic diet (cholesteroI2%, sodium cholate 2%, vitamin mixture 2%,
oligoelements 0.2 %, salt mixture 5.8 %, coconut oil
20%, cellulose 4%, sucrose 44%, casein 5%, drakettprotein 15%) supplied by Altromin-Rieper (BolzanoItaly).
Group II was given only the hypercholesterolemic
diet for 30 days (controls); group III, also fed with a hypercholesterolemic diet for 30 days, received lyophylized stem decoction of S. persica, from the 15th to 30th
day, once a day. Blood was collected at the end of treatment (30th day).
In order to verify the eventual protection exercised by
the S. persica decoction against the insurgence of hypercholesterolemia, another group of animals (IV) was
treated with lyophilized decoction simultaneously with
the hypercholesterolemic diet for 30 days. Blood samples for assays were collected after 30 days of treatment.
Triton-induced hypercholesterolemia in rat

The experiments were carried out according to the

method reported by Moss and Dajai (1972).
The animals of the groups V, VI, VII and VIII, fasted
for 18 hours, were injected intraperitoneally with Triton WR-1339 (Isooctylpoly-oxyethilenephenol; Tyloxapol, Sigma-Chemical Co., St. Luis, MO) (100 mg/kg
dissolved in 0.9% NaCl solution).
Lyophilized stem decoction of S. persica (500 mg/kg)
was administered by gavage to the animals of groups
VII and VIII just after the triton injection.
Blood samples were collected 18 and 27 hrs after triton and S. persica decoction administration.

Results and conclusion

The results showed that S. persica decoction, under our
experimental conditions, influenced lipid metabolism.
A hypercholesterolemic diet administered for 30 days
increases serum cholesterol and triglyceride levels. The

Salvadora persica L.: hypolipidemic activity on experimental hypercholesterolemia in rat

183

DHDL mgldl
DLDL mgldl

o triglycerides mgldl
I?J cholesterol mgldl

cholesterol mgldl

trlglycerldes mg/dl

Fig. 1. Cholesterol, HDL, LDL,

triglyceride plasma levels in rat
with diet-induced hypercholesterolemia, after 15 and 30 day-treatment with stem decoction of Salvadora persica L. (500 mg/kg).

Standard diet
Hyperchol. diet
Hyperchol. diet +
S. perslca 15 days
Hyperchol.dlet+
S. perslca 30 days

oral administration of S. persica decoction for 15 days,

significantly reduced cholesterol and DL, respectively
by 10% and 18%.
Treatment with S. persica decoction, administered simultaneously with the hypercholesterolemic diet for 30
days had more marked effects on cholesterol and LDL
(23% and 38%).
In triton-induced hypercholesterolemia, after administration of S. persica decoction, it has to be noted that,
after 18 hr, cholesterol and triglyceride plasma levels
remained unchanged, but were lowered significantly,
27 hr after administration. The percentage reduction of
cholesterol and LDL respectively was 30% and 51 %.
In all experiments HDL and triglyceride concentrations were unchanged.
In rats kept on a hypercholesterolemic diet, hypercholesterolemia is exogenous, thus endogenous cholesterol biosynthesis proceeds at a very low rate to compensate the high serum cholesterol levels introduced by
the diet.
Under these experimental conditions S. persica decoction lowers cholesterol and LDL plasma levels in
both tests (15 and 30 days), proving to be more active
at 30 days of treatment. The results obtained clearly
demonstrate that the decoction has a significant hypocholesterolemic activity and provides a considerable
protection against insurgence of diet-induced hypercholesterolemia (Fig. 1). These effects of S. persica decoction can be due to one or more mechanisms involving inhibition of intestinal absorption of cholesterol,
enhancement of cholesterol degradation and interference with lipoproteins (Moss and Dajai, 1972).

The systemic administration of triton results in a rise

in plasma cholesterol and triglyceride levels (Moss and
Dajai, 1972). This hypercholesterolemia is biphasic. Initially, there is a sharp increase in serum cholesterol levels (Phase I), and the hypercholesterolemia falls off
within the next 24 hrs (Phase II).
The results obtained at 18 hr, show that S. persica decoction was inactive in the anabolic phase (Phase I),
whereas at 27 hr, it was able to reduce cholesterol and
LDL plasma levels in the catabolic phase (Phase II)
(Fig. 2). Therefore we hypothesize that S. persica decoction enhances cholesterol excretion in the form of
bile acids or of other sterols.

standard diet

o triton 27h

216
192
168

o triton S.persica
decoction 27 h

144

:E 120
~ 96

72
48
24

CHOLESTEROL

LDL

27 hours

Fig. 2. Cholesterol and LDL plasma levels in rat with tritoninduced hypercholesterolemia at 27 hrs after administration
of stem decoction of Salvadora persica L. (500 mglkg).
(M S.E.) " P < 0.05 compared to controls; Student's t-test.

184

E. M. Galati et al.
-.- controls
-'500mglkg
-.-Hyperchol. controls

350
300
250

E200
'0",150
100
50
15

30 days

Fig. 3. Effect of daily oral administration of Salvadora persica L. decoction on body weight in rat. (M S.E.) * P < 0.05
compared to controls; Student's t-test.

Chronic administration of S. persica decoction also

caused a significant decrease in mean body weights of
rats, without reduction in food consumption (Fig. 3),
and showed hypoglycemic activity (Trovato et al.,
1997). Therefore we suggest that it might interfere with
the absorption processes from the lumen of the small
intestine.
The absence of a remarkable HOL increase and the
presence of a significative LOL decrease might be related to up-regulation of LOL hepatic receptors which
catabolize LOL (Kovanen, 1981). It was also confirmed by the effect of S. persica decoction on the catabolic phase of triton-induced hypercholesterolemia.
The active principles contained in S. persica probably
interfere simultaneously with several biochemical pathways. Therefore further work is needed to clarify the
mechanisms of these biological actions.
It is well known that LOL plays an important role in
atherogenesis and that hypercholesterolemia is associated with a defect relating to the lack of the LDL receptors. The decrease of cholesterol and LOL plasma
levels exercised by S. persica decoction, demonstrated a
possible protection the insurgence of exogenous hypercholesterolemia and the harm this condition brings
about. In conclusion, the use of this plant, widely
known in Traditional Arabic Medicine, appears particularly recommendable.

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Address
E. M. Galati, Pharmaco-Biological Department, School
of Pharmacy, Vill. SS. Annunziata, 98168 Messina, Italy