Indian Journal of Experimental Biology
Vol. 49, April 2011, pp. 282-288
Anti-hyperlipidemic and antioxidant potential of different fractions of Terminalia
arjuna Roxb. bark against PX- 407 induced hyperlipidemia
Department of Pharmacology, PSG College of Pharmacy, Coimbatore 641 004, India
Department of Pharmacology, KMCH College of Pharmacy, Coimbatore 641 048, India
Subasini Uthrapathi, Victor Rajamanickam Gnamanickam & Govinda Prasad Dubey
Department of Pharmacology, Centre for Advanced Research in Indian System of Medicine
SASTRA University, Thanjavur 613 402, India
Received 10 February 2010; revised 12 January 2011
The three fractions diethyl ether, ethyl acetate and ethanol. of T. arjuna exerted hypolipidemic and antioxidative effects at
two different doses levels of 175 and 350 mg/kg body weight in Poloxamer (PX)-407 induced hyperlipidemic albino Wistar
rats. The hypolipidemic and antioxidant effects of T. arjuna fractions were noticed as EtOH>diethyl ether>ethyl acetate. The
results suggest that ethanolic fraction of T. arjuna possesses the potent properties of being antioxidant and hypolipidemic than
other fractions. In turn, it has therapeutic potential for the prevention of coronary arterial disease.
Keywords: Antioxidant, Coronary heart disease, Hyperlipidemia, Poloxamer 407, Terminalia arjuna
Coronary heart disease caused by atherosclerosis
continues to be a leading cause of mortality in
developed and developing nations of the world1.
Hyperlipidemia: the disorders of lipid metabolism
have been ranked as one of the greatest risk factors
contributing to the prevalence and severity of
atherosclerosis, stroke and coronary heart diseases2,3.
Hyperlipidemia is characterized by elevated serum
total cholesterol, low density lipoprotein, very low-
density lipoprotein (LDL, VLDL) cholesterol and
decreased high-density lipoprotein (HDL) levels.
Therefore, the treatment of hyperlipidemia may
reduce the risk of developing ischemic heart disease
or the occurrence of further cardiovascular or
cerebrovascular disease in patients4. Presently existing
hypolipidemic drugs have been associated with a
number of side effects5. The consumption of synthetic
drugs leads to hyperuricemia, diarrhoea, nausea,
myositis, gastric irritation, flushing, dry skin and
abnormal liver function6. The herbal treatment for
hypercholesterolemia has no side effects, relatively
cheap and locally available. They are effective in
reducing the lipid levels in the system7. Although a
variety of in vitro screening test systems for
hypolipidemic agents have been developed, the results
of these experiments do not always match with in vivo
hyperlipidemia in rats is one of the most commonly
used animal models
hypolipidemic property of the drugs8-11.
Terminalia arjuna Roxb. (Family: Combretaceae)
is used in traditional medicine for the treatment of
heart disease12. It has wound healing13, antibacterial14,
constituents of T. arjuna include tannins, triterpenoid
saponins (arjunolic acid, arjunic acid, arjungenin,
arjunglycosides), flavonoids (arjunone, arjunolone,
luteolin), gallic acid, oligomeric proanthocyanidins
(OPCs), polyphenols, calcium, magnesium, zinc and
Anti-dyslipidemic and antioxidant activities of
different fractions of T. arjuna stem bark in Triton
WR-1339 induced hyperlipidemia in rats have been
reported18. In the present study, PX-407 induced
hyperlipidemia has been studied in rats. In PX-407
for the screening of
Cell: +91 - 7708901770
SUBRAMANIAM et al.: ANTI-HYPERLIPIDEMIC ACTIVITY OF TERMINALIA BARK FRACTION
model, the stable lipid profile is maintained up to 30 h
that reaches to normal lipid levels at the end of the 48
h. Whereas, in WR-1339 model, the altered lipid
profiles is maintained up to 16 h and it reaches to
normal lipid levels at the end of 24 h. Although the
mechanism of induction of hyperlipidemia was
identical in both the models, PX-407 model has been
designed to investigate and document the longer
duration of lipid lowering action and free radical
scavenging property of the different fractions of T.
arjuna up to 24 h.
Materials and Methods
Plant materialsT. arjuna supercritical powder was
procured from M/s Elles Pvt Ltd, Chennai and
authenticated by the Department of Botany, Centre for
Advanced Research in Indian System of Medicine
(CARISM), SASTRA University, Thanjavur. A
voucher specimen (No.0066) has been deposited in the
Fractionation of T. arjunaSequential solvent
fractionation method was adapted to fractionating the
T. arjuna bark powder. Supercritical bark powder
(1500 g) was soaked in petroleum ether for 7 days for
defatting purpose. Similarly, in subsequence of every 7
days the fractionation was done with different solvents
from diethyl ether (TA-01), ethyl acetate (TA-02) and
ethanol (TA-03) in the same extract powder as
described by Row et al19. All the fractions were dried
under reduced pressure and the brown colour
precipitate was separated out.
Phytochemical screeningPhytochemical screening
of fractions TA-01, TA-02 and TA-03 was performed
to test the presence of phenolic compounds, tannins,
glycosides, saponins, alkaloids and flavonoids in the
bark of T. arjuna using appropriate tests20.
AnimalsFemale Swiss albino mice (25-30 g) and
male Wistar rats (150–250 g) obtained from National
Animal Facility Centre, SASTRA University,
Thanjavur, were housed individually in poly propylene
cages and kept in a room maintained at an average
temperature (22oC ± 3oC) and 55.6% RH, with 12:12 h
L:D cycle (lights on, 06:30 – 18:30 h) and fed with
standard laboratory diet (Tetragon Pvt.
Bangalore.) and water ad libitum. They were
acclimatized for one week before the start of
experiment. The animals were kept in cages with raised
floors of wide wire mesh to prevent coprophagy. The
study was conducted after obtaining institutional
ethical committee clearance (27/SASTRA/IAEC/RPP).
obtained from M/s BSFA Pvt. LTD, USA. The
biochemical kits for measuring the lipid profiles were
procured from Biosys, Bangalore and Ketamine from
Neo Pharmaceuticals, Bangalore,. All other chemicals
and solvents used in this study were obtained from
Merck, India and were of analytical grade.
Acute oral toxicity studyIn an acute toxicity
study, using the up- and down-procedure, all fractions
were suspended in peanut oil (OECD 425; accepted
vehicle) and administered orally to female Swiss
Albino mice. The mice were approximately 6 weeks
old and weighed 25-30 g. The general procedure was
as follows: one mice was administered with 175
mg/kg body weight and if no mortality or overt
toxicity occurred within 48 h, another mice was
administered with 550 mg/kg body weight. In the
absence of toxicity, a third mice was administered
with 2000 mg/kg body weight and, if again no
evidence of toxicity was observed, two additional
mice were administrated with 2000 mg/kg body
weight level21. In all cases the volume of test drug
was fixed at 10 ml/kg body weight. The mice were
observed for clinical signs of toxicity at 0-0.5, 0.5-1,
1-2, 2-4, and 48 h post dosing (with special attention
during the first 4 h). The body weight of each mice
was recorded prior to administration of test drugs
administration and at 7- and 14-days post dosing.
Once daily the mice were observed for changes in
their skin fur, eyes and mucous membrane (nasal) and
also respiratory rate, circulatory (heart rate and blood
pressure), autonomic (salaivation,
perpiration, piloerection, urinary incontinence and
defecation) and central nervous system (ptosis,
drowsiness, gait, tremors and convulsion) changes.
The blood plasma was collected through retro orbital
sinus (1ml) for the hematological assessments. The
mice were sacrificed by high intravenous dose (22
mg/kg body weight) of ketamine on 14 days post
dosing. The time of death, if any, was recorded.
Necropsy included a gross examination of all the
major organs. Same protocol was adopted for all three
fractions. The study was conducted in compliance
with OECD Test Guideline 425 (Revised: 17
December 2001) and followed OECD GLP principles
reports are interpreted
Selection of dose of the fractionsThe lethal dose
(LD50) of T. arjuna fractions was calculated as
per OECD guidelines for fixing the dose for biological
and chemicalsPoloxamer-407 was
INDIAN J EXP BIOL, APRIL 2011
evaluation. The LD50 of all three fractions of TA (TA-
01, TA-02 and TA-03) falls under class four values
with no signs of acute toxicity at 2000 mg/kg in mice.
For biological evaluation in rats, the mice LD50 dose
was converted into rat dose based on the body surface
area and metabolic rate constant. (FDA Guidelines,
2002). Hence, it was found that 1750 mg/kg and from
which the biological evaluation was carried out at
doses of 175 and 350 mg/kg in rat.
Poloxamer 407 induced hyperlipidemiaRats
were divided into following 10 groups of 6 animals
each group. Group 1: control animals, Group 2:
normal animals received vehicle (vehicle control),
Group 3: PX-407 induced (diseased control)
hyperlipidemic animals received TA-01 (175 and 350
mg/kg), Groups 6 and 7: hyperlipidemic animals
received TA-02 (175 and 350 mg/kg), Groups 8 and
9: hyperlipidemic animals received TA-03 (175 and
350 mg/kg), Groups 10: Hyperlipidemic animals
received atorvastatin (0.4 mg/kg). All three fractions
and atorvastatin were suspended in peanut oil and
administered orally to the respective groups. Groups 2
and 3 were received peanut oil orally. After 18 h of
treatment the animals were anaesthetized with
ketamine (20 mg/kg) and midazolam (5 mg/kg)
through intraperitoneal injection. Blood (1 ml) sample
was withdrawn from retro-orbital sinus puncture and
centrifuged at 2500 g for 10 min at 4oC and separated
serum was stored in –20oC until the completion of
Biochemical analysisAll the samples were used
for following biochemical investigations. The blood
serum under this model has been analyzed for the
marker parameters such as total cholesterol (TC), TC
in (high density lipoprotein) HDL, (low density
lipoprotein) LDL and (very low density lipoprotein)
VLDL as well as TG. The HDL-TC was done by
precipitation method22. All the parameters were
analyzed by semi auto analyzer (GSK-Qualisys,
AK601) with biochemical kit23,24.
Free radical scavenging activityLipid peroxide
(LPO)25: To 300 µl of the serum sample 1.5 ml of 10
% (w/w) triple distilled water was added and was
allowed to stand for 15 min at room temperature. The
tube was centrifuged and to the supernatant 1.5 ml of
TBA solution was added and was heated in a boiling
water bath for 15 min. After cooling to room
temperature, 3 ml of chloroform was added and the
mixture was shaken vigorously for 3 min and
Groups 4 and 5:
centrifuged for 10 min at 1500 rpm. The absorbance
of the chromophore was measured at 532 nm. A
standard curve was constructed used TEP hydrolysed
MDA containing 5-30 µg. The level of lipid peroxide:
the thiobarbituric acid reactive substance (TBARS)
was expressed as nano mole of malonaldehyde per mg
Reduced glutathione (GSH)26: To 200 µl of the
serum 0.4 ml of buffer, 0.2 ml sodium azide, 0.2 ml
EDTA, 0.2 ml of hydrogen peroxide and 0.2 ml of
reduced glutathione was added and made up to a
volume of 2 ml with water. The tubes were incubated
at 37oC for 10 min. TAA (1 ml) was added to
terminate the reaction. The reaction mixture was
centrifuged and with the supernatant, 8 ml of
disodium hydrogen phosphate was added. DTNB (1
ml) was added just prior to the analysis. The
absorbance was read at 412 nm against a blank which
contained only 8 ml phosphate solution and 1 ml
DTNB reagent. A standard graph was constructed
using 20 to 100 µg of reduced glutathione. The
activity was expressed as nmol GSH/mg of protein.
Statistical analysisAll the experimental results
were expressed as mean ± SE. Data were analyzed by
analysis of variance (ANOVA) followed Dunnett’s
test with the level of significance set at P<0.01.
Fractionation and phytochemical investigationThe
yields (g %) of the fractions TA-01, TA-02 and TA-
03 were found to be of 0.42, 0.978 and 24.16%,
respectively. The yield of the ethanol fraction was
much higher (i.e. 24.16%) than the other fractions.
The preliminary phytochemical analysis revealed that
above fractions contained
triterpenoid, saponins, anthraquinone glycosides,
alkaloids and flavonoids.
Acute toxicity studiesThe acute oral toxicological
study didn’t show any deviation from the normal
behaviour of the mice during the entire study period.
So, there were no acute toxicological changes for the
TA-01, TA-02 and TA-03 fractions of TA up to 2000
mg/kg. Hence, the biological evaluation was carried
out at the doses of 175 and 350 mg/kg body weight.
Poloxamer 407 induced hyperlipidemia in rats
Diethyl ether fraction (TA-01)Though decrease
in body weight was observed, it was not significant.
No reference had shown that T. arjuna fractions cause
decrease in the body weight. Plant control group was
required to prove this hypothesis. The drug was able
SUBRAMANIAM et al.: ANTI-HYPERLIPIDEMIC ACTIVITY OF TERMINALIA BARK FRACTION
to decrease the TC and Tg level significantly
(P<0.01). After 12 h analysis, the fraction decreased
the TC and Tg significantly (P<0.01) but less
significant after 24 h of TC level (P<0.05) and Tg
were shown non significant (P>0.05) with disease
control at low dose of 175 mg/kg, whereas in high
dose i.e. 350 mg/kg, both 12 h and 24 h had shown a
significant effect (P<0.01). After 24 h analysis, the
fraction was able to decrease the LDL level by 18.71
and 19.37% and Tg level by 5.08 and 17.75% at 175
and 350 mg/kg body weight dose, respectively. These
results show that the fraction is hypolipidemic in
nature (Table 1). In both the dose levels, HDL has
shown the non-significant change when compared to
the disease control. The hypolipidemic effect of
diethyl ether fraction has already been studied by
WX-133926 and the results indicate that diethyl ether
fraction is able to decrease cholesterol and
Ethyl acetate fraction (TA-02)No abnormal
increase or decrease in body weight was observed
during treatment with TA-02 when compared to the
control groups. The drug was able to decrease the
cholesterol and Tg level significantly (P<0.01). After
12 h analysis, the fraction has decreased TC and Tg
significantly (P<0.01). But less significant after 24 h
of cholesterol level (P<0.05) and triglycerides had
shown non significant (P>0.05) with disease control
at low dose of 175 mg/kg, whereas in high dose i.e.
350 mg/kg, both 12 h and 24 h analysis had shown a
significant effect (P<0.01). After 24 hr analysis, the
drug was able to decrease the level of cholesterol,
LDL, Tg, VLDL and increase the level of HDL at 175
and 350 mg/kg body weight respectively but the lipid
lowering activity was not significant (P>0.05)
(Table 1). The hypolipidemic effect of ethyl acetate
fractions was not yet studied.
Ethanol faction (TA-03)No abnormal increase or
decrease in body weight was observed during
treatment with ethanol fraction when compared to the
control groups. The EtOH fraction was able to
decrease TC and Tg level significantly (P<0.01).
After 12 h analysis, the fraction decreased the total
cholesterol (P<0.01), triglycerides (P<0.01) and HDL
(P<0.05) significantly at low dose of 175 mg/kg,
whereas in high dose i.e. 350 mg/kg, both 12 h and
24 h analysis has shown a significant effect (P<0.01)
in cholesterol, triglycerides and HDL at the doses of
175 and 350 mg/kg body weight respectively. After
24 h analysis, the drug was able to decrease the level
INDIAN J EXP BIOL, APRIL 2011
of cholesterol by 17.52 and 28.3 %, LDL level by
26.16 % and 41.12 % and TGL by 17.07 and 30.01 %
at the doses of 175 and 350 mg/kg body weight,
respectively (Table 1).
Free radical scavenging activity
Lipid peroxide (LPO)Changes in the lipid
peroxide in serum was studied for three fractions at
high dose level. The inhibition of lipid peroxidation
was significant with standard, DE and EtOH fractions
(P<0.01) treated groups, when compared to the
hyperlipidemic control. Non significant effect was
shown by the EA fraction (P>0.05) (Fig. 1a).
Reduced glutathione (GSH)Changes in the
reduced glutathione formation in serum was studied
for three fractions at high dose level. The inhibition of
reduced glutathione was significant in standard
(P<0.01) and EtOH fraction (P<0.05) treated group
when compared to hyperlipidemic control group,
whereas diethyl ether and ethyl acetate groups have
shown the non significant (P>0.05) effect when
compared to the disease control (Fig. 1b).
PX-407 causes these effects by activating HMG-
CoA reductase activity and by inhibiting lipoprotein
lipase activity27,8. PX-407 induced hyperlipidemia is
one of the animal model used for evaluation of
hypolipidemic activity of drugs8-11,28. The PX-407
inducing hyperlipemia model has shown relatively
low species differences between experimental
animals29. Treatment of hyperlipidemic rats with T.
arjuna fractions TA-01, TA-02 and TA-03 at the
doses of 175 and 350 mg/kg po reversed the serum
levels of lipid with varying extents. The order of
lipid lowering activity by these fractions in above
model is: EtOH>diethyl ether>ethyl acetate. The
hypocholesterolemic effect of fractions of TA may be
due to interference with the absorption of dietary
cholesterol as well as bile acids from the intestine30,
increased elimination of faecal sterols31, increased
stimulation of bile acid synthesis may lead to an
increased utilization of cellular free cholesterol32.
Atorvastatin and test fractions of TA are able to
decrease the level of LDL-TC. Thus, the present study
suggests that the herbal product is a potential agent for
reducing or controlling atherogenesis and cholesterol
deposition in body tissues including blood vessels which
are further strengthened by reduction in the levels of
VLDL-TC a precursor of LDL33. Low LDL-cholesterol
could be due to decrease of VLDL-cholesterol synthesis
and secretion from the liver leading to a long term
decrease in LDL concentrations34,35. Lowering elevated
Fig. 1Effect of TA fractions on (a) lipid peroxide and (b) reduced ghitathione [Values are mean ± SE from 6 animals in each group;
Compared treatment groups with diseased control; One way ANOVA (Dunnett: parametric method P values: ns>0.05; *<0.05 **<0.01
SUBRAMANIAM et al.: ANTI-HYPERLIPIDEMIC ACTIVITY OF TERMINALIA BARK FRACTION
levels of LDL cholesterol can retard progression of
Hypertriglyceridemia is a possible risk factor for
the development of ischaemic heart disease. The
atherogenic property of Tg is related to its lipoprotein
transport and metabolism. In hypertriglyceridemia,
one expects a marked reduction in clearance of VLDL
and LDL which are highly atherogenic.
Hypertriglyceridemia is also associated
hypercoagulability due to decreased fibrinolytic
activity38. The results of the present study match well
with reported value of Ghatak et al.39. Here the
hypocholesteolemic effect of TA results from the
increased elimination of cholesterol feces. TA is an
important component of increase in the fecal
excretion of cholesterol and enhances
serum/plasma lecithin cholesterol acyl transferase
(LCAT) activity in addition to accumulation of
receptor mediated catabolism of LDL40.
Hypolipidemic action is mainly due to its anion
exchange property. The hypolipidemic action of
gugulipid is due to its chloride retention and bile acid
sequestration power41. Such distinctive exchange
property is attached here by increase LDL, VLDL, Tg
and increases HDL Level. HDL-cholesterol levels
reported in human studies have been inconsistent with
reports of increases42, no effects43,44 and reductant45,46.
In case of T. arjuna, HDL cholesterol increases in the
The data of the present study have shown that ethyl
acetate, diethyl ether and ethanol fractions of TA have
excreted the lipid lowering activity in vivo. This
suggests that arjunic acid as well as its derivatives
when undergo biotransformation through hepatic drug
metabolizing cascade, produce common active
molecules which may be responsible for lipid
lowering activity in vivo. The quantity of arjunic acid/
arjunoglycoside (I, II, II and IV) in solvent ether
fraction and ethyl acetate is comparatively very less
than those of its derivative in ethanolic fraction and
due to this, at the same doses ethanolic fraction are
more effective than solvent ether and ethyl acetate
In conclusion, the results suggest the effectiveness
of different fractions of T. arjuna as hypolipidemic
and antiatherogenic agent based on its ability to
inhibit LDL atherogenic modifications and lipid
peroxides formation in hyperlipidemic rats. The
flavonoids, tannins and/or phenolic rich fractions
intake in the form of diethyl ether, ethyl acetate and
ethanolic fraction to PX-407 rats, resulted in
beneficial effects on serum lipids, lipoprotein
concentrations and antioxidant activities, and thereby
delayed the onset of atherosclerosis. Moreover, the
ethanolic fraction shows the better effect than the
remaining two fractions. The multi-targeted action of
ethanolic fraction is due to the presence of beta
sitosterol as well as flavones acting on the intestinal
absorption of cholesterol and inhibiting the HMG
CoA reductase enzyme respectively. However, studies
are required in human subjects to prove its clinical
efficacy as a hypolipidemic agent.
The authors are grateful to Prof. R. Sethuraman,
Vice Chancellor, SASTRA University for facilities.
1 Davey Smith G, Cholesterol lowering and mortality: The
importance of considering initial level of risk, Int Med J, 306
2 Grundy S M, Cholesterol and coronary heart disease: A new
era, J Am Med Assoc, 256 (1986) 2849.
3 Saravanan R, Rajendra Prasad N & Pugalandi KV, Effect of
Piper beetle leaf extract on alcoholic toxicity in the rat brain,
J Med Food, 6 (2003) 261.
4 Davey Smith G & Pekkanen J, Should there be a moratorium
on the use of cholesterol lowering drugs?, Br Med J, 304
5 Brown S L, Lowered serum cholesterol and low mood, Br
Med J, 313 (1996) 637.
6 Speight T M & Avery’s, Drug treatment principles and
practice of clinical pharmacology and therapeutics, (ADIS
Press Ltd, Hong Kong) 1987, 599.
7 Berliner J A & Heinecke J W, The role of oxidized
lipoproteins in atherogenesis, Free Radic Biol Med, 20
8 Johnston T P & Palmer W K, Mechanism of Poloxamer 407-
induced hypertriglyceridemia in the rat, Biochem Pharmacol,
9 Palmer W K, Emeson E E & Johnston T P, The poloxamer
407-induced hyperlipidemic atherogenic animal model, Med
Sci Sports Exercise, 29 (1997) 1416.
10 Wasan K M, Subramanian R, Kwong M, Goldberg I J,
Wright T & Johnston T P, Poloxamer-407 mediated
alterations in the activities of enzymes regulating lipid
metabolism in rats, J Pharm Pharmaceut Sci, 6 (2003) 189.
11 Johnston T P, The P-407-induced murine model of dose-
controlled hyperlipidemia and atherosclerosis: A review of
findings to date, J Cardiovas Pharmacol, 43 (2004) 595.
12 Dwivedi S & Jauhari R, Beneficial effects of Terminalia
arjuna in coronary artery disease, Indian Heart J, 49 (1997)
13 Rane M M & Mengi S A, Comparative effect of oral
administration and topical application of alcoholic extract of
Terminalia arjuna bark on incision and excision wounds in
rats, Fitoterapia, 74 (2003) 553.
INDIAN J EXP BIOL, APRIL 2011 Download full-text
14 Perumal Samy R, Ignacimuthu S & Sen A, Screening of 34
Indian medicinal plants for antibacterial properties, J
Ethnopharmacol, 62 (1998) 173.
15 Kaur S, Grover I S & Kumar S, Antimutagenic potential of
extracts isolated from Terminalia arjuna, J Environ Pathol
Toxicol Oncol, 20 (2001) 9.
16 Gupta R, Singhal S, Goyle A & Sharma VN, Antioxidant and
hypocholesterolemic effects of Terminalia arjuna tree-bark
powder: A randomized placebo-controlled trial, J Assoc
Physicians India 49 (2001) 231.
17 Miller A L, Botanical influences on cardiovascular disease,
Altern Med Rev, 3 (1998) 422.
18 Chander R, Singh K, Khanna AK, Kaul S M, Puri A, Saxena
R, Bhatia G, Rizvi F & Rastogi A K, Antidyslipidemic and
antioxidant activities of different fractions of Terminalia
arjuna stem bark, Indian J Clin Biochem, 19 (2004) 141.
19 Row L R, Murti D S, Subba Rao GSR, Sastry C S P & Rao
K V F, Chemical examination of Terminalia species: Part III-
Isolation and structure determination of arjunetin from
Terminalia arjuna species, Indian J Chem, 8 (1970) 772.
20 Kokate C K, Practical pharmacognosy, (Vallabh Prakashan,
New Delhi, India) 1994, 107.
21 Cremer D R, Rabeler R, Roberts A & Lynch B, Safety
evaluation of Alpha-lipoic acid (ALA), Regul Toxicol
Pharmacol, 46 (2006) 29.
22 Allain C C, Poon L S, Chan C S G, Richmond W & Fu P C,
Enzymatic determination of total serum cholesterol, Clinical
Chem, 20 (1974), 470.
23 Foster L B & Dunn R T, Stable reagents for the determination
of serum triglycerides by a colorimetric Hantzch condensation
method, J Clin Chem, 19 (1973) 338.
24 Friedwald R I, Levy & Friedrickson D S, Estimation of
concentration of LDL cholesterol in plasma without
preparation or ultracentrifugation, Clin Chem, 18 (1972) 449.
25 Ohara Y, Peterson T E & Harrison D G, Hypercholesterolemia
increases endothelialm superoxide anion production, J Clin
Invest, 9 (1993) 2546.
26 Rotruck Pope J T A L, Ganther H E, Swanson A B, Hafeman
D G & Hoekstra W G, Selenium: Biochemical role as a
component of glutathione peroxidase, Science, 179 (1973) 588.
27 Wout Z G M, Pec E A, Maggiore J A, Williams R H,
Palicharla P & Johnston TP, Poloxamer-407 mediated changes
in plasma cholesterol and triglyceride following intraperitoneal
injection to rats, J Par Sci Tech, 46 (1992) 192.
28 Johnston T P, Coker J W, Paigen B J & Tawfik O, Sex does
not seem to influence the formation of aortic lesions in the P-
407-induced mouse model
atherosclerosis, J Cardiovas Pharmacol, 39 (2002) 404.
29 Johnston T P, Baker J C, Jamal A S, Hall D, Emeson E E &
Palmer W K, Potential downregulation of HMG- CoA
reductase after prolonged administration of P-407 in C57BL/6
mice, J Cardiovas Pharmacol, 34 (1999) 831.
30 Srinivasan M N & Srinivasan K, Hypocholesteolemic efficacy
of garlic smelling flower Adenocalymma alliaceum in
experimental rats, Indian J Exp Biol, 33 (1995) 64.
31 Subba Rao D, Chandrasekhara N, Satyanarayanan M N &
of hyperlipidemia and
Srinivasan M, Effect of curcumin on serum and liver
cholesterol levels in the rat, J Nutr, 100 (1970) 1307.
32 Godkar P B, Narayanan P & Bhide S V, Hypocholesterolemic
effect of Turmeric extract on Swiss mice, Indian J Pharmacol,
28 (1996) 171.
33 Chatterjee S, Rao A T, Das S N & Agarwal S K,
Antiatherogenic action of “Cardipro”- a herbal proprietary
formulation, Anci Sci life, 20 (2001) 81.
34 Brown M S & Geldstein J L, Lipoprotein receptors in the liver
control signals for plasma cholesterol traffic, J Clin Invest, 72
35 Cara L, Armand M, Bore P, Senft M, Portugal H, Pauli A,
Lafont H & Lairon D, Long-term wheat germ intake
beneficially affects plasma lipids and lipoproteins in
hypercholesterolemic human subjects, J Nutr, 122 (1992) 317.
36 Brensike J F, Levy R I, Kelsey S F, Passamani E R,
Richardson J M, Loh I K, Stone N J, Aldrich R F, Battaglini J
W & Moriarty, Effects of therapy with cholestyramine on
progression of coronary arteriosclerosis: Results of the NHLBI
type II coronary intervention study, Circulation, 69 (1984)
37 Levy R I M, Brenskie J F, Epstein S E, Kelsey S E, Passama E
R, Richardson J M Loh I K, Stone N J, Aldrich R F &
Battaglini J W, The influence of changes in lipid values
induced by cholestyramine and diet on progression of coronary
artery disease: Results of NHLBI Type II Coronary
Intervention Study, Circulation, 69 (1984) 325.
38 Andersen P, Hypercoagulability and reduced fibrinolysis in
hyperlipidemia: Relationship to the metabolic cardiovascular
syndrome, J Cardiovas Pharmacol, 20 (1992) S2.
39 Ghatak A & Asthana
hyperlipoproteinaemias and its pharmacotherapy, Indian J
Pharmacol, 27 (1995)14.
40 Shaila H P & Udupa A L, Hypolipidemic effect of Terminalia
arjuna in cholesterol fed rabbits, Fitoterapia, 68 (1997) 405.
41 Gaur S P S, Ghatak A, Srivastavo J S, Asthan O P, Srimal R C
& Dhawan B N. Comparative study of hypolipidaemic effects
of guargum and gugulipid, J Assoc Physicians, 39 (1991) 137.
42 Ginsberg H N, Barr S L, Gilbert A, Karmally W, Deckelbaum
R, Kaplan K, et al, Reduction of plasma cholesterol levels in
normal men on an American heart association Step 1 diet or a
Step 1 diet with added monounsaturated fat. N Engl J Med,
322 (1990) 574.
43 Dreon D M, Vranizan K M, Krauss R M, Austin M A & Wood
PD, The effects of polyunsaturated fat versus monounsaturated
fat on plasma lipoproteins, JAMA, 263 (1990) 2462.
44 Sharma R D, Raghuram T C & Rao V D, Hypolipidaemic
effect of fenugreek seeds: A clinical study, Phytother Res, 5
45 Phillipson B E, Rothrocj D W, Conner W E, Harris W S &
Illingworth D R, Reduction of plasma lipids, lipoproteins, and
apoproteins by dietary
hypertriglyceridemia, N Engl J Med, 312 (1985) 1210.
46 Mata R, Camacho M, Mendoza S & Cruz M C, Phenylstyrene
from Hintonia latiflora, Phytochemistry, 31 (1992) 3199.
OP, Recent trends in
fish oils in patients with