A Comprehensive Review on Antihyperlipidemic Activity of Various Medicinal Plants

Abstract

Hyperlipidemia is the greatest hazard factor of coronary heart disease. At present allopathic antihyperlipidemic drugs have been associated with large number of side effects. Herbal treatment for hyperlipidemia has no side effects and is relatively contemptible and locally available. Medicinal plants are the " backbone " of traditional medicine so considered as good source of life for all people due to its wealthy therapeutic properties and being 100% natural. Medicinal plants are extensively used by majority of populations to treat various diseases and have high impact on the world's economy. Traditional therapeutic systems which mainly rely on plants, herbs and shrubs always played a fundamental role in the global health system. Natural products are generally less toxic, have less side effects and easily available so the requirement for herbal drugs is rising. The review article is undertaken to investigate the herbal Plants for antihyperlipidemic activity and various models use in this investigation. This review is specified on the anti-hyperlipidemic activity of the most recognizable therapeutic plants of medicine.

Full text

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International Journal of Current Pharmaceutical Review and Research; 7(6); 407-415
ISSN: 0976 822X
Review Article
*Author for Correspondence: hemabhardwaj7037@gmail.com
A Comprehensive Review on Antihyperlipidemic Activity of Various
Medicinal Plants
Rajesh Asija, Charanjeet Singh, Hemlata*
Maharshi Arvind Institute of Pharmacy, sec-9, Mansarovar, Jaipur, Rajasthan. 302020
Available Online: 25th December, 2016
ABSTRACT
Hyperlipidemia is the greatest hazard factor of coronary heart disease. At present allopathic antihyperlipidemic drugs have
been associated with large number of side effects. Herbal treatment for hyperlipidemia has no side effects and is relatively
contemptible and locally available. Medicinal plants are the “backbone” of traditional medicine so considered as good
source of life for all people due to its wealthy therapeutic properties and being 100% natural. Medicinal plants are
extensively used by majority of populations to treat various diseases and have high impact on the world’s economy.
Traditional therapeutic systems which mainly rely on plants, herbs and shrubs always played a fundamental role in the
global health system. Natural products are generally less toxic, have less side effects and easily available so the requirement
for herbal drugs is rising. The review article is undertaken to investigate the herbal Plants for antihyperlipidemic activity
and various models use in this investigation. This review is specified on the anti- hyperlipidemic activity of the most
recognizable therapeutic plants of medicine.
Keywords: Hyperlipidemia, Medicinal plants, Coronary heart disease.
INTRODUCTION
Hyperlipidemia is a disarray of lipid metabolism produced
by elevation of plasma concentration of the diverse lipid
and lipoprotein fractions, which are the source of cardiac
disease. It is define as increase serum TC, TG, VLDL,
LDL and HDL which are responsible for different
complications like: heart attack, coronary artery syndrome,
stroke, atherosclerosis, myocardial infarction and
pancreatitis. Hyperlipidemia can be either primary or
secondary type, the primary syndrome may be treated by
hypolipidemic drugs, but secondary induced by diabetes,
hypothyroidism or renal lipid nephrosis which treated by
treating the original disease moderately than
hyperlipidemia1.Genetic disorders and lifestyle diet rich in
calories, fat, and cholesterol play a vital role to cause
dyslipidemia around the world2. The main factor which are
responsible for hyperlipidemia includes changes in life
style habits in which risk factor is mainly poor diet i.e. fat
intake greater than 40 percent of total calories, saturated
fat ingestion more than 10 percent of total calories; and
cholesterol ingestion larger than 300 milligrams per day3.
For hyperlipidemia large number of synthetic drugs
available, not a bit is helpful for all lipoprotein disorders,
and each drugs are linked with a number of adverse effects.
Therefore, now a day other materials are search from
natural sources with the intention of less toxic, less
expensive, and provide superior safety and efficacy on a
long term practice. Natural products from plants are a rich
source of medicine used for centuries to treat various
diseases4.
Hyperlipidemia
Hyperlipidemia is a medical state characterized by an
elevation of any or all lipid profile or lipoproteins in the
blood5. The lipid metabolism is synchronized in many
different ways. Enzymes are most important regulators of
lipid metabolism. 3-Hydroxy-3-methylglutaryl coenzyme
A reductase enzyme responsible for cholesterol
biosynthesis6.
While elevated low density lipoprotein cholesterol (LDL)
is thought to be the best gauge of atherosclerosis.
dyslipidemia (abnormal amount of lipids in the blood) can
also express prominent total cholesterol (TC) or
triglycerides (TG), or low levels of high density
lipoprotein cholesterol (HDL5. Hyperlipidemia is a
medical as well as social problem, especially associated
with diabetes mellitus leading to increasing morbidity and
mortality. The chief risk factors of hyperlipidemia are
associated with atherosclerosis which predispose ischemic
heart disease and cerebrovascular disease7.
Many allopathic hypolipidemic drugs like statins are
available in the market, but they cause many side effects
like hyperuricemia, diarrhoea, myositis, hepatotoxicity,
etc. As they are mainly enzyme inhibitors, so they may be
inhibit other grave enzymes in the body. Moreover, statins
are intake on a long-term basis so it cause chronic toxic
effects over a life time use Therefore attention is now
rewarded much to investigate natural hypolipidemic agents
from plant sources8.
Classification of hyperlipidemia
Hyperlipidemia may be classified as either familial (also
called primary) caused by definite genetic abnormalities,
or acquired (also called secondary) that leads to change in

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plasma lipid and lipoprotein metabolism.
Familial (primary): Familial hyperlipidemia are classified
as:
Type I - Raised cholesterol with high triglyceride
Type II - High cholesterol with normal level of triglyceride
Type III - High cholesterol and triglycerides
Type IV - Raised triglycerides, and raised uric acid
Type V - Raised triglycerides
Acquired (secondary)
Acquired hyperlipidemias (also called secondary
dyslipoproteinemias) in which increased risk of
atherosclerosis, when associated with marked
hypertriglyceridemia, may cause pancreatitis and various
complications of the chylomicronemia disease.
Most ordinary causes of acquired hyperlipidemia are:
Diabetes Mellitus (Type 2)
Use of drugs such as diuretics, beta blockers, and estrogens
etc.
Animal models for evaluation of antihyperlipidemic
activity9
High Cholesterol diet induced method
High Fructose diet induced method
Triton induced hyperlipidemic method
Streptozotocin induced diabetic method
Alloxan induced diabetic method
Tylaxapol induced hyperlipidemic method
High fat diet induced hyperlipidemic method
Hydrocortisone induced hyperlipidemic method
Atherogenic diet induced hyperlipidemic method
The other models which can be used10:
Diagnosis3
S.No
Test name
Normal values
Indicators
1
Total
Cholesterol
Total Cholesterol: < 200
mg/dL (desirable) (< 180
optimal)
200-239 mg/dL = Borderline High (borderline
risk for coronary heart disease > 240 mg/Dl
Hypercholesterolemia
2
Total Cholesterol for children
< 180 mg/Dl
> 180 mg/dL may lead to Atherosclerosis
3
Triglyceride Levels
Less than 150 mg/dl
150-199 mg/dL is Border line High 200-499
mg/dL is High 500 mg/dL or above isVery
High.
4
VLDL cholesterol
The VLDL normal range
is between 0–40 mg/dL
and the suggested
optimum range is between
0–30 mg/dL
>40 suggest increase the risk of developing
heart disease
5
C-reactive Protein (CRP)
CRP< 1 mg/dl
CRP> 1mg/dl (> 10mg/dl suggests
inflammation
6
LDL Cholesterol
< 100 mg/dL (optimal)
100-129 mg/dL (near
/above optimal)
130-159Mg/dL Borderline
High 160-189 Mg/dL High ≥190 Mg/dL Very
High
7
HDL Cholesterol
> 60 mg/dl is enviable
HDL levels < 40 Mg/dL increases risk for
CHD. women with levels < 47 mg/dL and men
< 37 mg/dL have increased risk.
Hyperlipoproteinemia
Occurrence
Imperfection
Elevated
Lipoprotein
Symptoms
Appearance of
Serum
Type I
A
B
C
Very rare
Reduce
lipoprotein
lipase
Chylomicrons
Stomach ache,
retinalis, eruptive skin
xanthomas
hepatosplenomegaly
Creamy top
layer
Very rare
Distorted Apo
c2
Very rare
LPL inhibitor
in blood
Type II
A
Less ordinary
LDL receptor
LDL
Xanthelasma, tendon
xanthomas
Apparent
B
Usual
Reduce LDL
receptor &
augmented
Apo B
LDL and
VLDL
Lucid
Type III
Atypical
Imperfection
in Apo E 2
synthesis
IDL
Opaque
Type IV
Average
VLDL
Cloudy
Type V
Ordinary
VLDL and
Chylomicrons
Creamy top
layer

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Medicinal plants with hypolipidemic activity
S. no.
Plant name
Family
Part used
Dose
Models used
Reference
1
Abelomoschu
s esculentus
Malvaceae
Whole
plants
300mg/kg
Tylaxapol induced
method
13
2
Achyranthus
aaspera Linn
Amaranthaceae
Whole
plant
250-500mg/kg
Alloxan induced
method
14
3
Aegle
marmelos
Rutaceae
Leaf
250 mg/kg
Oil fed hyperlipidemic
rat
15
4
Ajuga iva
Labiatea
Whole
plant
10mg/kg
Streptozotocin induced
method
16
5
Allium
sativum
Alliaceae
Fresh
fruits
10mg/kg
TritonX 100 induced
method
17
6
Alpinia
Galangal L.
Zingiberaceae
Rhizome
200& 400mg/kg
Triton induced method
18
7
Alstonia
Scholarin
Apocynaceae
Leaves
100,200,400mg/
kg
Streptozocin induced
diabetic rat
19
8
Amaranthus
Viridis
Amaranthaceae
Leaves
200,400mg/kg
Streptozocin induced
diabetic rat
20
9
Andrographis
paniculata
Acanthaceae
Leaves
25mg/kg
Tyloxapol induced
method
21
10
Anethum
Graveolens
Apiaceae
Essential
oil
45,90,180mg/kg
High cholesterol diet
induced method
22
11
Anogeissus
Latifolia
Combretaceae
Fresh
gum
250,500,750mg/
kg
Atherogenic diet
induced method
23
12
Anthocephalu
s Indicus
Rubiaceae
Roots
500mg/kg
Tyloxapol induced
method
24
13
Apium
Graveolens
Apiaceae
Seed
213,425mg/kg
High cholesterol diet
induced method
25
14
Asparagus
Racemosus
Liliaceae
Roots
150mg/kg
Alloxan induced
method
26
15
Amaranthus
caudatus L.
Amaranthaceae
Leaves
200-400mg/kg
Triton induced method
27
16
Bauhinia
purpurea
Fabaceaae
Leaves &
unripe
fruits
300mg/kg
Tylaxapol induced
method
28
17
Bauhinia
variegate
Linn.
Ceasalpiniaceae
Roots &
Stem
200 &400mg/kg
Triton induced method
29
18
Commiphora
mukul
Burseraceaae
Resin
part
250mg/kg
High fat diet induced
method
30
19
Caesearia
sylvestris
Flacourtiaceae
Leaves
300mg/kg
Streptozocin induced
method
31
20
Capparis
Deciduas
Capparidaceae
Bark,Flo
wer,Fruit
500mg/kg
Streptozocin induced
method
32
21
Capparis
spinosa
Capparidaceae
Fruits
200& 400mg/kg
Tylaxapol induced
method
33
22
Carica
papaya
Caricaceae
Seed,Lea
ves
100-400mg/kg
Alloxan induced
method
34
23
Cassia fistula
Fabaceae
Legume
100,250,500mg/
kg
High cholesterol diet
induced method
35
24
Catharanthus
roseus Linn
Acanthaceae
Leaves
150mg/kg
Streptozocin induced
method
36
25
Celastrus
paniculatus
Celastraceae
Seed
65mg/kg
High fat diet induced
method
37
26
Curcuma
longa
Zingiberaceae
Rhizome
300mg/kg
Streptozocin induced
method
38
27
Cymbopogon
citrates
Graminaceae
Leaves
100&200mg/kg
Dexamethasone
induced method
39

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28
Coccinia
indica
Cucurbitaceae
Leaf
200 mg/kg/b.w
Alloxan induced
method
40
29
Cassia
auriculata
Caesalpiniaceae
Flowers
150,300,450mg/
kg bw
Tylaxapol induced
method
41
30
Cynara
scolymus
Asteraceae
Leaves
150,300,600mg/
kg
Cholesterol diet
induced method
42
31
Eclipta
prostate (L.)
L.
Asteraceae
Leaves
100&200mg/kg
Atherogenic diet
induced method
43
32
Elaeis
guineensis
Arecaceae
Root
250&500mg/kg
Olive oil induced
method
44
33
Eugenia
Jambolana
Myrtaceae
Seed
Kernel
100mg/kg bw
Streptozocin induced
method
45
34
Ficus
racemosa
Linn.
Moraceae
Bark
100-500mg/kg
bw
Alloxan induced
diabetic rat
46
35
Garcinia
cambogia
Guttiferae
Peel of
matured
fruits
400mg/kg
bw/day
High fat diet induced
method
47
36
Glyccyrrhiza
glabra
Fabaceae
Rhizome
250-500mg/kg
High fat diet induced
method
48
37
Gymnena
sylvestre
Asclepiadaceae
Leaf
200mg/kg
High cholesterol diet
induced method
49
38
Hibiscus
rosa sinesis
Malvaceae
Root
500mg/kg/day
Tylaxopol induced
method
50
39
Hibiscus
Sabdariffa
Linn.
Malvaceae
Leaves
&
Calyces
500mg/kg/ day
High cholesterol diet
induced method
51
40
Icacina
senegalensis
Icacinaceae
Root
100,200&
400mg/kg
Alloxan induced
method
52
41
Lagenaria
siceraria
Mol.
Cucurbitaceae
Fruits
200&400mg/kg
bw
Triton induced method
53
42
Luffa
acutangula
Cucurbitaceae
Fruit
200-400mg/kg
Streptozocin along
with nicotinamide
54
43
Lycium
barbarum
solanaceae
Fruits
250&500mg/kg
Alloxan induced
method
55
44
Morinda
Citrifolia
Rubiaceae
Fruits
0.25-1.00g/kg
Streptozocin induced
diabetic rat
56
45
Moringa
oleifera
Moringaceae
Leaf
100mg/kg/ bw
Cadmium exposed rat
57
46
Melothria
Maderaspata
na
Cucurbitaceae
Aerial
parts
100&200mg/kg
b.w
Streptozocin induced
method
58
47
Morus alba
Moraceae
Leaves
30mg/kg
Tylaxopol induced
method
59
48
Morus indica
L.
Moraceae
Leaves
500mg/kg
Streptozocin induced
method
60
49
Mucuna
Prurines
Leguminoseae
Leaves
200mg/kg
Alloxan induced
method
61
50
Nelumbo
Nuficera
Nelumbonaceae
Fruit
100-1000mg/kg
Poloxamer407 induced
method
62
51
Ocimum
basilicum
Lamiacea
Whole
plant
20mg/kg
Streptozocin induced
method
63
52
Ocimum
Tenuiflorum
Lamiaceae
Leaves
250-500mg/kg
Streptozocin+nicotina
mide induced method
64
53
Pipper
longum
Piperaceae
Root
200mg/kg
Streptozocin induced
method
27
54
Psidium
guajava linn
myrtaceae
leaves
200& 400mg/kg
Cholestrol diet induced
method
27

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Hereditary hypercholesterolemia in experimental animals
like rats.
Hereditary hyperlipidemia in rabbits:
Transgenic animals- apoprotein E knock out model
Fructose induced hypertriglyceridemia in laboratory
animals rats
Pathophysiology of hyperlipidemia
The pathophysiology of hyperlipidemia is deliberate
beneath the two basic classifications of hyperlipidemia,
i.e., primary and secondary hyperlipidemia.
Primary hyperlipidemia involve the
hyperchylomicronemia in which defect in lipid
metabolism lead to hypertriglyceridemia and
hyperchylomicronemia cause by a imperfection in
lipoprotein lipase activity or the lack of surface apoprotein
CII. Further, in primary hyperlipidemia, the LDL
cholesterol is elevated.
In secondary hyperlipidemia, absorption of chylomicrons
from the G.I tract within a 30-60 min, after ingestion of a
meal containing fat that may enhance serum triglycerides
for 3-10 hours. The diabetes mellitus patients have been
noted to acquire low LPL activity which caused high
synthesis of VLDL cholesterol by the liver leading to
hyperlipidemia. Moreover, hypothyroidism-induced low
LPL activity and lipolytic activity responsible to reduce
hepatic degradation of cholesterol to bile acids. Moreover,
hyperadrenocorticism enlarged the synthesis of VLDL by
the liver cause hypercholesterolemia and
hypertriglyceridemia. Liver disease hypercholesterolemia
caused by reduced seepage of cholesterol in the bile.
Moreover, in nephritic syndrome, the common pathway
55
Piliastigma
thonningii
Musecea
leaf
50-200mg/kg
Serum lipid profile of
male albino rat
27
57
Peucedanum
pastinacifoliu
m Boiss.
Apiaceae
Aerial
parts
125,250,500mg/
kg
High cholesterol diet
induced method
65
58
Plumeria
rubra L.
Apocynaceae
Fresh
flowers
250mg/kg b.w
Alloxan induced
method
66
59
Pterocarpus
marsupium
Fabaceae
Wood &
bark
150-300mg/kg
Alloxan hydrate
inducde method
27
60
Rosa
laevigata
Michx.
Rosaceae
Fruits
25and50mg/kg
High fat diet induced
method
67
61
Randia
dumetorum
Rubiaceae
Fruit
200-400mg/kg
Streptozocin &
nicotinamide induced
method
68
62
Sphaeranthus
indicus
Asteraceae
Flower
head
500mg/kg/day
Atherogenic diet
induced method
69
63
Sesbania
grandiflora
Fabaceae
Leaves
200mg/kg
Tylaxapol induced
method
70
64
Stevia
rebaudiana
Asteraceae
Leaves
150mg/kg/ bw
Alloxan induced
method
71
65
Salvodora
persica
Salvadoraceae
Root
250-500mg/kg
Streptozocin induced
method
72
66
Spergularia
purpurea
Caryophyllaceae
Whole
plant
10mg/kg
Streptozocin induced
diabetic rat
27
67
Salvadora
oleoides
Salvadoraceae
Aerial
Parts
1g,2g/kg
Alloxan induced
method
73
68
Syzigium
alternifolium
Myrtaceae
Bark
100,200mg/kg
High fat diet
&Dexamethasone
74
69
Terminalia
arjuna
Combretaceae
Bark
10-50mg/kg
High fat diet induced
method
75
70
Terminalia
chebula
Combretaceae
Pericarp
fruit
1.05 ,2.10mg/kg
Atherogenic diet
induced method
76
71
Trianthum
portulacastru
m
Azoaceae
Whole
plant
100,200mg/kg
High fat diet induced
method
77
72
Urtica dioica
Urticaceal
Leaves
50mg/kg
Alloxan induced
method
78
73
Withania
somnifera
Solanaceae
Roots
and Leaf
100,200mg/kg
Alloxan induced
method
79
74
Zingiber
Officinale
Zingiberaceae
Rhizome
500mg/kg
Streptozocin induced
method
80

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for albumin and cholesterol causes low pressure leading to
improved cholesterol synthesis11.
Primary disorders are classified into six categories.
Lipoprotein elevations include the following: I
(chylomicrons), IIa (LDL), IIb (LDL + VLDL), III
(intermediate-density lipoprotein, or HDL); IV (VLDL),
and V (VLDL + chylomicrons). Secondary hyperlipidemia
also be present and various drugs may increase lipid levels
(e.g., progestins, thiazide, glucocorticoids, protease
inhibitors, cyclosporine, mirtazapine,). Primary defect in
hypercholesterolemia is the inability to bind LDL to LDL
receptor (LDL-R) or, a defect of LDL-R complex into the
cell after binding. This leads to lack of LDL deprivation by
cells and unfettered biosynthesis of cholesterol, with total
cholesterol and low density lipoprotein being inversely
proportional to the insufficiency in low density lipoprotein
receptors5.
Etiology/Causes of Hyperlipidemia
Acute intermittent porphyria
Acromegaly
Obesity
Anorexia nervosa
Autoimmune disease
Hypothyroidism and
Cushing’s disease
Hepatitis12
Diabetes mellitus (type 2)
Glucocorticoids
Monoclonal gammopathies
Nephrotic syndrome
Other factors may include medications (eg, beta blockers
and oral contraceptives, thiazide diuretics,
glucocorticoids)3.
Treatment5
Treatment therapy consist of two approaches, which are
Non-pharmacological therapy and Pharmacological
therapy.
Non pharmacological therapy
The aim of non pharmacological therapy is decrease the
ingestion of total fat, saturated fatty acids and cholesterol.
This therapy involves;
Decreased saturated fat intake to 7 percent of daily calories
Decreased total fat intake to 25 to 35 percent of daily
calories
Inadequate dietary cholesterol less than 200 mg per day
Consumption of 20 to 30g of soluble fiber, which is found
in oats, peas, beans, and certain fruits; and Increased
ingestion of plant sterols, substances found in nuts,
vegetable oils, corn and rice, to 2 to 3 g daily. Other foods
that can assist to control cholesterol consist of cold-water
fish, for example mackerel, sardines, and salmon.
Soybeans found in soy nuts and many meat substitutes
restrain a powerful antioxidant that can decrease LDL
level.
Pharmacological therapy
HMG-CoA reductase inhibitors (Statins): Lovastatin,
Simvastatin, Pravastatin, Atorvastin, Rosuvastin.
Bile acid sequestrants (Resins): Cholestyramine,
Colestipol.
Activate lipoprotein lipase (Fibric acid derivatives):
Clofibrate, Gemfibrozil,Benzafibrate and Fenofibrate.
Inhibit lipolysis and triglyceride synthesis: Nicotinic acid.
Others: Ezetimibe, Gugulipid
CONCLUSION
Hyperlipidemia is a crtical condition of elevated lipid
levels in the body that ultimately lead to the development
and progression of various CVDs. The link between
hyperlipidemia and occurance of CVDs has already been
established, the problem of enchanced cholesterol levels in
blood is still prevailing and is being a cause for many
coronary disorders. Studies reveal that an increase in HDL
cholesterol and decrease in TC, LDL cholesterol and TG is
associated with a decrease in the risk of ischemic heart
diseases.Though many drugs are available to treat
Hyperlipidemia. The antihyperlipidaemic activity of plants
plays an important role in the reduction of CVD. Plant
parts or plant extract are sometimes even more potent than
known hypolipidemic drugs. Currently used
hypolipidemic drugs are associated with so many adverse
effects and withdrawal is associated with rebound
phenomenon which is not seen with herbal preparations.
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