PHARMACEUTICAL AND BIOLOGICAL EVALUATIONS

October 2015; vol. 2 (Issue 5): 142-151.

www.onlinepbe.com ISSN 2394-0859

Review Article

Lupeol as a magical drug

Ankita Wal1*, R.S. Srivastava2, Pranay Wal1, Awani Rai1, Shivam Sharma1
1
Pranveer Singh Institute of Technology, Kanpur - Agra - Delhi National Highway - 2, Bhauti, Kanpur, Uttar
Pradesh 209305, India
2
IIT-BHU, Varanasi, India

ABSTRACT
*For correspondence
Dr. Ankita Wal, Lupeol, a triterpene found in white cabbage, green pepper, strawberry,
Assistant Professor olive, mangoes and grapes was reported to possess beneficial effects as a
Pranveer Singh Institute of therapeutic and preventive agent for a range of disorders. Last 15 years
Technology, Kanpur - Agra - have seen tremendous efforts by researchers worldwide to develop this
Delhi National Highway - 2, wonderful molecule for its clinical use for the treatment of variety of
Bhauti, Kanpur, Uttar Pradesh disorders. Natural products and herbal remedies used in traditional
209305, India. folklore medicine have been the source of many medically beneficial
Email:
drugs because they elicit fewer side effects, relatively cheap, affordable
[email protected]
and claimed to be effective. However, in order to make these remedies
acceptable to modern medicine, there is a need to scientifically evaluate
them to identify the active principles and to understand their mechanism
of action. Calotropis gigantea commonly known as milk weed or
swallow-wort, is a medicinal plant widely used as a folk medicine in
India. It exhibits a wide array of pharmacological activities including
wound healing and antimicrobial properties. Lupeol, a pentacyclic
triterpenoid was extracted for the first time from the latex of C. gigantea
and characterized by spectral studies. The presence of lupeol in the latex
in appreciable amounts may account for its various biological activities.
Received: 19 September 2015
Accepted: 27 September 2015 Keywords: Anti-inflammatory, Lupeol, Antibacterial activity, HPTLC,
Plasmodium falciparum, Gallic acid, Antitumar, Calotropis gigantea

Introduction membranes just as cholesterol does in animal

cell membranes.2 Most triterpenes contain 28 or
There is a growing interest in natural 29 carbons and one or two carbon-carbon double
triterpenoids, also known as phytosterols, due to bonds, typically one in the sterol nucleus and
their wide spectrum of biological activities.1 sometimes a second in the alkyl side chain.2
Triterpenes are a wide-spread group of natural Triterpenes are natural components of human
compounds with considerable practical diets. In the West, an average of 250 mg per day
significance which are produced by arrangement of triterpenes, largely derived from vegetable
of squalene epoxide in a chair-chair, chair-boat oils, cereals, fruits and vegetables is consumed.3
arrangement followed by condensation. During the last decade, there has been an
Triterpenes are important structural components unprecedented escalation of interest in
of plant membranes, and free triterpenes serve to triterpenes. Most of this interest has focused on
stabilize phospholipid bilayers in plant cell the cholesterol-lowering properties of

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triterpenes, and evidence of this phenomenon plants has been performed and is summarized
include at least 25 clinical studies, 20 patents in (Table 2).7
and at least 10 major commercially triterpene-
based products currently being sold all around Chemical structure and analysis
the world. It is estimated that well over 2400
subjects have taken part in clinical studies with The chemical structure of lupeol is presented
different types of triterpenes with dosage up to in [Figure 1].6 The chemical formula of Lupeol
25 g or more per day with no adverse effect is C30H50O and its melting point is 215–216 °C.
reported.3 Properties computed from the structure of
Lupeol show that it has a molecular weight of
Source of lupeol 426.7174 [g/mol], H-B donor 1, H-B acceptor 1.
The infra-red spectrum of Lupeol shows the
Lupeol, is found in vegetables such as white presence of a hydroxyl function and an olefinic
cabbage, pepper, cucumber, tomato, in fruits moiety which show their presence in the
such as olive, fig, mango, strawberry, red grapes spectrum at 3235 and 1640 cm-1, respectively.6
and in medicinal plants such as American The presence of seven methyl singlets and an
ginseng, Shea butter plant, Tamarindus indica, olefinic function in the 1H-NMR spectrum
Allanblackia monticola, Himatanthus revealed that Lupeol is pentacylic triterpenoidal
sucuuba,Celastrus paniculatus, Zanthoxylum type in nature.11 Study conducted by
riedelianum, Leptadenia hastata, Crataeva Martelanc et al., using high-performance liquid
nurvala, Bombax ceiba and Sebastiania chromatographic (HPLC) method with UV and
adenophora used by native people in North mass spectrometric (MS) showed that Lupeol
America, Latin America , Japan, China, Africa exhibits a parent ion peak at m/z 409.12
and Caribbean islands.4-10
Quantitation estimation of lupeol
The list of selected plants which have been
reported to possess Lupeol in significant  In U.V - UV spectra of lupeol display the
amounts is presented in (Table 1).6 The max value was found to be 350nm.13
quantification of Lupeol in fruits and medicinal

Figure 1: Chemical structure of lupeol.

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Table 1: List of selected plants containing lupeol.

Table 2: Content of lupeol in fruits and in plants.

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 In I.R - IR spectra of lupeol, a very intensely in various pharmaceutical forms and are being
broad band at 3384 cm-1 and moderately sold in pharmacies and natural product stores.18
intense band at 1192 cm-1 and 672 cm-1 were The development of methods for detection and
observed for the O-H bond vibration of quantitation of an active substance is
hydroxyl group. The out of plane C-H fundamental for quality control of either
vibrations of the unsaturated part was medicinal plants or phytopreparations. Gas
observed at 826 cm-1. The corresponding chromatography (GS) and High Performance
C=C vibration was shown around 1654 cm-1 Thin Layer Chromatography (HPTLC)
was weakly intense band. The stretching and techniques are the most employed methods to
bending vibrations of methyl part were quantitate lupeol in medicinal plants. HPTLC is
noticed by the intence band 2916 cm-1 and cost efficient, flexible and quick. Silica gel 60
medium intensity band at 1460 cm-1.13 F254 is used as the stationary phase; the plate
development can be carried out with a variety of
Natural occurrences solvents system like toluene/methanol (9:1) , n-
hexane/ ethyl acetate (5:1) and lupeol is detected
Lupeol is found in a variety of plants, and quantified by densitometry after reaction
including mango, Acacia visco and Abronia with anisaldehyde- sulfuric acid, Lieberman-
villosa. It is also found in dandelion coffee.14 Burchard reagent or antimony trichloride.19,20
Synthesis
Pharmacological activities of lupeol
The first synthesis of lupeol was reported
by Gilbert Stork et al [15]. In 2009, Surendra Antiprotozoal
and Corey reported a more efficient and
Several of the most severe disease in the world
enantioselective total synthesis of lupeol,
are caused by protozoa and primarily distress
starting from (1E, 5E)-8-[(2S)-3, 3-
developing nation’s populace. Some of these so
dimethyloxiran-2-yl]-2, 6-dimethylocta-1, 5-
called neglected diseases, such as leishmaniasis
dienyl acetate by use of a polycyclization.16
and malaria, persist without effective treatment
Isolation of lupeol either by natural reasons, e.g, resistant strains, or
from industrial disinterest due to economics in
Plant material- The botanically identified plant finding more efficient drugs.21
material of Crataeva nurvala was used.
Based on the traditional knowledge.22 Carried
Method out a photochemical bioassay guided study and
found plumbagin as the main active constituent
C. nurvala stem bark powder was extracted (IC50 5.0 µg/ml) an action of displayed by lupeol
exhaustively with petroleum ether by cold against varied strains of Leishmania and
percolation and the resulting extract was eluted trypanosome species (Table 3).23 Furthermore,
successively with hexane, hexane: benzene and the bioassay guided research of a plant used in
benzene. The benzene elute on concentration the treatment of malaria symptom by a pygmy
deposited a white component lupeol which was tribe from Cameron led to the isolation of an
filtered and recrystallised from methanol: alkaloid rich fraction along with lupeol and its
acetone (60:40).17 derivatives 13,14 and 20 ( Figure 5).23 These last
four compound displayed low individual
Quantitation and detection potencies against two different strains of
plasmodium falciparum (Table-3)23 and the
Currently, the use of medicinal plants is
suggestion of synergic effect among the
massively increasing as a low cost alternative to
metabolites.23 Biological tests aiming for natural
the pricey industrial drugs and due to more
antimalarial agents revealed that lupeol
natural treatment requirements that display
moderates in vitro growth inhibition of
fewer side effects. Therefore, several products
plasmodium falciparum, but lack activity in an
based on plants species are being manufactured

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vivo assay.24 Since then lupeol and related One of the most promising library members was
compounds have been tested by several bioassay on P. falciparaarum NF-54 strain (IC50
scientists against different strains of some of 14.8 µM) and P. berghei and same
protozoa species (Table-3).23 discrepancy between the in vitro and in vivo
activities was observed.25
For example, A 96 member lupeol based library.
Table 3: Antiprotozoal activities of lupeol and its related compounds.

Table 4: Plants containing lupeol with anti-inflammatory use.

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Table 5: Anticancer activity of betulinic acid.

Table 6: Antibacterial activity of lupeol, betulinic acid and betulinaldehyde.

Anti- inflammatory
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Anti- inflammatory 1. Unlimited growth of abnormal cells

2. Self- sufficiency in growth signals
Inflammation is a cascade of biochemical 3. Insensitivity to growth inhibitors
events, involving the local vascular system and 4. Evasion of apoptosis
the immune system, characterized by five basic 5. Sustained angiogenesis
symptoms: rubor (redness), calor (heat), tumor 6. Inflammatory microenvironment
(swelling), dolor (pain), and loss of function. It 7. Eventually tissue invasion and metastasis
happens as a response to either injurious agents
such as chemical irritants, toxins, pathogens, and Antitumor activity began in the 1970 when the
burns.26 The synthesis and release of several cancer chemotherapy national service centre
inflammatory mediators by different types of reported the tumor inhibiting effects of an
defense cells are involved in the process, which extract from Hyptis emoryi containing betulinic
regulated by diverse enzyme. acid as its main constituent.32 Betulin is also a
lupeol analogue isolated from the roots of
In general, the monocytes differentiate into Sarracenia flava, demonstrated antitumor
macrophages that synthesize various signaling activity against human epidermoid carcinoma of
molecules, among them the protein interleukin the nasopharynx while lupeol isolated from the
1β, which triggers a second wave of cytokines same plants displayed antitumor activity against
responsible for the migration of the neutrophils lymphocytic leukemia P-388 cells.33,34
to the injured tissue. Macrophages also produce
reactive intermediates of oxygen such as Shortly after, betulinic acid isolated from
hydrogen peroxide, and nitric oxide, important Vauquelinia corymbosa also demonstrated
agents in edema development.27 The antitumar activity against p-388 cells.35 When
uncontrolled release of many of those signaling the betulinic acid was screened in vitro against a
molecules is the basis for the development of panel of human cancer cell lines, strong
different type of inflammatory diseases like inhibition was show against several human
asthma and arthritis. melanoma lines with ED50 value ranging from 1
to 5 µg/ml.36
Several plants employed in folk medicine to
treat inflammatory symptoms have been show to Antimicrobial
contain lupeol as one of their active principle
First tested against Mycobacterium tuberculosis,
(Table 4),28 corroborating the popular uses.
lupeol did not show any antibacterial activity.
Lupeol decreases the IL-4 (interleukin 4)
Betulinaldehyde and betulinic acid both
production by Th2 cells (T-helper type 2).28
presented minimal inhibitory concentration of
Potent anti-inflammatory activity of lupeol in an 25µg/ml.37 Lupeol and betulinic acid were
allergic airway inflammation model as inactive against three bacterial species but
evidenced by significant reduction in eosinophils revealed MIC of 63 and 16 µg/ml against
infiltration and in Th2 associated cytokines (IL- Enterococcus faecalis.
4, IL-5, IL-13) levels that trigger the immune
Lupeol was also inactive against eight bacteria
response in asthma.29 Lupeol reduced the LPS-
species displaying MIC >200 µg/ml.38 Lupeol
induced IL-6 secretion to 27.6% at a
showed significant zones of inhibition in the
concentration of 1 µM. The topical anti-
culture of 18 strains of the gram negative
inflammatory activity of Pimenta racemosa
bacteria Pseudomonas aeruginosa and
extract containing lupeol was associated with the
Klebsiella pneumonia at a concentration of 30
reduction of neutrophils into the inflamed
µg/100 µl.39 Zone of inhibition were observed in
tissues.30
Pseudomonas aeruginosa, Salmonella typhi and
Antitumor Escherichia coli cultures using lupeol, betulinic
acid, betulinic acid impregnated disks at a
Cancer is a disease recognized by seven concentration of 10 µg/ml.40 While lupeol
hallmarks.31 acetate did not display any activity against gram

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negative bacteria and fungi but displayed a and treatment of cancer. Nat Rev Cancer.
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Phytosterols, phytostanols, and their
Conclusions conjugates in foods: structural diversity,
quantitative analysis, and health-promoting.
Triterpenoid, lupeol (3ˇ-hydroxylup-20(29)- Prog Lipid Res.2002;41:457–500.
ene), is an immense bioactive compound present 4. Beveridge TH, Li TS, Drover JC.
in different medicinal plants. A wide range of Phytosterol content in American ginseng
bioactivities and bioassays of lupeol are seed oil. Food Chem. 2002;50:744–50.
reviewed, which suggest its useful medicinal 5. Alander J, Andersson A. The shea butter
properties with diversity of action against family – the complete emollient range for
different diseases. Natural products have been skin care Formulations. Cos Toil Man
used as remedies to treat human diseases. Worldwide. 2005:28–32.
Lupeol, a phytosterol and triterpene, is widely 6. Imam S, Azhar I, Hasan MM, Ali MS,
found in edible fruits, and vegetables. Extensive Ahmed SW. Two triterpenes lupanone and
research over the last three decades has revealed lupeol isolated and identified from
several important pharmacological activities of Tamarindus indica linn. Pak J Pharm Sci.
lupeol. Various in vitro and preclinical animal 2007;20:125–7.
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as an anti-inflammatory, anti-microbial, anti- Azebaze AG, Alaoui K, Asongalem AE.
protozoal, anti-proliferative, anti-invasive, anti- Anti-oxidative and anti-inflammatory
angiogenic and cholesterol lowering agent. activities of some isolated constituents from
Employing various in vitro and in vivo models, the stem bark of Allanblackia monticola.
lupeol has also been tested for its therapeutic Inflammopharmacology. 2009;17:37–41.
efficiency against conditions including wound 8. De Miranda AL, Silva JR, Rezende CM,
healing, diabetes, cardiovascular disease, kidney Neves JS, Parrini SC, Pinheiro ML. Anti-
disease, and arthritis. Lupeol has been found to inflammatory and analgesic activities of the
be pharmacologically effective in treating latex containing triterpenes from
various diseases under preclinical settings (in Himatanthus sucuuba. Planta Med.
animal models) irrespective of varying routes of 2000;66:284–6.
administration viz. topical, oral, intra-peritoneal 9. Harish BG, Krishna V, Santosh Kumar HS,
and intravenous. It is noteworthy that lupeol has Khadeer Ahamed BM, Sharath R, Kumara
been reported to selectively target diseased and Swamy HM. Wound healing activity and
unhealthy human cells, while sparing normal docking of glycogen-synthase-kinase-3-
and healthy cells. beta-protein with isolated triterpenoid lupeol
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Funding: No funding sources
10. Lima LM, Perazzo FF, Tavares Carvalho
Conflict of interest: None declared
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