Indian J.Pharm.Biol.Res.

2013;1(4):152-167

CODEN (USA): IJPB07 ISSN: 2320-9267

Indian Journal of Pharmaceutical and Biological Research (IJPBR)
Journal homepage: www.ijpbr.in

Review Article

Nelumbo Nucifera (Lotus): A Review on Ethanobotany,

Phytochemistry and Pharmacology
Nishkruti R Mehta*, Ekta P Patel, Pragnesh V Patani, Biren Shah

Arihant School of Pharmacy & Bio-Research Institute, Adalaj, Gandhinagar, Gujarat, India.

ARTICLE INFO: ABSTRACT

Article history:
Received: 30 October 2013 Nelumbo nucifera Gaertn (Nymphaeaceae), a perennial aquatic plant, has been used as a
Received in revised form: medicinal herb in China and India. It has been recorded in the most famous medicinal book in
8November 2013 China for more than 400 years. Different part of plant (leaves, seeds, flower, and rhizome)
Accepted: 18 November 2013 can be used in traditional system of medicine. In traditional system of medicine, the different
Available online 7 December 2013 parts of plant is reported to possess beneficial effects as in for the treatment of
Keywords: pharyngopathy, pectoralgia, spermatorrhoea, leucoderma, smallpox, dysentery, cough,
Ethanobotany Nelumbo haematemesis, epistaxis, haemoptysis, haematuria, metrorrhagia, hyperlipidaemia, fever,
nucifera Pharmacological cholera, hepatopathy and hyperdipsia. Following the traditional claims for the use of
activities Phytoprinciples N.nucifera as cure of numerous diseases considerable efforts have been made by researchers
Traditional uses to verify it’s utility through scientific pharmacological screenings. The pharmacological
studies have shown that N.nucifera posseses various notable pharmacological activities like
amti-ischemic, antioxidant, anticancer, antiviral, antiobesity, lipolytic, hypocholestemic,
antipyretic, hepatoprotective, hypoglycaemic, antidiarrhoeal, antifungal, antibacterial, anti-
inflammatory and diuretic activities. A wide variety of phytoprinciples have been isolated
from the plant. The present review is an effort to consolidate traditional, ethnobotanic,
phytochemical and pharmacological information available on N.nucifera.

1. Introduction

Nelumbo nucifera, now placed in the mono-generic family species, requiring plenty of space and full sun in order to thrive. It
Nymphaeaceae, has numerous common names (e.g. Indian lotus, has stout, creeping, yellow rhizomes and green fruits. Leaves are
Chinese water lily and sacred lotus) and synonyms (Nelumbium large, of both types, aerial as well as floating orbicular 20-90 cm.
nelumbo, N. speciosa, N. speciosum and Nymphaea nelumbo)[1]. in diameter, abruptly acute to form a short tip, petiolate, entire
Worldwide, there are only two species of Nelumbo: N. lutea glaucous, non-wettable, strong cupped in case of aerial leaves and
Willd. (synonyms: N. pentapetala (Walter) Fernald and flat in case of floating ones. Fruit is an aggregate of indehiscent
Nelumbium luteum Willd.) and N. nucifera (synonyms: N. nut-lets. Ripe nutlets are ovoid, roundish or oblongish upto 1.0
speciosa Willd, Nelumbium speciosum Willd, Nelumbium N. cm long 1.5 cm broad, with hard smooth, brownish or grayish
Druce and Nymphaea N. L)[2,3]. N. nucifera Gaertn., the Indian black pericarp which is faintly longitudinally striated,
or sacred lotus, is found throughout Asia and Australia, whereas pedunculated and one seeded. Seeds fill in the ripe carpel
N. lutea, the American lotus or water chinquapin, occurs in [6].There are two varieties of ‘kamala’: one has white flowers and
eastern and southern North America[4]. N. lutea is considered to is commonly called ‘pundarika’ or ‘sveta kamala’; the other has
be a subspecies of N. nucifera[5]. In India, N. nucifera, commonly pink or reddish-pink flowers and is called ‘rakta kamala’[7]. The
known as lotus, kamala or padma, is an aquatic whole plant with flowers is known as ‘padmini’, the rhizomes as

Corresponding Author: Nishkruti R Mehta, Arihant School of Pharmacy & Bio-Research Institute, Adalaj, Gandhinagar,
Gujarat, India. E-Mail: nishkrutimehta@yahoo.com
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‘kamalkand’, the tender leaves as ‘sambartika’, the peduncle as ‘padmakosa’, the seed as‘karnika’ or ‘padmaksya’, and the honey
‘mrinal’ or ‘visa’, the stamens as ‘kirijalaka’, the torus as formed in the flowers by the bees feeding
upon padma is known as ‘makaranda’ or ‘padma- Madhu’[8]. The
sepals, petals and stamens are spirally arranged, passing gradually
one into another [9]. The plant is often cultivated for its elegant contained in the plumule (l3 g per plumule) and cotyledons (164 g
sweet scented flowers, which are the national flower of India. The per cotyledon) of N.nucifera; the amount of total plumule
present review is a comphrensive account of traditional uses and increases gradually in the maturing seed. The reduced form of
ethnobotonacial, phytochemical and pharmacological glutathione is dominant in the early stages, while the amount of
investigations carried out on the plant, which may explain the oxidised form exceeds that of the reduced form at the end of
multifaceted role of this medicinal herb. maturation. The amount of the reduced form of glutathione in the
unripe fruit decreases markedly upon storage for l year. In
1.2 Uses described in traditional medicine general, the rate of germination of the stored seeds seems to be
closely related to the content of reduced glutathione[21,22].
Plants have been used as source of medicine by mankind since Normally, lotus seeds are rich in protein, amino acids, unsaturated
ancient times. The indigenous knowledge of many tradition fatty acids and minerals[23]. Nelumbo seeds have also been found
communities has been formulated, been documented and to contain a variety of minerals such as chromium (0.0042%),
eventually become organized systems of medicine such as sodium (1.00%), potassium (28.5%), calcium (22.10%),
ayurveda, siddha, unani, and other systems out of India. In magnesium (9.20%), copper (0.0463%), zinc (0.0840%),
Ayurveda this plant is used as a diuretic and anthelmintic and in manganese (0.356%) and iron (0.1990%). Other relevant
the treatment of strangury, vomiting, leprosy, skin diseases and nutritional elements include total ash (4.50%), moisture (10.50%),
nervous exhaustion[1,10,11]. In popular medicine it is used in the crude carbohydrate (1.93%), crude fibre (10.60%), fat (72.17%),
treatment of tissue inflammation, cancer, skin diseases, leprosy and protein (2.70%); its energy value is 348.45 cal per 100 g.[24]
and as a poison antidote[12,13]. Rhizomes are prescribed as The major secondary metabolites present in the seeds (Figure 1)
demulcents for haemorrhoids and are beneficial in dysentery, are alkaloids such as dauricine (1), lotusine (2), nuci-ferine (3),
chronic dyspepsia, and have nutritive, diuretic and cholagogue pronuciferine (4), liensinine (5), isoliensinine (6), roemerine (7),
activities[14,15]. The stem is used in indigenous Ayurvedic neferine (8) and armepavine (9).[25,26,27,28,29,20,30,31] Procyanidin
medicine as a diuretic, anthelmintic, to treat strangury, vomiting, (10) was isolated from the seedpod of N. nucifera. [19] Seeds also
leprosy, skin disease and nervous exhaustion. The leaves are used contain gallic acid (11), D(–)-3 0- bromo-O-methyl-
for the treatment of haematemesis, epistaxis, haemoptysis, armepavine(12) D–1,2,3,4-tetrahydro-6-methoxy-1-(p-methox
haematuria, metrorrhagia and hyperlipidaemia[16]. The flowers benzly) -2-methyl-7-isoquino- linol (13), saponins and
are useful in the treatment of diarrhoea, cholera, fever and gastric carbohydrates[34]. The seed polysaccharides have also been
[12]
ulcers. The seeds and fruits are used as a health food in Asia isolated and characterized. Acid hydrolysis and methylation
and to treat many ailments, including poor digestion, enteritis, showed that seed polysaccharides are mainly composed of four
chronic diarrhoea, insomnia, palpitations, spermatorrhoea, types of monosaccharide: D-galactose, L arabinose, D-mannose
leucorrhoea, dermatopathy, halitosis, menorrhagia, leprosy, tissue and D-glucose[32]. 13C-NMR and insource pyrolysis–mass
inflammation, cancer, fever and heart complaints, and as an spectrometry analysis showed that the fruit wall and seed coat of
antiemetic, poisoning antidote, diuretic and N. nucifera are composed of a complex of polysaccharides, based
refrigerant[12,17,8,18]. Lotus seedpods are sometimes used as a primarily on galactose and mannose units and insoluble tannins.
traditional medicine for haemostatic function [19]. The seed Curie-point pyrolysis–gas chromatography–mass spectrometry
powder mixed with honey is useful in treating cough [10]. analysis of the fruit walland seed coat of Nelumbo produced some
Embryos of lotus seed are used in traditional Chinese medicine to pyrolysis polysaccharide products, including 2-furaldehyde, 2-
overcome nervous disorders, insomnia, high fevers (with hydroxy methyl furan ,(SH)- furan-2-one, 2,3-dihydro-5-
restlessness) and cardiovascular diseases (e.g. hypertension, methylfuran-2-one, 2-hydroxy-3- methyl-2-cyclo penten-l-one, 5-
arrhythmia)[20]. hydroxymethyl-2-furaldehyde, anhydrosugar(levogalactosan),
1,2benzenediol 4-methyl-1, 2-benzenediol,1,6-anhydro-a –D-
1.3 Chemical constituents glucopyranose, 2,6-dimethoxy 4- ethnylphenol and 4-carboxy-2-
methoxyphenol[33].

A wide variety of chemical constituents are isolated from various

parts of N.nucifera. The structures of major chemical constituents II.Leaves
of plant are shown in figure.
Combined gas/liquid chromatography–mass spectroscopy has
I. Fruits and seeds shown that the leaves are rich in a number of alkaloids. In the
analysis of non-phenolic fractions of the leaf extract (Figure 2),
The seeds of N. nucifera are rich in asparagin, fat, protein, starch the major components had retention data and mass spectra
and tannin[22]. The lotus seed is composed of three parts – identical to those of nuciferine, roemerine, anonaine (14),
integuments, plumule and cotyledons, which comprise 3.74%, pronuciferine and N-nornuciferine (15). Two benzylisoquinoline
3.03% and 93.23% of the mass, respectively. The average weight alkaloids, (+)-1(R)-coclaurine (16) and (–)-1(S)-norcoclaurine
of 100 seeds is 87.35 g. A large amount of glutathione is (17), were also found in leaf extract of N. nucifera[21]. Six non-
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phenolic bases were identified: roemerine, nuciferine, ano-
naine,pronuciferine, N-nornuciferine and liriodenine(18) and two

glucopyranoside (41), kaempferol 3-O-a-L-rhamnopyranosyl-( 1-

phenolic bases, armepavine and N-methyl-coclaurine (19), were 6)-β -D-glucopyranoside (42), kaempferol 3-O-a-L-
also found in N. nucifera leaf extract.[36] Dehydro- emerine (20), rhamnopyranosyl-(1-2)- β -D-glucopyranoside (43), kaempferol
dehydronuciferine (21), dehydroanonaine (22), N- 3-Oa-L-rhamnopyranosyl -(1-2)- β- D-glucurono-pyranoside (44),
methylisococlaurine (23), anonaine, pronuciferine, N- kaempferol-3- O- β- D-glucurono-pyranoside (45), kaempferol 3-
nornuciferine, O-nornuciferine (24), nuciferine, remerine (25), O-β-D-glucuronopyranosyl methylester (46), myricetin 3 0 ,5 0 -
roemerine, armepavine, liensinine, isoliensinine, negferine, dimethylether 3-O- β -D-glucopyranoside (47), quercetin 3-O- β -
asimilobine (26) and lirinidine (27) were isolated from leaves and D-glucopyranoside(48),nelumborosideA(49)and
petioles[38,35,37,39,40]. The leaves also contain a glycoside, nelumboroside B (50). It also contains two isorhamnetin
nelumboside (28), and flavonoids such as quercetin (29) and glycosides: isorhamnetin 3-O-β-D-glucopyranoside (51) and
leuco-anthocyanidin which were identified as leucocyanidin (30) isorhamnetin 3-O-a-L-rhamnopyranosyl- (1→6) -β -D-gluco-
and leucodelphinidin (31)[37,42]. The presence of some other pyranoside (52)[44,45,46]. Some non-flavonoid compounds,
flavonoids in the leaves such as quercetin 3-O-a- including adenine, myo-inositol, arbutin (53) and β-sitosterol
arabinopyranosyl-(1!2)-β-galactopyranoside, quercetin-3-O-β-D- glucopyranoside (54), have also been identified in stamen
glucuronide (32), rutin (33),(+)-catechin (34),hyperoside (35), extract[46].
isoquer-citri (36) and astragalin (37) has also been
reported[38,41]. Scanning electron microscopy and chemical IV.Rhizomes
analysis of the chloroform extract of leaves showed that the wax
was composed of a mixture of aliphatic compounds, principally The rhizomes of lotus are consumed as a vegetable in Asian
nonacosanol and nonacosanediols. Analysis of gas countries. They are used as health foods because of their mineral
chromatography spectra of lotus leaves waxes showed a much content. Abundant starch grains are present throughout the tissue.
lower proportion of the secondary alcohol nonacosan-10-ol Fresh rhizome contains 31.2% starch, which shows no
(16.2%by weight) compared with nonacosanediols (64.7%). Gas characteristic taste or odour. The binding and disintegration
chromatographic analysis of the extracted leaf waxes revealed properties of isolated Nelumbo starch have been compared with
nonacosan-10-ol (16.2 ± 1.1%), triacontan-7-ol (2.4 ± 0.4%), maize and potato starch; Nelumbo starch was found to be superior
nonacosane-4, 10-diol (18.6 ± 0.5%), nonacosine -5, 10-diol (34.1 as an adjuvant in the preparation of tablets. It has been reported
± 1.9%), nonacosane-10, 13-diol (12.0 ± 0.7%), hentriacontane- that 50% (v/v) alcohol is required for maximum extraction of the
12, 15-diol (1.8 ± 0.0%), tritriacontane-9, 10-diol (0.7 ± 0.0%) constituents[48]. The methanol extract of the rhizome has been
and octadecanoic acid (0.7 ± 0.0)[43]. found to possess a steroidal triterpenoid – betulinic acid [49].
Fresh rhizome contains 83.80% water, 0.11% fat, 1.56% reducing
III. Flower sugar, 0.41% sucrose, 2.70% crude protein, 9.25% starch, 0.80%
fibre, l.10% ash and 0.06% calcium. The vitamins thiamine (0.22
Several flavonoids have been identified in the stamens of mg/100 g), riboflavin (0.6 mg/100 g), niacin (2.10 mg/100 g) and
N.nucifera (Figure 3). These include kaempferol (38) and seven ascorbic acid (1.5 mg/100 g) and an asparagine-like amino acid
of its glycosides: kaempferol 3-O- β -D-galactopyranoside (39), (2%) are also present in the rhizomes. The oxalate content of
kaempferol 3-O-β-D-glucopyranoside (40), kaempferol 7-O-β -D- rhizome was found to be 84.3 mg/100 g[47].
Fruit and seed

L .iensinine (5): R1=R2= H; R3=CH3

Isoliensinine (6): R1=R3= H; R2=CH3
Neferine(8):R1=H; R2=R3=CH3

Dauricine

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lotusine
Nuciferine (3) – R1=R2=R3=CH3
N-Nornuciferine (15) – R1=R2=CH3; R3=H
O-Nornuciferine (24) – R1=H; R2=R3=CH3

Pronuciferine Roemerine (7)

Armepavine(9)
Gallic acid (11)

Leaves

Anonaine (14)
Procyanidin (10)

D(–)-3’-bromo-O-methyl-armepavine (12)
Coclaurine (16): R1 = CH3
Norcoclaurine (17): R1 = H
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D-1,2,3,4-tetrahydro-6-methoxy-1- Liriodenine (18)

(p-methoxybenzly)-2-methyl-7-isoquinolinol (13)

Dehydroemerine (20): R1=R2=CH2; R3=CH3

Dehydronuciferine (21): R1=R2=R3=CH3
Dehydroanonaine (22): R1+R2=CH2; R3=H

Nelumboside (28)

Remerine (25)
Quercetin-3-O-β-D-glucuronide (32)

N-methyl-coclaurine (19): R1 = R3 = CH3; R2 = H

N-methylisococlaurine (23): R1 = H; R2 = R3 = CH3
Asimilobine (26): R1 = H
Lirinidine (27): R1 = CH3

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Quercetin (29)
Rutin (33)

Leucocyanidin (30): R1 = H
Leucodelphinidin (31): R1 = OH
Hyperoside (35)

(+)-Catechin (34)
Isoquercitrin (36)

Astragalin (37)

Flower

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Kaempferol (38): R1 = R2 = H
Kaempferol 3-O-β-D-galactopyranoside (39): R1 = Gal; R2 =
H
Kaempferol 3-O-β-D-glucopyranoside (40): R1 = Glc; R2 = H
Kaempferol 7-O-β-D-glucopyranoside (41): R1 = H; R2 = Glc
Kaempferol 3-O-β-L-rhamnopyranosyl-(1,6)- β-D-
glucopyranoside (42): R1 = Rha-(1®6)-Glc; R2 = H
Kaempferol 3-O-β-L-rhamnopyranosyl-(1→2)- β-D-
glucopyranoside (43): R1 = Rha-(1→2)-Glc; R2 = H
Kaempferol 3-O-β-L-rhamnopyranosyl-(1→2)- β-D-
glucuronopyranoside (44): R1 = Rha-(1→2)- Gln; R2 = H
Kaempferol 3-O-α-D-glucuronopyranoside (45): R1 = Gln;
R2 = H
Kaempferol 3-O-α-D-glucuronopyranosyl
Methylester (46): R1 = Gln-Me; R2 = H

Arbutin (53)

Myricetin3’,5’-dimethylether 3-O-β- D glucopyranoside (47)

Nelumboroside A (49): R1 = H Quercetin 3-O-β-D-glucopyranoside (48): R1 = Gln

Nelumboroside B (50): R1 = Rha

Isorhamnetin 3-O-β-D-glucopyranoside(51): R1 = Glc β-sitosterol glucopyranoside (54)

Isorhamnetin 3-O-β-L-rhamnopyranosyl- (1→6)-β-D-gluco
pyranoside (52): R1 = Rha-(16)-Glc

Rhizomes

Betulinic acid (55)

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2. Pharmacological activities III. Hepatoprotective activity

N.nucifera has been screened scientifically for various An ethanolic extract of the seed of N.nucifera was studied for
pharmacological activities like anti-ischaemic activity, hepatoprotective effects in carbon tetrachloride and aflatoxin B1-
antioxidant activity, hepatoprotective activity, anti-inflammatory induced hepatotoxicity models. Cell death caused by carbon
activity, anti-fertility activity, anti-arrhythmic activity, anti- tetrachloride was significantly inhibited in a dose-dependent
fibrosis activity, antiviral activity, antiproliferative activity, anti- manner by the ethanolic extract at concentrations between 10 and
diarrhoeal activity, psychopharmacological activity, diuretic 500 mg/ml. The same extract reduced the genotoxicity of
activity, antioxidant activity, antipyretic activity, aflatoxin B1, showing complete inhibition at a concentration of
immunomodulatory activity, hypoglycaemic activity, aldose 250 mg per plate[51].
reductase inhibitory activity, antibacterial, aphrodisiac activity,
antiplatellet activity, cardiovascular activity, anti-obesity activity, IV. Anti-inflammatory activity
lipolytic activity, hypocholesterolaemic activity, hepatoprotective
activity, anticancer activity. The seed extract of N. Nucifera, at a dose of 10 mg/kg, inhibited
the production of pro-inflammatory cytokine tumour necrosis
2.1Seeds factor-a (TNF-a) and increased anti-inflammatory cytokine IL-10
I. Anti-ischaemic activity in female BALB/c mice with systemic inflammation induced by
an intraperitoneal injection of lipopolysaccharide (LPS)[52].
The seed of N. nucifera shows potent anti-ischaemic effects in the Studies in LPS-challenged mice showed that a high dose of 20
isolated rat heart. The effective amount of seed extract against mg/day of seed extract significantly decreased TNF-a levels in
ischaemia induced in the isolated rat heart was assessed by the serum and significantly increased the levels of IL-10
measuring cardiac output, blood pressure, aortic flow and produced by peritoneal macrophages. This result demonstrated
coronary flow; doses of 0.1–30 mg/ml were tested. Maximal that administration of the N.nucifera seed extract before systemic
recovery was seen at a dose of 10 mg/ml, although cardiac output inflammation attenuates acute inflammation in vivo[52].
was similar after treatment with 3 or 10 mg/ml doses (63.5 ± 3.2
and 65.8 ± 4.0 ml/min, respectively). Thus, the 3 mg/ml dose was V. Anti-fertility activity
determined to be the optimum dose for anti-ischaemic effects in
the rat. N.nucifera extract has distinct anti-ischemic effects Chauhan et al evaluated the effect of Nelumbo nucifera Gaertn.
through calcium antagonism[50]. (Nymphaeaceae) on male reproductive function and fertility, 50%
ethanolic extract of its seeds was administered orally to male rats
at the dose levels of 50, 100 and 200 mg/rat per day for 60 days.
II. Antioxidant activity The body weights were not affected, whereas the weights of
reproductive organs decreased significantly after this treatment.
The ethanol extract of the seed has been evaluated for its
Significant suppression of cauda epididymal sperm count and
antioxidant activity using the 2,2-diphenyl-1picrylhydrazyl
motility was observed. Fertility was decreased in this treatment
(DPPH) free radical assay. Potent free radical scavenging effects
by 100% in Nelumbo nucifera-treated rats. The testosterone level
were seen, with a median inhibition concentration (IC50) of 6.49
of serum was declined significantly.Thus the ethanolic extract of
mg/ml[51]. Procyanidin and condensed tannin isolated from the
seed pod of N. nucifera have several pharmacological activities, N.nucifera seed was antispermatogenic effect in male rats. [53] The
including lipid auto-oxidation, lipoxygenase inhibition and free 50% ethanol extract of N.nucifera seed has been reported to
radical scavenging comparable to butylated hydroxytoluene possess anti-fertility activity in inbred Wistar strain cyclic female
(0.1%). At a concentration of 62.5 mg/ml, procyanidin inhibited albino rats– at a dose of 800 mg/kg. oral administration of
lipoxygenase activity by more than 90%, with an IC50 value of N.nucifera extract brought about a significant decline in the
21.6 mg/ml[19]. Furthermore, the antioxidant activity of the weight of Ovary; Control (43±4.75mg), N.nucifera extract treated
hydroalcoholic extract of seed has been reported using the DPPH (25±3.86mg), Uterus; Control (236±0.004mg), N.nucifera extract
and nitric oxide methods[34]. The hydroalcoholic extract treated (214±0.007mg) and Vagina; Control (221±0.002mg),
exhibited strong free radical scavenging activity, with IC50 values N.nucifera extract treated (178±0.003mg). In addition, the
of 6.12 ± 0.41 mg/ml in the DPPH assay and 84.86 ± 3.56 mg/ml diestrous phase of the estrous cycle was found to be prolonged;
in the nitric oxide assay. These values were lower than those of Control (1.81±0.21) days, N.nucifera extract treated (3.62±0.42)
rutin, a standard free radical scavenger. Administration of the days. N.nucifera extract has the anti-estrogenic nature without
hydroalcoholic extract of seed to Wistar rats at 100 and 200 altering the general physiology of the female rats[54].
mg/kg for 4 days before carbon tetrachloride treatment caused
significant dose-dependent increases in the levels of superoxide VI. Anti-arrhythmic activity
dismutase (SOD) and catalase, and a significant decrease in the
Neferine, an alkaloid isolated from the seed embryo of N.
level of thiobarbituric acid reactive substances. These changes
nucifera, has been reported to have anti-arrhythmic effects on
observed at 100 mg/kg were comparable to those observed with
rabbit sinoatrial nodes and clusters of cultured cardiac myocytes
vitamin E at 50 mg/kg[34].

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from neonatal rats[55,56]. Neferine inhibits the slow HeLa cells. The antiviral actions of NNFR is therefore likely to
transmembrane Na+ and/or Ca2+ current of the myocardium, be mediated through inhibition of immediate early transcripts,
which leads to its anti-arrhythmic action[55,56]. Neferine causes such as infected cell protein (ICP) 0 and ICP4 mRNA and then
non-specific inhibition of the Na +, Ca2+ and K+ cardiac blocking the downstream accumulation of all viral products[61].
transmembrane currents in guinea-pig papillary muscles and atria,
which relates to its anti-arrhythmic activity[27]. Experiments in IX. Antiproliferative activity
anaesthetised cats showed that neferine, when administered
intravenously, at concentrations of 1–10 mg/kg dose-dependently The ethanolic extract of N. nucifera seed suppressed cell cycle
decreased the amplitude and prolonged the duration of the progression, cytokine gene expression and cell proliferation in
monophasic action potential, decreased left ventricular pressure human peripheral blood mononuclear cells (PBMC). To study the
and prolonged the sinus cycle length. These effects demonstrated effects on PBMC proliferation, resting cells or cells activated with
that neferine has similar electromechanical properties in the heart phytohaemaglutinin (PHA) were treated with 100 mg/ml of an
as quinidine[57]. Liensinine is another alkaloid isolated from the ethanolic extract of N. nucifera seed[13]. Cell proliferation was
seed of the lotus which has been reported to have anti-arrhythmic determined on the basis of uptake of tritiated thymidine. PBMC
proliferation was not affected by DMSO treatment. Ciclosporin
effect; its mechanism may be related to blockade of Ca 2+ and Na+
blocked PHA-activated PBMC proliferation. Ethanolic extract of N.
influx. Intravenous liensinine at dose 3 mg/kg temporarily
nucifera seed (100 mg/ml) significantly suppressed PBMC
inhibited all parameters of haemodynamics in anaesthetised and
proliferation stimulated with PHA. The ethanol extract of N.
pithed rats. Its effects were slightly stronger than those of
quinidine (3 mg/kg); the inhibitory effects of liensinine (12 Nucifera suppressed proliferation in PHA-activated PBMC. The
mg/kg) on all haemodynamic parameters were comparable to stimulated cell cycle progression in PHA-activated PBMC was
those of verapamil (1 mg/kg). The haemodynamic effects of significantly arrested at G0/G1 stage, and gene expression and
liensinine may be similar to verapamil but different from production of interleukin(IL)-2, IL-4, IL-10, interferon gamma (IFN-
g) and cyclin-dependent kinase 4 in activated PBMC were also
quinidine.[58] Liensinine at 10–100 mM was shown to
decreased by N. nucifera extract[13]. Liu and co-workers have
concentration-dependently decrease the amplitude of the action
potential. The effects of liensinine on slow action potentials and isolated (S)-armepavine (C19H23O3N; molecular weight 313) from N.
slow inward currents have also have been studied and suggest that nucifera seed extract. (S)-Armepavine inhibited the proliferation of
liensinine possesses calcium antagonistic effects[59]. human PBMCs activated with PHA and gene expression of IL-2 and
IFN-g without direct cytotoxicity, which leads to the improvement of
VII. Anti-fibrosis activity autoimmune diseases in MRL/MpJ-lpr/lpr mice[29]. The mechanism
involved in these inhibitions is blockade of membrane-proximal
The inhibitory effect of isoliensinine isolated from the seeds of effectors such as IL-2- inducible T cell kinase and phospholipase C g
N.nucifera was studied on bleomycin-induced pulmonary fibrosis in in a phosphatidylinositol 3-kinase-dependent manner[63]. An
mice.[60] Administration of isoliensinine remarkably suppressed the isoliensinine alkaloid isolated from the seed embryo had inhibitory
increase in hydroxyproline content and abated the lung tissue injury effects on the proliferation of porcine coronary arterial smooth
induced by bleomycin. It enhanced SOD activity and decreased the muscle cells induced by angiotensin II. Its mechanisms were
malondialdehyde level in a concentration-dependent manner. investigated by counting cultured cell number, the MTT assay,
Moreover, isoliensinine significantly inhibited the over-expression of immunohistochemistry and Western blotting. Angiotensin II (0.1
TNF-α and transforming growth factor- β (TGF- β) induced by mM) significantly evoked
bleomycin. These results indicated that isoliensinine possesses cell proliferation by 42%, which could be dosedependently
significant inhibitory activity against bleomycin -induced pulmonary inhibited by 0.01–3 mM isoliensinine; the percentage of
fibrosis, probably due to its inhibition of isoliensinine was 25% at 0.01 mM. These results
antioxidant and/or anti-inflammatory activities and inhibitory suggest that isoliensinine possesses antiproliferative effect, which
effect on TNF-a and TGF-b induced by bleomycin.[60] is related to a decrease in the over-expression of platelet-derived
growth factor, basic fibroblast growth factor and proto-oncogenes
VIII. Antiviral activity c-fos, c-myc and hsp70[63]. The effect of neferine on platelet
aggregation, thromboxane A2/prostaglandin (PG) I2 and
Ethanol extract of the N.nucifera seed (100 mg/ml) significantly cAMP/cGMP balance were studied using turbidimetry and
suppressed replication of herpes simplex virus-1 (HSV-1), with an radioimmunoassay. It significantly inhibits rabbit platelet
IC50 of 50 mg/ml. Furthermore, a sub-fraction of N. Nucifera aggregation induced by ADP, collagen, arachidonic acid and
(NNFR) has an inhibitory effect on HSV-1. NNFR at a platelet-activating factor with IC50 values of 16, 22, 193 and 103
concentration of 50 mg/ml inhibited HSV-1 replication in HeLa mM, respectively. Neferine was found to increase vascular 6-
cells by up to 85.9%, attenuating aciclovir-resistant HSV-1 keto-PGF1a and platelet cAMP levels in a dose-dependent
propagation.[61] In a bioassay-guided fractionation, NNFR manner, but inhibited arachidonic acid-stimulated thromboxane
significantly blocked HSV-1 multiplication in HeLa cells without A2 release from platelets[64].
apparent cytotoxicity. The production and mRNA transcription of
infected cell protein was found to be decreased in NNFR-treated X. Immunomodulatory

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The immunomodulatory activity of N.nucifera seed extract was IV. Diuretic activity
evaluated using various in vivo models including the total and
differential leukocyte count (TLC and DLC), nitroblue- The diuretic activity of N. nucifera rhizome was reported. The
tetrazolium reduction (NBT) test, neutrophil adhesion test, methanol extract of the rhizome induced significant diuresis in
phagocytic response and delayed type hypersensitivity (DTH) rats at doses of 300, 400 and 500 mg/kg. There was a dose-
reaction. Sheep red blood cells (SRBC, 5×109 cells/ml) were used dependent increase in the volume of urine, with Na + and Cl-
to immunize the animals. N.nucifera seed extract at the doses of excretion, accompanied by a significant excretion of K +. The
100 and 300 mg/kg was administrated. A dose-dependent increase in volume of urine was less than with the standard
potentiation of DTH reaction induced by SRBC was observed diuretic Furosemide (20 mg/kg). There was a significant increase
from the extracts. The percentage of neutrophil adhesion to the in natriuretic and chloruretic activity but kaliuresis was less than
nylon fiber was increased in rhizome extract treated groups (54.86 natriuresis[70].
and 54.23%).The extract of seeds of N. nucifera altered the total
and differential WBCs count, potentiated the effect on DTH V. Anti-inflammatory activity
response and phygocytosis. Thus extract of seed of N. nucifera
stimulate defense system by modulating several immunological The anti-inflammatory activity of the methanol extract of
parameters[65]. N.nucifera rhizome as well as of betulinic acid, a steroidal
triterpenoid isolated from it, were evaluated on carrageenin and
2.2 Rhizomes serotonin induced rat paw oedema[49]. The rhizome extract at
I. Antidiarrhoeal activity doses of 200 and 400 mg/kg, and betulinic acid at doses of 50 and
100 mg/kg (administered orally) showed significant anti-
The antidiarrhoeal potential of N. nucifera rhizome extract has inflammatory activity; the effect was comparable to that of the
been reported. A study was undertaken to evaluate the effects of standard drugs phenylbutazone and dexamethasone[49].
methanolic extract of rhizomes of N.nucifera Gaertn for its
antidiarrhoeal potential against several experimental models of VI. Antioxidant activity
diarrhoea in rats. The extract produced significant inhibitory
effects against castor-oil-induced diarrhoea and PGE2-induced Yang and coworkers have performed in-vitro studies of the
enteropooling; the propulsive movements of a charcoal meal were antioxidant activity of methanol and acetone extracts of the N.
also reduced significantly[66]. nucifera rhizome using the DPPH assay.[71] The methanol and
acetone extract showed highest DPPH scavenging activity, at 66.7
and 133.3 mg/l, respectively; the methanol extract exhibited a
higher antioxidant activity coefficient than ascorbic acid. The
rhizome knot also exhibited radical scavenging activity, measured
spectrophotometrically and by electron spin resonance[72].
 II. Hypoglycaemic activity
The oral hypoglycaemic effect of N. nucifera was demonstrated
using an methanolic extract of the rhizome, which markedly
reduced the blood sugar level of normal, glucose-fed
hyperglycaemic and streptozotocin-induced diabetic rats, when VII. Antipyretic activity
compared with control animals. The extract (300 mg/kg and 600
mg/kg, orally) caused a reduction of blood glucose levels in The methanolic extract of N. nucifera rhizome showed antipyretic
streptozotocin-induced diabetic rats by 53% (p<0.001) and 55% activity in rats with yeast-induced pyrexia. Yeast suspension (10
(p<0.001) respectively at the end of 12 h. The results of this study ml/kg, s.c.) increased rectal temperature after 19 hr of
indicate that the methanol extract of the rhizome possesses administration. Oral doses of the extract of 200, 300 and 400
favourable hypoglycaemic activity in hyperglycaemic animals mg/kg produced significant dose-dependent lowering of normal
taking chlorpropamide as a standard[67]. An anti-diabetic body temperature and yeast-provoked elevation of body
constituent (tryptophan) has been isolated from the nodes of lotus temperature in rats. The result was comparable to that of the
rhizome by the analysis of spectroscopic evidence.[ 68] In glucose- standard antipyretic drug paracetamol (150 mg/kg
fed hypoglycaemic mice, the methanolic extract of nodes at a intraperitoneally)[47].
dose of 400 mg/kg and 100 mg/kg of isolated tryptophan showed
potential anti-diabetic activities[68]. VIII. Immunomodulatory activity

III. Psychopharmacological activity The immunomodulatory activity of N.nucifera rhizome extract

was evaluated using various in vivo models including the total
The methanol extract of the rhizome of N. nucifera produced and differential leukocyte count (TLC and DLC), nitroblue-
significant psychopharmacological actions in rats and mice. tetrazolium reduction (NBT) test, neutrophil adhesion test,
Reduction in spontaneous activity and a decrease in exploratory phagocytic response and delayed type hypersensitivity (DTH)
behaviour in the head dip and Y-maze tests were reported. Thus, reaction. Sheep red blood cells (SRBC, 5×109 cells/ml) were
the extract possesses most of the pharmacological characteristics used to immunize the animals. Rhizome extract at the doses of
of a minor tranquilizer[69]. 100 and 300 mg/kg was administrated. The TLC and lymphocyte

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count increased significantly but the neutrophil count was in both models at oral doses of 200 and 400 mg/kg. The stalk
decreased for rhizome extract treated groups compared to the extracts showed dose-dependent lowering of body temperature up
control. A dose-dependent potentiation of DTH reaction induced to 4 h; the results were comparable to those with paracetamol[75].
by SRBC was observed from the extracts. The percentage of
neutrophil adhesion to the nylon fiber was increased in rhizome IV. Aldose reductase inhibitory activity
extract treated groups (63.22 and 62.91%). This finding suggests
that the extract of rhizome of N. nucifera stimulate defense Two glycosides, namely kaempferol 3-O-a-L-rhamnopyranosyl-
system by modulating several immunological parameters[65]. (1,6)-_-D-glucopyranoside and isorhamnetin 3-O-a-
Lrhamnopyranosyl-( 1!6)-_-D-glucopyranoside, isolated from the
2.3 Flower methanol extract of stamens of N. nucifera exhibited a high
I. Hypoglycaemic activity degree of inhibitory activity against rat lens aldose reductase in
vitro, with IC50 values of 5.6 and 9.0 mM, respectively[46].
Sun-dried flower powder of N.nucifera, as well as the aqueous
and alcoholic extract of the flower, produced significant V. Antibacterial Activity
hypoglycaemia in fasting normal albino rabbits. There was no
significant difference in the activities of 1000 mg/kg of the test The hydroethanolic extract of flowers of N.nucifera Gaertn in
drug (sun-dried powder of the flower) and equivalent amounts of vitro was reported to possess antibacterial activity. The
the extracts. Glucose tolerance studies with normal rabbits antibacterial activity was screened against different bacterial
showed that oral doses of both extracts, equivalent to 1000 mg/kg strains like Escherichia coli Klebsiella pneumonia Pseudomonas
of the test drug, produced significant depression of the peak rise aeruginosa Bacillus Subtilis Staphylococcus aureus by detecting
in fasting blood sugar after glucose load; the effects of both zone of inhibition and minimum inhibitory concentration (MIC).
extracts were 50% to that produced by 250 mg/kg of tolbutamide. The maximum zone of inhibition was exhibited by N.nucifera
A study of glucose tolerance curves shows that the duration of flowers against Escherichia coli (14mm), Bacillus Subtilis
hyperglycaemia was also notably reduced compared with the (13mm) and Staphylococcus aureus (11mm). The moderate zone
controls. In normal rabbits, the extract at a dose of 1000 mg/kg of inhibition was found against Klebsiella pneumonia (10mm)
significantly lowered hyperglycaemia induced by subcutaneous and Pseudomonas aeruginosa (8mm). Gram-negative bacteria
injection of 0.5 mg/kg adrenaline hydrochloride[73]. were more susceptible to the N.nucifera flower extracts than
gram-positive bacteria which contradict the previous reports that
II. Antioxidant activity plant extracts are more active against gram-positive bacteria than
gram-negative bacteria. These results were compared with the
The potential of N. nucifera stamens to scavenge 1,1-diphenyl-2- standard antibiotic chloramphenicol (30µg/ml)[76].
picrylhydrazyl (DPPH) free radicals and peroxynitrites (ONOO–),
and the inhibition of total ROS generation by kidney homogenates VI. Aphrodisiac activity
using 2v,7’-dichlorodihydrofluorescein diacetate (DCHF-DA)
was examined[44].The methanol extract showed strong Adult wister albino rats were used for aphrodisiac activity
antioxidant activity in the ONOO– system and marginal activity protocol. Sexual behavioural parameters were observed on wister
in the DPPH and total ROS systems. Similarly, seven known albino rats. Blood samples were collected from control and
flavonoids were isolated from lotus stamens, most of which also experimental rats to measure hormone testosterone. Testosterone
showed potent antioxidant activity[44]. The glycosides levels showed significant increase in experimental animal
nelumboroside A, nelumboroside B, isorhamnetin glycoside and compared with control. The test drug may be effective as
isorhamnetin rutinoside isolated from N. nucifera stamens showed aphrodisiac through mechanisms such as vasodilation, generation
potent antioxidant activity in DPPH and ONOO– assays. [45] of nitric oxide, elevation of androgens and gonadotropins.
‘Yunyupju’, a liquor made from the blossoms and leaves of lotus, Stamens of N. nucifera white variety uniformly suspended in 2%
has been reported to have antioxidant activity. The maximum Carboxy Methyl Cellulose (CMC) in water (Test drug) to obtain
scavenging activity on hydroxyl radicals (40%) could be achieved 100mg/ml concentration as stock solution has definite positive
when lotus liquor was more than 500 μg. Lotus liquor also has a effect on male sexual behaviour and increased in hormone profile.
potent superoxide radical scavenging activity with value of 0.93 The test drug at 500mg/kg body weight, both Mount frequency
(MF) and Intromission frequency (IF) were increased (P<0.01)
unit mg−1 as superoxide dismutase equivalents with an IC50 value
compared to the 2% CMC in saline-administered control and
of 1.07 ± 0.04 mg[74].
body weight also significantly increased. Sildenafil citrate was
used as standard. The MF of the test drug treated animals was
III. Antipyretic activity
remarkably altered and it was statistically significant.
The ethanol extract of stalks of N. nucifera was evaluated for its Administration of single dose of test drug at 500mg/kg body
antipyretic potential on normal body temperature and yeast weight the EF increased significantly (P<0.01). Test drug at the
induced pyrexia in rats. In the model of yeast provoked elevation dose of 500mg/kg body weight could be used as a stimulator of
of body temperature, the stalk extract showed significant activity sexual behaviour in male rats and also indicates the profound

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increase in improvement of sperm health and possesses anti-obesity effect using mice with obesity induced by a high-fat
aphrodisiac activity[77]. diet. The extract showed a concentration- dependent inhibition of
the activities of a-amylase and lipase, and up-regulated lipid
VII. Antiplatellet activity metabolism and expression of uncoupling protein-3 mRNA in
C2C12 (mouse myoblast cell line) myotubes. It also prevented
The antiplatelet activity of hydroethanolic extract of N.Nucifera increases in body weight, parametrical adipose tissue weight and
flowers using platelet-rich plasma in different concentrations (100 liver triacylglycerol levels[80].
500μg/ ml) was reported. N.nucifera flower extracts showed dose-
dependent effective antiplatelet activity with maximum activity at V. Lipolytic activity
500μg/ml concentration; prevention of platelet aggregation was
50% of that achieved with standard aspirin[78]. A 50% ethanol extract of N. nucifera leaves was reported to
stimulate lipolysis in the white adipose tissue of mice.
2.4 Leaves Chromatographic analysis of the extract showed that the
phytomolecules responsible for lipolytic activity included
I. Cardiovascular activity quercetin-3-O-a-arabinopyranosyl-(1→2)-β-galactopyranoside,
catechin, hyperoside, isoquercitrin and astragalin[41].
Two alkaloids that act as serotonin antagonists, namely
asimilobine and lirinidine, were isolated from the leaves of VI. Hypocholesterolaemic activity
N.nucifera. Both alkaloids inhibited serotonin-induced
contractions in isolated rabbit aorta (10 -6)[40]. The aqueous extract of N.nucifera leaves was studied for its
effects on serum lipids in a rat model. The rats were fed a high-fat
II. Antioxidant activity diet containing 1.5% cholesterol and 1% cholic acid. Subsequent
oral treatment with a crude aqueous extract of lotus leaves
Hydrogen peroxide-mediated cytotoxicity in Caco-2 cells was resulted in sharp decreases in serum total cholesterol, free
used to investigate the potential antioxidant activity of the cholesterol and phospholipids compared with the highfat- loaded
methanol extract from the N.nucifera leaf[79]. A dose-dependent control group[16]. The effect of N.nucifera leaf extract for the
protective effect against reactive oxygen species (ROS)- induced improvement of lipid metabolisms and the alleviation of liver
cytotoxicity was observed when Caco-2 cells were treated with damage in high fat diet treatment was studied in hamster model.
10 mM hydrogen peroxide in combination with the methanol The effects of flavonoid-enriched N. nucifera leaf extract
extract of the N.nucifera leaf (0.1–0.3 mg/ml). The N.nucifera supplement and two lipid-lowing drugs; silymarin and
extract also exhibited concentration-dependent antioxidant simvastatin, on the disorders induced by high fat diet were
activities against haemoglobin-induced linoleic acid peroxidation investigated. Flavonoid-enriched N.nucifera leaf extract
and Fenton reaction-mediated plasmid DNA oxidation[79]. supplement may significantly improve the high fat diet-induced
abnormal blood lipids and liver damage as significantly as the
common drugs[81].
III. Antiviral activity
VII.
The 95% ethanol extract of N.nucifera has been reported to show
anti-HIV activity (EC50 < 20 mg/ml). Some anti-HIV principles, An ethanolic extract of the leaves of N. nucifera was studied
including (+)-1(R)-coclaurine, (–)-1(S)-norcoclaurine and for its hepatoprotective activity against CCl4-induced liver
quercetin 3-O-_-D-glucuronide, were found in N. nucifera toxicity in rat. It was reported that the hepatoprotective
activity of N.nucifera leaf extract (LLE) at doses of 300 and
leaves.[38] Both (+)-1(R)-coclaurine and (–)-1(S)-norcoclaurine
500 mg/kg was comparable with that of a standard treatment
showed potent anti-HIV activity, with EC50 values of 0.8 and < comprising 100 mg/kg of silymarin[82].
0.8 mg/ml, respectively, and therapeutic index values above 125
and 25, respectively, whereas quercetin 3-O-_-D-glucuronide was
Hepatoprotective Activity
less potent (EC50 2 mg/ml). Other potent anti-HIV
bisbenzylisoquinoline alkaloids such as nuciferine, liensinine, VIII.
Methanol and acetone leaf extracts were used for anticancer
negferine and isoliensinine have also been isolated from the
activity by MTT assay. About 6.25 μg/mL to 100 μg/mL of
leaves of N. nucifera, with EC50 values below 0.8 mg/ml and sample was used for MTT assay. Methanol leaf extract showed
therapeutic index values of 36, > 9.9, > 8.6 and > 6.5, 27% and acetone leaf extract showed 7% in 100 μg/mL of
respectively[38]. MCF-7 breast cancer cell line. Both extracts showed less
anticancer activity against breast cancer. According to Weng
et al. (2009), armepavine (Arm, C19H23O3N), an active
compound from N. nucifera, has been shown to exert
immunosuppressive effects in

163

Anticancer Activity
IV. Anti-obesity activity

Ono et al reported the effects of leaf extract on digestive

enzymes, lipid metabolism and theromogenesis, together with the

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 Nishkruti R Mehta et al. / Indian J. Pharm. Biol. Res., 2013;1(4):152-167

in vitro. Arm (1-10 μM) concentration dependently attenuated al., 2009). Arm also suppressed TNF-α-induced collagen
TNF-α- and LPSstimulated α-SMA protein expression and AP-1 deposition, NFκB activation and MAPK (p38, ERK1/2 and JNK)
activation by HSC-T6 cells without adverse cytotoxicity (Weng et phosphorylation[83].

Activity Part of plant used Reference(s)

Aldose reductase inhibitory Flower [46]
Anti-arrhythmic Seed [55-57], [58, 59]
Anti- bacterial Flower [76]
Anticancer Leaves [83]
Anti-diarrhoeal Rhizome [66]
Anti-fertility Seed [54]
Anti-fibrosis Seed [60]
Anti-ischaemic Seed [50]
Anti-inflammatory Seed, Rhizome [52, 49]
Anti-obesity Leaves [80]
Antioxidant Leaves, Flower, Rhizome [79, 44, 45, 74,
71,72]
Antiplatellet Flower [78]
Anti-proliferative Seed [63,64]
Antipyretic activity Flower, Rhizome [75, 47]
Antiviral Seed, Leaves [61, 38]
Aphrodisiac Flower [77]
Cardiovascular activity Leaves [40]
Diuretic activity Rhizome [70]
Hepatoprotective Seed, Leaves [82]
Hypocholesterolaemic Leaves [81]
Hypoglycaemic Flowers, Rhizome [73, 68]
Immunomodulatory Seed, Rhizome [65]
Lipolytic Leaves [41]
Psychopharmacological Rhizome [69]

3. Conclusion studies on N.nucifera should be designed to investigate the

molecular mechanism(s) of action of isolated phytoprinciples
The pharmacological investigations carried on N.nucifera have using specific biological screening models and clinical trials, and
demonstrated that it’s various organic and aqueous extracts also to discover novel leads from them. Also studies should be
possess an array of multidimensional pharmacological activities extended to standardize the various extracts of N.nucifera for the
such as anti-ischaemic, antioxidant, hepatoprotective, anti- purpose of their use in specific herbal formulations. The data
inflammatory, anti-fertility, anti-arrhythmic, anti-fibrosis, presented here, emphasize the potential of tradition medicine
antiviral, antiproliferative, antidiarrhoeal, hypoglycaemic, Nelumbo nucifera.
psychopharmacological, diuretic, antipyretic, immunomodulatory,
aldose reductase inhibitory, antibacterial, aphrodisiac, Declaration of interest
antiplatellet, cardiovascular, , anti-obesity, lipolytic,
hypocholesterolaemic, anticancer activities. The plant is also The authors report no conflict of interest. The authors, alone are
reported to contain a wide range of chemical constituents. These responsible for the content and writing of the paper.
compounds could serve as leads in the search for novel medicinial
agents. With the availability of primary investigations, further
3. Sayre J. Native plants: propagation protocol for
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Cite this article as: Nishkruti R Mehta, Ekta P Patel Pragnesh V Patani; Biren Shah. Nelumbo Nucifera (Lotus): A Review
on Ethanobotany, Phytochemistry and Pharmacology. Indian J. Pharm. Biol. Res.2013;1(4):152-167.

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Review Article 167