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Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive

components with great functional potential

Article  in  Journal of Food Measurement and Characterization · October 2016

DOI: 10.1007/s11694-016-9410-4

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Food Measure
DOI 10.1007/s11694-016-9410-4
REVIEW PApEr
Stinging nettle (Urtica dioica L.): a reservoir of nutrition
and bioactive components with great functional potential
Khan Nadiya Jan1 · Khan zarafshan2 · Sukhcharn Singh1
Received: 11 November 2015 / Accepted: 19 September 2016
© Springer Science+Business Media New York 2016
Abstract  In recent years a lot of the scientific interest has
been concentrated on the identification of factors among
low cost herbs that can be helpful in improving the health
of humans. A shocking feature of herbal analysis has been
that rarely any rare, exotic and exquisite plant has proved
more fascinating. Typically some common, less famil-
iar, and disdained weed have been discovered to possess
undreamt of virtues. Urtica dioica is a weed and its seeds,
leaves and even roots are used for medicinal purpose. It
is a sensible reservoir of micronutrients and nutritional
elements which leads us to focus our study on this herb.
Despite of being wholesome, leaves are easily digested and
high in minerals (especially iron), vitamin C and pro-vita-
min A. U.dioica is used as both medicine and food in many
countries particularly in Mediterranean region because of
being widespread and having conjointly exceptional bio-
logical activities. This comprehensive review is an effort
to summarise the recent data on nutrition, pharmacologi-
cal and clinical effects of U. dioica keeping in view the
increased demand by patients to use natural products with
antioxidant activity, anti diabetic activity and having poten-
tial for treatment of inflammatory diseases. The review of
nutritional properties is also an important aspect as every
person needs general nutritional support in order to stay
well or become optimally healthy. This review provides an
overview of U. dioica in relation to antioxidant activity,
Khan Nadiya Jan
khan14diya@gmail.com
1
Department of Food Engineering and Technology, Sant
Longowal Institute of Engineering and Technology,
Longowal, Sangrur, India
2
Govt Medical College, Srinagar, India
anti diabetic activity, antimutagenic activity, antimicrobial
activity, analgesic effect and treatment of inflammatory
diseases that promotes its use.
Keywords  Urtica dioica · Nutritional properties ·
Antioxidant activity · Bioactive components ·
Functional aspects
Introduction
Urtica dioica (stinging nettle) belongs to family Urticaceae
and is native to Europe, Asia, Northern Africa and America.
It is a herbaceous perennial flowering plant and encom-
passes a long history as herbal remedy and nutritive addi-
tion in diets. For 100 of years U. dioica has been used to
treat a variety of disorders ranging from allergic rhinitis to
hypertension [1, 2]. It can be used as a vegetable, tea, and
juice mainly for rhinitis and as a tonic for blood nourishing.
Important property of nettle is that the entire plant can be
used for various purposes such as food, fodder, medicine,
cosmetic, biodynamic agriculture, and textile production [3,
4]. Young leaves cooked as a potherb are added to soups
and can also be dried for winter use [5]. Modern research
has justified the use of U. dioca in traditional medicine and
has also proved that its extracts have natriuretic, diuretic
and hypotensive effects [6]. Recently, it was discovered
that the leaf extracts from U. dioica have an anti-inflamma-
tory effect due to its inhibitory effect on NF-κB activation,
a family of transcription factors which are critical for the
inducible expression of many genes involved in inflamma-
tory responses [7]. Nutritional interest for leaves from wild
species was initially on the pro-vitamin A carotenoids, as
they provide the major source of dietary pro-vitamin A in
several countries [8]. Expanded interest in plant carotenoids
13
2 K. N. Jan et al.

was stimulated in the 1980s by epidemiological and labora-

tory studies indicating they may have anti-carcinogenic [9]
anti-ulcer [10] or anti-ageing properties [11]. Besides culi-
nary and medical uses, the plants are harvested commer-
cially for the extraction of the chlorophyll, which is used
as a green colouring agent (E140) in foods and medicines.
Some experimental data also suggest that chlorophyll may
have some anti-mutagenic and anti-carcinogenic potential;
it may help to protect against some toxins, and ameliorate
some drug side effects [12]. The objective of this review
was to survey the chemical composition, bioactive compo-
nents, antioxidant activity (in vitro and in vivo) and func-
tional properties of U. dioica. The review of these aspects
can give a scientific justification to the use of U. dioica in
medicines and as a potential source of natural antioxidant
food. Though some publications have described the nutri-
tional composition and some functional properties of net-
tle but the information is limited and hence this review is
attempted to bridge the gap thereby linking its nutritional
composition and functional potential.

Botanical description

Genus Urtica plants include both annual and perennial
herbs. U. dioica is a dioecious herbaceous perennial,
which reproduces not only by seed, but also through creep-
ing underground rhizomes and reaches upto height of
1–2 m (Fig. 1). U. dioica is actually an aggressive weed
commonly found in moist soils throughout the USA and
Europe [13]. Flowering and fruiting time is from J une to
October. Rhizomes and stolons, are bright yellow in colour
and spread widely. The soft green leaves are 3–15 cm in
length, serrated and are located oppositely on an erect wiry
green stem. U. dioica contains small greenish or brownish
numerous flowers in dense axillary inflorescences and is
found in every province and state of Canada and the United
States, except for Hawaii and also can be found in Mexico.
Its abundant growth is seen in places where annual rainfall
is high.
Stinging trichomes cover the stem and leaves of the
plant. These trichomes enter the skin and causes blistering
[14]. It contains serotonin and histamine that are involved in
the cascade of stimulation, affecting levels of nerve growth
factor which in turn increases activation of nociceptive pain
neurons [15]. Stinging hairs can be destroyed by steaming or
cooking prior to ingestion. These hairs contain 5-hydroxy-
tryptamine, histamine, formic acid, acetic acid, acetylcho-
line, leukotrienes, and other irritants [16, 17]. Seeds exhibit
physiological dormancy and most likely require a prolonged
stratification period to soften the hard seed coats and break
the physiological dormancy [18]. This plant grows in waste
places, roadsides, stream banks and ditches, particularly in
Fig. 1  Different parts of Urtica dioica plant
soils containing more nitrogen. It can be invasive but are
easily controlled by pulling out dormant rhizomes.
Bioactive components
Phenolic compounds present in U. dioica are p-hydroxyben-
zoic acid, gentisic acid, quinic acid, protocatechuic vanillic
acid, caffeic acid, ferulic acid, 5-O-caffeoylquinic, esculetin,
scopoletin, chrysoeriol, β-sitosterol, scopoletin Kaempferol,
isorhamnetin, kaempferol 3-O-glucoside, quercetin 3-O-glu-
coside, plastocyanins, quercitrin, glycoproteins, rutin, amen-
toflavon. Most abundant phenolic compounds present in U.
dioica are shown in (Fig. 2) [19]. Therapeutic benefits of
nettle are attributed to its phenolic compounds. The inflores-
cence extracts were richest source of phenolics, amounting
2.5–5.1 % by weight with 5-O-caffeoylquinic acid contrib-
uting up to 3.6 % of aqueous methanolic extract by weight.
However root extracts were poor in phenolics. The roots of
U. dioica contain chemicals like scopoletin, sterols, fatty
acids, polysaccharides and isolectins. Prominent compounds
detected from root extracts were secoisolariciresinol, quinic
acid, p-coumaric acid, and scopoletin with total content not
exceeding 0.086 % of extract by weight [20]. Ethyl acetate
soluble portion of the whole plant of U. dioica was charac-
terized and diocanol a new benzene derivative was isolated

13
Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great…
Fig. 2  Abundant bioactive
compounds exhibiting anti-
oxidant activity in U. dioica
extracts. 1 Rutin; 2 quercetin;
3 5-0-caffeoylquinicnacid; 4
isoquercetrin
from the extract along with known constituents β-amyrin,,
stigmasterol, β-sitosterol and oleanolic acid [21]. U. dioica
herb and roots were found to consist of enzymes such as cho-
lineacetyl transferase, polyphenoloxidase, invertase, ribu-
loso-1,5-bisphosphatecarboxylase, and inhibitors of α- and
β-d-glucosidases [22–25]. U. dioica leaves were extracted
with hexane and the Gas chromatography-mass spectrom-
etry and the anlaysis of extract showed presence of different
bioactive components like 2,6,10,15-tetramethylheptadec-
ane (12.82 %), heptadecyl ester (9.45 %), butyl tetradecyl
ester (4.73 %), hexyl octyl ester (6.31 %), 2,7,10-trimeth-
yldodecane (5.60  %), octadecan-1-ol (4.45  %), 1,2-ben-
zenedicarboxylic acid (4.38 %), neophytadiene (19.96 %),
4,6-di-tert-butyl-m-cresol (4.32 %) and 2,4-ditert-butylphe-
nol (4.30 %) [26]. U. dioica has good antioxidant activity,
phenolic and flavonoid content (Table 1).
Nutritional status
Nutritional aspect of U. dioica is basically due to two parts
of plant: green leaves and seeds. Young leaves and shoots
are used as food as it is a rich source of polysaccharides,
vitamins (β-carotene), iron, potassium, manganese, cal-
cium protein, silicon, phosphate and vitamin c for absorp-
tion of iron as shown in Table 2. Being low in saturated fat
however, its leaves contain ample amount of essential fatty
acids such as α-linolenic acid and linoleic acid, essential
3
aminoacids and carbohydrates, carotenoids which include
Omega-6 fatty acids, lutein, β-carotene. Leaves are included
in the human consumption, for strengthening the body, in
preparation of soups and as a natural source of food fla-
vouring due to its high nutritive value [34]. Deproteinated
biomass of stinging nettle comprises 52.4 % of dry nettle
biomass, 69.5 g/kg of non-starchy polysaccharides such as
pectin, hemicellulose, and cellulose at 196.7, 334.5, and
128.5 g/kg, respectively. Nettle can be an important source
of dietary fiber due to high pectin content [35]. Chlorophyll
content in U. dioica leaves was found to be 1–5, 75 % of
which was α-chlorophyll and 25 % was β-chlorophyll [36].
Caffeyl-malic acid 1.6 %, chlorogenic acid 0.5 %, small
amounts of neochlorogenic and free caffeic acids were
detected in U. dioica leaf extract analysed by Gel-exclusion
HPLC [37]. Chlorogenic acid is actually an antioxidant.
U. dioica herb collected in western Georgia yielded three
anthocyan glycosides, two of them were identified as pel-
argonidin monoxyloside and pelargonidin xylobioside [38].
The Tinctures of homeopathic matrices (THM) extract
of U. dioica consisted of fatty acids, mainly present as ethyl
esters. Palmitic, linolenic and nonadecanoic acids were
dominating fatty acids in lipophilic fraction of THM. THM
obtained from dried raw material consisted of ethyl esters of
heptadecenoic, 8,11-eicosodienoic, arachinoic, heneicosa-
noic and behenic acids [39]. Different parts (leaves, stems,
roots and seeds) of U. dioica L. were analysed for fatty acids
and carotenoids. The pre-dominant fatty acid in leaves was
13
4 K. N. Jan et al.

Table 1  Antioxidant activity, phenolic and flavonoid content of U. dioica as determined by different researchers
Plant part examined Type of extract DPPH total scav- Phenolic content Total flavonoid References
enging activity (%) content

Leaves Ethyl acetate 62.537 25.00 ± 0.16a ND Chahardehi

et al. [27]
Leaves Methanolic 98.35 b 6.35a ND Kataki et al. [28]
Flowers Aqueous ethanolic 48.7 b f Güder et al. [29]
160.6 ± 8.0 103.0 ± 5.3
Leaves Aqueous ethanolic 54.2 132.0 ± 6.5b 65.8 ± 3.5f Güder et al. [29]
b
Roots Aqueous ethanolic 46.2 164.0 ± 8.4 21.0 ± 0.8f Güder et al. [29]
Seeds Aqueous ethanolic 60.5 b f Güder et al. [29]
213.6 ± 11.1 19.1 ± 0.9
Leaves Aqueous ethanolic ND b f Moldovan et al.
90.09 ± 82 31.03 ± 1.93
[30]
Leaves Aqueous ethanolic ND 1026d ND Dogan et al.
[31]e
Leaves Acidified aqueous ND 6.9 ± 0.1a ND Proestos et al.
methanolic [32]
Leaves Methanolic 70.8 24.1 ± 1e 43.3 ± 0.37f Pourmorad et al.
[33]
ND not determined
a
mg GAE/g extract
b
μg/mg catechin equivalent
c
mg caffeic acid/g d.w
d
mg/100 g
e
mg/g
f
mg quercetin/g d.w.

α-linolenic acid and seeds were rich in linoleic acid. Leaves
consisted of nine carotenoids among these lutein, lutein iso-
mers, β-carotene and β-carotene isomers were the major carot-
enoids. All parts of the plant were analysed and consisted of
high amounts of palmitic acid with 17.9 % in mature leaves
and 25.4 % in seeds. All these parts consisted of low amounts
of stearic acid. Monounsaturated fatty acids were present in
low amounts with palmitoleic acid 0.5 % in stems and 2.6 % in
roots. Oleic acid was higher in roots 8.7 % compared to other
parts. Gadoleic acid was also higher in roots 1.2 %, seeds con-
sisted of 1.2 % of erucic acid. Polyunsaturated fatty acids like,
linoleic acid ranged from 11.6 % in mature leaves to 34.3 % in
roots 2.3 % of α-linolenic acid was found in roots and 40.7 %
in mature leaves. Vitamin A content was found to be 16.2 and
36.2 mg per 100 g of fresh and aged leaves, respectively [12].
The monomeric protein lectin with high contents of gly-
cine, cysteine, and tryptophan was first isolated from roots
of U. dioica in 1984. The pharmacological action of nettle
preparations for prostate hyperplasia is associated with this
compound and its content in nettle roots is 0.1 % [39]. In
another study higher protein content content was determined
in leaves followed by stem and root. The highest determined
values for the protein content in leaves expressed to the dry
mass were 26.89 % in leaves, 14.54 % in stem and 10.89 %
in root. Leaves also consisted of greater amount of minerals
with calcium being higher than magnesium. Leaves consisted
of calcium ranging from 2.63 ± 0.05 to 5.09 ± 0.04 % and
magnesium ranging from 2.51 ± 0.15 to 3.56 ± 0.07 %, other
minerals included Cu (17.47 ± 0.09 mg kg−1 dry mass), Zn
(27.44 ± 0.23 mg kg−1 dry mass), Mn (17.17 ± 0.06 mg kg−1
dry mass) and Co (0.21 ± 0.06 mg kg−1 dry mass) [40].
Lipophilic fraction of homeopathic matrix tinctures (HMT)
of U. dioica was studied to determine the qualitative and
quantitative contents of amino acids and N-containing sub-
stances. 18 amino acids were identified in leaves, rhizome,
and seeds of U. dioica total content of which varied from 0.23
to 13.5 %. Aspartic acid, threonine, serine, and alanine domi-
nated in leaves; aspartic acid and alanine (glutamic acid was
not observed), in root, aspartic acid, threonine, and serine (glu-
tamic acid, tyrosine, and phenylalanine were not observed), in
seeds. Most of the amino acids were present in free form and
few in bound form. Aspartic acid, asparagine, glutamic acid,
alanine, and threonine dominated in HMT from U. dioica, his-
tidine was found to be present in a bound form. Methionine
and tryptophan were not observed in all analyzed samples.
Aminoacids content in free form was about 0.02–0.21 % and
in bound form about 0.32–0.29 %. Hydrocarbons (squalene),
terpenoids (apiol, eugenol), and other substances were also
observed in the lipophilic fraction of U. dioica HMT [41].
Crude ethyl acetate extract of U. dioica was stud-
ied to determine the phytochemical constituents and
minerals. It consisted of flavonoid (1.88  mg/100  g),

13
Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great… 5

alkaloid (1.32 mg/100 g), phenol (0.09 mg/100 g), saponin Table 2  Nutrient composition in Urtica dioica as per USDA
(1.64 mg/100 g) and tannins (0.8 mg/100 g). Minerals pres- Constituents Unit Amount
ent included Na 6.231 ± 0.2, k 4.453 ± 0.2, Ca 0.008 ± 0.2, (per100
Mg 11.312 ± 0.2, Zn 0.012 ± 0.2, Fe 7.932 ± 0.2 and Mn g)
0.437 ± 0.2 U. dioica plant contains Flavonoids (glycosides
Water g 87.67
of quercetin, kaempferol, and rhamnetin), acids (caffeoyl-
Energy kcal 42
malic, hydroxybenzoic, chlorogenic, malic, elagic, citric,
Protein g 2.71
succinic, caffeic, fumaric, etc.), tannins, amines sitosterol,
Total lipid (fat) g 0.11
carotenoids, glucoquinones, enzymes, lectin (agglutinin),
Carbohydrate, by difference g 7.49
polysaccharides, scopoletin, vitamins B, C, K and trace ele-
Fiber, total dietary g 6.9
ments are present in root of herb. Root of nettle has shown
Sugars, total g 0.25
beneficial effect upon enlarged prostate glands [42].
Minerals
Calcium, Ca mg 481
Iron, Fe mg 1.64
Functional aspect
Magnesium, Mg mg 57
Urtica. dioica L. has a long history as herbal remedy and Phosphorus, P mg 71
nutritious addition in diets. The functional properties of U. Potassium, K mg 334
dioica L. cannot be under estimated, it is well known for its Sodium, Na mg 4
health or medicinal benefits in addition to antimicrobial prop- Zinc, Zn mg 0.34
erties. All aerial parts are used for medicinal purpose. Leaves Vitamins
of this herb have important antioxidant [43] and antimicrobial Thiamin mg 0.008
[44] effects on fermented meat products. Medicinal properties Riboflavin mg 0.160
are due to presence of phytochemicals. In 2011–2012 study Niacin mg 0.388
was designed to identify the functional groups present in U. Vitamin B-6 mg 0.103
dioica by using Fourier transformer infra-red (FTIR) Spec- Folate, DFE μg 14
trophotometer. Hexane, dichloromethane, ethyl acetate and Vitamin A, RAE μg 101
ethanol crude extracts of the herb were used for analysis, and Vitamin A, IU IU 2011
functional groups like: aldehydes, alkenes, amines, amides, Vitamin K (phylloquinone) μg 498.6
alcohols, phenols, carboxylic acids, isonitriles, organic halo- References: USDA National Nutrient Database for Standard Refer-
gen compounds aromatics, anhydride, esters, lactones, ethers, ence release 26 full report (all nutrients) nutrient data for 2013 sting-
nitriles, quinones, and carbohydrates were identified. Medici- ing nettle blanched (northern plains Indians)
nal properties of U. dioica are attributed to the presence of
these functional groups [45]. Roots exhibit antiviral activity free radical scavenging, superoxide anion radical scaveng-
in vitro against HIV-1, HIV-2, CMV, RSV, and flu virus A due ing,, and metal chelating activities were used to evaluate
to the presence of lectins (agglutinin, UDA) [46]. Dry extract its antioxidant properties. 50, 100 and 250 µg amounts of
of U. dioica leaves inhibits lipopolysaccharides that stimulate WEN showed 39, 66 and 98 % inhibition on peroxidation
tumor necrosis factor and production of interleukin-1 beta of linoleic acid emulsion, respectively, while 60 µg/mL of
there by showing immunomodulating, antirheumatic, and α-tocopherol, exhibited only 30 % inhibition. Thus WEN
anti-inflammatory activity [47]. Chronological progression was observed to have powerful antioxidant activity and can
of functional properties is shown in Table 3. be used as a possible food supplement or in pharmaceutical
industry [54]. Oxidative stress is caused by the lipid per-
oxidation resulting in the development of rancidity, unpleas-
Antioxidant activity ant odors and tastes thereby causing the color changes and
nutritional losses. It was also observed that lipid oxidation
The most important and well characterized functional can be inhibited by lyophilized U. dioica L. water extract
aspect of U. dioica is the antioxidant activity. It is a good (LUWE) as the quality of ground beef can be protected best
source of polyphenols and phytochemicals related to its using 500  ppm LUWE and Modified atmosphere packag-
high antioxidant activity. Antioxidant activity of nettle is ing (MAP) with 80 % O2 + 20 % CO2. Using only MAP
mainly due to the presence of quercitin, rutin and ascorbic with 80 % O2 + 20 % CO2 was unsuitable as it resulted in
acid. Study was done to determine the antioxidant proper- increased lipid oxidation [55]. In another study extracts of
ties of water extract of nettle (WEN). Different antioxidant U. dioica L. plant parts were studied at concentration of
tests like reducing power, hydrogen peroxide scavenging, 100 µg/mL and compared to same concentration of BHA,

13
6 K. N. Jan et al.

Table 3  Chronological progression of different functional properties in the antioxidant enzyme levels. However treatment with
of Urtica dioica UD for 60 days decreased the elevated lipid peroxidation
Researcher Functional activity Plant part and also increased the reduced antioxidant enzyme levels in
CCl4-treated rats [57]. In another study healthy wistar rats
Dizaye et al. [48] Hypotensive and diuretic Water extract of whole
were used and fed with dried, chopped nettle mixed with
effect plant
normal lab chow. The electron spin resonance was used to
Ghaima et al. [49] Antibacterial and Ethyl acetate extract
antioxidant of leaves measure the level of oxidative stress. Nettle supplementation
Sayhan et al. [50] Protective effect on I/R Seed oil was found to decrease the concentration of free radicals in
injury in the rat kidney cerebellum as well as the frontal lobe of rat’s brain and hence
Güder et al. [29] Antioxidant Hydroalcoholic was considered as an effective antioxidant [58].
extracts of leaf,
flower, seed and root
Kataki et al. [28] Antioxidant, hepato- Concentrated metha- Antimicrobial activity
protective and nol extract of leaves
anthelmintic
Das et al. [51] Antihyperglycemic and Water extract of
The presence of phenolic compounds in the plants indicates
antihyperlipidemic leaves that these plants may be anti-microbial agent [57]. Water
Monfared et al. Antioxidant Water and diethyl extract of nettle (WEN) exhibits noticeable antimicrobial
[52] ether extract of activity against Gram-positive bacteria, gram–negative
aerial parts of nettle bacteria and some yeast like Pseudomon as aerugin osa,
Chahardehi et al. Antioxidant Methanol, Chloroform Escherichia coli, Proteus mirabilis, Citrobacter koseri,
[27] Diethyl ether, ethyl
acetate and butanol
Staphylococcus aureus, Streptococcus pneumoniae, Entero-
extract of leaves bacter aerogen es, Micrococcus luteus, Staphylococcus
Kan et al. [53] Antimicrobial effect Seed oil epidermidis an d Can dida albican s when compared with
Gülçin et al. [54] Antioxidant, antimi- Water extract of aerial standard antimicrobial compounds such as ofloxacin,
crobial, antiulcer and parts of nettle miconazole nitrate, amoxicillin-clavulanic acid, and netilm-
analgesic icin [54].
Lyophilized extract of U. dioica along with MAP was
BHT and α-tocopherol. Seeds, roots, flowers and leaves of studied for its antimicrobial activity. 500 ppm of Lyophi-
stinging nettle showed antioxidant activity of about 81.7, lized extract of U. dioica (LUWE) and MAP showed sig-
79.8, 78.3 and 76.4 % respectively while as BHA, BHT and nificant effects on mesophilic, psychrotrophic, lactic acid
α-tocopherol exhibited 66.2, 70.6, and 50.1 % inhibition on bacteria and Pseudomonas counts in ground beef stored at
peroxidation of linoleic acid emulsion [29]. 2 ± 0.5 °C for 14 days. Their count decreased depending on
In Vitro antioxidant activity of extract of leaves of U. dio- the level of LUWE [55]. Pyrazine and pyrazole derivatives
ica L. (MEUD) was investigated and the results indicated were detected from homeopathic matrix tinctures (HMT)
powerful antioxidant activity of the extract at 250 µg/mL of U. dioica like 4-ethyl-4,5-dihydro-5-propyl-1H-pyrazol-
compared to standard antioxidant compounds α-tocopherol. 1-carboxyaldehyde isomers and hexahydropyrrolo [1, 2-a]
The percentage inhibition of peroxidation of the extract in pyrazin-1,4-dione derivatives with 3-alkyl and 3-phenyl-
linoleic acid system was found to be 62.34 % and percent- methyl substituents in addition to 5,10-diethoxy-2,3,7,8-
age inhibition of 250 µg/mL concentration of α-Tocopherol tetrahydro-1H,6H-dipyrrolo[1,2-a; 1′,2′-d] pyrazine these
was found as 34.41 % [28]. Aqueous infusion of Mediter- compounds have antibacterial activity towards M. luteus
ranean U. dioica, has exhibited antioxidant activity towards and P. aeruginosa [43]. Also the alcoholic extract of U. dio-
iron-promoted oxidation of phospholipids, linoleic acid, and ica was observed to have fungicidal activity against Alter-
deoxyribose [56]. Antioxidant activity of ethyl acetate extract n aria altern ata, Fusarium oxysporum, Fusarium solan i
of U. dioica was studied and the extract resulted 76 % lipid [59]. Hexane extract of nettle has shown good antibacte-
peroxidation inhibition of linoleic acid emulsion compared rial activity against both the fish and human pathogens as
to α-tocopherol 65 %. This may be due to its phenolic con- observed by serial dilution method [26].
tent and active compounds like alkaloids and tannins [49].
Only few animal experiments have been carried out to
determine the antioxidant activity of nettle and much research Anti-inflammatory activity
is needed there by supporting the vast literature available on
in-vitro antioxidant activity of nettle. In a study wistar albino Recently, it has been discovered that the leaf extracts from
rats were treated with CCl4 for 60 days. CCl4 treatment U. dioica have an anti-inflammatory effect due to its inhibi-
resulted in the increase in the lipid peroxidation and decrease tory effect on NF-κB activation, a family of transcription

13
Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great…
factors which are critical for the inducible expression of
many genes involved in inflammatory responses [7].
An in vitro anti-inflammatory activity of nettle extract
was examined and it resulted in inhibition of several key
inflammatory events that cause the symptoms of seasonal
allergies. These include inhibition of mast cell tryptase
there by preventing degranulation and subsequent release
of a range of pro-inflammatory mediators that cause allergy
symptoms related to hay fever such as sneezing, nasal
congestion, itchy and watery eyes. Further the bioactive
constituents in the nettle extract inhibit the Hematopoietic
Prostaglandin D2 synthase (HPGDS), Cyclooxygenase-1
(COX-1), Cyclooxygenase-2 (COX-2) enzymes thus inhib-
iting the production of Prostaglandin [60].
Anti-inflammatory effect of U. dioica may be due to the
presence of quercetin. Which appears to be due to inhibi-
tory and antioxidant effects of quercetin on inflammation
producing enzymes like cyclooxygenase, lipoxygenase and
also due to inhibition of inflammatory mediators, including
leukotrienes and prostaglandins [61]. Anti-inflammatory
activity of nettle is mainly due to inhibition of human leu-
kocyte elastase. Ethanolic extract from the roots of nettle
WS1031 inhibited bovine leukocyte elastase (IC50 68 µg/
mL) [62].
Efficacy in benign prostatic hyperplasia (BPH)
patients
Noncancerous enlargement of the prostate gland is termed
as benign prostatic Hyperplasia. Effect of nettle in reduc-
ing symptoms of benign prostatic hyperplasia in the patients
was studied. Patients were divided into two groups one
group was given U. dioica in capsule form and another
was given placebo capsules for about eight weeks. Clini-
cal symptoms of BPH were determined by using AUA
Score. The average score of AUA scale in the group tak-
ing nettle was assessed 26.511 ± 0.264 before treatment and
2.118 ± 0.431 (P = 0.000) after treatment, which was statis-
tically significant, but average score of AUA scale in the
group with placebo capsules was determined 27.854 ± 0.744
before treatment and 27.853 ± 0.766 after treatment respec-
tively (P = 1.000) which was not statistically significant.
The results showed that nettle had a better effect in relieving
clinical symptoms in BPH patients [63]. Further combina-
tion of nettle and saw palmetto was used for relieving the
symptoms of BPH. It was found that the combination has
the same efficacy as finasteride in improving symptoms of
BPH in a 48-week, double-blind trial [64]. Results of these
studies are convincing because of their confirmation with
placebo controlled study.
Effect of hexane, ether, ethyl acetate extract, and the
butanol extract of U. dioica roots on the Na+, K+-ATPase
7
of the tissue of benign prostatic hyperplasia (BPH) was
analysed. The Na+, K+-ATPase fraction of membrane was
prepared from a patient with BPH. These extracts resulted
in 27.6–81.5 % inhibition of enzyme activity. Hydrophobic
constituents in stinging nettle roots like steroids inhibit the
membrane Na+, K+-ATPase activity of the prostate which
can finally supress prostate-cell metabolism and growth [65].
Urtica dioica aqueous extract; an alcoholic extract,
agglutinin, and stigmasta-4-en-3-one were examined for
their ability to modulate binding of sex hormone-binding
globulin to its receptor on human prostatic membranes. Out
of all these only aqueous extract was capable of inhibiting
the binding of I-SHBG (sex hormone binding globulin) to
its receptor and this inhibition started at 0.6 mg/mL with
complete inhibition at 10 mg/mL there by preventing the
Benign prostatic hyperplasia [66].
Diuretic effect
Thirty two patients with myocardial or chronic venous insuf-
ficiency were treated with 15 mL of nettle juice three times
daily for 2 weeks. A significant increase in daily volume
of urine was observed throughout the study, the volume by
day 2 being 9.2 % higher than the baseline value in patients
with myocardial insufficiency and 23.9 % higher than the
baseline value in those with chronic venous insufficiency.
It has been proposed that the diuretic activity of aqueous
extracts of nettle may be attributed to the high potassium
content [67].
Eighteen local domestic rabbits were used for in vivo
study. A significant increase in urine volume and urinary Na+
excretion without significant changes in K+ excretion rates
in experimental rabbits was observed due to intravenous
infusion of 20 mg/mL of U. dioica dried leaf extract. Vaso-
dilatation or vasoconstriction of isolated pulmonary arteries
of the rabbit did not occur after applying the aqueous extract
of U. dioica [48]. U. dioica is applied as a diuretic for the
treatment of kidney problems [68]. Survey was undertaken
in different areas of oriental Morocco, to select the main
medicinal plants used for arterial hypertension and U. dio-
ica was among 18 vegetal species which was used for arte-
rial hypertension [69]. The hypotensive result could be due
to the diuretic property of the plant extract [70]. Diuretic is
being considered as one of the best choices for the treatment
and management of uncomplicated hypertension.
Antirheumatic
Leaf extracts from stinging nettle, are used as anti-inflam-
matory remedy in rheumatoid arthritis. Treatment with
extract potently inhibits transcription factor NF-κB. An
13
8 K. N. Jan et al.
inhibitory effect is shown in different cell types including
T cells, macrophages, fibrosarcoma and epithelial cells,
as well as in response to several stimuli, suggesting that
Urtica extracts interfered with a common target in the
NF-κB pathway. This study reveals that Urtica extracts sta-
bilize the inhibitor NF-κB-α by preventing its proteolytic
degradation. As inflammatory processes are strictly depen-
dent on NF-κB activity, this results suggest a molecular
basis for the antiinflammatory effects of Urtica extracts
[71]. In another study (in vitro) commercial preparation of
U. dioica leaf (IDS-23) was added to whole human blood
which resulted in an inhibition of LPS-stimulated TNF α
and IL-1β secretion, correlating with drug ingestion. This
preparation also inhibited phytohaemogglutinin-stimulated
production of T helper cell 1 (Th1)-specific interleukin-2
(IL-2) and interferon-γ (IFNγ) in culture in a dose-depen-
dent manner up to 50 and 74 %, respectively. It was also
suggested that nettle leaf extract acts by mediating a switch
in T helper cell-derived cytokine patterns and may inhibit
the inflammatory cascade in autoimmune diseases such as
rheumatoid arthritis [72].
Antifungal and antinematodocidal activity
The alcohol extract of U. dioica has shown fungicidal activ-
ity against A. alternata, F. oxysporum, F. solani, Rizoctonia
solani and candida spp [59, 73]. Also shown nematodocidal
activity against larvae of Haemonchus contortus [74]. Small
sized lectin present in rhizomes of U. dioica shows binding
specificity towards chitin and inhibits the growth of several
phytopathogenic and saprophytic chitin-containing fungi in
vitro [75].
Antiulcer activities
Forty albino Sprague–Dawley male rats were used and
were divided into five groups. Three groups were injected
with different doses of WEN. Remaining two groups were
injected with famotidine and saline solution. After 30-min-
period, all the animals were given 1 mL of ethanol (70 %)
by oral gavages. Ethanol produced multiple mucosal lesions
in the rat stomach. Pre-treatment with WEN and famotidine
were found to inhibit the ethanol-induced gastric mucosal
injury in rats. 50, 100 and 200 mg/kg WEN showed pre-
ventive effects depending on the dose. Percent inhibitions
on mucosal lesions were 67.7, 61.1 and 77.8, compared to
control. Percent inhibition by famotidine was found to be
34.4 [54]. Another study has reported that Urtica extract
(40–70 nm fragments) diminishes the acidity of stomach
juice in experimental peptic ulcer and its antiulcer activity
is comparable to the effect of buckthorn oil [76].
13
Analgesic effect
Animals were divided into five groups and pretreated with
50, 100 and 200 mg/kg doses of WEN and 200 mg/kg dose
of metamizol as reference drug. All animals received an
equal volume of 0.9 % NaCl in distilled water. WEN and
metamizol were found to inhibit the acetic acid-induced
writhing in mice. Inhibitory effects of 50, 100 and 200 mg/
kg WEN were 62.1, 70.4 and 89.2 % compared to control
these effects depended on the dose. Inhibition of acetic
acid-induced writhing by metamizol was 39.4 % compared
to control [54]. A study showed that the aqueous leaf extract
of U. dioica was able to inhibit pain sensation and hence
there is possibility of finding analgesics in its extract that
act by inhibition of inflammatory pathways responsible for
pain. The highest analgesic effect of the extract has been
observed at dose 150 mg/kg for acute pain and dose 100
and 150 mg/kg body weight for chronic pain. This analgesic
effect might be related to presence of bioactive compounds
and phytochemicals present in U. dioica [77].
Hepatoprotective activity and hypotensive effect
Hepatoprotective potential of the extract was evaluated
against CCl4-induced hepatic injury in Wister rats as the
treatment of animals with CCl4 is known to cause severe
hepatic injury [78]. Wister rats were treated with CCl4 for
60 days which resulted in the liver fibrosis. Then they were
treated with U. dioica for 60 days which resulted in the
decrease in liver enzymes and also prevented CCl4-induced
hepatotoxicity in rats [79]. Six male albino rats were used
for studying the effects of intraperitonial injection of U. dio-
ica extract on blood pressure, there was profound drop in
blood pressure [48].
Antihelmintic activity
Antihelmintic activity of methanol extract of leaves of U.
dioica L. (MEUD) was investigated. 100 mg/mL concen-
tration of MEUD has the highest potency as an anthelmin-
tic (took least time to cause paralysis and death of worms)
when compared to standard drug piperazine citrate and
albendazole [28].
Antidiabetic and antihyperlipidemic activity
Diabetes if not controlled can lead to acute and chronic com-
plications most common being atherosclerosis. In an in vivo
study the active component of U. dioica named F1 increased
serum insulin accompanied by a drop in glucose level of
Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great…
blood serum in normal and streptozotocin diabetic rats that
were injected intraperitoneally with the active ingredient of
the extract [80]. Adult, male Long-Evans rats, were used for
the study, Type 2 diabetes was induced in them by a single
IP injection of streptozotocin. These rats were divided into
three groups, first fed with deionized water selected as con-
trol, second group treated with glibenclamide, third group
fed daily with aqueous extract of U. dioica. There was sig-
nificant decrease of serum glucose level, in aqueous extract
treated group on day 28 (7.1 mmol/L) with respect to the
control group (13.7 mmol/L). However, serum glucose level
in glibenclamide treated group on day 28 (6.2 mmol/L)
was found to be significant with respect to control group
(13.7 mmol/L). In same study rats were used for antihyper-
lipidemic study. Body weight of these rats was also noted
at initial, 14th and at 28th day. At a 14 day interval body
weight of each rat was taken. There was an increase in body
weight in all groups as compared with the initial value. The
body weight of UD extract treated rats was significantly
lower on the 14th and 28th day as compared with that of the
glibenclamide treated and the control group on the same day
[51]. Use of nettle leaf as supportive therapy in patients with
lower urinary tract infections (combined with immune and
antimicrobial therapy) and to prevent and treat formation
of urinary gravel has been approved by German Commis-
sion E [81]. It was also widely used as as an astringent for
the removal of kidney stones and as a urinary aid in Greece
[82].
Urtica dioica extract has shown hypocholesterolemic
effects in animal models at doses of 100 and 300 mg/kg and
significantly reduced the levels of total cholesterol and LDL
and also markedly decreased liver enzymes and weight in
animals with a high cholesterol diet [83].
Treatment of renal ischemia/reperfusion injury
Reperfusion injury is actually a tissue damage caused by
oxidative stress and inflammation due to returned blood
supply after a period of ischemia or lack of oxygen. A study
was designed to investigate the effect of U. dioica L. (seeds)
in I/R induced renal injury in rat. U. dioica treatment signifi-
cantly attenuated the severity of intestinal I/R injury includ-
ing tubular damage, renal corpuscle atrophy, loss of brush
border, atrophy dilatation, hydropic epithelial cell degenera-
tions, glomerular shrinkage, and lowered tubulointerstitial
damage score than the I/R group. This study suggested that
UD treatment has a protective effect against renal damage
induced by renal I/R. This protective effect can be due to its
ability to inhibit I/R induced renal damage, apoptosis and
cell proliferation. These results suggest potential clinical
benefits of UD in patients undergoing partial nephrectomy
or renal transplantation [50].
9
Conclusion
Urtica dioica L. is a miraculous herb that functions as both,
food as well as herbal medicine. Plantation of this herb can
help to provide over fertilized soils. This review shows that
U. dioica extract is a rich source of 5-O-caffeoylquinic acid,
rutin and isoquercitrin compounds with confirmed antioxi-
dant, DNA-protective, anti-inflammatory and antihyperten-
sive activities there by justifying its use as food as well as
traditional medicine. It is an updated review of nutrition,
bioactive components and functional potential of nettle and
from this review it can be concluded that U. dioica can be a
good source of antioxidants and a valuable medicinal plant.
This review also shows that the research on nettle is mostly
emphasized on in vitro antioxidant studies and in vivo stud-
ies remain under-tapped. It can be a potential functional
food because of its proven beneficial effects on human
health. This paper has presented various plant part formula-
tions of the herb that have been pharmacologically tested
and shown to be of effective against various disorders. U.
dioica can be considered as a cheap source of good protein
and antioxidants that are easily available. Apart from leaves
roots and seed as well as seed oils are exploited for their
antimicrobial and antioxidant properties thereby protecting
cell membranes against damage caused by oxygen radicals
and consequently cardiovascular disease and cancer. Use of
U. dioica as food can benefit patients with digestive and kid-
ney diseases or injuries after renal transplantation, as well as
those with diabetes or some sort of seasonal allergies. One
of the most overlooked aspects of nettle is its use as food,
though the leaves of nettle have been used as food but, there
are no researches to support this.
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