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Current Traditional Medicine, XXXX, X, ?????????????
REVIEW ARTICLE
2215-0838/XX $65.00+.00 © XXXX Bentham Science Publishers 1
An Updated Review on Traditional and Modern Aspects of Vitex negundo
Summaya Perveen1#, Mohammad Aasif Khan1#, Rabea Parveen1,3#, Areeba Insaf2, Bushra Par-
veen2, Sayeed Ahmad2 and Syed Akhtar Husain2,*
1Human Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi-110025, India; 2Bioactive
Natural Product Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education
& Research, Jamia Hamdard, New Delhi-110062, India
Abstract: Vitex negundo is a traditional herb known for its medicinal properties in Unani, Ayurve-
da, Siddha, Chinese, Roman, and other traditional systems of medicine. Traditionally, it is used as
anthelminthic, antitoxin, aphrodisiac, contraceptive, antimalarial, analgesic, antiinflamatory, anti-
asthmatic, vermifuge, etc. All parts of V. negundo contain a number of phytoconstituents like alka-
loids, fatty acids, flavonoids, glycosidic irridoids, lignans, phenols, steroids, tannins and di- and ses-
quiterpenes. Due to the presence of a variety of secondary metabolites, V. negundo is used in dif-
ferent types of diseases or disorders by traditional practitioners for the treatment of spermatorrhoea,
stomachache, asthma, cold, diarrhoea, indigestion, gallstone, hernia, eye disorders, rheumatism, irri-
table bladder and dysmenorrhea, headache, migraine, kwashiorkor, neck gland sores, tubercular
neck swelling, reddened, arthritis, jaundice, urticaria, eczema and liver disorders. It is most widely
used for curing disorders of the reproductive system like vital power, depression, frail erection
without libido, self-contempt for sexual abuse, stool containing prostatic fluid, and testicle pain.
Facts were gathered from databases such as PubMed, Google Scholar, Springer, Scopus, and Sci-
enceDirect, as well as literature found in books on medicinal plants. It has recently been reported to
have cytotoxic properties against various types of cancer cells. It works by inducing apoptosis via
the mitochondrial and TRIAL pathways and stopping the cell cycle. This review sheds light upon
the ethnomedicinal uses, phytochemistry, different extraction procedures, and pharmacology of V.
negundo. In conclusion, it was found that this traditional herb had an emerging past, exciting present
and promising future for the treatment of several diseases.
A R T I C L E H I S T O R Y
Received: February 22, 2022
Revised: April 12, 2022
Accepted: May 05, 2022
DOI:
10.2174/2215083808666220827115915
Keywords: Vitex negundo, nirgundi, anticancer activity, traditional herb, plant, diseases.
1. INTRODUCTION
From ancient times, plants and their derivatives have
acted as an important source of therapeutic agents for curing
numerous diseases [1]. These plants were the means for
traditional medicine as well as modern medicines [2]. The
Indian flora is rich in plant species and reported for about
45,000 plant species, among them, many have shown excel-
lent therapeutic effects by curing various diseases [3]. Since
these medicinal plants are safer and have no or lesser side
effects compared to allopathic drugs, hence they acquire
more attention for treating various diseases [4].
Vitex negundo is a putative herb known for its medicinal
attributes in various traditional systems such as Unani,
Ayurveda, Siddha and Chinese [5]. V. negundo is popularly
*Address correspondence to this author at the Bioactive Natural Product
Laboratory, Department of Pharmacognosy & Phytochemistry, School of
Pharmaceutical Education & Research, Jamia Hamdard, New Delhi-
110062, India; E-mail: shusain@jmi.ac.in
#These authors contributed equally to this work.
called as Nirgundi in Hindi and five leaved chaste tree in
English [6]. In Sanskrit, the word Nirgundi defines a plant
or any substance that protects the individual from any ail-
ment [7]. V. negundo belongs to family Verbenaceae [8],
which is often known as the verbena or vervain family and
consists of about 35 genera and 1,200 species [9]. The genus
Vitex comprises of 250 species, out of which 14 species are
found in India [10]. The common species of Vitex in India
are V. negundo, V. leucoxylon, V. pinnata, V. glabrata, V.
trifolia and V. penduncularis [11].
V. negundo is a large aromatic shrub having a thin grey
coloured bark, five foliate leaves, and quadrangular branch-
es [6] growing up to a height of 2-5 metres and the flowers
of this plant are bluish purple in colour [12]. The plant is
endemic to India, Pakistan, Srilanka, Afghanistan, West
Indies, Taiwan [7], China, Japan, Indonesia, South America,
East Africa [13], Philippines [11] and also to Mediterranean
countries [6].
V. negundo is known by its traditional names such as
Five leaved chaste tree or Chinese chaste tree in English
Current Traditional Medicine, XXXX, Vol. X, No. X ????????????? Perveen et al.
2
[11] hivari in Hindi, Nirgundi in Ayurveda, Vaavili in Telu-
gu, Vellanocchi in Malayalam [6], Aslok in Assamese [14].
Beguna and Nishinda in Bengali, Nallanocci in Tamil, Sam-
bhalu or Nishinda in Unani [5], Sambhalu and Banna in
Punjabi, and Nagod in Gujarati. It is also known as
Huangjing in Chinese [13], Marvandaey in Pakistan,
Nilnikka or Nika in Srilanka [11] and Lagundi in the Philip-
pines [15].
2. TRADITIONAL USES
In ancient times, V. negundo leaves were used by the
women of Roman society to reduce their sexual urge [7];
also, the berries of the plant were chewed by the monks for
the same reason, and therefore it was also called as Monks
pepper or Monks berry [16].
The uses of V. negundo have been described in the most
ancient textbook of Ayurveda, i.e., Charaka Samhita [12],
which categorises V. negundo as krmighna-anthelminthic
and visaghna-antitoxin [7]. In the Ayurvedic system of med-
icine, V. negundo is a plant with rasa katu [pungent], tikta
(bitter), virya ushna (hot) [17], ruksha (causes dryness),
guna laghu (light for digestion), vipaka katu (pungent in
post digestion) and doshakarma kapha-vata shamaka [18].
Moreover, sleeping on pillows stuffed with leaves of V.
negundo helps to cure catarrh and headache and to treat
neck gland sores, sinus infection, and tubercular neck swell-
ing, crushed leaf poultice is applied. A solution of root bark
of V. negundo provides relief from rheumatism, irritable
bladder and dysmenorrhea [12]. The bark of the plant is also
effective in the treatment of gridhrasi.
V. negundo is called Nishinda in the Unani system of
medicine. When dispensed along with milk and dry ginger,
it acts as an aphrodisiac, the powdered seeds are given in
spermatorrhoea [19]. It also acts as a contraceptive and is
used in curing malarial fever [16]. Seeds of V. negundo help
in the reduction of swelling when given with sugarcane vin-
egar [11].
In the Chinese system of medicine, V. negundo is ad-
vised in the treatment of reddened, sore and swelled eyes,
arthritis, headache [12], stomachache, asthma, cold, diar-
rhoea, indigestion, gallstones, hernia, eye disorder and bron-
chitis [16].
In Homeopathic medicine, Nirgundi helps in curing dis-
orders related to the reproductive system, such as vital pow-
er, depression, frail erection without libido, self-contempt
for sexual abuse, stool containing prostatic fluid and testicle
pain. In the Siddha system of medicine, V. negundo helps in
the treatment of joint swelling [16].
V. negundo has been used in folk medicine for about
many years in India as well as in other Asian countries [13].
In Andhra Pradesh, V. negundo is used to cure cancer,
toothache, and asthma. In Jharkhand, the bark leaves are
used to reduce the pain of muscles and headache [16]. In
Assam, it treats jaundice, urticaria, eczema, and liver disor-
ders and in Himachal Pradesh, it is used to reduce bodyache
and treat kwashiorkor. In Karnataka, the plant treats tooth-
ache, migraine, febrile, and rheumatic affliction [12].
The plant V. negundo cures eye disorder, toothache,
rheumatism, and vermifuge in Srilanka. In China, it cures
the common cold, cough, and flu, and in the Philippines, it
is used as a medication for treating cancer [19]. In Pakistan,
it is used in the treatment of skin diseases and cholera and in
Iran and Bangladesh, V. negundo leaves are used to improve
memory and regulate diabetes. In southeast Asian countries,
especially Laos, Cambodia, and Vietnam, V. negundo helps
in the treatment of beriberi and paralysis and also in wound
healing [16].
V. negundo has been exhaustively used for the prepara-
tion of ayurvedic formulations and herbal products that are
used against bad health conditions; some of them are listed
in Tables 1 and 2 [19-27].
3. PHYTOCONSTITUENTS OF VITEX NEGUNDO
The phytochemical screening of V. negundo has shown
the presence of different types of secondary metabolites like
lignans, volatile oil, flavonoids, triterpenes [20], diterpenes,
sesquiterpenes, glycosidic iridoids, polyphenolic compounds,
Table 1. Ayurvedic formulations containing V. negundo.
S No.
Formulations
Major Plant Drug (Botanical Name)
Indication
Refs.
1
Nirgundi Thailam
Nirgundi (V. negundo)
Peenisarogum (Inflammation in paranasal sinuses)
[19]
2
Nirgundi Patra pinda sweda
Nirgundi (V. negundo)
Sandhigata vata (osteoarthritis)
[20]
3
Nirgundi churna
Nirgundi (V. negundo)
Kidney pain
[21]
4
Dashamoola Taila
Bilva (Aegle marmelos)
Kashtartava (dysmenorrhea)
[21, 22]
5
Trivikrama Rasa
Nirgundi (V. negundo), tamra (copper)
Mutrashmari (Urolithiasis)
[23]
6
Vishatinduka Taila
Vishatinduka (Strychnous nux-vomica)
Vatarakta (gout)
[23]
7
Manasamitra Vataka
Bala moola (Sida acuta)
Generalized anxiety disorder (GAD)
[23]
8
Vatagajankush Rasa
Hartaki (Terminalia Chebula)
Gridhrasi (sciatica)
[22]
(References 19-22)
Updated Review on Traditional and Modern Aspects ??????????????? Current Traditional Medicine, XXXX, Vol. X, No. X
3
Table 2. Herbal products containing V. negundo, available in market.
S No.
Brand
Indication
Manufacturers (country)
Refs.
1
Antiseptic cream
Burns, wounds
Himalaya Drug co., Bangalore (India)
[23]
2
Dental cream
Bleeding gums, toothaches
3
Muscle and joint rub
Muscle strains
[24]
4
Pilex tablets and cream
Haemorrhoids
[24]
5
Rumalaya gel and tablets
Inflammatory muscoskeletal disorders
[24]
6
Liv 52
Detoxification of liver
[21]
7
V-gel
Cervicitis, vaginitis
[21]
8
Acne-n-pimple cream
Acne
[25]
9
Joint care b cream
Rheumatic disorders
[21]
10
Himcolin cream
Erectile dysfunction
[25]
11
Relieef cream
Stiff back, joint and muscle pain
Surya Herbal Ltd., Noida (India)
[24]
12
Ostranil gel
Lumbago, osteoarthritis
13
Amgesic arthritis tablets
Arthritis
Ambica Research & Development Pvt. Ltd., New Delhi (India)
[26]
14
Jigreen
Liver ailments
Hamdard Laboratories, New Delhi (India)
[25]
15
Syrup and tablet
Cough, asthma
Pascual Labs (Philippines)
[27]
16
Arthrill capsules
Joint pain, arthritis
IndSwift Ltd., Chandigarh (India)
[23]
17
Massage oil
Frozen shoulder, cervical spondylitis
(References 23-27)
Table 3. List of phytoconstituents present in different parts of V. negundo.
Plant Part
Class of Secondary Metabolite
Compound Name
Refs.
Leaves
Alkaloids
Nishindine
[25]
Aliphatic alcohol
Linalool; n-hentraiaconatol; p-hydroxybenzoic acid
[19]
Terpenes
α-Pine binene
[5]
Diterpenes
Vitexilactone
[27]
Sesquiterpenes
Viridiflorol; β-caryophyllene
[18, 26]
Glycoside
Luteolin-7-glucoside; 5, 7-dihydroxy-2- (3, 4-dihydroxyphenyl)-4H-chromen-4-one; 5-
hydroxy-3, 6, 7-trimethoxy-2-(3, n- 5, 6, 7, 8, 3’, 4’, 5’ Heptamethoxy
[25, 26]
Flavonoids
flavone; corymbosin; vitexicarpin; 5-hydroxy 3, 6, 7, 3’ 4- pentamethoxy flavone; 5-O-
desmethoxynobieletin flavone; 5, 7 dihydroxy- 6, 4' dimethoxy flavanone; 5 hydroxy-7,
4' dimethoxy flavone; 7, 8 dimethyl herbacetin-3-rhamnoside; casticin; artemitin; 4, 4-
dimethoxy trans- stilbene; gardenin A; gardenin B; 4, 5-diethyl-3′-ethoxy-pyro-flavone
[18, 28, 29]
Iridoid glycoside
Nishandaside; 2-p-hydroxybenzoyl mussaenosidic acid; negundoside; lagundinin;
aucubin; agnuside
[27]
Steroids
β-Sitosterone; β-sitosterone acetate; stigmasterone
[30]
Furanoeremo-philane
α-Cedrene
[27]
(Table 3) Contd…
Current Traditional Medicine, XXXX, Vol. X, No. X ????????????? Perveen et al.
4
Plant Part
Class of Secondary Metabolite
Compound Name
Refs.
Seeds
Lignans
Vitexdoin A-I; vitrofolal E; vitrofolal F; vitedoamine A; vitedoamine B; vitelignin A; 4-
oxosesamin; sesamin; vitexin
[30, 31]
Hydrocarbon
n- Tritriacontane; n- nonacosane; n- pentatriacontane; n- hentriacontane
[32]
Phenols
5- Oxyisophthalic acid; p-hydroxybenzoic acid; 3, 4 dihydroxybenzoic acid
[33]
Amino acids
Guanine; alanine; valine; leucine
[27]
Fatty acids
Lionleic acid; stearic acid; palmitic acid; oleic acid
[27]
Flavonoids
Chrysoplenetin; casticin chrysosplenol D; 4′, 5-dihydroxy-3, 6, 7- trimethoxyflavone
[30]
Stem bark
Phenols
Vanillic acid
[27]
Flavonoids
5- Hydroxy-3, 6, 7, 3ʹ, 4ʹ-pentamethoxy flavone; 4′-O- methylmyricetin-3-O-(4′-O-β-D-
galactosyl)-β-D-galactopyranoside; vitexin cafeate
[32]
Glycoside
Leucocyanidin-7-O-rhamnoglucoside
[27]
Sesquiterpenoids
4, 6-Dimethyl-11-dimethoxymethyl -1-oxo-4H,2,3-dihydronaphthofuran; 1, 6-dioxo-
2(3), 9(10)-dehydro-furanoeremophilane; 6-dimethyl-11-formyl-1-oxo-4H, 2, 3- dihy-
dro-naphthofuran
[30]
(References 28-33)
Table 4. Various extraction procedures performed on different parts of plant using specific solvents.
S No.
Parts of Plant Used
Extraction Procedure
Solvent Used
Purpose
Refs.
1
Leaves
Soxhlet extraction
Ethanol
Antioxidant activity
[34]
2
Leaves
Boiling
Water
Antioxidant activity
[34]
3
Leaves
Soxhlet extraction
Hexane & ethyl acetate
Antioxidant activity
[34]
4
Leaves
Percolation
Ethanol
Antifungal activity
[24]
5
Leaves
Soxhlet extraction
Petroleum, ether & chloroform
Phytochemical analysis & antioxidant activity
[24]
6
Leaves
Percolation
Petroleum ether, chloroform, ethyl acetate & methanol
Macrofilaricidal activity
[24]
7
Leaves
Cold extraction
Ethyl alcohol
Antioxidant & hypoglycaemic activity
[35]
8
Seed
Sonication
Methanol
Anticancer activity
[36]
9
Seed
Soxhlet extraction
Hydro-alcoholic [Aqueous+ alcohol]
Phytochemical analysis & antioxidant activity
[37]
10
Root
Reflux
Methanol
Antimicrofilarial activity
[38]
(References 34-38)
alkaloids, steroids [11], flavones and stilbene derivatives [5]
(Table 3) [28-33].
The chemical composition of the essential oil prepared
from the leaves of V. negundo are cis-ocimene, citronellal, β-
curcumene, α-guaiene, valencene, caryophyllene epoxide,
palmitic acid, α-murolol [21], δ-guaiene, α-selinene, β-
selinene, p-cymene [12], β-elemene, ledol, α-pinene, sabinene
[22] , β-phellandrene, caryophyllene, β-farnesene, epiglobulol
[23], β-terpinene, 4-terpineol, β-caryophyllene [22], thujene,
1-oceten-3-ol, β-pinene, myrcene, limonene, eugenol, hu-
mulene, δ-cadinene, γ-eudesmol [24].
The chemical constituents of the volatile oil prepared from
the flowering twigs of V. negundo are 3-hexen-1-ol, 2-
methylcyclopentanol, nonanol, sabinene hydrate, elemol, di-
hydromyrcenol, etc. [24]. Some of the flower and dried fruit
oil constituents of V. negundo are formic acid, n-heptane,
trans-α-bergamotene, germacren-4-ol, α-cedrene, α-copaene,
aristolene, guaia-3, 7-diene and germacrene D [21]. Structures
of some of the major phytoconstituents are shown in Fig. (1).
4. EXTRACTION PROCEDURE FOR ISOLATION OF
PHYTOCONSTITUENTS FROM V. NEGUNDO
For the analysis of the plant, extraction is an essential
step as it is important to isolate the required chemical com-
ponents to study further pharmacological activities of the
plant [25, 26]. Extraction is the process of separation of ac-
tive phytoconstituents of the plant using specific solvents
via standard protocol [27]. Some of the common techniques
used in the extraction processes are decoction, maceration,
percolation, soxhlet extraction [Hot continuous extraction],
microwave assisted extraction, counter current extraction,
ultrasound extraction [sonication], supercritical fluid extrac-
tion, accelerated solvent extraction and distillation techniques
either water or steam distillation. The solvents used in the
extraction processes are water, ethanol, methanol, chloroform,
ether and acetone [26]. The solvents are chosen on the basis
of the phytoconstituents being extracted [25]. Table 4 repre-
sents the different types of extraction procedures that have
Updated Review on Traditional and Modern Aspects ??????????????? Current Traditional Medicine, XXXX, Vol. X, No. X
5
Fig. (1). Structures of some of the major phytoconstituents; (a) Casticin (b) Isoorientin (c) luteolin (d) p-hydroxybenzoic acid (e) Sabinene
(f) Linalool (g) Terpinen-4-ol (h) β-caryophyllene (i) α-guaiene (j) Globulol (k) Negundoside (l) Vitexin (m) Vitexicarpin.
been performed on V. negundo for the isolation of phytocon-
stituents [34-38].
5. PHARMACOLOGICAL ACTIVITIES
The plant V. negundo has various phytoconstituents that
are present in different parts of the plants such as triter-
penes, lignans, flavonoids, alkaloids, etc., and because of
these phytoconstituents, the plant exhibits numerous biolog-
ical activities [6]. V. negundo shows anti-inflammatory,
antinociceptive [39], antioxidant, anticonvulsant [28], hepa-
toprotective and CNS depressant activity [12]. It also exhib-
its antimicrobial, anti-tumor, insecticidal, hypoglycemic
[29], anti-arthritic and larvicidal activity [5]. In modern
practises, the application of flowers of V. negundo cures
fever, diarrhoea, and hepatic problems and the fruits are
given in headaches and catarrh [18].
5.1. Anti-Inflammatory Activity
Inflammation is a condition that acts during acute agita-
tion of homeostasis, for instance, injury, infection, or vul-
nerability to some contamination. Inflammation is related to
many human diseases and conditions such as allergy, can-
cer, arthritis, atherosclerosis and autoimmune disorder [30].
The plant V. negundo is one of the best anti-
inflammatory plants as it has the richest source of vitamin C
[40]. The various extracts of V. negundo showed the anti-
inflammatory property in acute and sub-acute inflammation
[19] . The aqueous extract of the leaves of V. negundo re-
ports anti-inflammatory activity in Wistar male rats having
formaldehyde-induced and carrageenan-induced paw edema
[12]. The chloroform extract obtained from the seeds of the
plant exhibited anti-inflammatory effects in Sprague Daw-
ley rats (male) against carrageenan-induced edema. The
seeds, seed oil, bark, and volatile oil of V. negundo display
preliminary anti-inflammatory activity. It is also reported
that the ethanol leaf extract demonstrates anti-inflammatory
activity in albino rats of either sex in the cotton pellet granu-
loma model [41]. The hydro-alcoholic extract of V. negundo
leaves along with Murraya coenigii exhibited anti-
inflammatory activities in rats [31]. The petroleum ether leaf
extract of V. negundo exhibited anti-inflammatory action
against cotton pellet granuloma model and carrageenan-
induced hind paw edema [13]. The ethanolic extract of
flowers exhibited anti-inflammatory activity in albino
Wistar rats [32]. The ethanolic extract of the roots was ob-
served to reduce inflammation in adult albino rats [male] by
using plethysmometer method [33]. Studies reveal that the
chromone derivatives obtained from V. negundo had report-
ed anti-inflammatory activity [30]. Tris (2, 4-di-tert-
butylphenyl) phosphate (TDTBPP) is a novel compound
isolated from V. negundo leaves, which acts as an anti-
inflammatory drug that is used in the reduction of inflamma-
tion in the carrageenan-induced paw edema model. Vitexin,
a flavonoid, shows anti-inflammatory activity by regulating
the activation of macrophages and the recruitment of neu-
trophil [34]. Using AutoDock, virtual screening involves
docking of vitexin with three different targets responsible
for activating the collagenase enzyme. When compared to
Current Traditional Medicine, XXXX, Vol. X, No. X ????????????? Perveen et al.
6
docking results of TNF converting enzyme (TACE) and
human inhibitory kinase (hIK) proteins, the binding energy
of vitexin and TNF receptor1 (TNFR1) was found to be
slightly higher. BIOVIA discovery studio visualizer was
used to visualise the molecular interactions and it suggest-
ed vitexin has improved pharmacological benefits, which
must be confirmed using in vitro and in vivo tests [35].
Vitedoamine A and 6-hydroxy-4- (4-hydroxy-3-methoxy-
phenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-phtha
ldehyde), a lignin, shows anti-inflammatory activity in ear
edema test, where inflammation is induced by dimethyl
benzene [36]. The leaf extract of V. negundo can also be
taken orally along with the standard anti-inflammatory drug
such as phenylbutazone as an adjuvant treatment [37].
5.2. Analgesic Activity
Pain is a warning signal, which is defined as an unpleas-
ant sensory and emotional occurrence related to the actual
tissue or organ damage that causes discomfort [38]. For al-
leviating integumental and visceral pain, the plant V. negun-
do may be applicable [42].
The methanol and petroleum ether leaf extracts of V.
negundo showed peripheral analgesic properties in a dose-
dependent manner in young Swiss albino mice of either sex
by inhibiting writhing caused by acetic acid [43]. The meth-
anolic extract showed a higher analgesic effect than petrole-
um ether extract. The hydroalcoholic extract of V. negundo
leaves also exhibited central analgesic activity in mice in the
tail immersion test [5]. The aqueous extract of the mature
fresh leaves of V. negundo suppressed the pain and showed
analgesic activity in Wistar rats (female) using tail flick, hot
plate and formalin tests [44]. The analgesic activity of V.
negundo is because of the inhibition of prostaglandin syn-
thesis [42] and suppression of oxidative stress [45].
The methanolic root extract also exhibited analgesic ac-
tivity in albino rats of either sex using Eddy’s hot plate and
radiant heat tail-flick method [46]. The ethanolic extract of
V. negundo flowers also showed analgesic activity in Swiss
albino mice using the tail flick test and writhing test [32].
5.3. Antioxidant Activity
Antioxidants are substances which have a very signifi-
cant role in the human body's defence system. It inhibits or
delays the process of oxidation even at a very low concen-
tration [47]. The antioxidant elements of the plants act as
radical scavengers against free radicals and inhibit them
from causing problems related to human health like cancer,
heart disease, aging, etc. [12]. V. negundo comprises poly-
phenolic compounds, these compounds have high antioxi-
dant potential that results in the antioxidant activity of the
plant [48].
The methanolic leaf extract of V. negundo was evaluated
for its antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl
(DPPH) radical scavenging assay, lipid peroxidation inhibi-
tory assay [49], nitric oxide radical scavenging assay, hy-
drogen peroxide scavenging assay and superoxide scaveng-
ing assay [50]. The ethanolic leaf extract reports antioxidant
activity, in which DPPH assay, hydrogen peroxide scaveng-
ing assay, total antioxidant capacity assay [51], β-carotene
linoleic acid assay [52] and phosphomolybdenum assay [53]
were carried out. The antioxidant activity of hexane extract
and essential oil of the leaves of V. negundo was evaluated
via DPPH assay, ferric ion reducing antioxidant power
(FRAP) assay and β-carotene linoleic acid assay [54]. The
antioxidant activity of the essential oil was examined
through 2, 2’-azino-bis (3-ethylbenzthiazoline-6-sulphonic
acid) (ABTS) radical scavenging assay [55]. The acetone
and aqueous leaf extract of V. negundo exhibited antioxidant
activity by DPPH radical scavenging assay [56]. The antiox-
idant activity of chloroform extract of the leaves of V.
negundo was determined by phosphomolybdenum method
and nitric oxide scavenging assay [57]. The ether extract of
the leaves showed good antioxidant activity in DPPH assay
[58]. The leaf extract of V. negundo helped in lowering the
levels of superoxide dismutase, glutathione peroxidase, and
catalase in Freund’s adjuvant induced arthritic in a rat model
[19]. The antioxidant activity of V. negundo was studied in
rats using an oxidative stress model induced by ethanol [12].
The seed extract of V. negundo showed antioxidant activity,
which was evaluated using in vitro lipid peroxidation assay
in rat liver homogenate [59].
5.4. Antimicrobial Activity
Medicinal plants are considered an abundant source of
antimicrobial agents [60]. In 1998, Perumal et al. investigat-
ed 34 Indian medicinal plants for their antimicrobial activi-
ties using the disk diffusion method. They confirmed that
different extracts of leaves of V. negundo showed antimi-
crobial activity against various bacterial strains [13].
The aqueous leaves extract of V. negundo showed anti-
microbial activity against Staphylococcus aureus, Klebsiella
pneumoniae and Escherichia coli [61]. The methanolic ex-
tract of V. negundo leaves was tested for antimicrobial
properties against E. coli, Enterococci, S. aureus and
Klebsiella [62]. The methanol extract of V. negundo leaves
also showed antibacterial activity in both in vivo and in vitro
conditions. In in vitro conditions, it showed potent activity
against Vibrio cholerae epidemic strains, V. parahaemolyti-
cus pandemic strain, and various strains of V. mimicus, Shi-
gella, Aeromonas and E. coli using disk diffusion assay and
in the in vivo condition, the intestinal environment of the
infant mice, it showed activity against V. cholera [34]. An-
timicrobial effect of ethanol leaves extract was also studied
on E. coli, K. pneumoniae, S. aureus [63], Salmonella typhi
[64], S. paratyphi [65], Bacillus subtilis and Pseudomonas
aeruginosa [36]. The n-hexane and petroleum ether extracts
of leaves showed promising antimicrobial properties against
methicillin-resistant S. aureus [66], and the chloroform ex-
tract showed activity against P. aeruginosa and S. typhi
[64].The crude leaves powder extract showed good antimi-
crobial activity against B. subtilis and E. coli [67]. The su-
percritical fluid extract of leaves of V. negundo exhibited
significant antimicrobial activity against S. aureus and B.
subtilis [68]. The essential oil from the V. negundo leaves
showed antimicrobial activity against E. coli, S. aureus, P.
Updated Review on Traditional and Modern Aspects ??????????????? Current Traditional Medicine, XXXX, Vol. X, No. X
7
aeruginosa, B. subtilis [69], K. pneumoniae and Micrococ-
cus luteus [70]. The ethyl acetate extract of the V. negundo
flower and fruit showed antimicrobial activity against Xan-
thomonas axonopodis, p.v. citri and P. solanacearum [71].
The oil obtained from the V. negundo flower showed signif-
icant antimicrobial activity against P. aeruginosa [21] . The
ethanol, methanol, and aqueous extract of V. negundo bark
exhibited promising antimicrobial activity against S. aureus
and E. coli, whereas the petroleum ether and chloroform
extracts exhibited activity against S. epidermidis, S. aureus
and B. subtilis [63, 72]. The free and bound flavonoid ex-
tract of flower buds showed antimicrobial activity against K.
pnemoniae and Raoultella planticola, respectively [73] .
5.5. Antifungal Activity
V. negundo showed antifungal activity against phyto-
pathogenic fungi [74]. The chloroform and methanol extract
of bark showed the highest minimum inhibitory concentra-
tion against C. albicans [60]. The stem of V. negundo also
showed potent antifungal activity against Aspergillus niger
and C. albicans [75]. The ethanol extract of seeds of V.
negundo proved antifungal activity against Fusarium solani
(90%) and Microsporum canis (60%) and had no effect on
C. albicans [76]. The chloroform extract of leaves showed
antifungal activity against C. albicans and C. tropicalis,
whereas methanolic leaf extract showed activity against C.
albicans [77] and Penicillium sp. [64]. The ethanolic leaves
extract showed remarkable antifungal activity against Scle-
rotinia sclerotiorum [74] and C. albicans [64]. Benzene and
water: ethanol (1:1, v/v) extracts of leaves inhibited the
growth of Aspergillus niger, A. flavon and C. albicans [75].
The extract from V. negundo leaves exhibited antifungal
activity against Fusarium oxysporum, Colletotrichum trun-
catum, and Macrophomina phaseolina, which cause differ-
ent diseases of soybean [13]. The chemicals agnuside (-
5.8055), negundoside (-5.4376), and protocatechuic acid (-
5.0584) of V.negundo showed the least significant docking
scores when compared to others in a high throughput virtual
screening using schrodinger [78].
5.6. Anticonvulsant Activity
Epilepsy is a disorder of the brain that affects a large
number of the population, characterised by a long-term pre-
disposition to generate seizures with secondary neurobiolog-
ic, cognitive, psychological and social outcomes [79]. It
occurs because of the disordered, synchronous, and rhyth-
mic firing of brain neurons [80].
The oil isolated from the dried fruits of V. negundo
showed significant anticonvulsant activity by providing
100% protection against PTZ (pentylenetetrazole)-induced
clonic convulsions and in MES (maximal electroshock)-
induced convulsions, it eliminated the extensor phase dura-
tion. The essential oil extracted from V. negundo leaves
showed remarkable anticonvulsant activity in the PTZ-
induced clonic convulsion test [81].
The alcoholic root extract showed good anticonvulsant
activity in Swiss albino mice at a dose level of 750 mg/kg,
using MES and PTZ-induced convulsion methods [80]. The
petroleum ether extract of leaves and roots of V. negundo
showed anticonvulsant activity against MES and Leptazole-
induced convulsions, respectively [82].
The anticonvulsant activity of methanol leaf extract of V.
negundo has also been investigated using MES, PTZ,
strychnine, picrotoxin, and lithium-pilocarpine-induced
convulsions in swiss albino mice and albino Wistar rats. The
extract was found to be effective against MES-induced con-
vulsions, and in the PTZ-induced convulsion, the extract
displayed potentiating effect [83]. The ethanol extract of
leaves exhibited anticonvulsant activity in Swiss mice with
PTZ-induced seizures. Moreover, the anticonvulsant actions
of valproic acid and diphenylhydantoin are potentiated by
the ethanolic extract of V. negundo, indicating its applica-
tion in adjuvant therapy [28]. The ethanolic extract was also
tested for its anticonvulsant activity using MES in albino
rats and was found effective at a 2000 mg/kg dose level
[84].
5.7. Anxiolytic Activity
Anxiety is an emotion that actually occurs in response to
perceived fear and apprehension. It can be seen in many
individuals, and it could be transient or episodic [85]. About
one-eighth of the world’s population is affected by anxiety.
In recent years, it has been discovered that the secondary
metabolites produced by some of the plants can directly or
indirectly act as an anxiolytic drug [82].
The ethanolic extract of the leaves of V. negundo
showed anxiolytic activity in Swiss albino mice using an
elevated plus maze test [85]. The ethanolic root extract has
reported anxiolytic activity in Swiss albino mice [male] us-
ing light-dark exploration and elevated plus maze test [86].
The anxiolytic action of the stem of V. negundo was
studied using an elevated plus maze test in laca mice, and it
was found that the aqueous extract of the stem showed
moderate anxiolytic activity [87].
5.8. Hepatoprotective Activity
The liver is an essential organ of the human body and
helps in metabolism and excretion processes [88]. Liver
diseases such as jaundice and cirrhosis are more prevalent
nowadays and are the major cause of mortality [89]. Many
medicinal plants have been explored for their hepatoprotec-
tive activity, and one amongst them is V. negundo [90].
The aqueous leaf extract of V. negundo was studied for
hepatoprotective activity in carbon tetrachloride intoxicated
albino rats at 500 mg/kg body weight. It showed a signifi-
cant reduction in enzyme level (alanine transaminase (ALT),
aspartate aminotransferase (AST), alkaline phosphatase
(ALP) and bilirubin) and an increase in total protein level
[90].
The ethanolic extract of leaves showed hepatoprotective
activity in Wistar albino rats against ibuprofen-induced
hepatotoxicity [91], toxicity induced by the amalgamation
of three anti-tubercular drugs (rifampin, isoniazid and pyra-
Current Traditional Medicine, XXXX, Vol. X, No. X ????????????? Perveen et al.
8
zinamide) [92] and hepatic injury induced by paracetamol
[89]. The ethanolic extract was also reported for the hepato-
protective effect against thioacetamide (TAA)-induced
hepatotoxicity in Sprague Dawley male rats [88]. The hepa-
toprotective activity shown by the ethanolic extract of V.
negundo could be because of the presence of higher content
of flavonoids [91].
Negundoside (2'-p-hydroxy benzoylmussaenosidic acid),
an iridiod glycoside that is extracted from the leaves,
showed hepatoprotective activity against CYP2E1-
dependent carbon tetrachloride-induced hepatotoxicity in
HuH-7 liver cells by enhanced intracellular calcium homeo-
stasis, reduction of lipid peroxidation and inactivation of
Ca2+ dependent proteases [93].
The seed of V. negundo have been investigated for hepa-
toprotective activity and it was reported that the alcoholic
extract of seed has a protective effect in rats against carbon
tetrachloride-induced liver damage [13].
5.9. Anticancer Activity
Cancer is a fatal disease that is identified by an irregular
proliferation of the cells [1] and sometimes metastasis i.e.,
the spreading of cancerous cells from one part of the body to
another [94]. In both developed and developing countries,
cancer has become a vital health burden [95]. The plant V.
negundo has been extensively studied for its anticancer ac-
tivity [13].
5.9.1. Preclinical Studies
Lignans are a group of polyphenolic antioxidants present
in plants that are widely used for cytotoxic studies. A mix-
ture of lignan compounds was isolated from V. negundo
seeds, and it was titled EVn-50. The two major neolignans
present in EVn-50 are VB1, i.e., 6-hydroxy-4- [4hydroxy-3-
methoxyphenyl]-3-hydroxymethyl-7-methoxy-3, 4-dihydro-
2 naphthaldehyde and VB2 i.e., 6-hydroxy-4-[4-hydroxy-3-
methoxyphenyl]-3-hydroxymethyl-5-methoxy-3, 4-dihydro-
2-naphthaldehyde. EVn-50 showed anticancer activity
against breast cancer cells (SK-BR-7, MCF-7, MDA-MB-
231, MDA-MB-435s and ZR-75-1), prostate cancer cells
(PC-3 and LNCaP) and ovarian cancer cells (COC1). The
purified lignan VB1 also possessed strong anticancer activi-
ty against ZR-75-1, MDA-MB-231, COC1, and MCF-7
cells in a dose-dependent manner via down-regulating
Bcl2/Bax ratio and activating caspases [96]. The cytotoxic
effect of EVn-50 was also studied on lung cancer (A549,
SPC-A4), liver cancer (SMMC-7721, BEL-7402), ovarian
cancer (SKOV-3, HO-8910), gastric cancer (SGC-7901,
MKN-45), kidney cancer (786-O), pancreatic cancer
(BXPC-3, campan-1), colon cancer (HCT-116, HT-29) cell
lines and myelogenous leukemia showing broad spectrum in
vitro anticancer activity of EVn-50 [97]. The effect of neo-
lignan VB1 was also tested on hepatocellular carcinoma
cells (Hep3B, HepG2, and Huh-7) and human embryo liver
cells (L-02) via MTT assay. The most sensitive cell line to
VB1 was HepG2, and the least sensitive was L-02 [98]. The
methanol extract and n-hexane soluble fractions of V.
negundo bark showed good cytotoxicity against the THP-1
cell line via brime shrimp lethality bioassay [99].
The methanolic extract of fruits of V. negundo has re-
ported anticancer activity against human pancreatic cancer
cells (PANC-1). Phytochemical analysis resulted in the ex-
traction of the two most active constituents, i.e., chryso-
splenol D and chrysoplenetin. The isolated active compound
chrysoplenetin was further evaluated against a panel of 39
human cancer cell lines (JFCR-39) and it was found that the
compound was cytotoxic to many of the cell lines at submi-
cromolar concentration. The most sensitive cells of the
JFCR-39 are the lung (NCIH522), prostate (PC-3), and
ovarian (OVCAR-3) cells with GI50 values of 0.12, 0.17
and 0.18 µM, respectively [100]. The hydroalcoholic extract
of the aerial parts was tested against EAC (Ehrlich ascites
carcinoma) and DAL (Dalton’s ascites lymphoma) cell
lines, and it was confirmed that the extract shows notable in
vitro cytotoxic activity [5].
The ethanolic extract of leaves was analyzed for its anti-
cancer activity against DAL cell line-induced tumor in
Swiss albino mice. The experimental criteria used for as-
sessing its anticancer activity were viable tumor cell count,
tumor volume, mean survival time, and increase in life dura-
tion. It was observed that the ethanolic leaf extract exhibited
anticancer activity as the life span of the mice treated with
the extract increased as compared to the control group [101].
In a chemosensitive cytotoxic assay, the ethanolic extract of
V. negundo displayed a cytotoxic effect against the L-929
(mouse lung fibroblast) cell line [101]. The antitumor activi-
ty of ethanolic leaf extract of V. negundo was tested against
EAC cell lines (in vivo) bearing Swiss albino mice. The
mice treated with the extracts of V. negundo showed in-
creased life span, decreased tumor volume, and an increase
in non-viable cell count in a dose-dependent manner, there-
by confirming the good antitumor activity of V. negundo
[94]. The antitumor activity of V. negundo was studied
against WRL68 and HepG2 cells using MTT assay. The
ethanolic extract of the fresh leaves showed cytotoxicity
against HepG2 cells in a dose and time-dependent manner.
No cytotoxic effect of the extract was recorded on WRL68
cells. The cytotoxic activity of the ethanol extract on HepG2
cells was because of caspase dependent apoptotic death,
which might be due to the presence of flavones and glyco-
sides [102].
The in vivo anticancer activity of V. negundo leaves
aqueous extract was tested on DAL bearing Swiss albino
mice. It was observed that the extract reduced the weight of
the tumor and increased the life span of the mice treated
with aqueous extract by 65%, hence confirming the anti-
cancer activity of V. negundo [103].
The acetone extract of leaves of V. negundo showed an-
titumor potential against EAC bearing adult Swiss albino
mice (male). It was observed that at 200 µg/ml concentra-
tion, 88% of the EAC cells were found to be dead [104].
The cytotoxic effect of the ethyl acetate and hexane extracts
of leaves was studied against Artemia salina nauplii. The
ethyl acetate extract showed 93.5 % mortality at 200 ppm,
Updated Review on Traditional and Modern Aspects ??????????????? Current Traditional Medicine, XXXX, Vol. X, No. X
9
and the hexane extract showed 79.2% mortality at 200 ppm
[105].
The chloroform extract of V. negundo leaves showed a
remarkable cytotoxic effect against Lu1 (human lung can-
cer) cell line with an IC50 value of 3.4 µg/ml. The bioassay-
guided fractionation led to the identification of vitexicarpin
as a major component. The compound vitexicarpin isolated
from the chloroform extract showed broad cytotoxicity
against a number of human cancer cell lines such as HU-
VEC (human umbilical vein endothelial), hTERT-RPE1
(human telomerase reverse transcriptase retinal pigment
epithelial), LNCaP (human hormone-dependent prostate
cancer) and Lu1. The cytotoxic effect of vitexicarpin can be
enhanced by producing its different derivatives. One of the
acylated derivatives 5,3’-dihexanoloxy-3,6,7,4’-
tetramethoxyflavone has also shown a good cytotoxic effect
on all above-mentioned cell lines except the Col2 (human
colon cancer) [106].
The crude methanol extract from V. negundo leaves was
partitioned into petroleum ether and carbon tetrachloride
fraction using kupchan method. The antitumor activity of
these extracts was screened using brine shrimp lethality bio-
assay against Artemia salina. The petroleum ether and car-
bon tetrachloride extracts showed a notable cytotoxic effect
with LC50 values of 1.55 and 1.56 µg/ml, respectively
[107]. The methanolic extracts of V. negundo leaves were
reported to have a cytotoxic effect on the THP-1 leukemia
cell line [108] and SH-SY-5Y (human neuroblastoma cells),
which was determined by MTT assay [109]. The aqueous
and ethanolic extract of V. negundo was analysed for its
antiproliferative activity against MCF-7 cell line. The aque-
ous and ethanolic extract at 500 µg/ml showed 36.44% and
39.04% viability, respectively [110]. The methanolic extract
showed antitumor activity against Agrobacterium tumefa-
ciens strains AtS10105, AtTa0112, and AtAc0114 using
potato disc bioassay [111].
The antitumor activity of Vitexin compound 1 (VB1),
that is isolated from V. negundo seeds, was studied on the
human choriocarcinoma cell line (JEG-3). It was observed
that VB1 restricts the proliferation of choriocarcinoma in
SCID mice (female). In JEG-3 cells, Vitexin compound 1
prohibits the proliferation of cells, induces apoptosis via a
caspase mediated cascade and prevents mTOR signalling
[112]. The antiproliferative activity of VB1 was also tested
against A375, Sk-Mel-5 and Sk-Mel-28 cell lines, which are
human malignant myeloma cell lines [113] Vitexin Com-
pound 1, a Novel Extraction from a Chinese Herb, Sup-
presses Melanoma Cell Growth through and colorectal cell
line (HCT116 and LoVo) by CCK-8 assay. VB1 also pro-
motes apoptosis through PUMA (p53 upregulated modula-
tor of apoptosis) dependent pathway. In cancer cell lines,
PUMA is an essential activator of apoptosis [114]. Luteolin,
extracted from V. negundo exhibited antitumor activity be-
cause it acts as a eukaryotic topoisomerase I inhibitor,
which further inhibits the synthesis of DNA [115].
The anticancer activity of silver nanoparticles against
HepG2 (hepatocarcinoma) cells [116], HCT15 and HT29
colon cancer cell lines were carried out. The compound
SPHT (sodium para-hydroxybenzoate tetrahydrate) isolated
from V. negundo was used as a reducing agent in the bio-
synthesis of Ag nanoparticles. The in vitro cytotoxicity of
silver nanoparticles was evaluated using MTT assay. The
results showed that at a very low concentration, SPHT-silver
nanoparticles showed good anticancer activity. This con-
cluded that the plant-based silver nanoparticles possess sig-
nificant anticancer activity, and they can be further used for
clinical studies [117]. Also, Using AutoDock 4.2 and Auto-
Dock Vina, computational techniques will aid in the identi-
fication and screening of lead compounds. The use of com-
putational approaches will aid in the identification and
screening of leads. We gathered six phytochemicals from
the literature and tested their inhibitory effect on Wnt-
associated signalling proteins in this study. AutoDock was
used to authenticate phytocompounds and Wnt-associated
signalling proteins [118]. In an investigation by Prasad M E.
et al., [119] all docked substances were discovered to have
an interaction with the Adenosine receptor via an oxygen
atom. All docked compounds and GLY 135, GLN 137,
GLN 140, HIS 143, GLU 145, GLN 145, GLN207, ASP
209, HIS 232, THR 300, and HIS 311 established common
H-bonding interactions in the binding pocket. The docking
results were consistent with in vitro data, which demonstrat-
ed that 5,3′-dihydroxy-7,8,4′-trimethoxyflavanone had
stronger Adenosine receptor inhibitory action than other
drugs.
5.9.2. Mechanism of Action
5.9.2.1. Induction of Apoptosis
Apoptosis is a process of programmed cell death that is
shown by normal cells, and dysregulation of apoptosis can
lead to cancer [120]. The compounds extracted from V.
negundo are reported to have anticancer activity by induc-
tion of apoptosis. The EVn-50 activated caspases (caspase-3
and caspase-9) from its proforms, and the activated caspases
further activate poly (ADP-ribose) polymerase (PARP), i.e.,
a 116 kDa protein, leading to its cleavage into a C- terminal
fragment (85kDa), which is a significant biomarker of apop-
tosis. Bax and Bcl-2 also played a major role in the process
of apoptosis [96, 121]. In many cancers, Bcl-2 is highly ex-
pressed and causes initiation and progression of cancer and
resistance to medications. EVn-50 treatment on cancerous
cells showed a notable decline in Bcl-2 and a relatable ele-
vation in Bax protein. This resulted in the increase of
Bax/Bcl-2 ratio, which causes apoptosis and further explains
the anticancer mechanism of V. negundo [96].
In most of the cancer cells, AKT is constitutively active
and promotes cell survival and resistance to apoptosis.
ERK1/2 kinase regulates various activities ranging from
gene expression to apoptosis, mitosis, and metabolism. VB1
induced apoptosis in cancer cells by inhibition of AKT by
siRNA and ERK1/2 by MEK1/2, which synergistically acti-
vated FOXO3a transcription factor, i.e., a downstream me-
diator of AKT and ERK1/2 kinases. The activation of the
FOXO3a transcriptional factor leads to the upregulation of
Current Traditional Medicine, XXXX, Vol. X, No. X ????????????? Perveen et al.
10
TRAIL, DR4, Bim, and DR5 proteins, which are apoptosis
associated target gene products. Thus, VB1 appears to be a
vital agent for the prevention and treatment of cancer [98,
122].
5.9.2.2. Cell Cycle Arrest
The neolignan compound VB1 showed anticancer activi-
ty by arresting the cells at the G2/M phase. The cell cycle
arrest by VB1 occurred by a different-mechanisms:
Ø Tubulin destruction: The G2/M phase arrest is a
standard phenomenon induced by anti-tubulin
drugs. VB1 also induces cell cycle arrest by dam-
aging tubulins and hence acts as an antitubulin
drugs [97].
Ø Phosphorylation of Ser 10 of Histone 3: The ser
10 phosphorylation of histone 3 is a marker of mi-
totic cells and is associated with condensation of
the mitotic chromosomes. The exposure of VB1 to
cancer cells elevated the levels of phosphorylated
Ser 10 of histone 3, indicating that the cells are ar-
rested at G2/M phase [97].
Ø Inactivation of Cdk1/cyclin B complex: The pro-
gression of the eukaryotic cell cycle requires acti-
vation of Cdks, i.e., cyclin dependent kinases,
which is associated with regulatory cyclins. A
complex between Cdk1 and cyclin B1 is important
for the progression of cells to M phase. VB1 treat-
ment increased the expression of cyclin B1, which
is followed by increased phosphorylation of Cdk1
at Tyr15, which is a critical phosphorylation site
for restricting the function of Cdk1. Moreover, the
higher level of phosphorylation was further sup-
ported by a decrease in the expression of Cdc25C, a
phosphatase, which helps in the removal of the
phosphate groups at Tyr15 of Cdk1, once the cells
are ready to enter the M phase. These observations
suggest that the treatment of VB1 inactivated
Cdk1/cyclin B complex and resulted in cell cycle
arrest [97]. Fig. (2) shows the different anticancer
mechanisms by which V. negundo exerts its cyto-
toxic effect.
CONCLUSION
V. negundo is an essential medicinal plant used in Unani,
Ayurveda, Siddha, Chinese, Roman, and other traditional
medicinal systems. The plant has a lot of potential as a
common medicinal plant, and it is no surprise that it is
known in Indian traditional circles as sarvaroganivarini,
which means remedy for all diseases. There is a large
amount of literature on various aspects of the plant, from
traditional to biochemical, ethnobotanical to pharmacologi-
cal; however, many gaps remain. The aim of this review is
to collect information on its medicinal properties, phyto-
chemical and pharmacological activities, traditional uses,
and scientific approaches derived from research using con-
temporary scientific methods and innovative scientific tools.
Plant extracts have traditionally been used to treat a wide
range of human diseases. Anti-diabetic, antibacterial, anti-
inflammatory, antifungal, antinociceptive, anti-androgenic,
Fig. (2). Anticancer mechanism of V. negundo via cell cycle arrest and activation of apoptosis. (A higher resolution / colour version of this
figure is available in the electronic copy of the article).
Updated Review on Traditional and Modern Aspects ??????????????? Current Traditional Medicine, XXXX, Vol. X, No. X
11
anticonvulsant, antioxidant, and antitumor agents have all
been found in the chemical components of this plant.
CONSENT FOR PUBLICATION
Not applicable.
FUNDING
None.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
Declared none.
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