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590 Chiang Mai J. Sci.

2014; 41(3)

Chiang Mai J. Sci. 2014; 41(3) : 590-605


http://epg.science.cmu.ac.th/ejournal/
Contributed Paper

Wedelia trilobata L.: A Phytochemical and


Pharmacological Review
Neelam Balekar [a,b], Titpawan Nakpheng [a] and Teerapol Srichana*[a,b]
[a] Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University,
Hat-Yai, Songkhla 90112, Thailand.
[b] Department of the Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla
University, Hat-Yai, Songkhla 90112, Thailand.
*Author for correspondence; e-mail: teerapol.s@psu.ac.th
Received: 8 November 2012
Accepted: 11 July 2013

ABSTRACT
Studies on the traditional use of medicines are recognized as a way to learn
about potential future medicines. Wedelia is an extensive genus of the family Asteraceae,
comprising about 60 different species. Wedelia trilobata Linn. has long been used as
traditional herbal medicine in South America, China, Japan, India and for the treatment
of a variety of ailments. The aim of this review was to collect all available scientific
literature published and combine it into this review. The present review comprises the
ethnopharmacological, phytochemical and therapeutic potential of W. trilobata. An
exhaustive survey of literature revealed that tannin, saponins, flavonoids, phenol,
terpenoids constitute major classes of phytoconstituents of this plant. Pharmacological
reports revealed that this plant has antioxidant, analgesic, anti-inflammatory,
antimicrobial, wound healing, larvicidal, trypanocidal, uterine contraction, antitumor,
hepatoprotective, and in the treatment of diabetes, menstrual pain and reproductive
problems in women. W. trilobata seems to hold great potential for in-depth investigation
for various biological activities, especially their effects on inflammation, bacterial
infections, and reproductive system. Through this review, the authors hope to attract
the attention of natural product researchers throughout the world to focus on the
unexplored potential of W. trilobata, and it may be useful in developing new formulations
with more therapeutic value.

Keywords: Wedelia trilobata (L.), ethnopharmacological use, phytochemistry,


pharmacological activity

1. INTRODUCTION
The manufacture and clinical evaluation significant contribution to the delivery of
of herbal remedies and/or their healthcare [1]. Many medicinal plants
constituents have made it possible to contain large amounts of antimicrobial and
transform traditional medicine into a antioxidant compounds such as phenols
modern industry capable of making a and flavonoids. Phenolic compounds are a
Chiang Mai J. Sci. 2014; 41(3) 591

group of plant metabolites that have forests, forest margins, open woodlands,
numerous beneficial activities such as waterways, lake margins, wetlands,
anti-inflammatory, anti- bacterial, anti- roadsides, disturbed sites, waste areas,
mutagenic, anti-viral and antioxidant vacant lots, and coastal sand dunes in
properties [2]. This revival of interest in tropical and sub-tropical regions. It may
plant derived drugs is mainly due to the also encroach into lawns, footpaths and
current widespread belief that green parks from nearby gardens [7, 8].
medicine is safe, and clinically effective,
better tolerated by patients, less expensive 2.2 Geographical Distribution
and globally competitive [3,4]. Use of Native to Mexico, Central America
medicinal plants is becoming popular in (i.e. Belize, Costa Rica, Guatemala,
United States and Europe [5] and in most Honduras, Nicaragua and Panama), the and
of the developing world, plants or herbal throughout the Caribbean, where it is noted
products have forever played important as a weed in Trinidad, Puerto Rico, the
roles in the treatment of wounds, intestinal Dominican Republic, Jamaica, Panama, and
problems, coughs and sneezes, general tropical South America (i.e. French Guiana,
torpor etc [6]. Guyana, Surinam, Venezuela, Brazil, Bolivia,
Traditional knowledge about medicinal Colombia, Ecuador and Peru). Naturalized in
plants has without doubt served as an South Africa, Florida, Louisiana, Hawaii, Puerto
example for developing new drugs. Over Rico, and the Virgin Islands. Escaped in many
the past decades, it has been shown that tropical regions of the world, including
Wedelia trilobata L. contains high amount Australia (South-eastern Queensland and
of diterpene, eudesmanolide lactones and north-eastern New South Wales), the Pacific
luteolin with a variety of biological activities. Islands (i.e. American Samoa, the Cook
This review assesses the scientific information Islands, Fiji, French Polynesia, Guam,
on W. trilobata and focuses on the evidence Kiribati, the Marshall Islands, Nauru,
available on its therapeutic benefits. Niue, New Caledonia, Palau, Western
Wedelia, known officially by the scientific Samoa, Tonga and Hawaii), Malaysia,
name, Sphagneticola trilobata (L.) Pruski, but still Indonesia, Thailand, India, Papua New
commonly referred to by its former name, Guinea [9, 10].
W. trilobata (L.) Hitchc is a member of the
family Asteraceae (formerly Compositae), the 2.3 Scientific Classification
sunflower or daisy family. W. trilobata is a soil Kingdom: Plantae Plants; Subkingdom:
creeper and forms a thick carpet. The genus Tracheobionta Vascular plants; Super-
Wedelia, named in honor of Georg Wolfgang division: Spermatophyta Seed plants;
Wedel (1645-1721), Professor of Botany at Division: Magnoliophyta Flowering
Jena, Germany, has about 70 species of plants; Class: Magnoliopsida Dicotyledons;
tropical and subtropical regions. W. trilobata Subclass: Asteridae; Order: Asterales;
is a very attractive plant because of its nearly Family: Asteraceae Aster family; Genus:
constant and prolific blooming [7]. Sphagneticola O. Hoffmann creeping-
oxeye; Species: Sphagneticola trilobata (L.)
2. DESCRIPTION Pruski Bay Biscayne creeping-oxeye [9].
2.1 Habitat
A weed of urban bushland, closed
592 Chiang Mai J. Sci. 2014; 41(3)

2.4 Synonyms (glabrous), and slightly fleshy (succulent)


Complaya trilobata (L.) Strother, Silphium in nature. The single attractive bright-
trilobatum L., Thelechitonia trilobata (L.) H.Rob. yellow flower heads are daisy-like in
& Cuatrec., Wedelia carnosa Rich., Wedelia appearance and are borne on the end of
paludosa DC., Wedelia trilobata (L.) A.S. Hitchc., terminal and axillary stalks (peduncles) 2
Wedelia triloba (Rich.) Bello [9]. to 9 cm long, with 2 to 4 series of bracts
forming the involucre at the base of the
2.5 Common Names flower. Each flower-head has 8-13 yellowish
Atiat (Puluwat), Bay Biscayne creeping petals (ray florets) that are 6-15 mm long
oxeye, creeping daisy, creeping wedelia, with 1- to 3 finely toothed tips and are
rabbits paw, Singapore daisy, gold cup, yellow pistillate. In the centre of these flower-heads
dots, trailing daisy, water zinnia and wild there are numerous tiny yellow tubular disc
marigold (English), hansenfuss (Germany), florets 4-5 mm long, and mixed with chaffy
America hama-guruma (Japan), di jin hua bracts. The ray and disc florets are both
(China), kra dum tong (Thailand), wedelia yellow. The base of each flower-head
kuning (Malaysia), Singapore-madeliefie (capitulum) is enclosed in a row (involucre)
(Africa), ampelkrage (Sweden), ut telia of narrow (lanceolate) green bracts (about 1
(Marshall Islands), and arnica-do-mato, cm long). Flowering occurs throughout the
pseudo-arnica, vedelia (Brazil) [10]. year, but is most common from spring to
autumn. The fruit is a 2 to 4-angled achene,
2.6 Botanical Description with short, narrow pappus scales on the top
It is a long lived (perennial) herb with [11]. The seeds (i.e. achenes), when present,
a creeping or climbing habit. This mat- are 4-5 mm long and topped with a crown
forming herb often creates a dense ground of short fringed scales. They are elongated in
cover (usually 15-30 cm tall but occasionally shape, brown in colour and have a rough
upto 70 cm tall) that crowd out the growth surface texture. However, very few seeds
of other species. It may also climb a short reach maturity in cultivated or naturalised
distance up trees or over other vegetation. plants in Australia [12].
The stems are rounded, green or reddish
in color, and may be coarsely hairy. They
grow up to 2 m long and regularly develop
roots (adventitious roots) at their nodes.
Short, semi-upright (ascending), flowering
branches are produced of these creeping
stems. The leaves are attractive, bright shiny
green, somewhat fleshy oppositely arranged
and simple, the blade obovate to elliptic or
ovate and are stalkless (sessile) or borne
on short stalks (petioles). These leaves 2-9
cm long and 2-5 cm wide, acute at the apex
and winged and sessile at the base usually have
three lobes (hence the name trilobata) and
irregularly toothed (serrated) margins. They are Figure 1. Photograph of Wedelia trilobata
glossy in appearance, mostly hairless Linn.
Chiang Mai J. Sci. 2014; 41(3) 593

2.7 Ethnopharmacological Uses stopping of urine and for infections. Boiled


The aerial parts of this plant are used fresh stems and leaves were used for bathe
in traditional medicine in the Caribbean those suffering from backache, muscle
and Central America against bronchitis, cramps, rheumatism, or swellings. Used for
colds, abdominal pains, dysmenorrheal painful joints of arthritis, fresh leaves and
[13], and even as a fertility enhancer [14]. stems are mashed and spread on a cloth and
In folk medicine, it is employed to treat applied to area, wrapped securely with a
backache, muscle cramps, rheumatism, warm covering in South America. Wedelia
stubborn wounds, sores and swellings, and species is used in lower Thailand for
arthritic painful joints [15]. The Miskito headache and fever [22].
Indians of eastern Nicaragua use leaves for
treatment of kidney dysfunctioning, cold, 2.8 Phytochemical Reports
stingray wounds, snakebite, purge and The main secondary metabolites from
amenorrhea [16,17]. Coe and Anderson this plant mainly consist of terpenoids,
(1996) reported that fruits, leaves and stem flavonoids and polyacetylenes as well as
are used in childbirth and in the treatment steroids [20, 23-25]. The leaves and stem
of bites and stings, fever and infection [14]. contains eudesmanolide lactones, luteolin
W. trilobata, was utilized in Hong Kong and kaurenoic acid [26,27]. It has following
as a substitute for W. chinensis, a traditional different classes of phytoconstituents.
Chinese medicine used for the treatment Sesquiterpenoids, triterpenoid and
of the common cold, hepatitis, indigestion diterpenoid: from the aerial part [18,20, 23-
and infections [18]. In Trinidad and 25, 28-34] and the flower of W. trilobata,
Tobago, used for reproductive problems, [18,20, 23-25, 28-35], sterols: [23,25,31],
amenorrhea, dysmenorrheal [19]. It is used flavonoids: [25], Benzene derivatives: [25,
for the treatment of fever and malaria in 31].
Vietnam [20]. Wedelolactone was reported for
Unpublished reports indicate that hepatoprotective activity, antibacterial,
aqueous infusion has been employed anti hemorrhagic and antiepileptic activity
locally and empirically in Southern part of [36-38]. These necessitate estimation of
Brazil in the management of diabetes. In wedelolactone in Wedelia species for
fact, it is popularly referred to as insulina exploring its bioactivity. Wedelolactone
due to its observed antidiabetic properties was estimated by high performance thin
[20]. Flowers and leaf part of the plant were layer chromatographic technique. The
used in the ladies for the purpose of standard wedelolactone showed retention
amenorrhea, childbirth, abortion and to factor (Rf) value of 0.56 and this constituent
clear the placenta after birth [21,22]. The was found to be present in the tested
literature review reveals that the fresh ethanolic extract of W. trilobata. The Rf
entire plant is used as molluscicidal activity, values obtained for wedelolactone in the
antibacterial and antimycobacterial extracts was found to be 0.56. The amount
activity [21]. of wedelolactone was estimated by comparing
Surinames traditional medicine uses the peak area of standard and that present
the stem, leaves, and flower boiled in water in the ethanolic extract. The content of
for hepatitis, indigestion due to sluggish wedelolactone present in the extract was
liver, white stools, burning in the urine and found to be 0.084% w/w [21].
594 Chiang Mai J. Sci. 2014; 41(3)

Essential oils are valuable plant products decreased vitamin C and reduced
generally of complex composition glutathione in liver and kidney tissues of
comprising the volatile principles contained STZ-treated rats. In vitro data revealed that
in the plant and more or less modified W. trilobata caused an inhibition of lipid
during the preparation process. Most peroxidation under Fe 2+ or sodium
constituents of oil belong to the large group nitroprusside assaults. Conversely, W.
of terpenes. The essential oil obtained from trilobata also caused a reduction in the high
the leaves of W. trilobata was analyzed by levels of thiobarbituric acid reactive
GC/MS. - pinene (above 30%), - substances (TBARS) observed in the liver,
phellandrene (17.4%) and limonene (16.3%) kidney, and testes as well as high serum
were the major components [39]. triglyceride, ALT and AST of diabetic rats
The fourteen volatile components [41]. Rungprom et al. (2010) demonstrated
were identified from the essential oils of that the methanolic extract of W. trilobata
W. trilobata leaves, stem and flowers. The was found to be the potent -glucosidase
essential oil was characterized by a high inhibitor comparable to the authentic drug,
percentage of hydrocarbon sesquiterpenes Acarbose [42].
(HS) (25.5-86.4%), hydrocarbon monoterpenes Table 1. Secondary metabolites of Wedelia
(HM) (22.9-72.3%) and low levels of trilobata (L.)
oxygenated sesquiterpenes (OS) (0.0- 7.4%). Compound name Structure Plant part References

The major components of volatile oils were Diterpenes Aerial part 25, 32-35
ent-kaur-16-en-19 oic
germacrene D (11.9-35.8%), -phellandrene acid (Kaurenoic acid)

(1.4-28.5%), -pinene (7.3-23.8%), ent-kaura-9(11), 16- Aerial part 25, 31, 33


E-caryophyllene (4.6-19.0%), bicycloger- dien-19 oic acid
(Grandiflorenic acid) leaves 35
macrene (6.0-17.0%), limonene (1.8-15.1%)
ent-kaura-9(11), 16- Aerial part 25
and -humulene (4.0-11.6%). The content dien-19 oic acid
methyl ester
of the monoterpenes -pinene, -
phellandrene and limonene increased from 3- (senecioyloxy)-
ent-kaur-16-en-19 oic
Aerial part 32

the mid-rainy season until the middle of acid

the next dry season [40]. Table 1 shows the (3)-3-(angeloyloxy)- Aerial part 23-25, 32
ent-kaur-16-en-19 oic
chemical structures of phytoconstituent acid
present in W. trilobata. 3-(angeloyloxy) 9- Aerial part 23
hydroxy-ent-kaur-16-
en-19 oic acid
2.9 Pharmacological Activities Methyl-3-
(angeloyloxy) 9- Aerial part 23
Table 2 summarizes the pharmacological hydroxy-ent-
activity of W. trilobata. kaurenoate

(3)-3-(tiglinoyloxy)- Aerial part 23-25


ent-kaur-16-en-19 oic
Antidiabetic Activity acid

Male albino rats with diabetes induced (3)-3- Aerial part 23-25, 32
by the administration of streptozotocin (cinnamoyloxy)-ent-
kaur-16-en-19 oic acid
(45 mg/kg, i.v.) were treated with oral
(3)- (cinnamoyloxy)- Aerial part 23
administration of W. trilobata (50 mg/kg). 9 hydroxy-ent-kaur-
16-en-19 oic acid
It was found to reduce blood glucose levels Methyl-3-
and improved weight gained which was (cinnamoyloxy)-9 -
hydroxy-ent-
Aerial part 23

accompanied by a marked restoration of kaurenoate


Chiang Mai J. Sci. 2014; 41(3) 595

Table 1. Continued. Table 1. Continued.


Compound name Structure Plant part References Compound name Structure Plant part References

15-(cinnamoyloxy)- Aerial part 32 Wedelolide B Leaves 20


ent-kaur-16-en-19 oic
acid
(3)-3-
(cinnamoyloxy)-17- Aerial part 25 Wedelolactone Entire plant 21
hydroxy-ent-kaur-15-
en-19 oic acid
(Wedelidin A)
(3)-3- Ivalin Aerial part 25
(cinnamoyloxy)-17- Aerial part 25
oxo-ent-kaur-15-en-19
oic acid (Wedelidin B)
Germacrene D Aerial part 23
Wedelia-seco- Aerial part 23, 24
kaurenolide

Triterpenes -humulene Aerial part 23, 40

Friedelinol Aerial part 25

Caryophyllene Aerial part 23, 40


Friedelin Aerial part 25

Steroids
Sesquiterpenes Stigmasterol Aerial part 25
1, 4-dihydroxy-6-
isobutyryloxy-9- Aerial part 29
(tigloyloxy)
prostatolide (7)-7- Aerial part 25
9-(angeloyloxy)-1, hydroxystigmasterol
4-dihydroxy-6 - Whole plant 29
isobutyryloxy
prostatolide (3)-3-hydroxy Aerial part 25
1, 9-diacetoxy-4- stigmasta-5, 22-dien-
hydroxy-6 - Whole plant 29 7-one
isobutyryloxy
prostatolide Sitosterol Aerial part 23, 40
1, 9-diacetoxy-4-
hydroxy-6 - Whole plant 29
methacryloxy
prostatolide Daucosterol Aerial part 31

Wedeliatrilolactone B Aerial part 25

Squalene Aerial part 23, 40

Trilobolide 6-O- Flower 23


isobutyrate Leaves 28, 29 Flavonoids
Whole plant 18, 20,30 3-hydroxy-6- Aerial part 25
methoxychromen-4-
Trilobolide 6-O- leaves 23 one
angelate
Apigenin Aerial part 25

Trilobolide 6-O- leaves 20, 23


methacrylate
Diosmentin Aerial part 25

Oxidoisotrilobolide 6- leaves 23, 30


O-isobutyrate Benzene derivatives
Benzeneacetic acid 2- Aerial part 25
phenylethenyl ester
Oxidoisotrilobolide 6- leaves 23
O-angelate
Isocinnamic acid Aerial part 25

Oxidoisotrilobolide 6- leaves 23
O-methacrylate
4-methoxy catechol Aerial part 25

Wedelolide A Leaves 20
596 Chiang Mai J. Sci. 2014; 41(3)

Table 1. Continued. Antileishmaniasis activity


Compound name Structure Plant part References
Kaurenic acid (ent-kaur-16-in-19-oic),
p-cymene Aerial part 23, 40
isolated from the Venezuelan plant W. trilobata
was evaluated on Leishmania (V) braziliensis
Protocatechualdehyde Aerial part 31 both in vivo and in vitro. The compound
had a lethal effect on axenic amastigotes and
Caffeic acid Aerial part 31 promastigotes with LD50 of 0.25 and 0.78
g/ml, respectively, in 24 h. Additionally,
Cyclic terpenes
-phellandrene leaves 39, 40
a 70% reduction was observed in the size of
the skin lesions in Balb/c mice with no evident
toxic effect. The results indicated that this
-pinene leaves 40
compound has a potent leishmanicidal
effect on L. (V.) braziliensis [34].
d-limonene leaves 39, 40

Bicyclogermacrene leaves 40

Table 2. Biological and pharmacological activities (in vitro and in vivo) of W. trilobata.

Extract/compound Pharmacological activity Reference


ANTIBACTERIAL ACTIVITY
N-hexane extract of aerial Inhibitory effect on Gram positive bacteria, 44
part without flower Bacillus cereus, Bacillus subtilis, Mycobacterium
megmatis, Staphylococcus aureus, Staphylococcus
epidermidis and Gram negative bacteria, Proteus
vulgaris, Pseudomonas aeruginosa, Salmonella group C,
Salmonella paratyphi, Shigella sonnei
Ethyl acetate extract of Inhibitory effect on Gram negative bacteria, 44
aerial part without flower Salmonella group C
Ethanol extract of stem Inhibitory effect on Bacillus subtilis, Pseudomonas 27
fluorescens, Clavibacter michiganensis sub sp.
michiganensis, Xanthomonas oryzae pv. oryzae,
Xanthomonas axanopodis pv. malvacearum and
strains of Staphylococcus aureus, Escherichia coli,
Pseudomonas aeruginosa and Klebsiella pneumonia
Ethanol extract of leaves Strong inhibitory effect on P. aeruginosa, K. 27
pneumoniae, P. fluorescens, X. oryzae pv. oryzae, X.
axanopodis pv. malvacearum, moderately inhibited
the E.coli, C. michiganensis sub sp. michiganensis but
less activity was observed on S. aureus.
Ethanol extract of flower Strong inhibitory effect on Staphylococcus aureus, 27
X. oryzae pv. oryzae moderately inhibited the
K.pneumoniae, P. fluorescens, X. axanopodis pv.
malvacearum but less activity was observed on
E.coli, P. aeruginosa, Clavibacter michiganensis
sub sp. Michiganensis
Chiang Mai J. Sci. 2014; 41(3) 597

Table 2. Continued.
Extract/compound Pharmacological activity Reference
Methanol extract of flower Moderate inhibitory activity against Bacillus cereus, 46
Bacillus subtilis, Escherichia coli, Klebsiella pneumonia,
Staphylococcus aureus and Shigella flexneri

ANTIFUNGAL ACTIVITY
Ethanol extract of stem, Weak inhibition against Aspergillus flavus 27
leaves and flower A. niger, A. nidulans, A. Flaviceps, Fusarium solani,
F. oxysporum, F. verticilloides

ANTIOXIDANT ACTIVITY
Ethanol extract of leaf, DPPH radical scavenging activity was more for leaves 27
stem and flower than stem and flower

Ethyl acetate fraction of DPPH radical scavenging activity 40


Wedelia trilobata

Methanol extract of flower DPPH radical scavenging activity 46

ANTIINFLAMMATORY ACTIVITY
Ethanol extract of leaf, All the three extract was effective in inhibiting heat 27
stem and flower induced albumin denaturation. Maximum inhibition
87.14% was observed from leaf extract followed by
stem (86.76%) and flower (61.63%).

The extracts inhibited the heat induced hemolysis of 27


RBCs to varying degree. The maximum inhibitions
78.11% from leaf extract followed by stem (74.17%)
and flower (58.74%).

The ethanolic extract exhibited significant 27


antiproteinase activity from different parts. The
maximum inhibition was observed from leaf ethanolic
extract (84.19%), in decreasing order was stem
(81.84%) and flower ethanolic extract (67.17%).
WOUND HEALING ACTIVITY
Ethyl acetate (WEA) and The WEA displayed antibacterial and fibroblast 47
chloroform:methanol (50:50) stimulatory activities while WCM exhibited antioxidant
(WCM) fractions from activity
ethanolic extract of
W. trilobata leaves

ent-kaura-9(11), 16-dien-19- Offered wound healing activity due to a combination 35


oic acid isolated from of antimicrobial, stimulation of fibroblast growth
W. trilobata leaves

CNS DEPRESSANT ACTIVITY


The petroleum ether, The petroleum ether extract represented good 43
chloroform, ethyl acetate and CNS depressant activity
methanol extract of leaves

CYTOTOXIC ACTIVITY
n-hexane and ethyl alcohol The ethyl alcohol extracts of flower had good 45
extracts anti-migration and anti-invasion ability especially
on 80 g/mL dose
598 Chiang Mai J. Sci. 2014; 41(3)

Table 2. Continued.
Extract/compound Pharmacological activity Reference
ANALGESIC ACTIVITY
Ethanol extracts Blocked the writhing response by 49.17% 48

Kaurenoic acid, a diterpene Exhibited analgesic effect by inhibiting cytokine 49


obtained from Wedelia production and activation of the NO-cyclic
trilobata GMP-protein kinase G-ATP sensitive potassium
channel signaling pathway.

ANTILEISHMANIASIS ACTIVITY
Kaurenoic acid (ent-kaur- Potent leishmanicidal effect on L. (V.) braziliensis 34
16-in-19-oic), isolated from
the Venezuelan plant
W. trilobata

ANTIDIABETIC ACTIVITY
Aqueous extract of leaves Reduction in blood glucose level in streptozotocin 41
induced diabetes

Methanolic extract of aerial -glucosidase inhibitor 42


parts

Central nervous system (CNS) depressant activity against Bacillus subtilis, Mycobacterium
activity smegmatis, Staphylococcus aureus, and
The petroleum ether, chloroform, ethyl Staphylococcus epidermidis (Gram-positive
acetate and methanol extract of leaves of W. bacteria); along with Proteus vulgaris,
trilobata (30 mg/kg, i.p.) were evaluated for Pseudomonas aeruginosa, Salmonella group
CNS depressant activity using pentobarbitone- C, Salmonella paratyphi, and Shigella sonnei
induced sleeping time, and locomotor activity (Gram-negative bacteria). The ethyl acetate
in mice. The petroleum ether extract extract was active only against Salmonella
potentiated pentobarbitone sodium induced group C; and the aqueous extract was
sleeping time in mice than other extracts. The inactive against the tested bacteria. None
animal treated with petroleum ether extract of the tested extracts showed biological
showed reduction in the locomotor activity activity against the yeasts (Candida albicans,
scores was significantly higher than that of Candida tropicalis, Rhodotorula rubra) or the
standard drug diazepam and other extract. fungi (Aspergillus flavus, Aspergillus niger,
The petroleum ether extract represented Mucor sp., Trichophyton rubrum) [44].
good CNS depressant activity [43]. Ethanol extract of leaf, stem and flower
of W. trilobata (10 g/ml) was assessed for
Antimicrobial activity its antimicrobial efficacy using disc method
A biological screening of activity against different fungi (A. flavus, A. niger,
against Gram-positive and Gram-negative A. nidulans, A. flaviceps, Alternaria carthami,
bacteria, yeasts, and fungi of crude extracts Alternaria helianthi, Cercospora carthami,
from W. trilobata (10 g/ml) was reported. Fusarium solani, Fusarium oxysporum,
The N-hexane extract showed antibacterial Fusarium verticilloides and Nigrospora oryzae)
Chiang Mai J. Sci. 2014; 41(3) 599

and bacteria (B. subtilis, Pseudomonas activity than that of stem and flower. At a
fluorescens, Clavibacter michiganensis sub concentration of 0.1 mg/ml, the scavenging
sp. michiganensis, Xanthomonas oryzae pv. activity of ethanol extract of the stem and
oryzae, Xanthomonas axanopodis pv. flower and leaves reached 82.64, 55.41 and
malvacearum and strains of S. aureus, E. coli, 86.17% respectively but less than those of
P. aeruginosa and K. pneumoniae). The ascorbic acid (98%) and BHT (97.8%) at 0.1
ethanolic stem extract significantly inhibited mg/ml, the study showed that the extracts
the growth of almost all the bacteria isolates have the proton donating ability and could
but did not show any significant effect on serve as free radical inhibitors or
fungal isolates. The leaf extract showed more scavenging, acting possibly as primary
potent against P. aeruginosa, K. pneumoniae, antioxidants. The FRAP values for the
P. fluorescens, X. oryzae pv. oryzae, X. ethanol extract of leaf and stem were
axanopodis pv. Malvacearum [27]. significantly lower than that of ascorbic
W. trilobata flowers, leaves and stems acid but higher than that of BHT [27].
were extracted with ten times of ethyl alcohol. The methanolic extract of W. trilobata
The extract was then partitioned by N- flower showed good antioxidant activity
hexane, ethyl acetate, N-butyl alcohol and (IC 50 = 90 g/ml) in DPPH method.
water to evaluate its antimicrobial activity. Reference standard ascorbic acid showed
The result showed that most extracts had IC50 of 60 g/ml. The extract of W. trilobata
antimicrobial activities except the water flower exhibited higher ABTS (2,2-azino-
extracts from flower. The ethyl acetate bis (3- ethylbenzothiazoline-6- sulphonic
extract was the most effective among all the acid) radical scavenging activity with IC50
extracts [45]. of 80 g/ml whereas gallic acid showed
The methanolic flower extract of W. IC50 of 30 g/ml [46].
trilobata was screened for antibacterial
activity by disc diffusion method against Anti-inflammatory activity
Bacillus cereus, Bacillus subtilis, Escherichia Ethanol extract of leaf, stem and flower
coli, Klebsiella pneumonia, Staphylococcus (0.5 mg/ml) of W. trilobata was evaluated
aureus and Shigella flexneri. The extract for its in vitro anti-inflammatory using
showed a moderate inhibitory activity albumin denaturation, membrane stabiliza-
against all bacterial species with zones of tion assay and proteinase inhibitory assay.
inhibition of 10-16 mm in comparison with All the three extracts were effective in
chloramphenicol which showed zones of inhibiting heat induced albumin denaturation.
inhibition 12-24 mm [46]. Maximum inhibition 87.14% was observed
from leaf extract followed by stem (86.76%)
Antioxidant activity and flower (61.63%). All the extracts were
Ethanol extract of leaf, stem and flower effective in inhibiting the heat induced
(0.5 mg/ml) of W. trilobata was evaluated hemolysis. The extracts inhibited the heat
for its antioxidant activity by measuring induced hemolysis of RBCs to varying
the scavenging activity of 2,2-diphenyl-1- degree. The maximum inhibitions 78.11%
picrylhydrazyl (DPPH) radical and the from the leaf extract followed by the
ferric reducing antioxidant power (FRAP) stem (74.17%) and flower (58.74%).
assay. It was observed that ethanol extract The W. trilobata ethanolic extract exhibited
of the leaf of W. trilobata offered higher significant antiproteinase activity from
600 Chiang Mai J. Sci. 2014; 41(3)

different parts. The maximum inhibition stress induced by hydrogen peroxide


was observed from leaf ethanolic extract (94-80%) [35].
(84.19%), in decreasing order was stem
(81.84%) and flower ethanolic extract Cytotoxic activity
(67.17%) [27]. In transient transfection assay the
The ethyl alcohol and water extracts N-hexane and ethyl alcohol extracts of
of W. trilobata flowers were used to treat W. trilobata flower could activate PPAR.
RAW 264.7 macrophage, which induced In MTT assay of SK-Hep-1, extract of
inflammation by LPS. In the nitric oxide W. trilobata flower had the best inhibitory
assay, the extracts of W. trilobata flower ability. The ethyl alcohol extract of W.
had better inhibitory ability against LPS trilobata had the best ability to diminish
induced inflammation [45]. the expression of matrix metalloproteinase
(MMP)-9 and MMP-2. The ethyl alcohol
Wound healing activity extracts of flower had good anti-migration
An ethanolic extract of W. trilobata and anti-invasion ability especially on 80
leaves was subjected to column chromato- g/mL dose [45].
graphy. Hexane, ethyl acetate (WEA) and
chloroform:methanol (50:50) (WCM) Analgesic activity
fractions were obtained. The fractions were Comparative study in mice on the
tested using relevant in vitro wound healing analgesic activity of the ethanol extracts of
assays. WEA (3 g/mL) promoted fibroblast W. trilobata, W. biflora and E. alba was
L929 viability up to more than 90% before evaluated by acetic acid induced writhing
and more than 85% after hydrogen peroxide method. It was found that W. trilobata
induced oxidative stress. WEA (3 g/mL) extract showed dose-dependent blocking of
induced a 70% migration rate in the in vitro writhing response. Dose of 500 mg/kg of
scratch assay and the collagen content was W. trilobata extract and aspirin (500 mg/
increased to 261 g/mL compared to the kg) block the writhing response by 49.17%
control (57.5 g/mL) [47]. and 68.68% [48].
The ent-kaura-9(11), 16-dien-19-oic acid Kaurenoic acid (10 mg/kg) obtained
isolated from W. trilobata leaves offered from Wedelia trilobata kaurenoic acid
wound healing activity due to a combination inhibited overt nociception like behavior
of antimicrobial, stimulation of fibroblast induced by phenyl-p-benzoquinone,
growth and protection of the cells from complete Freunds adjuvant (CFA) and
hydrogen peroxide-induced injury, all of formalin. Kaurenoic acid (1-10 mg/kg p.o.)
which could play some role in its effect also inhibited acute carrageenin and PGE2
on tissue repair. It showed promising induced and chronic CFA induced
antibacterial activity with MIC value of mechanical hyperalgesia. [49].
15.62 g/mL against S. aureus and 7.81
g/mL against S. epidermidis. The Reproductive problems
ent-kaura-9(11), 16-dien-19-oic acid (2.5-0.08 Previous research has shown that
g/mL) produced an increase in the Caribbean women and Creoles have always
percentage viability of mouse fibroblast used bitter herbs to control their fertility.
L929 cells from 97-117% and protection of A study was conducted focused on the
the fibroblast L929 cells against oxidative plants used for reproductive purposes in
Chiang Mai J. Sci. 2014; 41(3) 601

Trinidad and Tobago. The plants used to trilobata at a concentration varying


address womens reproductive problems between 10- 250 g/ml. The effect of the
were used mainly for infertility, menstrual compound on cellular viability was
pain and childbirth. Results showed that evaluated using MTT assay Low toxicity
W. trilobata was used for menstrual pain was observed for J774-G8 macrophages
and for the female complaints. The non- with a LD50 of 25 g/ml and high viability
experimental validation method can be (70-92%), while a moderate viability was
used to advise the public on which plants observed for infected macrophages
are safe, effective and useful, and which are (37-81%), with concentrations of 25 g/
not; pending clinical trials. This is ml or less [34].
important since few clinical trials were
conducted on Caribbean plants [19]. 3. DISCUSSION
The present review emphasizes the
Other activity phytochemical, traditional, pharmacological
The methanolic extract of W. trilobata and, clinical reports on W. trilobata.
flower was tested for pTZ57R/T plasmid Tannin, saponins, flavonoids, phenolic,
DNA protection against hydroxyl radical, terpenoids constitute major classes of
evidenced by fragmentation assay. The phytoconstituents of this plant. The plant
extract showed stronger protective effect contains a range of phytochemical substances
against DNA damage by hydroxyl radical credited with various pharmacological
released by Fentons reaction [46]. properties. Recent research carried out
indicates its uses such as antioxidant, anti-
Toxicity studies inflammatory, antimicrobial, wound healing,
The ethanolic extract (25- 1.56 g /ml), antidiabetic activity. In recent years,
ethyl acetate fraction (6.25- 0.39 g/ml) and the search for phytochemicals possessing
chloroform: methanol fraction (22- 0.39 antioxidant, antimicrobial and anti
g/ml) of leaves of W. triolbata were inflammatory properties have been on the
evaluated for cytotoxicity using L929 rise due to their potential use in the therapy
mouse fibroblast cell using MTT (3-(4,5- of various chronic and infectious diseases.
dimethylthiazolyl)-, 5 diphenyltetrazolium Epidemiology and experimental studies
bromide) assay. At these concentrations have implicated oxidative cellular damage
extract as well as fractions produced cell arising from an imbalance between free
survivability of more than 80%. However radical generating and scavenging systems
at higher concentrations of the above as the primary cause of cardio-vascular,
dose levels there was evidence of diseases, cancer, aging etc. Due to risk of
cytotoxicity [47]. adverse effects encountered with the use of
The ent-kaura-9(11), 16-dien-19-oic acid synthetic antibiotics, medicinal plants
at dose range of 10- 0.08 g/ml produced may offer an alternative source for
cell viability of L929 mouse fibroblast in antimicrobial agent with significant activity
the range of 89-117%. Further increase in against pathogenic and infective micro-
concentration above 10 g/ml produced organisms. In addition, a number of
cellular damage resulting in cell death [35]. antibiotics have lost their effectiveness due
The J774-G8 macrophages were treated to the development of resistant strains,
with kaurenoic acid isolated from W. mostly through the expression of resistance
602 Chiang Mai J. Sci. 2014; 41(3)

genes. Strong antioxidants, antimicrobial the local knowledge system should be


and anti inflammatory activities specifically globalize which would increase the benefits
in the ethanolic leaf and stem extracts of obtained to wider population. There are
W. trilobata were observed. These activities no clinical data available that would
may be due to strong occurrence of provide evidence of efficacy of W. trilobata
polyphenolic compounds such as flavonoids, in humans. Extracts and constituents of W.
tannins, terpenoids, phenols and saponins trilobata may have considerable clinical
[29]. The authors are involved in evaluating potential in humans and need to be studied
the wound healing effect of W. trilobata further in in vivo models and ultimately
with a view to isolating bioactive in clinical studies.
phytoconstituent(s). One of the
phytoconstituent isolated and evaluated for DISCLOSURE STATEMENT
wound healing potential is grandiflorenic No competing financial interests exist.
acid (ent- kaura-9(11)-dien-19-oic acid) [37,
55]. The presence of a wide range of REFERENCES
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