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Journal of Medicinal Plants Research Vol. 7(xx), pp. xxx-xxx xx xxxx, 2013
Available online at http://www.academicjournals.org/JMPR
DOI:10.5897/JMPR012.897
ISSN 1996-0875 ©2013 Academic Journals
Review
Ethnobotany, phytochemistry and pharmacology of
Ageratum conyzoides Linn (Asteraceae)
S. Brojendro Singh1, W. Radhapiyari Devi1, Marina A1, W. Indira Devi2, N. Swapana3 and
Chingakham B. Singh1*
1Medicinal and Horticultural Plant Resources Division, Institute of Bioresources and Sustainable Development,
Imphal-795001, Manipur, India. (Department of Biotechnology, Govt. of India)
2Department of Life Science, Manipur University, Canchipur-795003, India.
3Department of Chemistry, S. Kula Women's College, Nambol, Manipur-795134, India.
Accepted 17 December, 12
In the present review, an attempt has been made to congregate the traditional, phytochemical and
pharmacological studies done on an important medicinal plant, Ageratum conyzoides Linn. (Family
Asteraceae) which is widely spread all over the world, especially in the tropical and subtropical region.
There are many reports on folk and traditional uses that include wound dressing, skin diseases,
ophthalmic, colic, ulcers treatment, diarrhoea, dysentery, fever, gynecological diseases, sleeping
sickness, mouthwash, anti-inflammatory, insecticides, etc. Phytochemical investigations have revealed
that many components are bioactive due to the presence of broad range of secondary active
metabolites such as terpenoids, flavonoids, alkaloids, steroids, and chromene. The plant has been
examined on the basis of the scientific in vitro, in vivo or clinical evaluations possessing the major
pharmacological activities that includes analgesic activity, antimicrobial activity, anti-inflammatory
activity, spasmolytic effects, gamma radiation effects, anti cancer and radical scavenging activity, anti-
malarial activity and others activities. The information summarized here is intended to serve as a
reference tool to practitioners in the fields of ethnopharmacology, natural product chemistry and drug
discovery related research.
Key words: Ageratum conyzoides, terpenoids, flavones, isoflavone.
INTRODUCTION
The genus Ageratum is derived from the Greek words ‘a
geras’ meaning non-aging which refers to long life-time of
plant and the species epithet ‘konyz’ is the Greek name
of Inula helenium which resembles the plant. Ageratum
conyzoides Linn. (Family Asteraceae, Tribe Eupatoriae)
is an annual herb with a long history of traditional
medicinal use in the tropical and sub-tropical region of
the world, commonly known as Billy goat weeds. The
stems and leaves of the plant are covered fully with fine
white hairs.
The leaves are ovate in shape and grow up to 7.5 cm
long. The flowers are arranged in terminal inflorescences
*Corresponding author. E-mail: kishore.ibsd@nic.in. Tel: 0385-
2446120. Fax: 0385-2446121.
which are white in colour. The fruits are achaenes and
easily dispersed by air. The mature plant is used for its
haemostatic, anti-inflammatory, antispasmodic,
antiasthmatic, properties for the treatment of wounds and
in bacterial infections (Kokwaro, 1976; Gonzalez et al.,
1991). The essential oil found in it can inhibit the growth
and production of toxigenic strain of Aspergillus
parasiticus (Patil et al., 2010), a new biological activity
which indicates as a useful tool for a better understanding
of the complex pathway of aflatoxin biosynthesis
(Nogueira et al., 2010). The plant extract is found to have
cardiovascular depressant activity, has antispasmodic
effects (Achola et al., 1994), antioxidant activity and
insecticidal activities (Amal et al., 2010). A. conyzoides
has larvicidal and growth inhibitory activity exhibited in
the 2nd and 4th instar larvae of the Anopheles stephensi
(Neetu et al., 2011). The water soluble fraction (WSF)
obtained from a hydroalcohol extract of A. conyzoides,
was evaluated for possible analgesic and anti-
inflammatory activities (Jose et al., 1997). It was also
demonstrated that WSF (20 to 50 mg/kg; i.p.) treatment
reduced the articular incapacitation induced by
carrageenin (300 μg) in rats. A number of flavones have
been isolated including 8-hydroxy-5, 6, 7, 3, 4, 5-
hexamethoxy flavones (Gill et al., 1978). Besides these,
the genus is well known for its chromenes and flavonoids
contents (Gonzalez et al., 1991). In India, ayurvedic study
has found out that the root of the plant is useful in fever
and possesses anti-helmintic and anti-dysentric
properties (Kirtikar and Basu, 1991). However, studies
reveal that the plant contains toxic properties and inhibits
the growth of other native plants of the invaded area,
thereby leading to declination of the productivity (Perumal
et al., 1999). The essential oil obtains by steam
distillation has been reported to have a powerful
nauseating odour (Sood, 1973). The plant is not eaten by
humans except when taken as medicinal purposes;
however, it is used to feed fish, domestic guinea pigs,
cattle and horses. In Manipur, India, the whole plant is
used traditionally as hair lotion known as ‘Cheng- hi’
which is prepared by boiling the plant with rice water. The
plant has also been found to be poisonous to rabbits due
to the presence of coumarin and hydrogen cyanide
(HCN) (Abbiw, 1990). It has also been reported that the
plant might contain allelochemicals when the acetone
extract residue of the plant inhibits the germination and
growth of the roots and shoots of other plants (Kato-
Naguchim, 2001). It has been said that crude extracts
from A. conyzoides offer the possibility of biocontrol of
plant pathogenic fungi (Iqbal et al., 2004). The leaves of
the plant are reported to have anti-inflammatory
properties, with no apparent hepatotoxicity (Moura et al.,
2005). The released water-soluble phenolic acids
contents from the leaf debris of the plant into the soil
environment affect the early growth of rice to a worst
extent (Daisy et al., 2009). The essential oil of A.
conyzoides has very strong smell and has been tested for
its anti-inflammatory, analgesic and anti-pyretic activities
(Abena et al., 1996b).
This review is aimed to summarize on pharmacological,
biological activities of this valuable herbs.
ETHANOBOTANY AND TRADITIONAL USES OF A.
CONYZOIDES
Traditionally, A. conyzoides has been used in various
parts of the world like Africa, Asia and South America as
folk medicine. The whole plant produces volatile strong
smelled oil which also possesses various biological
activities. It is used for wound dressing, curing various
skin diseases, ophthalmic, colic, ulcers treatment, as
purgative and febrifuge (Girthens, 1948). The decoction or
infusion of the herb is given in stomach ailments such as
diarrhoea, dysentery, intestinal colic, flatulence,
rheumatism fever (Chopra et al., 2002), and
gynaecological
diseases (
Sharma and Sharma,
1995).
Other folk remedies include
anti-itch, sleeping
sickness, and mouthwash for toothache,
antitusive,
vermifuge, tonic and killing lice (Burkill, 1985;
Kapur,
1993).
The leaves are used for application on cuts,
sores (
Ahluwalia, 1968;
Gangwar and
Ramakrishnan, 1990;
Dutta and Nath, 1998;
Sudhakar
and Chetty, 1998;
Upadhay et al., 1998
),
anti-
inflammatory agent, haemostatic (
Jain and Puri,
1990; Banerjee and Banerjee, 1986; Jamir, 1990;
Suresh
et al., 1995;
Kumar and Jain, 1998
),
insecticide
(
Ramachandran and Nair, 1981),
skin diseases
(Sankaran and Alagesaboopathi, 1995), ringworm
infection (Upadhye et al., 1986), antidote to snake
poison
(Neogi et al., 1989;
Jain and Sahu, 1993),
malarial fever,
antitetanus, uterine
problems (
Rajwar, 1983),
prolaps
of anus (
Siddiqui and Husain, 1992),
swollen piles
(
Singh, 1988),
throat infection, painful gums, abscess
for early
suppuration, wound healing and leucorrhoea
(
Sharma et al., 1985;
Sahoo and Mudgal, 1993; Dagar
and Dagar, 1996; Katewa and Arora, 1997) and infant
diarrhoea (Hemadri and Rao, 1989). It has been reported
to have nematocidal activity and
potential used in
controlling pests (
Gravena et al., 1993).
The plant has an
antienteralgic and antipyretic, for cuts as a wound
dressing (Nair et al., 1977). In India, it is used for leprosy
treatment and as an oil lotion for purulent opthalmia.
Besides these, it is used for preparing local hair lotion in
Manipur, India for treating dandruffs. In some parts of
Africa, the plant is used for headaches, dyspnoea, mental
and infectious diseases. The leaves crushed in water are
applied intravaginally for uterine troubles and also given
as emetic. In Central Africa, the plant is applied for
treating burnt wounds, while in Kenya it is used as
antiasthmatic, antispasmodic and for haemostatic effects
traditionally. In Brazil, the leaves of this plant are served
as anti-inflammatory, analgesic and anti-diarrhoeic. The
plant is also particularly used for treatment of
gynecological diseases in Vietnam (Nair et al., 1977).
The plant also has a number of magical and superstitious
attributes, like against snake bites. In western part of
Nigeria, it is believed that incantations help against
witches and bad medicine. In Congo, the leaf sap is
believed to improve luck of card players (Burkill, 1985).
The leaf of the plant is reported to have hematopoietic
potentials which could possibly cure anaemia (Burkill,
1985) and further reported to have gastroprotective
activity (Shirwaikar et al., 2003).
The plant is reported to be one among the selective
weeds which can be used successfully as substrate for
oyster mushroom cultivation and also helps to increase
its protein content and production time (Nirmalendu and
Mina, 2007). It was further reported to yield high value of
improved vegetative growth and numerous open flowers
when Ageratum was grown for a time period of 28 days
under a radiation mixture of blue, red or far-red light and
within a controlled closed system which is very helpful in
the field of horticulture for higher profit (Jeong et al.,
2006).
PHYTOCHEMISTRY OF A. CONYZOIDES
Monoterpenes and sesquiterpenes
So far, a total of 51 constituents have been reported from
the analysis of the Ageratum oil sample from Nigeria as
the highest which include 20 monoterpenes (6.6%) of
which 1% of it contains sabinene, 1.6% contains β-pinene
and β-phellandrene, 2.9% contains 1.8-cineole and
limonene, 0.6% contains terpenen-4-ol and 0.5%
contains α-terpineol and further found 20 sesquiterpenes
(5.1%) and that of single substance were found to be in
traces approximately 0.1%. Indian Ageratum oil is found
to contain 5.3% ocimene which was found in traces from
Nigerian plant, 6.6% α-pinene, 4.4% eugenol and 1.8%
methyleugenol (Rao and Nigam, 1973).
The major sesquiterpenes are beta-caryophyllene, 1.9
to 10.5% from an oil sample obtained from Cameroon
and 14 to 17% in a Pakistani oil sample. Another
sesquiterpene, δ- cadinene occurred in approximately
4.3% in the oil received from Indian plants (Rao and
Nigam, 1973). Sesquiphellandrene and caryophyllene
epoxide have been obtained in 1.2 and 0.5%,
respectively from leaves (Ekundayo et al., 1988). The
summary is as shown in Table 1.
Benzofuran, chromene, chromone and coumarin
Precocene I (Figure 1a) or 7-methoxy-2,2-
dimethlchromene ranging from 30 (Vietnamese oil) to
93% (Congo oil) (Pham et al.,1976; Sharma et al., 1980;
Wandji et al., 1996) while Precocene II (Figure 1b)
ranging from 0.7% (Quijano et al., 1982) to 55% (Pham et
al.,1976) while cumarine (5.01%) and trans-
caryophyllene (3.02%) are the most common
components of essential oil of A. conyzoides. They are
found to have Aspergillus flavus suppressing activity and
also completely inhibit the growth of Rhizoctonia solani
and Sclerotium rolfsii. Ageratochromene dimer is also
reported from the essential oil (Burkill, 1985) which
believes the genus is chemically closer to the Ageritanae
subtribe and possesses chemotaxonomic activity to the
Piqueriiae group (Burkill, 1985).
Seven other chromene derivatives are isolated from oil
in the aerial part of the plant. They are 2,2-
dimethylchromene-7-o-β-glucopyranoside (Figure 1c)
(Nair et al., 1977); 6-(1-methoxyethyl)-7-methoxy-2,2-
dimethylchromene; 6-(1-hydroxyethyl)-7-methoxy–2,2-
dimethylchromene; 6-(1-ethoxyethyl)-7-methoxy-2,2-
dimethylchromene; 6-angeloyloxy-7-methoxy-2,2-
dimethylchromene,3-(2-methylpropyl)-2-methyl-6,8-
demothoxychrom-4-one, 2-(2-methylethyl)-5,6-
dimethylbenzofuran and a mixture of ageratochromene
dimer (Figure 2a) and encecanescin (Figure 2b) (Nair et
al., 1977). 1.219% of coumarin and a minor amount of
benzofuran and its derivatives are yielded from its
essential oil.
Flavonoids and alkaloids
A total of 21 polyoxygenated flavonoids have been
reported from the species which includes 119
polymethoxylated flavones, namely scutellarein-5,6,7,1-
tetrahydroxyflavone, quercetin, quercetin-3-
rhamnopiranoside, kaempferol, 14 polymethoxy flavones
(Figure 3a), Eupalestin (Figure 3b), quercetin-3-
rhamnopiranoside (Figure 3c) and kaempferol 3,7-
diglucopiranoside (Nair et al., 1977). A novel isoflavone
glycoside, 5,7,2,19-tetrahydroxy-6,3-di-(3,3-dimethylallyl)-
isoflavone 5-O-α–L-rhamnopyranosyl–(1→19)–α-L-
rhamnopyranoside was isolated from the stems (Gill et
al., 1978).
Some alkaloids found in Ageratum species are
lycopsamine (Figure 4a), echinatine (Figure 4b), caffeic
acid (Figure 4c), phytol (Figure 4d), 2-(2'-methylethyl)
5,6-dimethyoxybenzofuran (Figure 4e), 2-(2-methylprop-
2-enyl)-2-methyl-6,7-dimethoxychromane-4-one, 2-(1'-
oxo-2'methypropyl)-2- methylpropyl)-2-methyl-6,7-
dimethoxychromene (Figure 4f) and 3-(2'-methylpropyl)-
2-methyl-6,8-demothoxychrom-4-one (Figure 4g)
(Adewole, 2002).
Pyrrolizidine alkaloids (PAS) are widely distributed in
Asteraceae family (particularly in tribes Senecioneae and
Eupatorieae), but only lycopsamine and echinatine
(isomeric) are isolated from this plant (Nair et al., 1977).
Other common compounds isolated are sesamin,
aurantiamide acetate, fumaric acid, caffeic acid, phytol
and hydrocarbons nC27 H56 to nC32 H66 (Nair et al., 1977;
Pari et al., 1998). The flowers were reported to contain
vitamins A and B (Nair et al., 1977; Tyagi et al., 1995).
Triterpenes and steroids
The oil from leaves and stems of this plant is reported to
contain sterols like friedeline (Figure 5a), beta-sitosterol
(Figure 5b) and stigmasterol as major constituents and
minor sterols include brassicasterol (Figure 5c)
(Okunade, 2002). The presence of beta-sitosterol and
stigmasterol in various tissue samples and plants parts of
A. conyzoides were confirmed by thin layer
chromatography (TLC) for beta-sitosterol (Rf 0.95,
Melting point 139 to 140) and stigmasterol (Rf 0.89,
Melting point 142 to 144). Sterols content were found to
be higher in 6 weeks old tissue of A. conyzoides. In case
of in-vivo plant parts, A. conyzoides was observed slightly
Table 1. Compounds isolated from A. conyzoides.
Compound
Class
Source
Country
Reference
Ageratochromene dimer
Chromene
Oil
India
Katsuri et al. (1973)
Β-caryophyllene
Sesquiterpene
Oil
India
Ekundayo et al. (1988)
Brassicasterol
Sterol
Oil
India
Dubey et al. (1989)
Caffeic acid
Secondary metabolites
Oil
India
Nair et al. (1977)
Caryophyllene epoxide
Sesquiterpene
Oil
India
Ekundayo et al. (1988)
Dihydrobrassicasterol
Sterol
Oil
India
Dubey et al. (1989)
Echinatine
Alkaloids
Whole plant
Mexico
Wiedenfeld and Roder (1991)
Eugenol
Terpenes
Oil
India
Ekundayo et al. (1988)
Fumaric acid
Secondary metabolites
Oil
India
Nair et al. (1977)
Kaempferol-3,7- diglucopiranoside
Flavonoid
Oil
India
Nair et al. (1977); Gill et al. (1978)
Lycopsamine
Alkaloids
Oil
Mexico
Wiedenfeld and Roder (1991)
Methyleugenol
Terpenes
Oil
India
Ekundayo et al. (1988)
Ocimene
Terpenes
Oil
India
Rao et al. (1973)
Precocene I(7-methoxy-2,2΄-dimethylchromene)
Chromene
Oil
Brazil
Wandji et al. (1996)
Precocene II (ageratochromene)
Chromene
Oil
India
Quijano et al. (1980); Iqbal et al. (2004)
Sesquiphellandrene
Sesquiterpene
Oil
India
Ekundayo et al. (1988)
Spinasterol
Sterol
Oil
India
Dubey et al. (1989)
Vitamins A& B
Vitamin
Flower
India
Tyagi et al. (1995)
α-pinene
Terpenes
Oil
India
Rao et al. (1973)
β-pinene
Terpenes
Oil
India
Ekundayo et al. (1988)
δ- cadinene
Sesquiterpene
Oil
India
Rao et al. (1973)
2-(1΄-oxo-2΄-methylpropyl)-2- methyl-6,7-dimethoxy- chromene
Chromene
Oil
India
Pari et al. (1998)
2-(2΄-methylprop-2΄-enyl)-2-Methyl-6,7-dimethoxychroman-19-one
Chromene
Oil
India
Pari et al. (1998)
-(2΄-methylpropyl)-2-methyl-6,8-dimethoxychrom-19-one
Chromene
Oil
India
Pari et al. (1998)
2-(2΄-methylethyl)-5,6- Dimethoxybenzofuran
Benzofuran
Oil
India
Pari et al. (1998)
5,7,2΄,19΄- tetrahydroxy-6,3΄-di-(3,3-dimethylallyl)- isoflavone 5-o-α-L- rhamnopyrosyl-
(1→19)-α L-rhamnopyranoside
Isoflavone
Stem
India
Yadava et al. (1999)
Methyl-6,7-dimethoxy chromene
Chromene
Oil
India
Pari et al. (1998)
(+) –sesamin
Alkaloids
Oil
-
Gonzalez et al. (1991)
a
b
c
a
b
c
a
b
c
f
d
e
Figure 1. Organic structures of (a) Procene I; (b) Procene II; (c) 2,2-dimethylchromene-7-O-
beta-glucopyranoside; (d) 3-(2’-methylpropyl)-2-methyl-6,8-demethoxychrom-4-one; (e) 2-
(2’-methylethyl)-5,6-dimethoxybenzofuran; (f) 14-Hydroxy-2H beta3-dihydroeuparine.
higher in stem (0.0868%) followed by leaves (0.0656%)
and roots (0.0533%) (Sarin and Bansal, 2011).
Yield of essential oils
The oil content was found to be 0.2% from water
distillation of the fresh flowers (Sood, 1973) and that of
leaves and root were found to be 0.11 to 0.58% and 0.03
to 0.18%, respectively, depending on the seasons. The
oil yielded from petroleum ether extract was reported to
be 26% (Devdhar and Rao, 1970).
PHARMACOLOGICAL PROPERTIES OF
A.CONYZOIDES
Analgesic activity
A. conyzoides extract showed strong indications of
biological activity in in vitro receptor radio ligand binding
a
b
Figure 2. Organic structures of (a) Ageratochromene dimer; (b) Encecanescin.
assays (Bradykinin II) expressed in Chinese hamster
ovary cells, Neurokinin1 expressed in astrocytoma cells
and calcitonin gene related peptide.
The WSF of the
plant extract produces
peripheral analgesic activity and
an anti-inflammatory
action, which seems to occur in
leucocyte-dependent
inflammatory events (Magalhaes et
al., 1997). They are implicated in the mediation of acute
pain in the mammalian central nervous system (Sampson
et al., 2000).
Antimicrobial activity and wound healing effects
Essential oil has strong
toxicity against the fungi causing
ringworm, Epidermophyton floccosum,
Trichophyton
mentagrophytes and Microsporum gypseum, with the
inhibition of the
mycelia being 80.28, 78.43 and 68.24%,
respectively (Mishra et al., 1991). The extract of leaves,
however, had no effect on the conidial germination of the
fungus D. oryzae (Ganesan and Krishnaraju, 1995).
Aqueous extract was tested against
three Gram-positive
bacteria and seven Gram-negative
bacteria and
evaluated by the filter paper disc diffusion method.
Results showed a significant control of the growth of
Alcaligenes viscolactis, Klebsiella aerogenes, Bacillus cereus
and Streptococcus pyogenes (
Moody et al., 2004).
In
vitro, the minimum inhibition concentration (MIC) and
anti-methicillin resistant Staphylococcus aureus test
(MRSA) for ethanol and water extracts were recorded as
30.6 to 193.0 and 195.19 to 71.0 µg/kg, respectively,
while the minimum bactericidal concentration (MBC) for
both extracts was found to be higher (Akinyemi et al.,
2005). Petroleum ether extract was found to be effective
against S. aureus. However, a study in Nigeria reported
that methanolic extract has no inhibition for various
strains of S. aureus (four strains), Escherichia coli (two
strains), Pseudomonas aeruginosa (one strain), Proteus
species (three strains), and Shigella species (one strain)
using the well diffusion method (Chah et al., 2006). The
essential oil has antimicrobial and anticonvulsant activities
(Whittle and Turner, 1981). The oil was reported to inhibit
20 bacteria out of 22 bacteria (Gram positive cocci and
rods and Gram negative rods) and 4 fungi namely
Candida albicans SP-14, Cryptococcus neoformas SP-
16, S. rolfsii SP-5 and T. mentagrophytes SP-12 out of 12
fungi (3 yeast like and 9 filamentous) (Pattnaik et al.,
1999). Further, the oil is effective against Penicillium
chrysogenum and Penicillium javanicum (Rao and
Nigam, 1973; Ekundayo et al., 1988). The oil also
provides 100% inhibition of the mycelial growth and
germination of the spores of Didymella bryoniae (Fiori et
al., 2000).
Wound healing properties were also
determined using the excision wound model. More than
90% wound healing was recorded in the extract, whereas
a
b
c
Figure 3. Organic structures of (a) 14 Polymethoxy flavones; (b) Eupalestin;
(c) Quercetin-3-rhamnopiranoside
72% healing was observed in the distilled water-treated
group (
Almagboul et al., 1985)
.
Methanolic extract was
found to have wound healing property (Chah et al.,
2006). On the other hand, it showed very potent
antibacterial activity against Helicobacter pylori, a Gram
negative microaerophilic bacterium which is a major
etiological agent in duodenal, peptic and gastric ulcers
(Roland et al., 2007). The wound healing effect of the A.
conyzoides methanolic extract was studied in Wistar rats
(n=10). Wounds prepared in excised areas of the skin
a
b
c
d
Figure 4. Organic structures of (a) Friedeline; (b) Beta-Sitosterol; (c) Brassicasterol; (d) Spinasterol.
were packed with gauze soaked by the extracts and were
determined histologically after 10 days. The Ageratum
sections showed fewer inflammatory cells and more
fibrosis than the controls. In a study, it was
found that
wounds treated with aqueous leaves extract
in
combination with honey and with solcosery ointment
significantly accelerate wound healing process and the
rates of wounds sterility compared to wounds treated with
honey alone (Mustafa et al., 2005).
Anti-inflammatory activity
A group of rats was orally treated with 250 mg/kg extract
for anti-inflammatory test using hydro alcoholic extract
and was found to have a 38.7% reduction in the cotton
pellet-induced granuloma (p<0.05) (Tailor and Goyal,
2012). The leaves have been used on cuts, sores, as an
anti-inflammatory agent (Abena et al., 1993a; Moura et
al. 2005). Aqueous extract of an association of A.
conyzoides, Cymbopogon citrates and Lippia multiflora
produced a significant reduction in mouse of writhings
induced by acetic acid and an increase of pain threshold in
the hot plate test in mice.
The presence of saponins and flavonoids supports the
observed activities and suggests that this association of
three plants could be used as traditional improved
preparation (Okemy et al., 2006). The development of
chronically induced paw edema was also reduced
significantly (p<0.05) and serum glutamic pyruvic
transaminase (SGPT) activity in the blood of rats treated
with 500 mg/kg was reduced to 30.2% (p<0.05) which
confirm the anti-inflammatory properties of A. conyzoides
(Moura et al., 2005). The biochemical and haematological
analysis of the blood of rats treated with daily doses of
250 or 500 mg/kg extract for 90 days did not show any
g
f
e
d
c
b
a
h
Figure 5. Organic structures of (a)Lycopsamine; (b) Echinatine; (c) Caffeic acid; (d) Phytol; (e) 2-(2’-
Methylethyl)5,6-dimethoxybenzofuran; (f) 2-(1’-oxo-2’methylpropyl)-2-methyl-6,7-dimeyhoxychromene; (g) 3-
(2’-Methypropyl)-2-methyl-6,8-dimethyoxychrom-4-one; (h) 2-(2’-Methylpropyl)-2-methyl-6,7-
dimethyoxychroman-4-one
treatment-related abnormalities in the biochemical or
haematological parameters towards toxicity. Therefore, no indications were found for an apparent hepatoxicity
(Moura et al., 2005). It has been reported that WSF
Table 2. The bioactivities of the extracts.
Extract
Source
Concentration used
Bioactivity
Reference
Alcoholic extract
Leaves
75 mg/kg
Scavenging reactive radicals of oxygen
Jagetia et al. ( 2003)
Alcoholic extract
Whole plant
0.25-900 mg/kg
Protection effects against gamma radiation
Jagetia et al. (2003)
Aqueous
Leaves
-
Analgesic activity
Abena et al. (1993)
Aqueous
Leaves
-
Prevent coagulation of whole blood
Abena et al. (1993)
Aqueous
Leaves
-
Treatment in chronic pain in osteoarthrotic Patients
Marques et al. (1988)
Aqueous
Root
-
Anti-tumour activity
Rosangkima et al. (2004)
Aqueous
Whole plant
-
Active against certain selected microrganisms
Perumal et al. (1999)
Aqueous
Whole plant
-
Dermatological remedy
Adolfo (2009)
Aqueous
Whole plant
-
Prostate problems
Cheryl (2007)
Ethanol
Leaf
200,1900, and 500 mg/kg
Haematopoitic properties (remedy anaemia )
Ita et al. (2007)
Ethanol
Whole plant
500 and 750 mg/kg
Gastro-protection in rats
Shirwaikar et al. (2003)
Ethanol
Whole plant
30.6 - 193.0 µg/kg
Acts against Staphylococcus aureus
Akinyemi et al. (2005)
Ethanol
Whole plant
500 -1000 mg/kg
Anti-coccidial effects
Nweze et al. (2009)
Ethanol
Leaf
200, 1900, and 500 mg/ml
Haematopoietic properties
Ita et al. (2007)
Hydro alcoholic
Whole plant
250 mg/kg
Anti-inflammation
Moura et al. (2006)
Lyophilized powder
Leave juice
50 and100 mg/kg
Precocious ataxia, sedation and slight ptosis
Abena et al. (1993)
Methanol
Whole plant
-
Wound healing
Chah et al. (2006)
Methanol
Aerial part and root both
100 mg/ml
Broncho-dilating and uterine activities
Achola et al. (1998)
Methanol
Whole plant
p<0.036
Wound healing material
Oladejo et al. (2003)
Methanol
Whole plant
15.1- >90 g/ml
Antiprotozoal and cytotoxic
Amal et al. (2010)
Petroleum ether
Whole plant
-
Acts against S. aureus
Durodola et al. (1977)
Petroleum ether
Whole plant
-
Active against against the mosquito C. quinquefasciatus larvae
Preeti et al. (2009)
Water
Leaves
0.1-0.5 g/kg
Induced quietness and reduced the spontaneous motility in rats and mice
Abena et al. (1993)
Water
Whole plant
0.01-10 mg/ml
Tonic contractions of the smooth muscles
Yamamoto et al. (1991)
Water soluble fraction (WSF)
Whole plant
0.2 and 0.19 mg/ml
Spasmolytic medicine
Yamamoto et al. (1991); Silva et al. (2000)
Water
Whole plant
195.19 to 71.0 µg/kg
Acts against S. aureus
Akinyemi et al. (2005)
obtained from a hydroalcohol extract of A.
conyzoides had analgesic and anti-inflammatory
activities. It was demonstrated that WSF (20 to
50 mg/kg) treatment reduced the articular
incapacitation induced by carrageenin (300 μg) in
rats (José et al., 1997). The effect on smooth
muscles using isolated rat uterus and intestine
smooth muscles, concluded that the fraction
possesses
substances, which provoke direct
relaxing effect on smooth muscles and inhibit
contraction induced by several agonists possibly by
blocking the entry of calcium and/or inhibiting
cAMP phosphodiesterase (
Margort et al., 2000).
Microscopically, pre-treated rats with aqueous
extract showed significantly marked inhibition of
gastric
lesions and marked reduction of
submucosal oedema as
compared to the control
group (
Mahmood et al., 2005
). The ethanolic
root extract of plant in a dose of 100 and
300
mg/kg significantly reduced the carrageenin-
induced hind paw oedema in rats with no acute
toxic effect in mice (Tandon et al., 1994). The anti-
inflammatory effect of A. conyzoides methanol
extract depends on the flavonoid fraction, which
could produce a protective action against free-
radical mediated damage in cells and tissue.
Therefore, it is possible to hypothesize that
flavonoids influence inflammatory gene protein
expression (Galati et al., 2001).
Spasmolytic effects
The WSF (0.2 and 0.19 mg/ml) studied in the rat uterus
and intestinal smooth muscles showed increase in the
EC50 values and decreased the maximum responses to
acetylcholine and calcium chloride. The WSF (0.5 to 3.3
mg/ml) produced direct relaxant effect on smooth muscle
preparations. Theophylline (10-3 M) potentiated the
relaxant action of the WSF and also prevented the
decrease in maximum response promoted by the WSF in
acetylcholine concentration-effect curves which seems to
be partially connected to calcium mobilization which
helped to inhibit the cyclic AMP phosphodiesterase
(Yamamoto et al., 1991; Silva et al., 2000).
Gamma radiation effects
The study of the mortality rate of mice exposed to 10 gray
of gamma radiations was found to be most effective at a
dose of 75 mg/kg alcoholic extract which is considered to
be the optimal dose for radio protection which reduce the
severe symptoms of sickness caused by radiation and
mortality at all exposure doses of radiation, thus increase
survivors rate at all doses and also protected mice
against the effects of the lethal gastrointestinal and bone
marrow depressions. The protection effects of the extract
against gamma radiation may be caused by scavenging
reactive free radicals of oxygen molecules. Thus, the
plant has appreciable anti-oxidant property (Jagetia et al.,
2003).
Anti-cancer, anti-radical scavenging activity and
gastric properties
Ethanol extract showed an IC50 values of 1.73 µg/ml in P-
388 cell line, while petroleum ether extract had IC50
values of 14.06, 13.77 and 0.71 µg/ml in A-549 (human
non-small cell lung cancer cell line), SGC-7901(human
gastric cell line) and P-0.0003 µg/ml in A-549, DU-145
(human prostrate carcinoma cell line), SGC-7901 and P-
388 (mouse leukemia cell line) cells, respectively.
Similarly, ethyl acetate extract had IC50 value of 0.68,
9.97, 14.88 and 0.0003 µg/ml in A-549, DU-145, SGC-
7901 and P-388 cells, respectively. The result therefore
showed that it possesses anti-cancerous and antiradical
properties (Adebayo et al., 2010).
Anti-malarial properties
Petroleum ether extracts of A. conyzoides with LC50
values 1925.60 and 267.90 ppm was found effective
against the mosquito, Culex quinquefasciatus larvae
(Preeti et al., 2009). The uses of each extraction parts of
this plant are shown in Table 2.
Anticoccidial activity
A recent study revealed that essential oil has efficacy in
treating caecal coccidiosis of broilers (Nweze and
Obiwulu, 2009). Acute toxicity test was done using 28
days old broiler chicks (250 to 3000 mg of extract/kg
body weight orally) which were divided into six groups of
five birds each in which group VI were given equal
volumes of distilled water where the observation was
done for 219 h for signs of toxicity. Acute toxicity test
gave no sign of toxicity, but it was found decreasing
steadily in all the treatment groups until it became zero
for the faecal oocyst per gram of faeces. Finally, the
packed cell volumes, weight and red blood cell counts of
the treated birds were found to be significantly (P< 0.05)
higher than those of the infected untreated control which
confirms the plant’s ethno-veterinary use in the treatment
of coccidiosis.
Schistosomicidal activity
For in vitro condition, A. conyzoides oil was studied for its
schistosomicidal activity against adult worms of
Schistosoma mansoni. It was found to be active which
leads to reduction in the number of eggs of the adult
worms in a dose-dependent manner even though less
than the positive control (praziquantel, PZQ) in terms of
separation of coupled pairs, mortality, decrease in motor
activity, and tegumental alterations. Precocene I (74.3%)
and (E)-caryophyllene (14.23%), the constituents of the
oil were found to be much less effective than the
essential oil and PZQ when tested both individually as
well as in mixture form in the ratio similar to that found in
the essential oil suggesting that the oil may help to
develop a new schistosomicidal agents (de Melo et al.,
2011).
Miscellanious activities
The crude extract of A. conyzoides is found to have
antioxidant property and is superior to vaseline gauze as
a wound dressing material. The ethanolic leaf extract is
reported to have haemopoietic properties in albino rats
(Ita et al., 2007) and reported to have gastroprotective
activity in rats by determining mean ulcer size, ulcer
number and ulcer index and found that the oral
administration of ethanol extract at dose level 500 and
750 mg/kg significantly protected gastric lesions by 80.59
and 89.33%, respectively as compared to Misoprostol
(719.193%) in the Ibuprofen model; by 97.09 and
99.219%, respectively in rats (Shirwaikar et al., 2003).
The root and aerial part extracts were reported to inhibit
86 and 79% activities of histamine and 5-hydroxy
tryptamine (5-HT), respectively which could be the
reason of inducing tracheal relaxant. They are also found
to have activities on isolated uterus of rat by inhibiting
uterine contractions induced by 5-HT which suggest that
the plant extract exhibits specific antiserotonergic activity
on isolated uterus (
Lans, 2007).
The leaf extract is also
used as pain relief in osteoarthrotic patients (Marques et
al., 1988) showing analgesic effect and articulation
mobility improvement without side effects. The aqueous
leaves extract are reported to act as anti-coagulant which
also decreases bleeding time (Akah, 1988). The leaf
extract has analgesic activity and was detected by hot
plate method (Abena et al., 1993a). A. conyzoides is also
found in the treatment of abdominal and menstrual pains
(Nair et al., 1977). In vitro receptor radio ligand assay of
the extract showed that it produced positive results (>
50% inhibition) in the bradykinin (BK II) responsible for
the initial bioactivity. The aqueous extract of A.
conyzoides roots was reported to decrease glutathione in
the liver and in the lymphoma cells of the tumour-bearing
mice which could be one step of producing the anti-
tumour effect (Rosangkima and Prasad, 2001). The leaf
extract was reported to change the electrocardiogram,
atrial impulse velocity and coronary vessel resistance in
the isolated guinea pig heart, but its effects disappeared
after wash. The plant (leaves and root) was devoid of in-
vivo cholinesterase activity (Gupta and Gupta, 1997). The
leaves
extract changes the electrocardiogram, atrial
impulse
velocity and coronary vessel resistance on
isolated guinea-pig heart (
Garcia and Carvalho, 1999).
Aqueous extract of an association of A. conyzoides, C.
citrates and L. multiflora produced a significant reduction
in mouse of writhings induced by acetic acid and an
increase of pain threshold in the hot plate test in mice. The
presence of saponins and flavonoids supports the
observed activities and suggests that plants could be used
as traditional improved preparation (Okemy et al., 2006).
Allelopathic property of A. conyzoides
Both the volatile oil and the aqueous extract of A. conyzoides
have been shown to have allelopathic effects on a number of
cultivated crops. These include radish, mungbean and
ryegrass (
Xu et al., 1999).
The saturated aqueous solution
of the isolated and purified precocenes I and II have been
reported to have significant inhibitory effect on the
seedling growth of radish, tomato and rye-grass (Hu and
Kong, 2002). The allelopathic potential of the aqueous
extract from different organs of A. conyzoides and from its
different development stages, especially from different
habitats, was different (
Kong et al., 2002).
It showed
strong inhibition on Raphanus sativus L. germination and
growth in a bioassay. It showed strong inhibition on R.
sativus L. germination and growth in a bioassay. The whole
plant show high potential of allelopathic property against
intercropped in citrus orchards. This activity may be due
to reversible transformation between ageratochromene
and its dimers in the A. conyzoides intercropped citrus
orchard soil (Kato-Naguchim, 2001; Kong et al., 2005).
Flavones released by the plant acts as a natural fungicide
in citrus orchids which is comparable with commercial
fungicide, carbengin (Kong et al., 2005). The residue of
the plant is believed to contain allelochemicals since it
inhibited the germination and the growth of roots and
shoots of Amaranthus caudatus, Digitaria sanguinalis,
Lactuca sativa. This plant may have potent
allelochemicals which may act as inhibiting agents which
may be economically useful (Saito et al., 2008). In India,
further study found that the leaf debris of the plant
released water soluble phenolic acids into the soil
environment (not through soil nutrient depletion) which
affects the early growth of rice (Oryza sativa)
deleteriously. However, it was reported that the effects of
such weeds can be reduced by planting legume fallows
like Leucaena and pigeon pea. Not only this, it was found
to increase soil nitrogen and phosphorus contents, but
not upland rice yields (Kuldip et al., 2009). The invasion
of A. conyzoides on the flora of the Shivalik hills of
Himachal Pradesh, India was reported to affect the
diversity and productivity of the invaded areas and found
that the amount of phenolic acids in the soil invaded area
was 60.90% more than the control area.
Insecticidal property
The most important considerable biological activity of this
plant is in fact, its insecticidal activity which may play a
valuable role in agriculture economically as well as
effectively. Both the oil as well as its extracts has
insecticidal activity. The oil and precocenes I and II, the
chromenes, the major constituents of its oil are reported
to have anti-juvenile hormonal activity (Vyas and
Mulchandani, 1980) and have been assayed on varieties
of insects namely Sitophilus oryzae, Thlaspida japonica,
Leptocarcia chinesis and Disdercus flavidus which results
to metamorphosis of the larvae, production of sterile,
moribund and dwarfish adults (
Fagoonee and Umrit,
1981).
It can exhibit insecticidal property against cowpea
weevil, Callosobruchus maculatus F. (Gbolade et al.,
1990) and high nymphal mortality, that is, 91% to the
nymphs of Schistocerca gregaria (Pari et al., 1998).
Petroleum ether extract is active against the mosquito, C.
quinquefasciatus larvae (Preeti et al., 2009).
The crude
plant extract also showed
insecticidal and pesticidal
activities against various types of insects and pests. Calle et
al. (1990) showed that the hexane extract of the whole
plant showed activity against Musa domestica larvae. The
methanolic extract of the plant was found to suppress the
population of the malaria
vector A. stephensi in higher
dosage, whereas in lower
dosage it was found to induce
several developmental defects and ultimately decrease the
growth index to a considerable
extent (
Saxena and
Saxena, 1992),
whereas the lower concentrations
were
found to induce developmental defects ultimately
decreasing the growth index of the treated second and
fourth instar larvae of
C. quinquefasciatus
(Saxena et al.,
1994).
The crude extract of the plant showed
insecticidal activity against nymphs of mustard aphid
L.
erysimi (Bhathal et al., 1994).
It might be a natural
herbicide for weed control in paddy fields to reduce the
dependence on synthetic herbicides (Xuan et al., 2004).
Toxicity
The presence of pyrrolizidine alkaloids in this plant has
been reported in the previous literature review; these
compounds are hepatotoxic and cause lung cancer and
variety of other ailments in rats (Couet et al., 1996). This
may be hazardous to human health. The toxicity was
observed in alcoholic extract of whole plant in mice at
>3000 mg/kg body weight (Jagetia et al., 2003).
However, the hydroalcoholic extract (HAE) does not
show any toxicity in rat during sub-acute treatment, but
found reduction of SGPT value during chronic treatment
of HAE (500 mg/kg body weight) significantly by p<0.05.
Further reports found that the cytotoxicity of the plant
may be due the oxidative dealkylation process.
CONCLUSIONS AND FUTURE PROSPECTS
Among the weeds, members of Ageratum seem to be the
most commonly spreading in agricultural areas
throughout the world. The species is believed to possess
various biological activities starting from its various
phytochemical contents. It offers many opportunities to
investigate the various functions and prospects in
pharmaceutical studies. A number of studies have
been
carried out using this plant as weed controlling agent.
It is believed
that detailed information as presented in
this review on
its phytochemistry and various
pharmacological properties of
the extracts and the
constituents might provide incentive for proper evaluation
of the use of the plant in medicine
and in agriculture.
Activities like its effects on spasmolytic and anti-
inflammatory properties of the flavonoids isolated from the
plant need to be studied.
Further studies in this
area
could serve as a means of controlling the Anopheles
mosquitoes and L. donavani. The ability to inhibit the
aflatoxin production is a new biological activity of A.
conyzoides L. which indicates that it may be considered
as a useful tool for a better understanding of the complex
pathway of aflatoxin biosynthesis and controlling of fungal
growth in agriculture.
Although, the pharmacological properties of A.
conyzoides seem to have been determined, the
mechanism of these principles is still unknown. The
bioassay guided for isolation and identification of the
bioactive components are still needed and detailed
researches are also required to reveal the structure activity
relationship of these active constituents. Outcome of the
future research in the aforementioned areas will provide a
convincing support for the future clinical uses of A.
conyzoides in modern medicine.
ACKNOWLEDGEMENTS
The authors thank the Department of Biotechnology, New
Delhi for their financial support and also to S.
Babuchandra Singh, N. Surjit Singh and Kh. Mangi Singh
for their co-operation. The authors are also thankful to Dr.
D. K. Hore Constultants IBSD for the manuscript
corrections.
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