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Scientific evidence for Mikania laevigata and
Mikania glomerata as a pharmacological tooljphp_1095 809..820
Marcelo H. Napimogaaand Regiane Yatsudab
aLaboratory of Biopathology and Molecular Biology, University of Uberaba and bLaboratory of
Physiology and Pharmacology, Federal University of Bahia, Brazil
Abstract
Objectives Historically, the majority of new drugs have been generated from natural
products as well as from compounds derived from natural products. In this context, Mikania
laevigata and M. glomerata, popularly known as ‘guaco’, have a long history of use.
Brazilian Indians have an ancient tradition of using ‘guaco’ for snakebites. In current herbal
medicine in Brazil, ‘guaco’ is used as an effective natural bronchodilator, expectorant and
cough suppressant employed for all types of upper respiratory problems including bronchi-
tis, pleurisy, colds and flu, coughs and asthma.
Key findings In Brazil, this plant has been widely used, even as commercial preparations.
Its medicinal properties are widely recognized, mainly in the treatment of inflammatory
conditions, bronchodilator activity, anti-ulcerogenic, antiophidian as well as antibacterial
and antiparasitic activity, although the efficacy of the antibacterial activity is so far
controversial.
Summary The studies on Mikania glomerata and M. laevigata have provided scientific
evidence that those plants have a considerable anti-inflammatory therapeutic potential.
Keywords inflammation; medicinal plant; Mikania glomerata;Mikania laevigata;
phytotherapy
Introduction
The use of medicinal plants in the world, and especially in South America, contributes
significantly to primary health care and knowledge on medicinal plants. Sometimes it is the
only therapeutic resource of some communities and ethnic groups.[1] In a constant attempt to
improve their quality of life, humans have used plants as sources of food, shelter, clothing,
medicine, cosmetics, and for seeking relief from the hardship of life. Some plants are known
as medicinal because they contain active substances that cause certain reactions, and bio-
active molecules with a considerable therapeutic potential.
The history of drug development has its foundation firmly set in the study of natural
medicine used to treat human diseases over the centuries. Analysis of medicinal plants,
bioactive cultures, and increased understanding of micronutrients in the food chain opened
the field to the development of purified and defined chemical compounds as dose-
controlled medicines. Efforts to subject botanicals to rigorous scientific research began
recently; however, there are still many problems associated with this area of research.
These include procuring the study agents, selecting the appropriate study method and
clinical trial design, navigating through regulatory obstacles, and obtaining funding.
Evidence-based botanical research can help to validate traditional uses and to facilitate new
drug development.[2]
Natural products have been the most productive source of leads for the development of
drugs. Over one hundred new products are in clinical development, particularly as anticancer
agents and anti-infectives.[3] Nowadays the application of molecular biological techniques is
increasing the accessibility of new compounds that can be suitably produced in bacteria or
yeasts, and combinatorial chemistry approaches are being based on natural product scaffolds
to create screening libraries that closely resemble drug-like compounds. To confirm that
natural products are the major source of new compounds which will be used by the
pharmaceutical industry, Newman and Cragg[4] demonstrated that, overall, of the 1184 new
chemical entities covering all diseases/countries/sources between 01/1981 and 06/2006 only
30% were synthetic in origin, thus demonstrating the influence of ‘other than formal
Review
JPP 2010, 62: 809–820
© 2010 The Authors
Journal compilation © 2010
Royal Pharmaceutical Society
of Great Britain
Received January 5, 2010
Accepted March 4, 2010
DOI 10.1211/jpp.62.07.0001
ISSN 0022-3573
Correspondence: Marcelo H.
Napimoga, Laboratory of
Biopathology and Molecular
Biology, University of Uberaba,
Av. Nenê Sabino, 1801, Uberaba,
Minas Gerais 38055-500, Brazil.
E-mail: marcelo.napimoga@
uniube.br
809
synthetics’ on drug discovery and approval. In this context, the
Mikania genus is an important source and a promissory plant
to be used in different diseases. In this review, we have
focussed on some scientific studies of Mikania laevigata and
M. glomerata to provide the evidence for the diversity of
medical applications provided by these plants.
Mikania species
Plants of the genus Mikania were described by Willdenow in
1804, receiving this nomenclature in honour of Professor
Joseph Gottfried Mikan, Prague. The genus Mikania Willd is
the largest genus of the tribe Eupatorieae (Asteraceae
family), including approximately 450 species. Many of these
species are found in South American countries, with its two
major diversity centres in the highlands of south-eastern
Brazil and the eastern foothills of the Andes from Bolivia to
Colombia, as well as tropical regions of Asia and Africa.[5–7]
The genus is widely distributed in Brazil with approximately
171 described species, with approximately 150 of these
being endemic, including M. laevigata.[6–9]
Mikania grows as a timbered shrub with a branched
cylindrical stem.[10] This plant is a sub-scrub creeper of
woody branches and brilliant-green leaves that release a
strong aroma reminiscent of vanilla.[11] The species are char-
acterized by their capitula which are composed of four florets
and involucres composed of four phyllaries that are sub-
tended by a subinvolucral bract. There is no variation from
this basic organization, and specific differences mostly
involve the type of capitulescence, size of habit, shape of
organs and plant texture.
Several species of the Mikania genus (Figure 1; growth
habit: creeper) are popularly known as ‘guaco’, for example,
M. cordifolia,M. laevigata Schultz Bip. ex Baker,
M. glomerata Spreng, M. scandens Willd., M. officinalis
Mart. and M. opifera DC.[8,12–16] M. laevigata Schultz Bip. ex
Baker is popularly known as ‘guaco’, ‘guaco of the home’
and ‘guaco of the bush’, and it is a native species of south-
ern Brazil. M. glomerata Spreng is popularly known as
‘guaco’, ‘smooth guaco’, ‘smelling guaco’, ‘caatinga-vine’,
‘heart of Jesus’, ‘putty-vine’ and ‘snake-herb’, and it is also
a native species found in Mata Atlântica in south-eastern
Brazil.[17,18]
M. glomerata Spreng was considered an official species in
the first edition of the Brazilian Official Pharmacopoeia,
while M. laevigata was described in the sixth volume in the
fourth edition of the Brazilian Official Pharmacopoeia.[19–21]
Coumarin (1,2-benzopyrone) is the main chemical marker
described for both species.[22] M. glomerata Spreng was iden-
tified by Sprengel in 1826, and is also known as Cacalia
trilobata Vell., M. amara,M. aspera,M. attenuata,M. scan-
soria DC., M. hederaefolia DC., Willoughbya glomerata
(Spreng), Willoughbya moronoa (Ktze). In southern Brazil,
M. laevigata is mostly harvested, rather than M. glomerata,
due to its local abundance.
M. laevigata and M. glomerata are very similar morpho-
logically. The main difference between them is their flowering
period: September for M. laevigata and January for M. glom-
erata. The leaves are slightly different, the lobes being more
prominent in M. glomerata, and both present the characteris-
tic odour of coumarin.[23] Their habitats are the shores and
inland forests, adapting very well to domestic cultivation. At
the time of flowering it becomes a very popular plant for
honey bees.[24]
History and popular use
Many plants are used in Brazil in the form of crude extracts,
infusions or plasters to treat common infections without any
scientific evidence of efficacy.[1]
M. laevigata Schultz Bip. ex Baker and M. glomerata
Spreng are the two medicinal plants in Brazil that are used
interchangeably and often at times with no distinction
between the two species.[1,25] The leaves of both species are
used in Brazilian folk medicine and other southern American
countries for several inflammatory and allergic conditions,
particularly of the respiratory system.[26]
Both have a long history of use by rainforest inhabitants.
Brazilian Indians have an ancient tradition of using guaco
for snake bites; preparing a tea with the leaves and taking it
orally as well as applying the leaves or the stem juice (in a
hurry) directly onto the snake bite. Other Amazonian
rainforest Indian tribes have employed the crushed leaf stem
topically on snake bites (as well as drinking the decoction of
leaves and/or stem) and have used a leaf infusion for fevers,
stomach discomfort and rheumatism. Indigenous people in
the Amazon region in Guyana warm the leaves to put on
skin eruptions and itchy skin. Several Indian tribes also
believe if you crush the fresh aromatic leaves and leave them
around sleeping areas the spicy scent will drive snakes away.
For this reason and because of its long history as a snakebite
remedy, it earned the name ‘snake-vine’ and ‘snake-herb’ in
herbal medicine systems.
Figure 1 Mikania glomerata
810 Journal of Pharmacy and Pharmacology 2010; 62: 809–820
The leaves of M. laevigata have been widely used as
infusions or plasters, while the crude extract of this species
is commonly commercialized as a phytomedicine, mainly to
treat inflammatory disorders, such as bronchitis, chronic
lung diseases and bronchial asthma.[24,27] In current herbal
medicine systems in Brazil, ‘guaco’ is well known and well
regarded as an effective natural bronchodilator, expectorant
and cough suppressant employed for all types of upper
respiratory problems, including bronchitis, pleurisy, colds
and flu, coughs and asthma, as well as for sore throats, lar-
yngitis and fever. The M. glomerata and M. laevigata plants
have been widely used based on their folk indications in
asthma and bronchitis, probably due to their anti-allergic,
bronchodilating, anti-inflammatory and anti-oedematogenic
properties.[28–32]
In 1870, a Brazilian herbal drug called Opodeldo de Guaco
was made from the leaf and stem of ‘guaco’ that was consid-
ered a ‘saint’s remedy’ to treat bronchitis, coughs and rheu-
matism. This ‘drug’ is still a popular home remedy today
throughout Brazil for the same purposes, but locals prepare it
themselves by boiling ‘guaco’ leaves into a tasty spicy cough
syrup. Nowadays, this plant and its syrup are commercialized
and distributed for free by Brazilian government health pro-
grammes to treat respiratory complaints such as asthma, bron-
chitis and cough. Although this clinical conduct has been
described as harmless and safe, neither the assessment of the
toxicity of ‘guaco’ syrup used by humans, nor its efficacy or
mechanisms of action have been investigated properly.[33]
Guaco is also popular in Brazil as an anti-inflammatory,
antispasmodic and pain-reliever for rheumatism, arthritis,
intestinal inflammation and ulcers. Adecoction of the leaves is
employed externally for neuralgia, rheumatic pain, eczema,
pruritus and wounds. Ethnopharmacological studies of the
Mikania genus showed pharmacological properties such as
tonic, depurative, antipyretic and appetite stimulant, and as a
treatment for influenza.[34,35]
Phytochemical analysis of M. glomerata
and M. laevigata
Analytical methods
Studies were conducted to evaluate the best preparation
methods for extracts of M. laevigata and M. glomerata.
Celeghini et al.[11] evaluated the sample preparation method,
comparing maceration and maceration under sonication. The
authors obtained statistically similar results; however, as the
extraction time of seven days by maceration is very long for
routine analysis, maceration under sonication was chosen as
the best method considering the time/yield ratio, since it
required a shorter extraction time (20 min). Through visual
evaluation and analysis using thin layer chromatography
(TLC), the best proportion of the extracting solvent was
established as being ethanol : water (1 : 1 v/v). For the two
methods tested, the extraction and two sequential re-
extraction tests, in the first extraction the percentage of
coumarin obtained was approximately 78.73%, being repro-
ducible and not justifying the implementation of serial
extractions. From the extraction and kinetics (yield of
extraction as a time function), the optimal extraction time
was determined using the mixture ethanol : water (1 : 1 v/v)
as the extracting solvent, and the inflection point of the
curve was found at 20 min, which was chosen as the optimal
extraction time.
Although the usage of M. glomerata and M. laevigata in
folk medicine is widespread around the world, for the safe
utilization of any plant as a medicine, its standardization is
necessary to guarantee plant drug authenticity and its content
of active principles according to the parameters utilized as
quality criteria. The results presented by these authors indi-
cated that high performance liquid chromatography–
ultraviolet analysis (HPLC-UV) may be a useful tool for the
quality control of hydroalcoholic extracts of M. glomerata,
since this method showed reproducibility and sensitivity
adequate for these extracts. There were other advantages also,
such as high efficiency, speed and the possibility of its utili-
zation in automated systems.[11]
A comparative study of the chemical composition of the
species M. glomerata and M. laevigata showed that adultera-
tions of plant raw materials often occur in the marketing of
herbal medicine, usually in the form of substitutions and/or
fakes. This may occur due to the difficulties of obtaining the
authentic plant material, or by an intentional use of a plant
species that has less economic value but shows similar mor-
phological features.
Despite M. glomerata and M. laevigata being commer-
cialized with no distinction in Brazil, they have been scarcely
studied chemically; however several compounds have been
isolated already, chiefly coumarins, diterpenes and essential
oils.[11,17,23,31,36–48] Phytochemical studies of the leaves from
M. laevigata and M. glomerata species indicated a similar
composition, presenting coumarins, diterpene acids (entkau-
rene derivatives), triterpenes and steroids (friedelin, stigmas-
terol and lupeol), flavonic heterosides, sesquiterpene lactones
and cinnamic acid derivatives.[11,14,17,23,31,36–49] However,
Oliveira et al.[17] did not find the presence of heteroside fla-
vones in either species. Bolina et al.[41] did not detect the
presence of genin or heteroside anthraquinones, saponins,
genin flavones, alkaloids, cardiotonic heterosides, tannins and
simple phenols in either species. However, the study con-
ducted by Oliveira et al.[17] reported the presence of alkaloids,
saponins, tannins and polyphenols in the aerial parts of M.
glomerata and M. laevigata.
The coumarin concentration has been determined in many
studies, as this substance is a known marker used as a refer-
ence.[31] In a phytochemical screening for coumarin detection,
the authors observed in the chromatographic profile two dif-
ferent species, o-coumaric acid and coumarin, of which
0.30% ⫾0.01 (w/w) of coumarin was obtained for M. glom-
erata and 0.43% ⫾0.02 (w/w) for M. laevigata.[41] These
values were in accordance with the contents (minimal of
0.1%, w/w) described by the monograph of ‘guaco’ in the
Brazilian Pharmacopoeia. The authors concluded that the
results indicated similar chemical profiles for M. glomerata
and M. laevigata, as well as comparable coumarin content,
thus suggesting that both species may be used with no dis-
tinction between them. dos Santos et al.[23] determined the
contents of coumarin and o-coumaric acid in hydroalcoholic
and aqueous extracts (lyophilized and freshly prepared), in
leaves of both ‘guaco’ species. They found that the
Scientific evidence for Mikania use Marcelo H. Napimoga and Regiane Yatsuda 811
concentration for the selected markers was larger for
M. glomerata than M. laevigata, not only for the aqueous fresh
extract but also for the hydroalcoholic extract of M. laevigata,
that presented considerable variations in concentration in terms
of geographical origin, when collected during the same season
and period and processed in the same way. The lyophilized
extract presented some alteration during the lyophilization
process, confirmed by a new peak detected in the correspond-
ing chromatograms and a diminished quantity of the selected
markers (60% for o-coumaric acid and 50% for coumarin) in
relation to the freshly analysed aqueous extract.
In another study, the major compounds of the hydroalco-
holic extract of M. laevigata identified were coumarin
(36.90%) and dihydrocoumarin (32.30%), a lower quantity
than shown by dos Santos et al.[23,31] The weight of dry crude
extract and coumarin concentration from M. laevigata were
determined in each month and no statistical difference was
detected, and did not substantially alter the basic pharmaco-
logical activity of guaco extract.[31] Yatsuda et al.[39] analysed
the relative percentage of the identified compounds by gas
chromatography (GC–MS) of the ethanolic extract of both
species of Mikania. They found 17.81% of coumarin in M.
laevigata but did not detect coumarin in the ethanolic extract
of M. glomerata, only in the ethyl acetate fraction of M.
glomerata, at a relatively low percentage (1.43%).
Thus, the percentage of compounds in both species
shows a great variation, as does the quality of compounds,
depending on the geographical origin of the plants.
Table 1[50] shows the chemical constituents identified in the
fractions of M. glomerata and M. laevigata collected from
different geographical origins.
Biological activity of fractions and constituents
identified from M. laevigata and M. glomerata
Initial screenings of plants for possible antimicrobial activity
typically begin by using crude aqueous or alcoholic extrac-
tions and can be followed by various organic extraction
methods. Since nearly all of the identified components from
plants active against microorganisms are aromatic or saturated
organic compounds, they are most often obtained through
initial ethanol or methanol extraction.
Pretreatment of rats with a dichloromethane fraction of
M. glomerata was able to reduced pleural oedema, showing
anti-allergic activity at the highest dose tested.[51] The admin-
istration of a dichloromethane fraction dose-dependently
inhibited leucocyte infiltration detected after antigen chal-
lenge. Experiments have demonstrated an anti-allergenic
effect of a dichloromethane fraction obtained from the
hydroalcoholic extract of M. glomerata leaves in rats.[28] The
Table 1 Chemical constituents identified in fractions of Mikania laevigata and Mikania glomerata
Reference Fractions Constituents
Veneziani et al.[36] The hexane soluble fraction of branches of
M. glomerata
Ent-kaur-16(17)-en-19-oic acid and ent-beyer-15(16)-en-19-oic acid,
en-15b-benzoyloxkaur-16(17)-en-19-oic acid
Veneziani et al.[36] The CH2Cl2soluble fraction of branches of
M. glomerata
Grandifloric acid, hydroxyl-ent-kaur-15(16)-en-19-oic acid
Veneziani et al.[36] The hexane soluble fraction of leaves of
M. glomerata
Stigmasterol, b-sitosterol and ent-15-b-isobutyryloxykaur-16(17)-
en-19-oic acid
Veneziani et al.[36] The CH2Cl2soluble fraction of leaves of
M. glomerata
Coumarin and ortho-hydroxycinnamic acid
Ferreira et al.[50] The hexane fraction of leaves of M. laevigata Lupeol acetate, lupeol, kaurenoic acid, beierenoic acid, coumarin,
diidrocoumarin, caryophyllene oxide and spathulenol
Ferreira et al.[50] Dicholoromethane fraction of leaves of
M. laevigata
Coumarin syringaldehyde and ortho-((50′-hydroxy)-cis-cinnamoyl)-
trans-cinnamic acid
Ferreira et al.[50] Ethyl acetate fraction of leaves of M. laevigata Ent-3a-O-b-d-glucopyranoside, 16a, 17-diidroxicauran 2b-((3-
O-(3-hydroxy-1-oxo-3-phenylropyl)-2-(3-methyl-1-butyryloxy)-
4-O-(a-l-rhamnopyranosyl)-b-d-glucopyranosyl)oxy)-13-15a-
dihydroxy-19-norcaur-16-en-18-oic acid), trans-melilotoside,
cis-melilotoside, adenosine, 3-O-b-d-glucosyl-patuletine,
3-O-b-d-glycosyl-kaempferol, 3-O-b-d-glucosyl-quercetin and
3,3′,5-trihydroxy-4′,6,7-trimethoxiflavone
Yatsuda et al.[39] The hexane fractions of leaves of M. laevigata Dihydrocoumarin, coumarin, spathulenol, hexadecanoic acid,
9, 12-octadecadienoic acid, 9,12,15-octadecatrineoic acid,
cupressenic acid, kaurenol, kaurenoic acid, isopropyloxi-
grandifloric acid, isobutyloxy-grandifloric acid
Yatsuda et al.[39] The hexane fractions of leaves of M. glomerata Spathulenol, caryophyllene oxide, hexadecanoic acid,
10, 13-octadecadienoic acid, 9,12-octadecadienoic acid,
kaurenoic acid, diterpenic acid, grandifloric acid,
isopropyloxy-grandifloric acid, diterpenic ester
Yatsuda et al.[39] The ethyl acetate fractions of leaves of
M. laevigata
Hexadecanoic acid, 9,12-octadecadienoic acid, 9,12,
15-octadecatrienoic acid, cupressenic acid, kaurenoic acid
Yatsuda et al.[39] The ethyl acetate fractions of leaves of
M. glomerata
Trans-cariofileno, coumarin, EPI-bicyclosesquiphellandrene,
spathulenol, hexadecanoic acid, 8,11-octadecadienoic acid,
9,12,15-octadecatrienoic acid, kaurenoic acid, diterpenic acid
812 Journal of Pharmacy and Pharmacology 2010; 62: 809–820
effects on isolated respiratory and vascular smooth muscle
have been investigated, testing the aqueous hydroalcoholic
extract, and a dichloromethane fraction obtained from the
hydroalcoholic extract of M. glomerata leaves.
Aqueous extracts and hydroalcoholic extract induced a
significant inhibition of histamine-induced contractions in the
guinea-pig isolated trachea, but the active dichloromethane
soluble fraction was more active than the hydroalcoholic
extract.[29] Chromatographic studies performed with the
dichloromethane fraction confirmed the findings of Lucas[24]
and Oliveira et al.,[17] showing the presence of coumarin in
leaves of M. glomerata. The concentration of coumarin in the
dichloromethane fraction was very high (11.4% w/w), and
coumarin probably had a very important role in the relaxant
effect of M. glomerata on respiratory smooth muscle. Experi-
ments performed by Soares de Moura et al.[29] showed that
coumarin had a significant inhibitory effect on guinea-pig
isolated tracheal rings precontracted with histamine, acetyl-
choline or K+. Therefore, it was likely that other active par-
ticipants contributed towards the bronchodilator activity of M.
glomerata fraction (MG1). The vasodilator effect (potency)
was lower than the bronchodilator effect of MG1. This sug-
gested that the compounds present in the extracts of M. glom-
erata were more active on the respiratory smooth muscle than
on vascular smooth muscle. In that study, the authors demon-
strated an inhibitory effect of the dichloromethane fraction on
the mouse hind-paw oedema induced by release of inflamma-
tory agents by Bothrops jararaca venom, confirming an anti-
infammatory action of M. glomerata as demonstrated by
Ruppelt et al.[52,53]
Duarte et al.[54] showed that the essential oil of M. glom-
erata exerted a strong anti-Candida activity. The essential oil
was also subjected to GC and GC–MS analyses. Among the
identified compounds, some had been reported previously to
have antimicrobial activity, including dl-limonene and
germacrene-D, and menthol.[55–57] Yatsuda et al.[39] showed that
the hexane fraction (with kaurenoic acid as a major com-
pound) from both species of Mikania was the most effective
against crude extract and ethyl acetate fractions in inhibiting
growth and cell adherence to a glass surface of mutans
streptococci. Another study detected that the ethanolic and
dicloromethane extracts did not present antibacterial activity,
and were detected only in the hexanic extract of M. glomerata
substances with antibacterial activity.[58] The results obtained
in both studies suggested that the biologically active com-
pounds were present mostly in the hexane fraction of both
Mikania species.
During the flowering period there is an increased concen-
tration of compounds in the plants; for the ‘guaco’ plants this
period is from August to December. Although these plant has
been widely used, even as commercial preparations, there
have been few studies on their biological properties. Some of
these compounds have shown good results in comparison with
positive controls in bioassays, as described in Table 2.[59–64]
The coumarins are the main biological markers found in
M. laevigata and M. glomerata and were identified in various
plants. The activities of coumarins are described as anti-
inflammatory, expectorant, anti-ulcerogenic, anticoagulant,
respiratory smooth muscle relaxant, anti-oedematous, bron-
chodilator, and antisnake venom.[23,24,29–31,60–62,65,66]
The biological effects of M. glomerata
and M. laevigata
Medicinal plants and the compounds derived from them are a
good source of new and specific inhibitors of the inflamma-
tory process. The past decade has witnessed many important
discoveries in this field, with new findings challenging the
more traditional views of researchers. In Table 3[67–72] the key
papers on the pharmacology of Mikania and their scientific
findings have been summarized.
Bronchodilator activity
Obstructive airway diseases, in which asthma is included,
show a variety of symptoms. Physiologically they are char-
acterized by maximal expiratory flow limitation, and patho-
logically by inflammation of the airways and the lung
parenchyma. Inflammation plays a major role in the gradual
aggravation of the lung function resulting in worsening
symptoms.[73] Studies are in progress to identify various
molecular targets in these pathways for the purpose of
Table 2 Bioactive constituents of Mikania laevigata and Mikania glomerata
Reference Biological activity Bioactive constituents
Oliveira et al.[17]
Yatsuda et al.[39]
Davino et al.[59]
Antimicrobial and anti-ulcerogenic, antispasmodic
and anti-inflammatory
Kaurenoic acid, grandifloric acids, stigmasterol,
coumarin and dihydrocoumarin
Lucas et al.[24] Expectorant action of the plant Coumarin glycoside
Bighetti et al.[60] Gastric antisecretory activity mediated by the
parasympathetic system
The coumarin and the crude hydroalcoholic
extract of M. Laevigata
Alves et al.[31] Anti-inflammatory The coumarin and the crude hydroalcoholic
extract of M. laevigata
Booth et al.[61] Anticoagulant effect 1,2-Benzopyrone
Santos et al.[23] Anticoagulant effect Coumarin and o-coumarin
Pedroso et al.[49] Stimulated docosahexaenoic acid synthesis in the
liver
Coumarin and o-coumarin
Pereira et al.[62] Anti-B. jararaca venom Coumarin
Born et al.[63] Rat liver toxicant Coumarin
Ulubelen et al.[64] Antifertility activity in mature female rats Coumarin
Scientific evidence for Mikania use Marcelo H. Napimoga and Regiane Yatsuda 813
developing novel therapeutic approaches. In this context,
natural agents have been used in numerous cultures for the
treatment of several medical conditions and have mostly
proven to be safe.
Bronchoconstriction plays a very important role in the
physiopathology of asthma, and compounds that relax respi-
ratory smooth muscles such as b2-agonists, theophylline and
cholinergic antagonists are usually used in symptomatic treat-
ment of the disease. M. laevigata and M. glomerata are tra-
ditionally used to treat respiratory illness in Brazil. The
‘guaco’ leaves are commonly used as an extract, syrup or
infusion to treat bronchitis, asthma and cough.[17] Experimen-
tal observations of the efficacy of ‘guaco’ use in airway dis-
eases have been consistent, and some studies demonstrated
the mechanisms of its action.
Fierro et al.,[28] using a model of allergic pleurisy in rats,
demonstrated that the animals treated with a fraction obtained
from the ethanolic extract of M. glomerata had a reduction of
pleural oedema at the highest dose tested, as well inhibition of
leucocyte infiltration detected after antigen challenge. Interest-
ingly, the ethanolic extract of M. glomerata inhibited pleural
eosinophilia, and this process is dependent on eicosanoids and
platelet-activating factor.[67] One possible explanation for the
inhibitory effect of ethanolic extract of M. glomerata on rat
allergic pleurisy is that it antagonizes the effects and/or the
release of this lipid although there is no inhibitory activity on
pleurisy triggered by histamine or serotonin.[28] Another study
demonstrated that the hydroalcoholic extract of M. glomerata
produced a decrease of the basal tonus of the isolated respi-
ratory smooth muscle of the guinea-pig trachea. When the
respiratory smooth muscle was contracted with histamine,
acetylcholine or high K+, in the presence of diverse pharma-
cological agents such as propranolol, atropine, mepyramine
or L-NAME, the presence of hydroalcoholic extract of
M. glomerata induced a significant concentration-dependent
relaxation. This suggested that the inhibitory effect of
M. glomerata was not dependent on inhibition of muscarinic
or histaminergic receptors, activation of b2-adrenoceptors,
release of nitric oxide and/or prostanoids or activation of K+
channels. Furthermore, the vasodilator effect was lower than
the bronchodilator effect of the hydroalcoholic extract of
M. glomerata. This suggested that the compounds present in
Table 3 Key papers on the pharmacology of Mikania and their scientific findings
Reference Key papers and their scientific findings
Fierro et al.[28] Ethanolic extract of M. glomerata reduced pleural oedema
Silva et al.[67] Ethanolic extract of M. glomerata inhibited pleural eosinophilia
Soares-de-Moura et al.[29] Extracts of M. glomerata were active on respiratory smooth muscle
dos Santos et al.[23] Hydroalcoholic extract of M. laevigata decreased significantly the influx of leucocytes, especially eosinophils,
to the bronchoalveolar space
Graça et al.[68] Hydroalcoholic extract from M. laevigata induced a concentration-dependent relaxation of rat trachea which
does not depend on epithelium-derived substances but involves changes in the cellular mobilization of
calcium
Freitas et al.[26] Extracts of M. glomerata and M. laevigata diminished lung inflammatory infiltration induced by coal dust
Alves et al.[31] The anti-neutrophil migration effects of extract from M. laevigata were associated with nitric oxide expression
dependent on iNOS activation and also inhibition of the production of cytokines and consequently
neutrophil migration
Bighetti et al.[60] Hydroalcoholic extract of M. laevigata decreased the ulcerative lesion index produced by indometacin,
ethanol, stress and reserpine in rats, as well as decreasing the hydrogen ion concentration
Do Amaral et al.[58] Hexanic extract of M. glomerata presented antibacterial activity against a multiresistant strain of
Staphylococcus aureus
Holetz et al.[1] Ethanolic fraction of M. glomerata presented only weak activity against both Gram-positive and
Gram-negative bacteria
Yatsuda et al.[39] The crude extracts of both Mikania did not show bactericidal activity against most of the clinical isolates.
Ethyl acetate fractions of both Mikania displayed negligible effects against mutans streptococci. On the
other hand the ethanolic extracts inhibited the growth of all microorganisms tested and the hexane fraction
of both species of Mikania showed remarkable antibacterial activity
Barratto et al.[69] The ethanolic extract of M. laevigata presented significant antimicrobial activity against S. aureus,E. coli,
P. aeruginosa,E. faecalis and E. faecium
Betoni et al.[70] Synergism of plant extract with antibiotics. M. glomerata presented synergistic effect with antimicrobial drugs
against S. aureus
Holetz et al.[1] Hydroalcoholic extract of M. glomerata had a moderate activity against Candida species
Duarte et al.[54] Extract of M. glomerata was not effective at any of the concentrations tested against C. albicans
Luize et al.[71] Extract of M. glomerata demonstrated 97.5% growth inhibition against amastigote forms of L. amazonensis,
as well as 49.5% of growth inhibition of epimastigote forms of T. cruzi
Maiorano et al.[66] Phospholipase A2activity induced by Crotalus durissus terrificus venom was totally inhibited by the aqueous
extracts of M. glomerata, while for Bothrops jararacussu venom no significant inhibition was observed
Da Silveira e Sá et al.[72] M. glomerata ethanolic extract does not interfere with the fertility in rats
Graça et al.[68] M. laevigata syrup presented no adverse effects on the spermatogenic process as well no toxicity in the
hepatic, renal or pancreatic systems
Soares-de-Moura et al.[29] M. glomerata extract fraction is devoid of genotoxicity since this fraction did not damage DNA either directly
or by producing reactive oxygen species
814 Journal of Pharmacy and Pharmacology 2010; 62: 809–820
the extracts of M. glomerata were more active on the respira-
tory smooth muscle than on vascular smooth muscle. Thus,
the probability of a large reduction in arterial blood pressure
would appear to be remote.[29]
Regarding M. laevigata, dos Santos et al.[23] used a mouse
model of allergic pneumonitis to demonstrate that the animals
treated with the hydroalcoholic extract of M. laevigata had
significantly decreased influx of leucocytes, especially of
eosinophils, to the bronchoalveolar space. Further, the analy-
ses of histopathological images demonstrated a haemorrhagic
profile in the lung tissue of the untreated animals which was
not observed in the animals treated with hydroalcoholic
extract.
Another study was conducted to investigate the efficacy
of a hydroalcoholic extract of the aerial parts of M. laevigata
as a relaxant agent in tracheal smooth muscle in vitro.[68] The
authors used acetylcholine to induce a sustained contraction
of the rat tracheal smooth muscle, which was fully relaxed
when the hydroalcoholic extract of M. laevigata was added.
This action was not dependent on epithelium-derived sub-
stances as the antagonists nitric oxide and guanylate cyclase,
both important regulatory mediators in airway function, did
not abolish tracheal relaxation elicited by the hydroalcoholic
extract of M. laevigata. On the other hand, the action was
largely dependent upon activation of tetraethylammoniun-
sensitive (but not glibenclamide- or 4-aminopyridine-
sensitive) potassium channel blockers, suggesting that the
direct stimulation of calcium-activated potassium channels
by M. laevigata extract may have contributed to the under-
lying mechanism by which M. laevigata acted as an anti-
asthmatic phytomedicine in humans.[68]
Pneumoconiosis is a respiratory disease characterized by
pulmonary inflammation caused by coal dust exposure,
inducing an aggregation of macrophages near the respiratory
bronchioles responsible for the formation of reactive oxygen
species.[74] Considering that coal dust exposure induces an
inflammatory response in lungs and that M. glomerata and
M. laevigata are plants used in Brazilian folk medicine for
several inflammatory conditions of the respiratory system,
Freitas et al.[26] investigated whether extracts from these
plants presented any effect on inflammatory and oxidative
damage indicators in the lungs of rats acutely exposed to
coal dust. The authors observed that lactate dehydrogenase
activity was increased by coal dust intratracheal instillation,
suggesting that coal dust exposure induced cellular death. M.
laevigata extract pretreatment prevented this effect, but M.
glomerata extract did not. Furthermore, total cell count was
increased in coal dust-exposed rats and both extracts inhib-
ited the increase in cell count. These results gave evidence
that coal dust led to inflammation and cellular death in lungs
of rats and that M. laevigata presented a protective effect in
these parameters. Besides, coal dust induced oxidation of
sulfhydryl groups, since protein thiol content was signifi-
cantly decreased in the lungs of the animals. M. glomerata
extract and M. laevigata extract prevented this effect,
leading to speculation that these extracts may present a pro-
tective role in oxidation of thiol groups caused by coal dust
acute exposure.[26]
In summary, both M. glomerata and M. laevigata have
been shown to possess efficient anti-asthmatic activity,
confirming their traditional popular use for respiratory
diseases.
Anti-inflammatory activity
The inflammatory response is orchestrated by a large range of
mediators able to promote vascular events, oedema and
recruitment of inflammatory cells. In response to injury or
infection, the body mobilizes cells of the immune system to
initiate an inflammatory response at the site of damage. A
critical step in this response is the adhesion of circulating
leucocytes to the endothelial cells lining the blood vessels,
allowing their subsequent migration across the endothelial
cell barrier to access the insult.[75]
As stated above, M. glomerata extract is largely used to
treat respiratory disease, however the beneficial effects of
M. glomerata in the treatment of respiratory disease such as
asthma may not only comprise a direct relaxation of the
respiratory smooth muscle but also an anti-inflammatory
effect. In this context, some studies demonstrated the anti-
inflammatory activity of Mikania extracts.
Recently, Alves et al.[31] assessed the pharmacological
properties and the underlying molecular mechanisms of the
hydroalcoholic extract of M. laevigata, to corroborate the
popular wisdom of it being a putative anti-inflammatory drug.
The authors observed an anti-inflammatory effect of M. lae-
vigata extract on carrageenan-induced peritonitis in mice,
since the ‘guaco’ extract reduced neutrophil migration and
vascular permeability in this animal model. However, to be a
good candidate for an anti-inflammatory drug with commer-
cial advantages, the chemical composition must not be influ-
enced by the season of collection. Thus, additional data was
provided, demonstrating that all monthly harvested ‘guaco’
extracts similarly inhibited neutrophil migration as compared
with carrageenan-injected mice, and no statistical significance
was detected among the analysed months.[31]
To understand the molecular mechanism by which the
hydroalcoholic extract of M. laevigata exerted its anti-
inflammatory activity, Alves et al.[31] performed several
experiments. The findings clearly demonstrated that treatment
with hydroalcoholic extract of M. laevigata strikingly pre-
vented the release of both tumour necrosis factor-a(TNF-a)
and interleukin-1b(IL-1b) in response to carrageenan injec-
tion. The inhibition of cytokine expression contributed to a
reduction in leucocyte adhesion and transmigration across the
endothelium, as observed by intravital microscopy.[31] It is
important to point out that the expression of surface molecules
on the vascular endothelium allowing the leucocytes to dia-
pedesis was influenced by the cytokine milieu in which the
endothelial cells resided. Furthermore, pretreatment of mice
with aminoguanidine followed by ‘guaco’ administration
completely abrogated the suppression of neutrophil migration
into mesenteric postcapillary venules and increased nitrite
content. These findings indicated that nitric oxide (NO), pro-
duced via inducible nitric oxide synthetase (iNOS) activation,
was associated with the suppression of neutrophil migration
caused by ‘guaco’ extract.[31] Thus, taken together, the results
suggested that use of the medicinal ‘guaco’ extract may have
been able to suppress the development of acute inflammatory
lesions, which were initiated by neutrophil recruitment.
Scientific evidence for Mikania use Marcelo H. Napimoga and Regiane Yatsuda 815
Another interesting result obtained with M. laevigata
extract was demonstrated in an inflammatory periodontal
disease model induced by a ligature placed around the man-
dible first molars of animals. Morphometrical analysis of
alveolar bone loss demonstrated that guaco-treated animals
presented a decreased alveolar bone loss and a lower expres-
sion of the activator of nuclear factor-kB ligand (RANKL)
measured by immunohistochemistry. Moreover, gingival
tissues from the guaco-treated group showed decreased neu-
trophil migration (myeloperoxidase assay). These results indi-
cated that ‘guaco’ extract may have been useful to control
bone resorption during progression of experimental periodon-
titis in rats (unpublished data).
Anti-ulcerogenic activity
Gastric and duodenal ulcers affect a great number of people
worldwide and are caused by multiple factors such as stress,
smoking, nutritional deficiencies and ingestion of nonsteroi-
dal anti-inflammatory drugs.[76] The current treatment has
its problems due to the limited effectiveness and severe side
effects of the available drugs. Protection of the gastric
mucosa involves acid-pepsin secretion, parietal cell activity,
mucosal barrier, mucus secretion, blood flow, cell regenera-
tion, and the release of endogenous protective agents,
especially prostaglandins and epidermal growth factors.
Numerous approaches have been used to combat gastric
ulcers, including the control of acid secretion, Helicobacter
pylori level, and H+/K+-ATPase activity, in an attempt to
reverse mucosal damage and inflammation.[77] The use of
natural products for the prevention and treatment of different
pathologies is continuously expanding throughout the world.
In this context, extracts and active principles from plants
could serve as leads for the development of new drugs.[78]
Bighetti et al.[60] evaluated the anti-ulcerogenic activity of
M. laevigata extract, employing different experimental models
in rats, to discern the pharmacological mechanism of action,
such as: the indometacin-induced ulcer model, which is used to
show cytoprotection and gastric acid secretion effects; the
ethanol-induced ulcer model, used to screen drugs for cytopro-
tection; high reserpine doses which produce an intense gener-
alized discharge of sympathetic nervous system mediators,
inducing ulcers within 24 h; and a stress model, with ulcers
induced by immobilization at low temperatures.[79–81] The crude
hydroalcoholic extract (1000 mg/kg) decreased the ulcerative
lesion index produced by indometacin, ethanol, stress and
reserpine in rats by 85, 93, 82 and 50%, respectively. Besides,
in the pyloric ligation model a decrease of hydrogen ion
concentration (53%) was observed, suggesting that the phar-
macological mechanism had a relationship to antisecretory
activity. Furthermore, the authors used several drugs to block
specific receptors to evaluate the mechanism by which the
extract of M. laevigata was inhibiting the ulcer lesions. The
blockage of the anti-ulcerogenic activity of the extract of M.
laevigata promoted by bethanechol suggested an anticholin-
ergic mechanism or an interruption of intracellular events that
were linked to acid secretion.[60]
Antimicrobial activity
Infectious diseases still represent an important cause of
morbidity and mortality among humans, especially in
developing countries. Even though the pharmaceutical indus-
try has produced a number of new antimicrobial drugs in the
last few years, resistance to these drugs by microorganisms
has increased. Conventional medicine is increasingly recep-
tive to the use of antimicrobial and other drugs derived from
plants as traditional antibiotics (products of microorganisms
or their synthesized derivatives) become ineffective and as
new, particularly viral, diseases remain intractable to this type
of drug. Another driving factor for the renewed interest in
plant antimicrobials over the past 20 years has been the rapid
rate of (plant) species extinction.[82] Newmman and Cragg[4]
related that with regards to antibacterial compounds, 76.5% of
the new chemical entities were related to natural products. In
this context, the Mikania genus also presents some antibacte-
rial effects. Thus some studies concerning the antibacterial
activity of M. laevigata and M. glomerata were analysed.
Antibacterial activities of different polarities of
M. glomerata extracts were evaluated against a multiresistant
strain of Staphylococcus aureus PI57. Only in the hexanic
extract of M. glomerata were substances with antibacterial
activity detected, since the ethanolic and dichloromethane
extracts did not present antibacterial activity.[58] Another
study evaluating different fractions of M. glomerata extract
demonstrated that the ethanolic fraction presented some
degree of activity (weak) against Gram-positive and Gram-
negative bacteria. In this study it was necessary to use a
considerable concentration of the ethanolic extract of M.
glomerata to inhibit Staphylococcus aureus (500 mg/ml),
Bacillus subtilis (250 mg/ml), Escherichia coli (500 mg/ml)
and Pseudomonas aeruginosa (>1000 mg/ml).[1]
Yatsuda et al.[39] evaluated the minimum inhibitory con-
centration (MIC) and minimum bactericidal concentration
(MBC) values of different fractions of the extracts from M.
laevigata and M. glomerata, such as ethanolic extracts (EE),
hexane fractions (H) and ethyl acetate fractions (EA). They
demonstrated that EA from both Mikania species displayed
negligible effects against mutans streptococci. The ethanolic
extracts inhibited the growth of all microorganisms tested,
except the strains of Streptococcus mutans D1 and Strepto-
coccus mutans P6. However, the crude extracts of both
Mikania did not show bactericidal activity against most of the
clinical isolates. In contrast, the hexane fraction of both
species of Mikania showed remarkable antibacterial activity,
displaying the lowest MIC (12.5–100 mg/ml) and MBC
(12.5–400 mg/ml) values. Furthermore, the extracts and frac-
tions of M. laevigata and M. glomerata were able to inhibit
the adherence of mutans streptococci cells to a glass surface at
sub-MIC levels and the hexane fractions were the most effec-
tive agents.[39] Baratto et al.[69] demonstrated that none of the
ethanolic extracts of M. laevigata presented significant anti-
microbial activity against S. aureus (25923), E. coli (25992),
P. aeruginosa (27853), Enterococcus faecalis (29212) and
Enterococcus faecium (10541).
Another interesting approach is the study of the syner-
gism of the mechanism of action of the plant extract with
antibiotics or with other medicinal plants. In a study
conducted by Betoni et al.[70] the synergism between 13
antimicrobial drugs and eight plant extracts, including the
M. glomerata extract, was verified. The antimicrobial
mechanisms of the drugs used were variable and the protein
816 Journal of Pharmacy and Pharmacology 2010; 62: 809–820
synthesis inhibitors were those that presented the strongest
synergistic effect (5.2 extracts per drug), together with folic
acid (4 extracts per drug) and bacterial cell wall synthesis
inhibitors (3.8 extracts per drug). Inhibitors of nucleic acid
synthesis resulted in two extracts per drug. The M. glom-
erata extract presented a synergistic effect with seven anti-
microbial drugs against S. aureus. There were three protein
synthesis inhibitors (tetracycline, chloramphenicol and
netilmicin) and four bacterial cell wall synthesis inhibitors
(gentamicin, vancomycin, penicillin and cephalothin). There-
fore, the results of the study seemed to be promising and
may enhance the natural product’s uses, showing the poten-
tial of the M. glomerata extract in the treatment of infectious
diseases caused by S. aureus.
Candida albicans is an opportunistic pathogen that can
cause local and systemic infections in predisposed persons,
commonly affecting immunologically compromised patients
and those undergoing prolonged antibiotic treatment.[83]
According to the literature, the investigation of natural prod-
ucts active against Candida spp. increased significantly in the
last 10 years, with the investigation of approximately 258
plant species, from 94 families. Holetz et al.[1] observed that
the hydroalcoholic extract of M. glomerata had a moderate
activity against C. krusei (500 mg/ml) and C. tropicalis
(500 mg/ml) and a weak activity against C. albicans
(>1000 mg/ml). Corroborating those results, the ethanolic
extract of M. glomerata was not effective at any of the con-
centrations tested against C. albicans.[54] On the other hand,
the authors observed a strong activity against C. albicans for
oils of M. glomerata at levels of 0.25 mg/ml.
Antiparasitic activity
Trypanosoma cruzi is an intracellular protozoan which causes
Chagas disease. Endemic to several regions in Latin America,
this disease persists as the major infectious heart disease in the
world. It is estimated that approximately 75 million people
live in risk areas and 13 million people are currently infected
in Central and South America. The global incidence of the
disease is considered to be 300 000 new cases per year.[84] The
therapeutic options currently available for Chagas disease are
limited. Most of the therapeutic measures are aimed at treat-
ing the consequences of the disease such as cardiac failure.
Leishmaniasis, caused by the intracellular protozoan
parasite of mononuclear phagocytes Leishmania, is endemic
in 88 countries. Leishmania amazonensis, a species trans-
mitted mainly in the Amazon region, has been associated
with localized cutaneous lesions, diffuse cutaneous disease,
and mucosal infection. The disease is neglected by the phar-
maceutical industry, even though no vaccine exists, and sig-
nificant side effects and signs of increasing resistance
continue to occur with the use of the few effective drugs
available.[85]
The immense chemical diversity and range of bioactivity
of plants has led to the development of hundreds of
pharmaceutical drugs. Luize et al.[71] reported the results of
preliminary screening tests for trypanocidal and leishmani-
cidal activities of crude extracts from 19 plants used in
Brazilian folk medicine for the treatment of various dis-
eases. Regarding M. glomerata, the results obtained demon-
strated 97.5% growth inhibition against amastigote forms of
L. amazonensis, as well as 49.5% growth inhibition of
epimastigote forms of T. cruzi. Furthermore, M. glomerata
extract did not show any haemolytic effect on sheep
blood.[71]
Antiophidian properties
Envenomation by snakes is often treated by parenteral
antiophidian serum administration, obtained from hyper-
immunized equine serum. Vegetal extracts constitute an
excellent alternative source of novel antiophidian agents. In
many countries, vegetal extracts have been traditionally used
in the treatment of envenomations evoked by snakebites.
Maiorano et al.[66] evaluated the ability of aqueous extracts,
from extract of M. glomerata, to inhibit pharmacological and
enzymatic activity of Bothrops and Crotalus snake venoms.
The results obtained demonstrated that phospholipase A2
activity induced by Crotalus durissus terrificus venom was
totally inhibited by the aqueous extracts of M. glomerata,
while, for Bothrops jararacussu venom, no significant inhi-
bition was observed. M. glomerata extract also inhibited the
haemorrhagic activity of the venoms tested, suggesting an
interaction between the extract components and metallopro-
teases, involving catalytic sites of these enzymes or essential
metal ions. Also, M. glomerata extract exhibited powerful
inhibition of the clotting activity, probably due to interaction
with thrombin-like enzymes.[66]
Impact of Mikania extracts on
reproductive organs
The plants of the genus Mikania contain many active com-
pounds that may be related to its different therapeutic prop-
erties according to folk medicine. Two of these compounds,
flavonoids and coumarin, have been reported to affect the
fertility of the male dog and female rat, respectively, in experi-
ments carried out using other plant genera.[64,86] Flavonoids
and coumarin are among the constituents of M. glomerata and
M. laevigata, with coumarin being one of the main active
substances from the leaves of this species.[39]
Previous studies have demonstrated that the long-term
(52 consecutive days) administration of the ethanolic extract
of the aerial parts of M. glomerata did not interfere with
fertility in rats.[72] In that study, the authors administered the
extract at a dose level of 3.3 g/kg, which was 600-times
higher than the human dose. Despite the long-term and high-
dose treatment, the results showed nontoxicity of the M.
glomerata extract as well as no alteration in androgen or
sperm production, and sperm morphology remained unal-
tered in the extract-treated animals.[72] Furthermore, in
another study in which animals were treated daily with M.
laevigata syrup over 90 days by oral gavage, there were no
alterations in body or organ weights, and no alteration in
sperm and spermatid numbers, or in sperm morphology of
the male rats, suggesting the absence of adverse effects on
the spermatogenic process.[68]
Toxicity and genotoxicity
Plants have been used for centuries to treat infections and
other diseases in humans, but controlled clinical studies have
Scientific evidence for Mikania use Marcelo H. Napimoga and Regiane Yatsuda 817
been scarce. In some cases, popular wisdom together with
research has meant that records have begun to be kept for the
safety and effectiveness of phytochemical treatments, but
these are generally uncontrolled and nonrandomized studies.
The oral and intraperitoneal acute toxicity of M. laevigata
syrup, containing controlled amounts of coumarin, have been
assessed, as well as the oral subchronic and chronic toxicity.
The calculated LD50 (lethal dose 50%) of M. laevigata syrup
after intraperitoneal administration was 0.904 g/kg in mice
(both sexes) and 0.967 and 0.548 g/kg in male and female
rats, respectively. However, the LD50 value of M. laevigata
syrup by the oral route was calculated to be up to 10 g/kg, in
both male and female mice and rats. Repeated dose 28- or
90-day oral treatment with M. laevigata syrup (75, 150 and
300 mg/kg) did not produce any disturbances in the
haematological or biochemical parameters of either male or
female rats, nor did it provide evidence of toxicity in the
hepatic, renal or pancreatic systems.[68] Furthermore, Alves
et al.[31] demonstrated the absence of effects on body weight
gain and behavioural patterns in mice subjected to the
repeated-dose 14-, 28- or 60-day treatment, indicating no
relevant toxicity induced by M. laevigata ethanolic extract in
mice. Besides, there were no alterations in haematological
parameters or serum aminotransferases (AST and ALT),
indicative of normal hepatic and biliary function, lack of liver
cell injury, and no alterations in urea, indicating the absence
of alterations in the kidney. Thus, the pharmacological con-
centration used in this study (3 mg/kg) presented no toxicity.
Also, the LD50 was found to be almost 75-times higher than
the pharmacological dose tested.
The potential genotoxicity of M. glomerata extract
fraction performed on plasmid DNA using an alkaline lysis
procedure was evaluated, in which plasmid DNA was treated
with SnCl2 and M. glomerata extract fraction. The role of
reactive oxygen species in DNA breakage was evaluated
also, by incubating M. glomerata extract fraction with
sodium benzoate, a hydroxyl radical scavenger. The results
have shown that M. glomerata extract fraction was devoid of
genotoxicity, since this fraction did not damage DNA either
directly or by producing reactive oxygen species (at least the
hydroxyl radical).[29] Another important criterion in the
search for compounds active against microorganisms with
therapeutic potential, is to determine whether they show
toxic effects on mammalian host cells. For this purpose,
Luize et al.[71] carried out a cytotoxicity test on sheep
erythrocytes to determine the ratio of selectivity to biologi-
cal activity. No haemolytic effects of the crude extract of
M. glomerata on sheep blood were observed after 60-min
incubation.
Conclusions
In recent years interest in phytomedicine has increased. In
Brazil, there is a national policy to increase the use of phy-
tomedicine for the treatment of some diseases, and ‘guaco’
syrup has been available since 2006, mainly indicated for
respiratory conditions. M. laevigata Schultz Bip. ex Baker
and M. glomerata Spreng are the two medicinal plants in
Brazil that are used interchangeably and often at times with no
distinction between the two species. Phytochemical studies of
the leaves from M. laevigata and M. glomerata species indi-
cated a similar composition; presenting diterpene acids (ent-
kaurene derivatives); triterpenes and steroids (friedelin,
stigmasterol and lupeol) and cinnamic acid derivatives as well
coumarins, diterpenes, and essential oils. However, the
amounts of these chemical compositions were different. Both
Mikania species possess immunomodulatory activity, reduc-
ing oedema formation as well as neutrophil migration in part
dependent on the nitric oxide pathway. M. laevigata and M.
glomerata are used traditionally to treat respiratory illness in
Brazil. The ‘guaco’ leaves are commonly used as an extract,
syrup or infusion to treat bronchitis, asthma and cough.
Experimental observations about the efficacy of ‘guaco’usage
in airway diseases are consistent, and some studies have dem-
onstrated the mechanisms of its action.
Declarations
Conflict of interest
The Author(s) declare(s) that they have no conflicts of interest
to disclose.
Funding
This work was supported by grants from PAPE-UNIUBE
no2007/002 and CAPES.
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