Sida acuta Burm. f.: A medicinal plant with numerous potencies

Abstract

Sida acuta is shrub belonging to Malvaceae family. The plant is widely distributed in the subtropical regions where it is found in bushes, in farms and around habitations. Surveys conducted in indigenous places revealed that the plant had many traditional usages that varied from one region to another. The most cited illnesses are fever, headache and infections diseases. Indeed, many laboratory screening have been conducted to show the scientific rationale behind these usages and many compounds have been isolated from the plant. In the present review we listed the plant usages in folk medicine in some regions where the plant grows and we discussed on the confirmed in vitro activities after laboratory screenings. The review ended with the pharmacological properties of several compounds isolated from S. acuta principally alkaloids.

Full text

African Journal of Biotechnology Vol. 6 (25), pp. 2953-2959, 28 December, 2007
Available online at http://www.academicjournals.org/AJB
ISSN 1684–5315 © 2007 Academic Journals
Review
Sida acuta Burm. f.: a medicinal plant with numerous
potencies
Simplice Damintoti Karou1,3*, Wendyam MC Nadembega1,2, Denise P Ilboudo1,2, Djeneba
Ouermi1,2, Messanvi Gbeassor3, Comlan De Souza3 and Jacques Simpore1,2
1Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA) 01 BP 444 Ouagadougou 01, Burkina Faso.
2UFR/SVT, Université de Ouagadougou 03 BP 7021 Ouagadougou 03; Burkina Faso.
3Faculté des Sciences, Université de Lomé, BP 1515, Lomé, Togo.
Accepted 12 November, 2007
Sida acuta is shrub belonging to Malvaceae family. The plant is widely distributed in the subtropical
regions where it is found in bushes, in farms and around habitations. Surveys conducted in indigenous
places revealed that the plant had many traditional usages that varied from one region to another. The
most cited illnesses are fever, headache and infections diseases. Indeed, many laboratory screening
have been conducted to show the scientific rationale behind these usages and many compounds have
been isolated from the plant. In the present review we listed the plant usages in folk medicine in some
regions where the plant grows and we discussed on the confirmed in vitro activities after laboratory
screenings. The review ended with the pharmacological properties of several compounds isolated from
S. acuta principally alkaloids.
Key words: Ethnomedicine, medicinal plants, natural substances.
INTRODUCTION
Sida acuta is a malvaceous weed that frequently
dominates improved pastures, waste and disturbed
places roadsides (Mann et al., 2003). The plant is native
to Mexico and Central America but has spread through-
out the tropics and subtropics (Holm et al., 1977). In
traditional medicine, the plant is often assumed to treat
diseases such as fever, headache, skin diseases,
diarrhea, and dysentery. Referring to the traditional
knowledge, studies have been carried out to confirm the
activities the plant is assumed to exert in vivo. The
described pharmacological properties of the plants in-
volve the antiplasmodial, antimicrobial, antioxidant,
cytotoxic activities and many other properties. Some
studies resulted in the isolation of single compounds
while the others just demonstrated the activity of the
crude extracts. The present review is focused on the
traditional usages of the plant, the in vitro laboratory
screening results and the pharmacological properties of
some compounds isolated from the plant.
*Corresponding author. Email: damin.karou@univ-ouaga.bf or
simplicekarou@hotmail.com.
TRADITIONAL USAGES
S. acuta is widely distributed in pantropical areas and is
widely used as traditional medicine in many cases. The
plant is also used for spiritual practices. Table 1 displays
the traditional usages of the plant in some regions where
it grows. Among illnesses the plant is used to cure, fever
is the most cited. The administration may be by oral route
for example in the case of fever or by external application
of the paste directly on the skin for skin diseases or
snake bites (Kerharo and Adam, 1974). The plant may be
used alone or in combination with other plants according
to the diseases or to the healers.
IN VITRO ACTIVITIES AND ISOLATED COMPOUNDS
OF SIDA ACUTA
Isolated compounds of the plant
Several phytochemical screenings resulted in the isola-
tion of various compounds from the plant involving
alkaloids and steroidal compounds (Cao and Qi, 1993;

2954 Afr. J. Biotechnol.
Table 1. Traditional usages of Sida acuta in several regions.
Locality Local name Used part Traditional usages
References
Guatemala,
Nicaragua - WP
Asthma, renal inflammation, colds,
fever, headache, ulcers and worms (Caceres et al., 1987 ;
Coee and Anderson, 1996)
India (Ghats) Pilla valatti
chedi WP Fever, bronchitis, ulcer, diarrhea,
dysentery, skin diseases.
The paste of leaves is mixed with
coconut oil and applied on head
regularly for killing dandruffs and also
for strengthening hair
(Ignacimuthu et al., 2006;
Malairajan et al., 2006)
Kenya (Digo) Mbundugo WP The plant is used to prepare
"Bundugo", a supplementary strength
magically added to a person
(Pakia, 2005)
Nigeria Iseketu WP, L malaria, ulcer, fever, gonorrhea,
abortion, breast cancer, poisoning,
inflammation, feed for livestock, stops
bleeding, treatment of sores wounds
antipyretic
(Kayode, 2006; Edeoga et
al., 2005 Saganuwan and
Gulumbe, 2006)
Togo - L Eczema, kidney stone, headache (Anani et al., 2000)
Western Colombia - WP Snakebites (Otero et al., 2000)
Sri Lanka - R, L Hemorrhoids, fevers, impotency,
gonorrhea, and rheumatism. In
mixture as aphrodisiac and for boils
and eye cataracts
(Dash, 1991; Pal and Jain,
1998)
Burkina Faso (Mossi
Central Plate) Zon-Raaga WP Fever, diarrhea, pulmonary affection,
snakebites, insects' bites. Paste of
leaves mixed with salt is applied on
skin to cure panaris
(Nacoulma/Ouedraogo,
1996)
-: non available data, L: leaves, R: roots, WP: whole plant.
Dinan et al., 2001). Figure 1 lists the chemical structure
of some. The alkaloids occurring in the plant belong to
the indoloquinolines family. The main alkaloids are
cryptolepine and its derivatives such as quindoline,
quindolinone, cryptolepinone and 11-methoxy-quindoline
(Jang et al., 2003). The major steroids of the plant are
ecdysterone, beta-sistosterol, stigmaterol, ampesterol.
Phenolic compounds such as evofolin-A, and B, scopo-
letin vomifoliol, loliolid and 4-ketopinoresinol have also
been isolated (Jang et al., 2003).
Antiplasmodial activity
The in vitro antiplasmodial activity of the plant was first
reported by Karou et al. (2003). The test was performed
on fresh clinical isolates of Plasmodium falciparum using
the in vitro semi microtest by light microscopy as
described by Le Bras and Deloron (1983). Ethanolic
extract of the plant was tested both with ethanolic extract
of four other plants. As S. acuta was the most active plant
of the study (IC50 value of 4.37 µg/mL), its extract was
brought under liquid-liquid separation between petroleum
ether, chloroform and water resulting in three fractions.
These fractions tested on the parasites revealed that the
chloroformic fraction and the aqueous fraction had similar
activities while the ether fraction was devoid of intrinsic
antiplasmodial activity. This suggested that alkaloids of
the plant may be responsible for the activity. The issue of
the study confirmed that the activity of the plant was
related to its alkaloids which displayed IC50 value of 0.05
µL/mg. Banzouzi et al. (2004) continued the work in the
same way using one reference strain of P. falciparum:
FcM29-Cameroon (chloroquine-resistant strain) and a
Nigerian chloroquine-sensitive strain. The antiplasmodial
assay was performed with ethanolic and aqueous extract
by flow cytometry with incorporation of [3H] hypoxanthine
(Desjardins et al., 1979; Schulze et al., 1997). The
ethanolic extract showed good activity on the two strains
with IC50 values between 3.9 and 5.4 µg/mL. The
purification of this active extract led to the identification of
cryptolepine as the antimalarial agent of the plant.
It is evidence that the plant showed a good in vitro
antimalarial activity related to its alkaloid contents.
Referring to the traditional practices where the drug is
often prepared by boiling plant material in water, this
activity may be reduce in vivo since alkaloid solubility in
water is pH-dependant.

Antibacterial activity
The antimicrobial screening of S. acuta revealed that
many compounds might be responsible for the activity of
the plant. The first antimicrobial screening of the plant
was conducted by Anani et al. (2000) using the disk
diffusion assay. The authors found that the methanolic
extract of the plant had a significant activity on Staphy-
lococcus aureus, Escherichia coli, Bacillus subtilis and
Mycobacterium phlei, however the extract was not active
on Streptococcus faecalis, Klebsiella pneumoniae,
Salmonella thyphimurium, Pseudomonas aeruginosa and
Candida albicans. The same findings were confirmed in
another study using methanolic extract and similar
microorganisms (Rajakaruna et al., 2002). Polyphenols
and alkaloids of the plant were tested separately on
several pathogenic bacteria including clinical strains and
reference strains of Enterobacteriaceae and Staphyloco-
ccaceae families. The tests were performed by agar well
diffusion (Perez et al., 1990) and the NCCLS (2000) broth
microdilution assays. The results revealed that the
phenolic compounds had a good in vitro antimicrobial
activity and this activity was much influenced by the
storage of the extract probably because of the phenolic
compounds oxidization. The inhibition zone diameters
varied from 11 to 25 mm for 250 µg polyphenols and
MBC values ranged from 20 to 2000 µg/mL (Karou et al.,
2005). Alkaloids of Sida acuta also displayed a good
antibacterial activity. The recorded inhibition zone
diameters varied from 16 to 38 mm for 100 µg alkaloids
and the MBC values from 80 to 400 µg/mL (Karou et al.,
2006). In another study, leaf/flower combination was
evaluated for antimicrobial activity using hexane, chloro-
form, methanol and aqueous extraction methods. The
antibacterial activities were exhibited by the four extract
on E. coli, S. pyogenes, Pasterella multocida and S.
typhimurium as there was no activity exhibited on S.
typhi, S. pneumoniae and K. pneumoniae (Sanganuwan
and Gulumbe, 2006).
As many other plants with antibacterial properties, S.
acuta contains phenolic compounds that are responsible
for the activity of the plant. The current problem with
phenolic compounds is the fact that they are vulnerable
to polymerization in air through oxidation reactions. This
oxidization may first affect the extractability of the
phenolic compounds that is crucial in drug preparation; in
this topic some authors suggested extracting the
compounds directly on fresh material in order to enhance
the yield (Scalbert, 1992). However, in our enquiries
many traditional healers always dry their plant materials
before the use, particularly when the plant does not grow
around habitations (Karou et al., 2007). Secondly, an
important factor governing the activity of phenolic
compounds is their polymerization size. Oxidized conden-
sation of phenols may result in the toxification of
microorganisms, while the adverse effects can be obser-
ved in some cases (Scalbert, 1991; Field and Lettinga,
Karou et al. 2955
1992). Recently in the case of S. acuta we observed that
the tested microorganisms were particularly susceptible
to the stored extract (Karou et al., 2006). Therefore, it is
now the time to think about how to prepare phenolics-
based drugs with traditional healers.
Other in vitro activities
Since S. acuta has several usages in folk medicine it has
been involved in many other pharmacological screenings.
The plant has been screened for its cancer chemo-
preventive properties by Jang et al. (2003). The study
resulted in the isolation of several compounds, among
them quindolinone, cryptolepinone and 11-
methoxyquindoline was found to induce quinone
reductase activity, while cryptolepinone, N-
transferuloyltyramine exhibited a significant inhibition of
7, 12-dimethylbenz-[a]anthracene-induce preneoplastic
lesions in mouse mammary organ culture model. These
observations suggested that cryptolepinone was a
potential chemopreventive agent.
The polyphenol extract of the plant was tested together
with polyphenol extract of other medicinal plants for
antioxidant activity through free radical scavenging. The
tests were performed using the phosphomolybdenum
reduction (Prieto et al., 1998) and the ABTS radical
cation decolorization assays (Re et al., 1999) with trolox
as standard antioxidant. The results showed that there
was a good correlation between the two methods (r = 0.9)
and S. acuta had a weak free radical scavenging
according to values recorded with bark extracts of K.
Senegalensis, P. erinaceus and C. micranthum in the
same study. The activities were highly correlated with the
total phenolic content determined by the Folin-Ciocalteu
reagent (Singleton et al., 1999) with gallic acid as
standard (r = 0.94 and r = 0.91 with the two assays
respectively).
In another study, Otero et al. (2000a, b) showed that
the ethanolic extract of the plant had a moderate activity
against the lethal effect of Bothrops atrox venom. In
Western Kenya where the plant is consumed as legume,
a study using Brine shrimp lethality tests revealed that
the plant was toxic (LC50 = 99.4 g/ml). The author
concluded that the plant can cause acute or chronic
toxicities when consumed in large quantities or over a
long period of time (Orech et al., 2005).
Malairajan et al. (2006) had demonstrated the
analgesic properties of the whole plant extract in animal
model. The authors conducted the tests using two
methods the hot plate method described by Woolfe and
Mac Donalds (1944) and the tail immersion method
described by Dykstra and Woods (1986). The screening
did not result in the isolation of single compounds but the
authors suggested that the observed analgesic activity
may be due to steroidal compounds the plant contains
(Figure 1).

2956 Afr. J. Biotechnol.
Figure 1. Chemical structure of compounds isolated from S. acuta.

PHARMACOLOGICAL PROPERTIES OF TWO SINGLE
COMPOUNDS ISOLATED FROM S. ACUTA:
CRYPTOLEPINE AND SCOPOLETIN
Cryptolepine
Cryptolepine (5-methyl indolo [2,3b]-quinoline) is a
natural alkaloid occurring in S. acuta, that was first
isolated from the roots of Cryptolepis triangularis. This
compound is the main alkaloid present in the roots of
Cryptolepis sanguinolenta, a plant traditionally used in
Central and West Africa for the treatment of rheumatism,
urinary and respiratory infections. Cryptolepine presents
a large spectrum of biological properties, including
hypotensive and antipyretic, antimuscarinic, antibacterial
and anti-inflammatory effects (Bonjean et al., 1998). It
also possesses potent in vitro activity against P.
falciparum, the main parasite species responsible for
malaria. The mechanism of action of this antimalarial
product remains unclear; at least two independent effects
may together lead to a potent activity. First, it behaves
like a DNA intercalator (Bonjean et al., 1998). Second, it
may act like chloroquine by inhibiting the detoxification of
heame in red blood cells (Wright et al., 2001). This is
supported by a fluorescent microscopy study, which
suggested that cryptolepine accumulates into parasite
structures that may correspond to the parasite nucleus
(Arzel et al., 2001). However, cryptolepine failed to cure
malaria in mice by oral route, by intra peritoneal injection
the compound showed toxic effects. These observations
led to the investigation of its synthetic analogues such as
2,7-dibromocryptolepine (Wright, 2005).
It has been proposed that crytolepine exerts its
cytotoxic action via the inhibition of DNA synthesis and
stabilization of topoisomerase II-DNA covalent
complexes. In a study conducted to elucidate the strength
and mode of binding to DNA of cryptolepine and two
other alkaloids by spectroscopy, Dassonneville et al.
(1999) found that the alkaloid binds tightly to DNA and
behaves as typical intercalating agent, thus it stabilizes
the topoisomerase II-DNA covalent complex and
stimulates the cutting of DNA by topoisomerase II, but the
drug does not exhibit a preference for cutting at a specific
base. However, the flow cytometry analysis showed that
the drug alters the cell cycle distribution, but no sign of
drug-induced apoptosis was detected when evaluating
the internucleosomal fragmentation of DNA in cells. The
authors suggested that cryptolepine-treated cells
probably die via necrosis rather than via apoptosis and
there was evidence that DNA and topoisomerase II are
the primary targets of cryptolepine. In another study, the
same authors found later that Cryptolepine induce
apoptosis in HL60 leukaemia cells (Dassonneville et al.,
2000). Recently, the structure of a cryptolepine-DNA
complex was elucidated by X-ray crystallography.
Lisgarten et al. (2002) demonstrated that the drug
interacts with the CC sites of the d(CCTAGG)2
oligonucleotide.
Karou et al. 2957
Scopoletin
Scopoletin (6-methoxy-7-hydroxycoumarin) is a coumarin
that has been isolated from many plants species. The
compound has been tested for many pharmacological
properties, we list below few examples of the described
properties of the compound. Yang et al. (2007) observed
that the compound significantly increased lipoprotein
lipase activity 3T3-L1 adipocytes in dose- and time-
dependent manners. Scopoletin did not release the
enzyme from the adipocyte membrane and, instead,
decreased the enzyme mRNA level, suggesting a post
transcriptional control. In the same study the compound
was also found to partially reverse tumor necrosis factor-
alpha-induced suppression of lipoprotein lipase activity,
thus the compound may act as a facilitator of plasma
triglyceride clearance. Looking for the possible mode of
action of scopoletin in the inflammatory cytokine
production using CCRF-CEM leukemia cells, Moon et al.
(2007) found that scopoletin was a potential regulatory of
inflammatory reactions mediated by mast cells.
Scopoletin was also found to inhibit leukemia cell
proliferation. Tested against multidrug resistant subline
CEM/ADR5000 cells together with standard cytostatic
drugs, doxorubicin, vincristin and paclitaxel the cells did
not exhibit cross resistance to the compound in contrast
with what was observed with the standard drugs (Adams
et al., 2006). However the compound was also found to
exert a cytotoxic effect on tumoral lymphocytes (Manuele
et al., 2006). Finally, scopoletin was found to inhibit the
thyroid function and hyperglycemia without hepatotoxicity
according to the study conducted by Panda and Kar
(2006).
CONCLUDING REMARKS
S. acuta is a plant of wide usage in traditional medicine.
Following these traditional usages many studies have
been conducted in laboratories for the efficiency of the
plant. It is now evident that the plant has a good
antiplasmodial activity due to its alkaloids principally
cryptolepine the main alkaloid of the plant. It is also
demonstrated that the plant is active on several bacterial
strains. Many other compounds which are demonstrated
to have interesting pharmacological properties alone
have been isolated from the plant, in addition the plant
may have many other properties since it has not been
tested for all desired pharmacological activities. However
it should be noted that all laboratory screenings have
been carried out with laboratory classical extractions as it
is often observed with other medicinal plants. No study
has been conducted with traditional preparation; this
must be the priority for two reasons. First people still use
the plant even if laboratory screenings do not confirm the
assumed activity, so the laboratory results in the
conditions of the traditional usage is more pertinent and
can directly improve this usage. Secondly most of theses

2958 Afr. J. Biotechnol.
extracts act sometimes by synergistic effects so the
fractionation may result in the lost of the activity, in
addition the establishment of the drug from pure single
compound may be too expensive so the drug may not be
affordable for our populations.
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