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The Journal of Phytopharmacology 2014; 3(1): 57-76
Online at: www.phytopharmajournal.com
Review Article
ISSN 2230-480X
JPHYTO 2014; 3(1): 57-76
January- February
© 2014, All rights reserved
Mamadou Kamagaté
Department of Clinical
Pharmacology, University of Félix
Houphouët Boigny-Abidjan, Côte
d'Ivoire
Camille Koffi
Department of Clinical
Pharmacology, University of Félix
Houphouët Boigny-Abidjan, Côte
d'Ivoire
N’goran Mathieu Kouamé
Department of Clinical
Pharmacology, University of Félix
Houphouët Boigny-Abidjan, Côte
d'Ivoire
Aminata Akoubet
Department of Pharmacognosy,
Crypogamie and Botany;
University of Félix Houphouët-
Boigny, Abidjan, Côte d'Ivoire
N’guessan Alain Roland Yao
Department of Clinical
Pharmacology, University of Félix
Houphouët Boigny-Abidjan, Côte
d'Ivoire
Henri Maxime Die-Kakou
Department of Clinical
Pharmacology, University of Félix
Houphouët Boigny-Abidjan, Côte
d'Ivoire
Correspondence:
Camille Koffi
Department of Clinical
Pharmacology, University of Félix
Houphouët Boigny-Abidjan, Côte
d'Ivoire
Tel: +225 07 19 40 24
Fax: +225 22 44 79 54
E-mail: koffi.camille@yahoo.fr
Ethnobotany, phytochemistry, pharmacology and
toxicology profiles of Cassia siamea Lam.
Mamadou Kamagaté, Camille Koffi*, N’goran Mathieu Kouamé, Aminata Akoubet,
N’guessan Alain Roland Yao, Henri Maxime Die-Kakou
Abstract
Cassia siamea is a shrub belonging to the Fabaceae family, native of Southeast Asia and better
known in folklore medicine, feeding, agriculture and manifacture all over the world including
Côte d’Ivoire. C. siamea has recently been shown to have antimicrobial, antimalarial,
antidiabetic, anticancer, hypotensive, diuretic, antioxidant, laxative, anti-inflammatory,
analgesic, antipyretic, anxiolytic, antidepressant, and sedative activities. Chromone
(anhydrobarakol), Chromone alkaloids (barakol, cassiarin A-B), anthraquinones (chrysophanol,
emodin), bianthraquinones (cassiamin A-B), flavonoids and phenolics compounds are the main
constituents which are reported in this plant. Barakol was identified as the major constituents of
C. siamea of leaves and flowers of the world. Due to the easy collection of the plant, it
widespread and also remarkable biological activities, this plant has become a worldwide
medicine. This review presents comprehensive analyzed information on the botanical, chemical,
pharmacological and toxicological aspects of C. siamea. Web sites of Google Scholar, Pubmed
and Hinari were searched for articles published. Some scientific data were collected through
Scientific Units of Research and Formation (UFR) of the University Felix Houphouet-Boigny of
Abidjan.
Keywords: Cassia siamea - Ethnobotany - Chemistry – Pharmacology - Toxicology.
Introduction
Cassia siamea (syn. Senna siamea) is an angiosperme native of Southeast Asia
(Burma, Ceylon, India, Japan, Malaysia, Sri-Lanka and Thailand) and widely
distributed in Africa (Cote d'Ivoire, Eritrea, Ethiopia, Ghana, Kenya, Malaysia, Nigeria,
Sierra Leone, South of Africa, Tanzania, Togo, Uganda and Zambia), in Latin America
(Cuba, Chile, Antigua and Barbuda, St Lucia, St Vincent and Grenadines and Trinidad
and Tobago), and in Oceania (Australia and Fiji).1-4 Firstly classified in Caesalpiniacae
family, then in those of Leguminoseae, C. siamea is now classified among the
Fabaceae.5 This plant is a shrub which has a medium-size, 10-12 m tall, occasionally
reaching 20 m.6 The bole is short; crown dense and rounded at first, later becoming
irregular and spreading. The young bark is grey and smooth, and later with longitudinal
fissures. The leaves are alternate, 15-30 cm long, compound, with 6-14 leaflets each
ending in a tiny bristle.7 The flowers are bright yellow, in large, up to 60 cm long,
upright, with pyramid-shaped panicles. The fruits are flat with indehiscent pod, 5-30
cm long, and constricted between the seeds. There are about 20 seeds per pod. The
seeds are bean-shaped, greenish-brown, and 8-15 mm long (Figure 1).1, 8
The Journal of Phytopharmacology January- February
58
1- Stem, 2- leaves, 3- flowering branch and flowers, 4- pods, 5-
stem bark
From: Photography of the plant in Abobo (Côte d’Ivoire)
Figure 1: Different parts of Cassia siamea
For a long time, C. siamea is better known by the tropical
populations for it various medicinal vertus.9-11 It is also
known for its various common uses in cattle rearing12,
agriculture, environment13-14 and founiture15. Since review
and systemic analysis of chemistry, pharmacology and
clinical profiles of C. siamea have not been reported; we
were prompted to provide current available information on
traditional and local knowledge, ethnobiological and
ethnomedicinal issues, and identification of
pharmacologically important molecules, pharmacological
and toxicological studies on this useful plant. This review
aims at gathering the research work undertaken till to date
upon this plant in order to provide sufficient baseline
information for future works and commercial exploitation.
The scientific information was collected through
researcher’s Floristic Center of Abidjan, and Units of
Research and Formation (UFR) of Medicine, Pharmacy
and Biology of Felix Houphouet Boigny university of
Abidjan. Scientific-medical publications were also
consulted in different databases (Sciencedirect, Pubmed,
and Hinari) using key words such as Cassia siamea, Senna
siamea, Fabaceae, Leguminoseae, Caesalpiniaceae,
ethnobotany, chemistry, pharmacology, and toxicology.
Ethnobotany
Vernacular names
The diverse vernacular names of the plant through the
different localities are given in table no. 1
Table 1: Vernacular names of C. siamea
Localities
Vernacular names
References
Benin
Kassia, cassiatin
16
Burkina Faso
Kasse tiiga
17
Côte d'Ivoire
Acassia gbêman, acassia oufoué
Ethiopia
Yeferenji digita
Ghana
Zangara tsi
18
Kenya
Ndek obino, Oyieko, Ndege owinu
19, 20
Malaysia
Sebusok, guah Hitam, juah, petai belalang, Johor
22
Nigeria
Bikini raskata, odan
Tanzania, Uganda
Mjohoro
Togo
Zangalati
24
France
Casse du siam, bois perdrix, de la casse
8
Creole isles
Kasia
Spain
Flamboyan Amarillo
23
Cambodia
Ângkanh
India:
Minjri, manjekonna, kassod, ponavari, vakai, simaiavari, kilek, Nela thangedu
21
Indonesia
Bujuk, dulang, johar,
21
Nepal
Criminal
21
Philippines
Robles
Thailand
Kassod tree, yellow cassia, shower thailand, thai pod copper, iron wood, siamese
senna, bombay blackwood, black cassia-wood, khilek or khilekluang, khilek-yai,
chili phak, khi lek ban, sino-Tibetan
21
Vietnam
Humbo, c [aa] y mu [oof] ng den, mu [oof] ng [egg], mu [oof] ng xi [ee] m
muoofng xieem.
21
The Journal of Phytopharmacology January- February
59
Therapeutic uses
The leaves, stems, roots, flowers and seeds of C. siamea
regardless the subspecies have been used for the treatment
of several illnesses including mostly malaria, a tropical
endemic disease with high morbimortality.8, 15, 23-26 In this
review, the preparation process of remedies was not clearly
described and the dosages prescribed were approximative.
Moreover, the treatments are supposed to be continued
until recovery.19 According to the ethnic differences of
populations from localities, the plant is used alone or in
combination with other plants or with natural substances
for the preparation, especially in decoction. 19, 27 For the
treatment, people mostly used the preparations by orale
administration route.
Leaves uses
The leaves are the most used parts’ the plant especially by
African and Asian population in preparation of the herbal
remedies. In Burkina Faso, fresh and dried leaves
decoction (boiled for 20 min in 1L of water) is drunk with
lemon juice or for body bath throughout the day to treat
malaria and liver disorders.17, 25, 28 In Côte d’Ivoire, the
decoction of leaves is administered orally (0.5 L, twice
daily) for treating cough, stomach pains29 and malaria2.
Also, in Sierra Leone and Togo, the leaves decoction is
drunk against malaria24, 30 and used as antimicrobial31. In
Nigeria, the dried leaves are mixed with lemon’s leaves
(Cymbopogon citratus), pawpaw’s leaves (Carica papaya),
and the lime’s leaves (Citrus lemonum) and are boiled
within an hour. The "tea" of the mixture is drunk against
malaria.32 In Uganda, the leaves are picked, cleaned and
chewed, and liquid swallowed to treat abdominal pains.33
In India, the leaves are cleaned thoroughly and boiled. The
decoction is filted in which is added honey. This
preparation is drunk ¾ glass (150 mL), 3 times a day
against anaemia and fever.34 In Laos, fresh and dried
leaves boiled at a ratio of 1:3 for 1 hour 2-3 times to
reduce the bitterness, and then crushed to get a paste in
which the pork bones are added. This dish called "chi om
leck" is taken before breakfast as a vegetable which has
sedative and euphorising effects.35-36 In Thailand, dried
leaves are sprayed to be regularly consumed in capsule
form as vegetable for its laxative effect and as sleeping
pill.37-39 Other authors reported that Cassia siamea leaves
decoction is drunk against constipation and hypertension
and are inhaled in toothache.30, 40
Roots uses
In Benin, root decoction is used against fever, constipation,
hypertension, and insomnia.16 In Kenya, the infusion,
decoction or maceration of mixture of the roots of C.
siamea and those of Zanthoxylum chalybeum are used as
antidote for snake bites.20 In Southeast and Sub-Saharan
Africa, and herbalists use the root decoction for the
treatment of diabetes mellitus.41 In these areas, the roots
are crushed and mixed then the aqueous extract is drunk to
treat sore throat.33 In Côte d’Ivoire, small repeative doses
of maceration or decoction roots’ bark are drunk to treat
angina and malaria, respectively.2, 42
Stems uses
In Burkina Faso, Ghana and Nigeria, the decoction of the
whole stem or stem’s bark is drunk or take for body bath
against malaria and liver disorders.18, 25, 33, 43-44 These same
uses were reported in Malaysia.22 Dried stems of C siamea
mixed with the fruit of Xylopia aethiopica is pulverized
and administered as laxative.37 The decoction of the stem
bark is drunk against diabetes. This decoction is used as a
mild, pleasant, safe, and purgative in Japan. Also, Dalziel
(1963) and Keharo (1974) indicated that its decoction is
used against scabies, urogenital diseases, herpes, and
rhinitis in Cambodia.41
Flowers and seeds uses
In Burkina Faso, flowers decoction is drunk or used in
body bath against malaria and liver disorders. This
decoction is also effective against insomnia and asthma.25,
33
The seeds are used to charm away intestinal worms30 and
as antidote for snake and scorpion bites46. The decoction of
the mixture of C. siamea and Ficus thonnigii fruits’ is
drunk to prevent convulsions in children and to treat
typhoid fever.34 In Sri Lanka and Thailand, the flowers and
young fruits are regularly consumed as vegetable and for
treating curries. It provides laxative and sleeping-aid
effect.37 This dish is also anxiolitic and effective against
dysuria.38
Whole plant uses
The decoction or the maceration of the mixture of different
part of C. siamea is used for the management of diabetes47
and used as laxative48. In China and Pakistan, the
decoction of the leaves and the stems mixture is used as an
aperitif, antirheumatic and against swellings.49 In Congo,
The Journal of Phytopharmacology January- February
60
this decoction is widely used in periodic fever and
malaria.30
Chemistry
Qualitative analyse
Preliminary phytochemical screening of C. siamea,
showed the presence of chromones and its derivatives
(chromone alkaloids, chromones glycosides,
dihydronaphthalenone compounds, bischromone),
polyphenols (anthraquinones, bianthraquinones, anthrone,
flavonoids, isoflavonoids, phenolics, tannins), alkaloids,
saponins, steroids, carotenoids, antinutrients (oxalate,
phytate), reducing sugars, vitamins, minerals and
enzymes.31, 49-56 Various bioactive compounds identified
from C. siamea are shown in Table n°2. The structures of
the main constituents are shown in figure n°2.
Table 2: Chemical composition of Cassia siamea
Plant
part
Extract
Molecular groups
Molecules
Reference
Leaves
Chloroform
Chromone
alkaloids
Barakol
61, 63,
64
Methanol
Chromone
Anhydrobarakol ; 5-acetonyl-7-hydroxy-2-methylchromone;
5-acetonyl-7-hydroxy-5-acetonyl-7-hydroxy-2-
hydroxymethylchromone
59, 60,
121
Chromone
alkaloids
cassiarin A, cassiarin B
66, 70
Anthraquinones
Chrysophanol; emodin, physion, rhein, sennosides
3, 121
Bianthraquinones
Cassiamin A, cassiamin B
60, 125
Bischromones
Chrobisiamone A; resins
Ethanol
Triterpenoid
lupeol
58
Flavonoid
D-pinitol, luteolin
58, 103
Dihydronaphthalen
one
4-(trans)-acetyl-3,6,8-trihydroxy-3-methyldihydronaphthalenone;
4-(cis)-acetyl-3,6,8-trihydroxy-3-methyldihydro-naphthalenone
58
Hydroalcoholi
c
Steroids
β- and γ-sitosterol
59
Carotenoids
Carotenes, xanthophylls
89
Vitamin
Vitamin A,C,E
Aqueous
isoflavone
glycoside
2',4',5,7-tetrahydroxy-8-C-glucosylisoflavone
85
Hexane
Mineral
Iron , magnesium, manganese, potassium; calcium; sodium;
copper; cadmium; lead; phosphorus
49
Stem
bark
Methanol
Bianthraquinones
4-4'-bis(1,3-dihydroxy-2-methyl-6,8-dimethoxy-anthraquinone;
1,1'-bis(4,5-dihydsroxy-2-methyl-anthraquinone, cassiamin A,
cassiamim B, cassiamin C; madagascarin
3, 80, 81
Anthraquinones
Chrysophanol; emodin; physcion; chrysophanol-1-O-β-D-
glucopyranoside; 1-[(β-D-glucopyranosyl-(1-6)-O-β-D-
glucopyranosyl)-oxy]-8-hydroxy-3-methyl-9,10-anthraquinone;
cycloart-25-en-3beta,24-diol
72, 77,
110
The Journal of Phytopharmacology January- February
61
NS, No specified
Flavonoid
Piceatannol
72
Triterpenoid
glycoside
19α,24-dihydroxyurs-12-ene-28-oicacid- 3-O-β-D-
xylopyranoside
77
Triterpenoid
Lupeol, friedelin
88, 110
Mineral
Iron, magnesium, manganese, potassium; calcium; Sodium;
copper; lead; chromium, nickel; zinc
51
Chloroform
Triterpenoid
Betulinic acid
105
Phenolic
Coumarin
Chromones
Siamchromones A-G
62
n-butanol
Chromone
glycosides
2-methyl-5-(2’(hydroxypropyl)-7-hydroxy-chromone-2’-O-β-D
glucopyranoside; 2-methyl-5-propyl-7,12-dihydroxy-chromone-
12-O-β-D-glucopyranoside
72, 73
Favonoid
Kaempferol
83
Root
bark
Methanol
Anthraquinones
Chrysophanol; emodin
76
Bianthraquinones
1,1’,3,8,8’-pentahydroxy-3’,6-dimethyl[2,2’-bianthracene]
9,9’,10,10’-tetrone; 7-chloro-1,1’,6,8,8’-pentahydroxy-3,3’-
dimethyl[2,2’-bianthracene]-9,9’,10,10’-tetrone; cassiamin A,
cassiamim B
79
Flowers
Chloroform
Chromone
alkaloids
Barakol ;10, 11-dihydroanhydrobarakol, cassiarin C, D, E, and F
40,
63,64,
68, 69
Methanol
Chromone
alkaloids
Cassiadinine
71
Phenolic acid
Gallic acid; protocatechuic; p-hydroxy benzoic acid; chorogenic
acid; Vanilic acid; caffeic acid; syringic acid; p-coumaric acid;
ferulic acid; sinapic acid
84
Flavoniod
Rutin; Myricetin; Quercetin; Kaempferol
Seeds
Hexane
Steroids
Cholesterol, stigmasterol, β-sitosterol
70
Fatty acid
palmitic, stearic, oleic and linoleic acids
Aqueous
Anthraquinones
Aloe-emodin, sennosides A1
74, 75
NS
Vitamin
Vitamin B1, B2, B3, C, E
93
Mineral
Calcium, phosphorus, sodium, magnesium, iron, zinc, copper
amino acids
Lysine, Valine, Leucine, Isoleucine, Threonine, Methionine,
Cystine, Tyrosine, Histidine, Arginine, Aspartic acid, Serine,
Glutamic acid, Proline, Glycine;Alanine
The Journal of Phytopharmacology January- February
62
Cassiarin A
1,1’,3,8,8’-pentahydroxy-3’, 6-dimethy-l[2,2’-bianthracene]-9,9’,10,10’-tetrone (9)
7-chloro-1,1’,6,8,8’-pentahydroxy-3,3’-dimethyl[2,2’-bianthracene]-9,9,10,10’-tetrone(10)
1,1’,8,8’-tetrahydroxy-3,3’-dihydroxymethyl [2, 2’-bianthracene]-9, 9’,10,10’-tetrone (11)
1,1’,3,8,8’-pentahydroxy-3-hydro-xymethyl-6-methyl [2, 2’-bianthracene]-9, 9’,10,10’-tetrone (12)
Barakol
Physcion
Chrysophanol (1) Emodin (2)
Aloe-émodin (3) 7-Chloroemodin (4)
Rhein
(19)
Sennoside A
Cassiarin B
4-4'-bis (1,3-dihydroxy-2-methyl-6,8-dimethoxyanthraquinone
Cassiamin A (5) Cassiamin B (6)
Cassiamin C (7) Madagascarin (8)
Chromone and derivatives
Anthraquinones
Bianthraquinones
Flavonoids and triterpene
Figure 2: Strcuture of the phytoconstituents of Cassia siamea
R1
R2
R3
1
CH3
H
H
2
CH3
OH
H
3
CH2OH
H
H
4
CH3
OH
CL
R1
R2
R3
R4
R5
5
H
OH
CH3
CH3
H
6
H
OH
CH3
CH3
OH
7
H
H
CH3
CH3
H
8
H
CH3
OH
CH3
OH
9
H
CH3
OH
CH3
H
10
CL
OH
CH3
CH3
H
11
H
H
CH2OH
CH2OH
H
12
H
CH3
OH
CH2OH
H
Cassiarin F
Chrobisiamone A
Anhydrobarakol
5-acetonyl-7-hydroxy-2-methylchromone
5-acetonyl-7-hydroxy-5-acetonyl-7-hydroxy-2-hydroxymethyl-
chromone
(5)
(1
0)
Cassiarin J
Cassiarin G
Lupeol (Triterpenoid)
Kaempferol (Flavonoid)
Luteolin(Flavonoid)
Cassiarin H
Cassiadinine
2-methyl-5-propyl-7,12-dihydroxy-chromone-12-O-β-D-glucopyranoside
Cassiarin K
Cassiarin H
The Journal of Phytopharmacology January- February
63
Quantitative analyse
The contents of the most bioactive compounds are not
known. Quantitative investigations of the leaves, stem bark
and seeds of C. siamea showed vitamin, amino acid,
elemental and proximate contents.89, 92-93 Indeed, the oil
from its seeds contains a high content of linoleic acid,
stigmasterol and β-sitosterol.90 The main compounds of the
essential oils of C. siamea are (E)-geranyl acetone (5.8%),
1-octen-3-ol (5.8%), linalool (7.8%), iso-italicene (15.4%)
and (E)-β-damascenone (11%).91 In the seeds, the highest
amounts of riboflavin, thiamine, niacin, ascorbic acid and
tocopherol (mg/100g) are 0.13, 0.72, 2.08, 8.80 and 3.60,
respectively. The elemental contents (mg/100g) of
methanol extract / hexane extract of leaves are: Iron
6.74/112, magnesium 126/876, manganese 0.72/35,
potassium 257/812; calcium 87.72/932; Sodium 350/612;
copper 0.49/0.84; and lead 0.06/0.34, respectively.49, 51 The
elemental contents of methanolic extract of stem bark are
(mg/100g): iron 5.51, magnesium 47.29, manganese 0.88,
potassium 116.82, calcium 96.49; sodium 263.16; copper
069, lead 0.11, chromium 1.05, nickel 3.36, and zinc
17.99.51 These results justify the traditional use of C.
siamea in feeding.
Pharmacology
As C. siamea is a mixture of various groups of chemicals,
it is of no surprise that it exhibits different modes of
actions. Its major actions include (i) antimalarial, (ii)
antidiabetic, (iii) antitumoral or anticancer, (iv)
hypotensive, (v) diuretic, (vi) antioxidant, (vii) laxative,
(viii) anti-inflammatory, (ix) analgesic, (x) antipyretic, (xi)
anxiolytic, (xii) antidepressant, (xiii) sedative, and (xiv)
antimicrobial activities.
Antimalarial effects
Various extracts of leaves, stem bark, and flowers of C.
siamea were screened for its antimalarial activity.98 Most
of the activities described were determined in vitro on
Plasmodium falciparum strains. Specified and bio-guided
fractionation was also based on this antimalarial test.
Activities were assessed on different strains, among which
are chloroquine sensitive (3D7), chloroquine resistant
(W2, FcM29-Cameroon) and multidrug resistant (K1) in
order to find effective compounds against resistant
malaria. In all studies, alkaloids fraction of the leaves
exhibited better aniplasmodial activity than other
extracts.95 This alkaloids fraction, the chloroform and
ethanol extracts of the leaves showed activity against 3D7
with IC50 value of 0.24, 2.41 and 7.06 µg/ml, respectively.
Cassiarin A is the alkaloid compound which has more
potential activities. Its activity is similar to that of
chloroquine against 3D7 with IC50 value of 0.005 and
0.006 μg/mL, respectively.96 The IC50 of this compound
was IC50 0.02 μg/mL against K1. Other compounds
isolated from leaves such as cassiarin J (IC50 0.3 µg/mL),
cassiarin K (IC50 1.4 µg/mL), chrobisiamone A (IC50 2.6 -
5.6 μg/mL), 5-acetonyl-7-hydroxy-2-methylchromone
(IC50 4.5 - 19.4 µg/mL), anhydrobarakol (IC50 7.8 µg/mL),
cassiarin B (IC50 22 μg/mL), cassiarin G (IC50 > 50
µg/mL), and cassiarin H (IC50 >50 µg/mL) showed
moderate activity against 3D7, respectively.60, 87, 97-99
Tested on W2, the chloroform, methanol, and
hydroalcoholic extract of this plant part showed moderate
activity with IC50 similar value up to 10 µg/mL; while the
aqueous extract showed the lowest activity with IC50 value
of 23.15 µg/mL.25
Among stem bark extracts, chloroform extract (IC50 21±3
µg/mL) was the most interesting with promising
antimalarial activity followed by ethanol extract (IC50 31±5
µg/mL) and aqueous extract (IC50 > 100 µg/mL) on
FcM2930. Against K1, Etyl acetate fraction of this part
plant was active with IC50 31±3 μg/mL and this activity
was associated to emodin and lupeol which displayed
similar IC50 value of 5 μg/mL.87-88
Phytochemical investigation of the flowers also afforded
cassiarin C and 10,11-dihydroanhydrobarakol which
possessed weak antiplasmodial activity with IC50 value of
24.2 μg/mL and 5.6 μg/mL against 3D7, respectively.100-101
Three others alkaloids isolated from the flowers such as
cassiarin D, E, and F with potent antimalarial activity were
reported.69, 100
These in vitro studies were confirmed by in vivo studies.
Indeed, the oral administration of C. siamea’s aqueous
extract of leaves including alkaloids and quinines reduced
parasitemia and hyperthermia in patients, significantly.102
Alkaloid fraction (ED50 0.47 mg/kg) exhibited most
antimalaria activity than chloroform extract (ED50 19.59
mg/kg) (po) and then ethanol extract (ED50 34.7 mg/kg).
The activity of cassiarin A (ED50 0.17 mg/kg) was similar
to that of chloroquine (ED50 0.21 mg/kg) (ip). So, cassiarin
A is a promising antimalarial drug.96, 101 This compound
reduces the cyto-adhesion via vasodilator action and
promotes the lysis of P. falcifarum.99, 103
The Journal of Phytopharmacology January- February
64
In addition, the effectiveness of C. siamea leaves’ aqueous
extract on mosquitoes larva was investigated against Aedes
aegypti by determining the median lethal concentration
(LC50) within 24, 48, 72, and 96 hours. The results
indicated that this extract exhibited 50 % inhibition of
mosquito larvas at 419.65 mg/mL for 24 hours and at
218.43 mg/mL for 96 hours, respectively.104 Also, in
chronic administration within 21 days, chloroform extract
of the stem bark including coumarin and betulinic exhibit
100 % and 90% of mortality on Aedes aegypti.105 So, C.
siamea could be used effectively as indigenous mosquito
control agents alternatively to conventional chemical
mosquito.
Antidiabetic and anti-lipemic effects
The potential effects of C. siamea (leaves, roots) on
endocrinological system were evaluated by several
methods. Ethanolic, ethyl acetate and hexane extracts of C.
siamea’s leaves at doses 150 and 300 mg/kg were tested
for antidiabetic activity in alloxan induced diabetes model
and the plasma blood glucose levels were estimated by
GOD-POD method at 0, 2, 4, 6, 8 and 12hr. So, ethyl
acetate extract of C. siamea’s leaves at both different doses
produced significant reduction when compared to ethanol
and hexane extracts (P<0.001).106 Ethanolic extract of
leaves of C. siamea exhibits a hypoglycemic and
antihyperglycemic effect in non-diabetic rats after
induction of hyperglycemia with 2 g/kg/bw of glucose
feeding within 1-5 hours. Indeed, this extract administrated
orally at the doses of 500 and 750 mg/kg/bw significantly
decreased blood glucose by 50.32 and 47.29 % per hour
with glibenclamide (10 mg/kg/bw) as positive control (P<
0.05).107 The aqueous extract of C. siamea’s root (1000 -
3000 mg/kg, orally) caused improvement blood glucose
level and body weights within 24 hours in alloxan-induced
hyperglyceamic rats, significantly (P< 0.05). We reported
that sun-dried and freshly uprooted root have the same
antidiabetic potential.41 In addition, administrations of
leaves’ methanolic extract (250, 500 mg/kg, orally) within
three week induced a significant decrease in streptozotocin
(STZ) diabetic rats with high blood glucose levels. It also
reduced their serum cholesterol and triglycerides and
improved their HDL-cholesterol level (P<0.01).108-109
Bioassay guided fractionation of the ethyl-acetate extract
of C. siamea afforded 6 known compounds such as
chrysophanol, physcion, emodin, cassiamin A, friedelin
and cycloart-25-en-3β-24-diol. These compounds were
further evaluated for pancreatic lipase inhibitory activity.
Cassiamin A was found to be most active with IC50 value
of 41.8 µM. Physcion and friedelin were found to be
moderate enzyme inhibitors. The results indicate the
antiobesity potential of C. siamea roots through pancreatic
lipase inhibition.110 Barakol seems to have no antidiabetic
effects.111 Overall; the results demonstrate significant
antihyperglycemic, antidiabetic and anti-lipemic activities
of C. siamea and justify the use of this plant in the
treatment of diabetes. However, further investigations are
therefore needed to go thoroughly into the molecular
mechanisms and identify other bioactive molecules
responsible for antidiabetic activity.
Antioxidant effects
An antioxidant is defined as any substance that when
present at low concentrations compared to those of an
oxidizable substrate, significantly delays or prevents
oxidation of that substrate.112 In this review, in vitro
studies showed that various extracts of C. siamea
possessed high antioxidant potential measuring using β-
carotene bleaching method, 2,2’-azinobis(3-
ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical
cation and superoxide anion radical scavenging assay.56, 89,
113 Indeed, methanol and aqueous extract of barks (800 and
1000 μg/mL) inhibited 60.5% and 51.34% free radicals
compared to those of rutin which exhibited 62.56%
inhibition, respectively. While at 1000 μg/mL hexane,
chloroform and ethyl acetate extracts of leaves showed
moderate antioxidant activities, respectively.113-114
DPPH radical scavenging activity of flowers has been
done. The results showed that the methanolic extract of
flowers (250 μg/ml) neutralized 96% of DPPH radicals.
This extract (500 μg/ml) scavenged 42.7%, 32.7% and
64.5% of the O2•-, H2O2• and NO, respectively.46 Also,
methanol extract of leaves reduced hydroxyl radicals
(OH•), peroxyl (ROO•) and superoxide (O2•-) with IC50
value of 349.9 μg extract/mg DPPH.115
In vivo, ethanol extract of flowers (50-150 mg/kg; p.o)
significantly protected against acute phase of
hepatotoxicity and histopathological changes (necrosis,
fatty degeneration) induced by a single intraperitoneal
injection of carbon tetrachloride (CCl4) in male Wistar
rats. These results showed that C. siamea could afford
significantly protection against oxidative damages to major
biomolecules in the liver.46, 84, 114
Many antioxidant compounds such as barakol, vitamin C,
Vitamin E, carotenoids, α-tocopherol, xanthophylls,
tannins, flavonoid, phénolic acids, and diverse enzymes
The Journal of Phytopharmacology January- February
65
(superoxide dismutase, catalase, and peroxidase) could be
responsible for this activity.53, 84, 116-117 So, barakol
scavenged the DPPH radical 1.3 times higher than those of
butylate hydroxytoluen (BHT) with EC50 value of 9.18
mg/mL.118 Mechanisms of action of some of these
identified natural antioxidants are known.34
Antitumor or anticancer effects
In research of natural or synthetic products as cancer
chemopreventive agents, in vivo and in vitro antitumor
activity studies were conducted with various extract of
leaves and stem bark of C. siamea. In male wistar rats,
feeding diet containing 4-5% of leaves of C. siamea for 2
weeks significantly reduced the activities of some hepatic
P450 dependent monooxygenases such as aniline
hydroxylase (ANH) and aminopyrine-N-demethylase
(AMD) as well as the capacity to activate the mutagenicity
of AFB1 towards Salmonella typhimurium TA100 is 31.73
% and 41 %. It increased the activities of glutathione S-
transferase (GST) for 250% and UDP-
glucuronyltransferase (UGT) for 220% which are phase II
detoxification enzymes. It also decreased the multiplicity
of mammary gland tumors as well as it slight delay of the
onset of tumor development in female Sprague Dawley
rats treated with carcinogenic agent such as 7,12-
dimethylbenz[a]anthracene (DMBA). This activity may be
partly due to its phase II enzyme inducing capacity as well
as its phase I enzyme inhibitory ability in rat liver.119-121 In
addition; dietary C. siamea’s leaves did not induce
micronucleus formation in mouse peripheral blood
reticulocytes. Furthermore, it showed anticlastogenic
potential against DMBA and cyclophosphamide-induced
reticulocyte micronucleus formation.122
In vitro, clinical trials demonstrated that the plant aqueous
extracts inhibited human recombinant hepatic cytochrome
P450 such as CYP2C9 and GSTM1-1 with IC50 value of
346.5 mg/ml and 50 mg/ml, respectively. This inhibition of
GSTs may be beneficial for cancer therapy.123 Also,
petroleum ether, dichloromethane, ethanol and aqueous
extracts of leave showed cytotoxicity against human
epidermoid carcinoma (KB) cell lines with IC50 value
between 67 and 100 μg/ml.124 However, methanol extract
of leaves was inactive on human oral epidermal carcinoma
(KB), breast adenocarcinoma (MCF-7) and small cell lung
carcinoma’s (NCI-H187) proliferation.115
The anticancer properties of C siamea could be due to
anthraquinones (emodin and its derivatives) and
bianthraquinones (cassiamin B and its derivatives).121, 125-
127 Indeed, twelve of these compounds have been tested for
their inhibitory activities on EBV-EA activation induced
by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji
cells using a short-term assay.125 Then, inhibitory effects of
emodin and cassiamin B on mouse two-stage skin
carcinogenesis model using DMBA or NOR-1 as an
initiator and TPA as a promoter were performed by skin
rubbing. All the results indicated that anthraquinone
monomers showed higher anticancer activity than
bianthraquinones.121, 125 The effects of these anti-tumor
promoters’ molecules were correlated to their standard
redox potentials and their electronic properties using PM3
method with CAChe MOPAC program.126-127
Antihypertensive effects
Studies on antihypertensive activities of C. siamea (leaves)
was undertaken to find the pharmacological basis for the
ethnomedical use of the plant. In vitro, chloroform and
methanol extract of leaves showed promising dose-
dependent vasorelaxant action by measurement of vascular
isometric force in endothelium-intact and -denuded
mesenteric artery rings.103 Two chromones alkaloids like
cassiarin A and barakol were responsible for this activity.
Indeed, acute pre-treatment with barakol (10 mg/kg, iv)
reduced thebeating heart rate for 89% with significant fall
of the systemic blood pressure in anesthetized rats for
86%128. Barakol also showed significant protective
effects on aconitine-induced ventricular fibrillation and
tachycardia in cats and rats. In contrast, vasorelaxant
action of barakol was attenuated by its chronic
administration (p<0.05).129-130 The mechanisms of action of
antihypertensive compounds were unclear and needed
further investigations. Nevertheless, preclinical assay
showed that cassiarin A vasorelaxant effect in wistar rats
was partially mediated by endothelium-derived releasing
factor (EDRF), nitric oxide (NO) and prostaglacycline
(PGI2).103, 129-131
Laxative effects
C. siamea (leaves, flowers) is known for its laxative effect
in Thailand. Several laxative compounds such as
anhydrobarakol, barakol, aloe-emodin, rhein-8-
monoglucoside, rhein, chrysophanic acid, anthrone,
dianthrone, chrysophanol, sennoside A were identified in
this plant.57, 132-136 For example, sennoside A of C. siamea
(20-30 mg/kg, po) in combination with other compounds
(guanethidine, neostigmine, castor oil and intraluminal
hypertonic glucose) induced a strong myoelectric
inhibition of the colon about 10 hours after administration
The Journal of Phytopharmacology January- February
66
which was followed by an abundant diarrhea in dog.137
Barakol caused laxative effect on small intestine and colon
via excitation of cholinergic motor neurons with EC50 0.3
and 0.4 mM, respectively.57 In this activity, barakol
stimulated chloride secretion without affecting
electrogenic sodium absorption in rat colonic epithelium.
The mechanisms involved basolateral Na+-K+-2Cl-
cotransporters and apical Cl- channels which were partly
mediated by the release of cyclooxygenase metabolites.
These results indicated that barakol and sennosides may
produce a purgative action in small intestine which may be
clinically important in patients with intestinal hypomotility
disorders.57, 132, 138
Anti-inflammatory, analgesic and antipyretic effects
Nsonde-Ntandou et al., (2010) have shown that ethanol
and aqueous extracts of C. siamea’s leaves and stem bark
(100 – 400 mg/kg, po, for 4 hours) had significant dose-
dependent anti-inflammatory, analgesic and antipyretic
activities using experimental rat models (p<0.01). The
results indicate that aqueous extracts had better anti-
inflammatory potential than diclofenac (5 mg/kg, po) on
paw oedema using hot plate test. The mechanisms of
action involved inhibition of cyclooxygenase. The
analgesic and antipyretic effects of these extracts were
more important than paracetamol (50 mg/kg, po) and
morphine (2 mg/kg, po) (p <0.001).124 Recently, Monin et
al. (2012) have been shown that leaves’ ethanol extract
exhibited high analgesic activity using acetic acid induced
writhing test in mice. They found that leaves’ ethanol
extract (500 mg/kg) exhibit significant inhibition of
writhing reflex by 61.98% while the diclofenac (25 mg/kg)
Na inhibition was found to be 85.95% (p<0.001).139 These
results justify the traditional use of C. siamea in fever.
However, the bioactive compounds of C. siamea
responsible to these activities were not specified.
According to the literature, four major families of
compounds may explain these activities: triterpenes
(lupeol, oleanolic acid, ursolic acid, friedelin, and betulin),
flavonoids (apigenin, kaempferol, and luteolin),
anthraquinones (emodin), phytosterols (stigmasterol, β-
sitosterol).124
Anxiolitic, antidepressant and sedative effects
C. siamea (leaves, flowers) is active on central nervous
system. Anxiolitic effect of aqueous extracts of leaves and
flowers (10 - 120 mg/kg, po) were demonstrated using an
elevated plus-maze (EPM) test in rats.140 Also, clinical
trials reported that leaves’ alcoholic extracts used as syrup
or tablet (10 mg/kg, po) caused drowsiness and improve
sleep quality in insomniac patients.141 Barakol was the only
compound identified in these neuropharmacological
activities. Indeed, barakol (10 mg/kg; ip) showed similar
anxiolitic activity as diazepam (1 mg/kg, ip) in wistar
rats.140 But, it increased locomotor behavior contrary to
diazepam.40, 142 The mechanism of action involved
inhibition of endogenous dopamine (DA) release and
turnover in the rat striatum. This inhibition was
antagonized by the dopamine D2 receptor antagonist
eticlopride, suggesting that the anti-anxiety activity of
barakol may be related to its agonistic action without a
change in dopamine uptake.143-144 However, the lowest
dose of barakol showed no effect on exploratory
behaviours using the holeboard test which indicates that
5HT mechanism and 5HT1A receptor may not be involved
in the anxiolytic effects.145 Then, barakol (10 - 100 mg/kg,
p.o.) had no anxiolytic effects in male wistar rats using an
EPM test.146-147 These constrast results suggest that
anxiolitic effect of barakol was dose-dependent and
required a peritoneal administration.
The antidepressant effect of barakol (5 - 30 mg/kg, po, for
7 days) was similar to that of imipramine (25 mg/kg, po).
Also, barakol (5 - 25 mg/kg, ip) decreased the duration of
immobility and increased struggling in isolated and
stressed rats using the forced swimming test (P<0.05). In
contrast, barakol (5 - 10 mg/kg ip) had not antidepressant
effect in the socially reared rats.140, 148 So, we must pay
attention to experimental conditions because socially
conditions of animal influence the antidepressive effect of
C. siamea.
The sedative effect of barakol was assessed in mice
behaviour using neurochemical tests. So, chronic
administration of barakol (10 - 100 mg/kg, po; for 30
days.) reduced spontaneous locomotor activity, increased
the duration of sleeping and prolonged the thiopental-
induced sleeping duration in wistar rats. 146 Its sedative
effect does not involve the GABA or glycine systems but
may be via the chloride ion channel like barbiturates.143, 149-
150 Thus, these studies suggest that the acute barakol
administration by intraperitoneal route exerts an anxiolytic
effect while the long-term treatment by oral administration
causes sedation. Therefore, it is essential to consider
carefully when assessing the value of barakol as anxiolytic
or sedative drugs.150
Antibacterial effects
The Journal of Phytopharmacology January- February
67
C. siamea (leave) has been valued for its use in the
treatment of infectious diseases. Recently, interest in C.
siamea has focused on its antibacterial activity evaluated
against various Gram positive and Gram negative bacteria
species by using cylinder plate assay.151
The methanol leave extract showed strong antibacterial
activity against Bacillus cereus and Listeria
monocytogenes with IC50 5.2 mg/mL and 20.8 mg/mL for
24 hours exposition at 37°C, respectively. In the same
conditions, it had low activity against Escherichia coli,
Klebsiella pneumoniae, Pseudomonas fluorescens,
Salmonella risen, Salmonella typhimurium, Staphilococcus
aureus, Yersinia enterocolitica, Lactobacillus planetarium
with IC50 up to 166.7 mg/mL.115 At 400 μg/disc hexane
extract showed high activities on Corynebacterium
diptheriae, Salmonella typhi, Shigella sonii, Pseudomonas
aeruginosa, Shigella boydii at 37°C within 24 hours but it
inactive on Proteus mirabilis, Staphylococcus aureus and
Staphylococcus pyogenes. Alkaloids, phenolics and sterols
could be responsible to this effects.152
The ethanol leave extracts (500 - 1000 μg/disc) showed
more activities than ciprofloxacin (30μg/disc) on
Staphylococcus aureus.59 It showed moderate activity on
Bacillus subtilis but it inactive on Escherichia coli and
Pseudomonas aeruginosa. At 40 mg/mL concentration for
18 hours exposition, it showed highest activity on
Salmonella thyphi with inhibition zone (iz.) value of 10
mm followed acetone and aqueous extracts with iz. 15, 8
and 3.5 mm, respectively. These effects were compared to
those of ampicillin, chloramphenicol, cotrimoxazole and
ciprofloxacin at 5 mg/mL which showed inhibition zone
value of 8, 16, 14, and 30 mm, respectively.153
Aqueous leave extract is active against various bacteria
Gram-. At 500 and 1000 μg/mL/disc, it inhibited
Pseudomonas aeruginosa (iz. 16 mm, respectively). At
0.1mL/disc/37°C for 24 hours, it showed inhibition on
Staphylococcus aureus (iz. 11.7 mm), Bacillus cereus (iz.
10 mm) and Escherichia coli (iz. 10.2 mm).59, 143, 154 But, it
was inactive against Staphylococcus aureus,
staphylococcus pyogens, E. coli, Salmonella typhi and
Shigella disenteriae. When this extract was mixed with the
extract of the fleshy part of Momordica charantia Linn,
the combination showed a powerful inhibitory action on
Bacillus cereus, Salmonella typhi and Staphylococcus
aureus. In addition, chloroform extract was found to be
active against Pseudomonas aeruginosa (iz. 8 -14 mm).155
These activities enumerated could be due to alkaloids
(barakol), steroids, saponins, tannins, resins, glycosides
and anthraquinones.59, 153, 156 So, barakol (50 mg/kg, ip)
was found to be associated with antibacterial activity
against Gram+ (Staphylococci aureus, Bacillus subtilis)
and Gram- (Echeriachia coli, Salmonella thyphi,
Salmonella dysenteriae and Pseudomonas aeruginosa).3
These results indicate that C. siamea has very higher
potential antibacterial. But, the mechanisms of action were
not investigated and need further researches.
Antifungal effects
Various fungi species found to be sensitive to hexane,
ethanol, methanol and aqueous extract of C. siamea. The
ethanol and aqueous bark extract (100 mg/mL) was active
on six strains of Candida (C. albicans, C. glabrata, C.
tropicalis, C. krusei, C. parapsilosis and C. guilliermondii)
and this activity was similar to fluconazole (25 μl/mL) for
24 hours exposition.157 But, ethanol leave extract was
inactive on C. albicans and Aspergillus fumigatus.92 The
methanol extracts of this plant (400 μg/mL/27°C for
7days) inhibited Microsporum canis (97.95%),
Trichophyton longifuses (92.45%), Fusarium solani
(84.53%), Macrophomina phaseolina (76.94%),
Trichophyton simii (22.98%), Pseudallescheria boydii
(9.91%) and Trichophyton schoenleinii (9.90%). This
activity was associated to phenols. But, this extract was
inactive on Candida albicans, Trichophyton
mentagrophyte, Rhizoctonia solani, Candida lipolytica,
Hanseniaspora uvarum, Pichia membranaefaciens,
Rhodotorula glutinis, Schizosaccharomyces pombe and
Zygosaccharomyces rouxii.152
Hexane extracts of leaves of C. siamea (400 μg/mL/27°C
for 7days) inhibited Pseudallescheria boydii, Aspergillus
Niger, Microsporum canis, Fusarium solani, and
Trichophyton schoenleinii. Its inhibition capacity was
similar to those of miconazole and ketoconazole and could
be due to sterols and alkaloids-like barakol. This extract
was inactive on Trichophyton longifuses, Candida
albicans, Trichophyton mentagrophytes, Trichophyton
simii, Macrophomina phaseolina, and Rhizoctonia
solani.31, 115, 152, 158 Through studies, we noted that C.
siamea could be useful in candidose and against growth of
fungi in agricultural products.
Toxicology
C. siamea seems less toxic justifying its wide use in
folklore medicine.70 Indeed, its stem bark’s aqueous extract
The Journal of Phytopharmacology January- February
68
(1600 mg/kg; po / 7 weeks) showed less sub-chronic
toxicity in male wistar rats.159 This extract and root’s
aqueous extracts were found to be relatively not toxic on
blood, hepatic and renal cells in wistar rats at 400 mg/kg
and 1500 mg/kg; p.o. for 4 weeks, respectively.23, 124
However, at a higher dose, diverse extracts of C. siamea
showed acute toxicity in various experiemental animals’
models. Indeed, its leaves’ ethanol extracts caused
mortality of experimental rats with an intraperitoneal LD50
of 9600 mg/kg within 24 h.160 The root’s aqueous extracts
(8000 mg/kg, po, 24 hours) showed hypersensitivity
reactions, cytotoxicity and increases aggressivity in rats.40
Also, the chronic toxicity studies showed that aqueous
extracts (2000 mg/kg; po / 2 weeks, respectively) led to
hepatic and renal cell destruction in albinos’ rats.161 This
toxicity involved a drastic reduction (p<0.05) in activities
of alkaline phosphatase (ALP), aspartate transaminase
(AST) and alanine transaminase (ALT) in the liver with a
corresponding increase in the serum levels.162 Authors
reported that male rat appeared to be more susceptible to
the toxic effect of C. siamea than female rats.161 In vitro,
ethanol and aqueous extracts of the leaves were absolutely
devoid of toxicity against vero (African green monkey
kidney) cells line with IC50 up to 100 μg/ml.124
In addition, clinical trials using C. siamea extracts were
investigated. These studies indicate that the crude extract
of the leaves in continual oral administration for six
months decreased the number of humans’ hematocrit and
neutrophiles. The powder induced irritation of the nose,
throat and eyes and it increased the rate of transaminase
after oral administration.163
According to the literature, these toxic effects could be due
to saponins, glycosides, alkaloids like barakol,
anthraquinones and tannins.160 In this review, barakol
seems most responsible for C siamea toxicity. Indeed, in
vivo, barakol showed an acute and subacute hepatotoxic
effect with LD50 2330 mg/kg in wistars rats164 and
subchronic toxicity effects on blood cells in rats fed with
normal and high cholesterol diets111. Barakol produced
acute toxicity and death in mice with LD50 324.09 mg/kg
by intraperitoneal injection. Also, barakol may disrupt
liver function and an increase of bilirubin in the rats,
especially at the dose 240 mg/kg.148
In vitro, cytotoxicity of barakol (5 mM) on hepatocytes of
carp fish (Cyprinus carpio) was found after 72 hours of
exposure.165 Also, in clinical trials, barakol (40 mg/kg; p.o,
60 days) induced an acute hepatitis in 29-81 years old
patients.166 Barakol showed cytotoxic effects in dose and
time-dependent manner with IC50 value of 0.68 mM within
96 hours of exposure on humans hepatoma cell line
HepG2. Mechanisms involved lactate dehydrogenase
leakage, which decreased GSH/GSSG ratio.167 It was also
showed that barakol-toxicity was mainly associated to the
ROS generation, followed by the ambalance of the
Bax/Bcl-2 ratio, and caspase-9 activation leading to
apoptotic cell death168. Apart from barakol, sennosides of
C. siamea showed very less hepatotoxicity with LD50 5000
mg/kg in rat and mice.132, 169 Continuous consumption of
barakol might not be suitable for health. All toxicity
studies showed that the toxic effects of C. siamea were
reversible after stopping administration.
Conclusion
The objective of this article is to show the recent progress
in the exploration of C. siamea as phytotherapy and to
illustrate its potential as a therapeutic agent. With the
current information, it is obvious that C. siamea has
pharmacological functions including antimalaria,
antidiabetic, antihypertensive, antioxidant, antitumor, anti-
inflammatory, analgesic, antipyretic, anxiolytic, sedative,
antibacterial, and antifungal activities. As the current
information shows more ninety bioactive compounds were
isolated from C. siamea. Pharmacological effects of most
of these compounds are not yet known. Nevertheless, from
the results of studies carried out, it is possible that
chromone alkaloids (barakol, cassiarin A), antraquinones
(emodin, chrysophanol), and biantraquinones (cassiamin
A, cassiamin B) might be useful in the development of
new drugs to treat various diseases. However, the present
results suggest a possibility that these compounds can be
further developed as a potential disease-curing remedy. It
must be kept in mind that clinicians should remain
cautious until more definitive studies demonstrate the
quality and effectiveness of C. siamea. For these reasons,
extensive pharmacological and chemical experiments,
together with human metabolism will be a focus for future
studies. Last but not the least, this review emphasizes the
potential of C. siamea to be employed in new therapeutic
drugs and provide the basis for future researches on the
application of transitional medicinal plants.
Acknowledgment
The authors are thankful to the authorities of FHB
University, for providing support to the study and other
The Journal of Phytopharmacology January- February
69
necessary facility like internet surfing, library and other
technical supports to write this review article.
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