Pharm. Méd. Trad. Afr. 2004. Vol. 13, pp. 57-66
ACllTE AND CHRONIC ANTIINFLA.MATORY PROPERTIES
OF Kalanchoe crenata Andr. (Crassulaceae) EXTRACTS
Agathe Lambou
FOn02,
Télesphore
Benoît NGUELEFACK\\ Théophile DIM02*,
Emmanuel A. ASONGALEl\\'e. Pierre KAMTCHOlJlNG2
'Department of Animal Biology, Faculty of Science, University of Dschang, BP 67 Dschang,
Cameroon
2Departement of Animal Biology and Physiology, Faculty of Science, University of Yaoundé
1, BP 812 Yaoundé, Cameroon
J Department of Physiological Sciences, Faculty of Medicine and Biomedical Sciences,
Pharmacology and Toxicology Unit, University of Yaoundé 1 P.O. Box 8283, Yaoundé.
*corresponding author: Email: ~
Abstract
Kalanchae crenata is used in folk medicine for the treatrnent of severa! inflammatory
disorders. Methylene chloride/methanol extract of K. crenata was successively exhausted in
hexane, methylene chloride. ethyl acetate and n-butanol. The anti-inflarnniatory profile of the
obtained extracts was investigated on carrageenan-induced paw oederna. The oral administration
of n-butanol extract (600 mg/kg) produced a maximum inhibition of about 45~'o of carrageenan-
induced paw oedema, The n-butanol extract also exhibited acute anti-inflammatory activity on
histamine (47.51%). serotonin (54.51%) and forrnalin (3597%) induced paw oedema. In the
chronic inflammation, this extract showed signiftcant maximum inhibition of 58.33°ô on the
ninth day of treatment. The ulcerogenic assay shows that ulcer indices after p. (J. treatrnent with
n-butanol extract were 0.0 ± 00 at 300 mg/kg and 0.4 ± 0.2 at 600 mg/kg. On the basis of these
findings, it may be inferred that K. creuata is an anti-inflammatory and anti-arthritic agent which
blocks the cyclooxygenase and histamine pathways The results are in agreement with the
traditional use of the plant in inflammatory conditions.
Key words: carrageenan. histamine, 5-HT, formaI in, anti-inflammatory activity, Kalanchoe
crenata
1-1ntroduction
Kalanchoe l'reno/a Andr. (Crassulaceae) commonly known as "never die" or "Dogs
livet" has been traditionally used for the treatment of many ailments such as earache, srnall pox,
headaches. inflammation. pain, asthrna, palpitations, convulsion and general debilitv. Aqueous
and alcoholic extracts of K. crenuto' s leaves contain alkaloids and saponins (Sofowora, 1993)
ln early studies. aqueous and ethanolic extracts of K. crenata was found to inhibit pain
induced by acetic acid, forrnalin hot plate and pressure (Nguelefack el al, 2004) This work was
57

Pharm. Méd. Trad. Afr. 2004. VoU3, pp.57-66
aimed at providing scientific validation of the clairned ethnopharrnacological properties, bv
investigating anti-inflamrnatory properties of the leaves extracts
2-Materials and methods
2- / -Plant materials
K. crenatas leaves were collected in Dschang City (West Cameroon) in October 2002.
and authentified by comparison with a voucher specimen number 50103IY A in the National
Herbarium, Yaounde. Cameroon. 2 kg of the air dried leaves were ground to a fine powder and
extracted with methylene chloride/methanol (CH2Cb/CH,OH) for 3 days (72 h) The resulting
extract was concentrated in vacuum over rotavapor to obtain 234.7g ofCH 2CI 2/ CH10H extract.
212.4 g of this extract were exhausted successively with hexane, methylene chloride, ethyl
acetate and n-butanol The following fractions were obtained: hexane (92.2 g); CH2C1 1 (4.7 g);
ethyl acetate (7.1 g): n-butanol (37 g) and aqueous residue (235 g). CH2CI 2/MeOH. CH2C1 2and
n-butanol extracts were dissolved in 2.5 ~·o DMSO and 2.5 ~..o Tween 20; while hexane and ethyl
acetate extracts were dissolved in 3% DMSO before giving orally at the doses of 300 and 600
mg/kg of the animals body weight.
2-2. Phytochemical screening
The total extract as weil as its fractions were submitted to the test of Liberman Buchard,
the ferric chloride test, the copo of magnesium test and the Vanillin-sulphuric acid test in the
goal to determine the presence of sterols. phenolic cornpounds, flavonoids and saponins
respectively
2-2 Chemicals
Indomethacin (Sigma), pyrilamine Maleate (Sigma). diclofenac, carrageenan (Sigma),
Histamine (Fluka), 5-hydroxytryptomine (S-HT) (Fluka) and formaldehyde (Roth) were used.
OlmI of oederna-inducing agents was administered into the plantar surface of the right
hind paw of the animaIs.
2-3 Animais
Male and female Wistar rats (140-190 g) were used for the investigations. They were
obtained from the Animal House, Department of Animal Biology and Physiology, University of
Yaoundé 1 Cameroon The animaIs were divided into groups of five and fasted 24 h before the
experimern.
2--/ Pharmacological studies
2--/-/ Carrageenan-induced paw oedema
The extracts (experimental groups) a control vehicle (solution contain 2.5% DMSO and
2.5% tween 20) (control group) and indornethacin 10mglkg (reference group) were given oraJly
one hour before subplantar administration of 1% carrageenan suspension in 0.9% NaCI The
volumes of the injected paws were measured 30. 60, 120, 180. 240, 300 and 360 min after
58

Pharm. Méd. Trad. Afr. 2004. Vol.13, pp. 57-66
induction of inflammation using Ugo Basile Plethysmometer N" 7! 50 as described bv winter el
al. (1962). The oederna was expressed as an increase in paw volume due ta carrageenan
injection
2--1-/ Histamin and Serotonin-induced paH' oedema
ln another set of experiment serotonin and histamine were used as phlogogen agents The
n-butanol extract of K. creuata (experimenta! groups) and control vehicle (solution contain 25%
DMSO and 2.5 % Tween 20) were administered one hour before injection of intlammatory
mediators
The respective
strength
of oedemogens, the volume
injecred and the time of
determination of oederna volumes are indicated in parcntheses ; serotonin (
1
10. g/ml, Olmi. 30
min) : histamine (10. 1 g/ml, 0,1 ml, 60 min) (Singh I!I al, 1996). The reference groups were
treated with indomethacin (10 mg/kg) or pyrilamine rnaleate (1 mg/kg) respectively.
The oedema volume was determined as mention previously.
2--1--1. Formalin-induced pail ocdctna
The inflammation
was produced
by subaponevrotic injection of 0.1 ml of 2°/0
forrnaldehyde one hour after oral administration of n-butanol extract of K. creuata. diclofenac (5
mg/kg) or control vehicJe (solution contain 2.5% DMSO and 2.5% tween 20) The oederna
volume was determined 1. 2 and 4 hours after injection of formaldehyde.
The same animais were further treated with the extract or diclofenac tor the following 9
days A second injection of formaldehyde was done on the third day (Hosseinzadeh and Younesi,
2002) The dai/y changes in paw size were measured plethvsmographically.
2--1--1.1 llcerogenic activtty
Two hours after test drugs administration {n-butanol extract of K. crenata, indomethacin
( 10 mg/kg) or control vehicle), animais were sacrified by cervical dislocation, stomach isolated
and opened along the greater curvature. Ulcerated surface was measured and scores were
attributed according to the table described by Martin el al. ( 1993J.
2--1-5. Statistical analysis
Ail values were presented as mean values ± S.E.M from fivc rats. The statistical
significance between the treated groups and the control group was calculated through the
analysis of variance (ANOVA) followed by the Students "t" test. P values less than 00:;
(P<OOS) were considered significant.
3-Results
3-/. l'hvtochemical screening
The phytochemical analysis revealed the presence of sterols in the CHIOH/CH2Cl z and
its hexane fraction. Sterols. flavonoids and saponins were found in the methylene chJoride and

Pharm. Méd Trad Afr. 2004. Vol.13, pp. 57-66
erhvl acetate fractions. Flavonoids and saponins have been detected in CH10 H/CH2(ï è extract
and its n-butanol fraction
3-2. ( 'arrageenan induced pmi! oedema
The effect of the K. crettata 's extracts on carrageenan induced-paw oedema is shown in
table 1. The CH2Cl2/MeOH, ethyl acetate extracts and aqueous residue showed at 600 mg/kg a
maximum anti-oedernatous effect of about 41.75; 40.10 and J571~'o respectively one hour afler
carrageenan administration. The hexane, CH2Ch and n-butanol extracts showed a maximum
anti-inflarnrnatory etTect ofabout 44.34 (30 min), 39.01 (1 h) and 45.80% (1 h) after carrageenan
administration respectively. This effect was maintained up to 25.16 and 30% for the hexane,
CH2Ch and n-butanol extracts respectively.
The anti-inflammatory effect induced by indomethacin progressively increased and
reached a maximum (6591%) at 3 h, and the effect was maintained up to 6 hours.
3-3. Serotonin and histamine induced pOli' oedema
Table 2 shows the effect ofthe n-butanol extract of K. crcuata on serotonin and histamine
induced paw oederna. At the dose of 300 mg/kg, the n-butanol extract of K. Crenata significantly
reduced the paw oedema formation induced by histamine (41.98%). The percent age inhibition at
the dose 0[600 mg/kg was 54.51 and 4751% on serotonin and histamine induced inflammation
respectively.
Pyrilamine
maleate
at
the dose
of
l mg/kg
inhibited
histamine-induced
inflammation by 58.01% while indomethacin exhibited a percent inhibition of 48.49% on
inflammation induced by serotonin.
3--1. Formalin induced pail' oedema
The n-butanol extract of K. crenata (300 and 600 mg/kg) and diclofenac (5 mg/kg)
produced significant inhibition of forrnalin induced inflammation by 32.57, 35.97 and 43.62%
respectively 4 h after formalin administration (table 3).
ln the chronic inflammation, the extract showed significant inhibition On the seventh day
of experiment. the inflammation of the paw of animais treated with extract (600 mg/kg) and
diclofenac (5 mg/kg) was 3140 and 3107% respectively, showing an inhibition of 5594%. An
inflammation of 21.37% was observed in rats treated with extract (600 mg/kg) on the ninth day,
presenting a maximum inhibition 01'58.33%
3-5. Ulcerogenic activitv
As shown in table 4, 300 mg/kg of the n-butanol extract of K. crenata fail to induce
gastric ulceration. At the dose of 600 mg/kg, 2 over 5 rats treated show blood vessels dilatation,
corresponding to general ulcer index of 0.4. Ali the animais that received indornerhacin
presented significant ulceration surface of 6.85 mrrr'. lndomethacin as weIl as n-buranol exrract
(300 mg/kg) significant reduced mucus weight.
60

Pharm. Méd. Trad. Afr. 2004. Vo!.13, pp. 57-66
4. Discussion
The experimental data of the present study indicates that K. crcnata extracts possesses
significant anti-inflarnmatory activities on various phlogistic agents.
Carrageenan induced intlammation involved three distinct phases of mediators release
including serotonin and histamine in first phase, kinins in second phase and prostaglandin in
third phase (Singh et al.. 1996) CHzCh/iVfeOH extract of K crenata and aqueous residue have
significantly inhibited carrageenan induced paw oedema only in the first phase, suggesting an
inhibitory effect on the release of histamine and/or serotonin Anti-inflamrnatory effect of the
ethyl acetate extract was prolonged to the third hour, suggesting an inhibition of the release of
kinins. Hexane, CHzClz and n-butanol extracts showed a significant inhibition of the oedema on
the three phases. This oedematous response was also significantly reduced in rats pre-treated
with indomethacin, compound known to be cyclooxygenase inhibitors. According to Chawla el
al. (1987) and Dongrno el al. (2001), 5-lipoxygenase inhibitors also possess anti-inflarnmatory
activity on carrageenan-induced oederna The inhibirory effect of the hexane and n-butanol
extract on the third phase of the oedema could be due to an inhibition of 5-lipoxygenase and/or
cyclooxygenase, both enzymes involved in the formation of 1eukotrienes and prostaglandins
respectivelv The n-butanol extract was more active than others extracts and was chosen for
further studies. Results obtained with n-butanol extract on the carrageenan-induced oedema were
confirmed on the acute inflammation induced by formalin. According to Yuh-Fung et al. (1995),
acute inflammation induced by formalin results from cell damage which provoked the
production of endogenous mediators
such as histamine,
serotonin,
prostaglandins
and
bradykinin. Formalin-induced oedema was significantly inhibited by n-butanol extract of K.
crenata.
ln order to ascertain the effect of the extract on mediators' activities, the extract was
tested against inflammation induced by histamine and serotonine. lt has been observed that n-
butanol extract of K creuata inhibited histamine and serotonin-induced oederna. The inhibitory
effect of K. crenata inferred that the extract mal' be acting like pyrilamine as an antagonist of
these mediators which also significantly inhibited inflammation induced by histamine
n-butanol extract of K. crenata was further essayed on chronic inflammation induced bv
formalin. It is weil known that inhibition of formalin-induced pedal oederna in rats is one of the
most suitable test procedures to screen anti-arthritic and anti-inflammatory agents as it closely
resembles human arthritis (Greenwald, 1991). Formalin-induced arthritis is a model used for the
evaluation of an agent with probable anti-proliferative activity. This experiment is associated
with the proliferative phase of inflammation (Banerjee el al., 2000) Since n-hutanol extract of K.
creuata could significantly inhibit this mode! of inflammation. it can be though that it possesses
"
61

Pharm. Méd. Trad. Afr. 2004. vot.ts, pp.57-66
anti-proliferative and anti-arthritic activities which have been observed with diclofenac. a
Icyc)ooxygenase inhibitor
Since results from the present study strongly indicate the non steroidal anti-inflammatory
like activity of the extract, its ulcerogenic effect was tested on starved animais Non steroidal
anti-inflamrnatory drugs are thought to impair the rnucosal defence properties of the stomach and
intestine. They act by inhibition of cyclooxygenase, therefore inhibiting the production of gastric
prostaglandins which leads to reduction of gastric mucus production and an increase in mucosa\\
permeability (Jain et al.. 2002). According to Kryvola el al. (2003), anti-histaminic agents
protect the gastric mucosa against ulceration by diminishing gastric acid production. The n-
butanol extract of K. crenata which reduced the mucus weight but induced little ulceration of the
gastric mucosa could act by dual inhibition of cyclo-oxygenase and histamine.
The presence of flavonoids in the n-butanol extract of K. L'relia/a may account for its anti-
inflarnmatory activity. Many compound From this class have been found to exhibit anti-
inflarnrnatorv effects (Martini et al., :2004; Toker c:/ al .. 2004)
ln conclusion, the results show the marked and dose-related anti-inflarnrnatory and anti-
arthritic activities of the K. L'ret/a/a extracts. These results corroborated the traditional use of the
plant in inflarnmatorv conditions Their active principles specifically inhibit certain chemicals-
induced oederna in rats.
References
J - Banerjee, S., Sur, T
K, MandaI, S, Chandra Das, P., Sikdar, S. (2000). Assessment of the
anti-inflarumatory effects of Swertia chirata in acute and chronic experimentalmodels in
male albino rats. ludiun Jourual (~r Pharmacology 32,21-24
2- Chawla, A. S., Singh, M., Murthy, M. S, Gupta, M P, and Singh, H. (1987). Anti-
intlammatory action of ferulic acid and its esters in carrageenan-induced paw oedema
mode!. Indian Journal (i Experimental RioloKY 25. 187-189
3- Dongrno, A. B.,
Karnanyi, A., Anchang, M. S, Chungag-Anye Nkeh, B., Njarnen. D.,
Nguelefack, T B.,
Nole. 1., Wagner H. (2001) Anti-intlammatory and analgesie
properties of the stem bark extract of /~/y/hrophlel/m suaveolens (Caesalpiniaceae),
Guillemin a Perrottet. Journal oflrhnopharmacology 7(2-3), 137-141
4- Greenwald RA (1991) Animal models for evaluation of arthritic drugs Meth t-ind Cli«
Pharmacol Vs, 75-83.
5- Hosseinzadeh, H. and Younesi, H (2002). Antinociceptive and anti-inflarnrnatory effects of
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and Epstein. 0
1. (2003)
Analgesie and anti-inflamrnatory activity of antibodies to

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histamine under experimental conditions Hnlletm oilxperimental Ifi%g\\' UIIU Medicine,
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8- Martin. 1\\1. J, Motilva, V and Alarcon De La Lastra (1993) Quercetin and Naringenin
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9- Martini. N. D. Katerere, D. R. P and EJoff
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j-j/1J/ojJhm'l1loc%j!;Y 93, 207-212
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Analgesie activities of aqueous and ethanolic extracts of the leaves of Kalauchoe cretuua
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activities from mots of Angelic« pubescens. l'lanta Medica 61, 2-8
63

Table 1: Effcct of K. crenaui cxtracts on carragccnan induccd pa" ocdcma in rats
Doses
-
p()lii-celllage,; d tuhibit1 < 1 1 \\ - - ' ----
luflunuuations (!',V L11 mIt
1
'l'rai telllellls
--.L.----;-__
- - - - - _..----:-:-----
(rn~lkt!1
30min
111
2h
~h
~h
5h
(,h
1 ~llmin
Ih
2h
Jh
4h
5il
611
. _ - - _ . _ - - - - _ . _ - -
Coutrul
/1
(J2.~± n.zz
IU61oO.Dl
OHl± (J.O.~
IU'h 0.02
0.7010 II.II.~
O.6-1± (l.fJ~
(I.(,(l± (J.(I~
O.()O
0.00
0.(1)
O,llI)
IUiO
0.00
Il.(11)
CII,Cl,ICI hOB
~IiO
O.2l\\±no~
IU7±0.04
07210 0.0(,
OX(~± 00'1
0.(,7± (lOR
072± o.o«
0.77± OOt)
-25.21
-3.2')
-X.OK
·1.00
~.2!1
-11.1/3
-If,l(,
exuuct
(,(10
OU±IJ.(J2"
021100.02"*
0.50±o.OX
0.7:'±OIO
O.()(,1o{J.IO
Il.71l±O.OI~
n.(,)1oo.1O
1 40.00
~17)
2.~.<j5
6(JI
"I:j
5.1~
-S..'3
R.i>l~
.~t~)
02R±O.fn
O.3.1±001
11.:'()±1i.0~
Oc>()±D.Il--I"
0.541oDU2 ....
O.52±O(J.1*
() :'(~0.05·· i -2:121
7.(,')
1~.l)7
17.0--1
21.71
197)
2~55
11",;\\lIe cxtruct
f
(,Of)
D.12101I.01·
1)2(,± Il liS
0 ~c>± Il.02''
O.S.\\±.0.lI4'"
0.51± 002'"
().~X± 0.0.'
O.~I± 0.02
1 -1-1.'-1
27.~7
2'J.'1~
32.X~
2h.no
25 ')2
.~X~2
~
300
lI.21± 1l.0~
[1. l ')10 lI.O~u
lI.Sfl± OO~
ON,±. O.Où
O.M,± 0 03
0.6:'± O.()~
n.!>.?: () 02
1
!If,,!
~()70
15.:'6
1(,7'1
) I~
-1.5~
(,2S
~
CII,Chc'.\\lnlcl
(,(JO
o l '-J±O.OI
O.22± OO'-l·
Il.~<J± l!.ll:'·
Il (.:'± li 07
Il.5R± 0 07
IfJ.2X
16..1)
.~().22
~
o.5ü o.1l5
OA2± (L05*
1
17..l9
J')OI
26.1).4
17.5~
l::l
~
f:t1l\\lm:elille
.100
0.27± 1J.(l4
[13-1± 0.D3
lI.7-l± Il.lIÙ
(Un1o o.o«
IJ.7.:!±. O.M
0.71± 0.06
O.7(~ 0.0(,
1 -21.7.'
--I.3l)
_11'17
-<J.77
-li.57
-1111
-7 ~X
01
+:>-
~
:'l
cxtrurt
600
O.17± o.m
O.2± 10.03·"
(J·II± (JlI7·
O.Wt tl.02*·
(J7~± 1!.l15
O.SII±IlIl'
075±IUl4
1221>1)
-lOlO
,,8.<>2
2~.XI
Il.110
·23.71'
·12 rt
t-v
a
n-butauol
.~(J(I
Il.21± 0.02
o.nt Il.O-I
0 f,l± (J.D~
0 I).~± lI.1l5"
lI:,l± IJ()(\\·
O(,I± 0.(J7
Of,m n 0(,
1
Id)
25.27
5 ..~8
21H1)
l3.~2
5X<>
u lX
a
~
~'lrarl
iloo
D.17± 0.02
0.20± D.02··
1l..'ll± 011-1"
[1 ~X± O.{J.~··
(I.-IX:!. (J.o~'"
lI~-,1o (I.IJ~.
li ~X1o ()o(,·· 1 2'-l..l<j
--l2X5
~:'.Xll
.~l)._'-f
308)
3271
~2.21
~
:--
AqUl:OUS
.~Oll
0.25± lI.02
tU')± ()(J.~
0 (,')± 0.05
(J.70± 0 03
O.6.H D.05
0,(. I± (l.O~
1).f)I~ n.o«
1
-9.5f,
-7.6')
-.'.59
lUX
lOlO
5 X6
'ilk
.......
~w
(,(JO
residuc
O.l~± 0.(J 1*
(J.2~± 0.01"
OAS± lun
0.?X± II.IJ:'
IU;:,± 0112
0.87± (J.O~
O.77± Il.02
3').1 J
35.71
2(;.'14
1.25
-22.2X
-.~4.25
·1 (,1 l,
~V,
hulomcthaci»
Jil
I/.I:'± lU»
II 1H±o.o.~n
02X± (Ulh"
Il.17± 11.07··
Il.2'1± 0 ..1l7··
U2'i± 0.04 u
U.3Il± 1/.05··
31.30
-IX.l)1)
57.7'1,
ilS') 1
57.~2
5401
:'~~,)
';'-l
0-
*p<O.OS. **p<O.O 1 comparcd with control
0-

Pharm. Méd. Trad. Afr. 2004. Vol.13, pp. 57-66
Table 2. Effcct of n-butanol cxtract of K crenata on histamineand scrotonin induced paw ocdcma
--- _._--_._
- - - - -
...
.._----".".
_--~_._-_ ... _--------~--------_.--_._----_
-
Group
Dose (p.o)
Mean ocdcrna volume (ml)
Pcrccntagc inhibition
- - - _..
Histamine
Serotonin
Histamine
Serotonin
Control
10 ml/kg
o 36 ± (J.(J2
0.53 ± O.(J-I
n-butanol
300 mg/kg
0.21 ± 0.04*
OAI ± 0.02
4198
2140
extract
600 mg/kg
019±OOI**
0.24±(JO/**
47.51.
54.51
Pyrilamine
1 mg/kg
o 15 ± (J.(l3**
5801
lndomethacin
10 mg/kg
027 ± 002**
4849
*p<O.O:'. **p<O.O 1 comparcd with control
Tablc J .Effcct of n-butanol of K. crenata on forrnalin induccd pa« ocdema
.._._--_.,---
._----.---_._-.~--_._------_._--
Dose
Mean oedema volume (ml)
Percent inhibition
Group
__
__
.
. _ - - - - _ . --_.
. _ -
(p. Cl)
Ih
2h
4h
lh
2h
4h
..
-~-_
- - - -
Control
10 ml/kg
O.'i2 ± 0.04
063 ± ()O6
O.70±OO6
n-butanol
300 mg/kg
OAI ± 00-1-
OAl) ± (l.O-l-
0.-1-7 ± O.Oô**
1992
2158
32.57
extract
600 mu/ku
035 ± 0.03*
(UX ± 00'+**
OA2 ± ()O5**
3295
3L).36
35.97
o
~
Diclofenac
5 mg/kg
0.32 + 0.02**
OA3 ± 001 *
03lJ ± 002**
37.93
3047
43.62
*p<005. **p<O.O 1 comparcd with control
65

Pharm. Méd. Trad. Afr. 2004. VoU 3, pp. 57-66
120
100
1
1
~
;:R
1
0
80
c
--<>-control
0
~ 60
-
- n-butaro 1300
E
E
CIl
- ·6· - n-butarol600
<;;::
40
C
____ diclo fenac
20
0
dl
d2
d3
d4
d5
d6
d7
dB
d9
d10
Time (day)
Figure 1. Effect of n-butanol extract of K. crenata on chronie inflammation induced by
formalin
*p<()(J:ï. **p<lJ.() l. ***p<()()(J 1 cornparcd with control
Table 4. Ulcerogcnic activitics of n-butanol cxtract of K crcnata
Doses
Mucus wcight
Ulccnucd
Ulceration
ulccratcd
ulccratcd
Drugs
(mg/Kg)
( mg)
surface (IIUU')
Indice
surface ('Yu)
animais «~.,.)
Control
(.2'>X ± ~sn
0.0 ± 00
0.0 ± 0.0
0
0
n-butanol
WO
~(j 'x, ± 1.6~ *
oo±oo
0.0 ± 00
0
0
cxtract
Blood vcsscl s
(,00
~5.32 ± (lO')
O~ ± 0.2
()
~O
dilation
indomcthacin
10
~O.S() ± 3.5')**
(,.X5 ± 1.')X**
2.66 ± O.l(~*"'*
tU\\!
JOO
-----------
*p<O.OS, **p<O.O 1, ***p<O.OO 1 eompared with eor.tro1
66