ArticlePDF Available

Effect of aqueous infusion from Cotinus coggygria leaves on indomethacin-induced gastric mucosal damage and oxidative stress in rats

Authors:

Abstract and Figures

Purpose: The Smoke tree (Cotinus coggygria) is well known medicinal plant that is used mainly externally by the Balkan folk medicine for its antiseptic and anti-inflammatory properties. There are scarce reports about the internal usage of decoctions from C. coggygria leaves against gastric ulcers. Our study was aimed to explore the effect of aqueous infusion from Cotinus coggygria leaves (AICCL) on indomethacin-induced gastric mucosal damage in Wistar rats and its possible effect on the gastric oxidative status. Material and Methods: Three AICCL (1/100, 2/100 and 4/100) were applied by gastric gavage (volume: 10 ml/kg) as a pretreatment 3 days before a single intragastric administration of indomethacin (dose: 100 mg/kg). Gastric ulcer formation was estimated morphometrically and histopathologically 4 h after the indomethacin administration. Malondialdehyde (MDA) in blood serum and stomach was measured as a biochemical marker of lipid oxidation. Gastric necrosis was also evaluated by alkaline phosphatase (ALP) and uric acid (UA) assays. Results: Morphometrical examinations of stomachs showed that the 2/100 AICCL significantly decreased the ulcer number and area. Histopathological studies demonstrated that AICCL induced a reduction of the depth and severity of indomethacin-induced mucosal lesions. AICCL reduced the elevated by indomethacin gastric MDA, ALP and UA levels. Conclusion: Indomethacin-induced gastric mucosal damage was accompanied by the development of oxidative stress. AICCL-pretreatment alleviated the gastric lesions, and reduced the indomethacin-induced elevation of ALP and UA. It could be suggested that the gastroprotective effect of AICCL was due to its antioxidant properties as evidenced by the decreased gastric MDA levels.
Content may be subject to copyright.
32 Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna
ORIGINAL ARTICLES
EFFECT OF AQUEOUS INFUSION FROM COTINUS
COGGYGRIA LEAVES ON INDOMETHACIN-INDUCED
GASTRIC MUCOSAL DAMAGE AND OXIDATIVE STRESS
IN RATS
Danail Pavlov1, Diana Ivanova1, Miroslav Eftimov2, Maria Tzaneva3, Milka Nashar1,
Ina Kobakova4, Stefka Valcheva-Kuzmanova2
1Department of Biochemistry, Molecular Medicine and Nutrigenomics, 2Department of
Preclinical and Clinical Pharmacology, 3Department of Preclinical and Clinical Sciences,
and 4Department of General and Clinical Pathology, Forensic Medicine and Deontology,
Medical University of Varna
Address for correspondence:
Danail Pavlov
Dept. of Biochemistry, Molecular Medicine and
Nutrigenomics, Medical University of Varna,
55 Marin Drinov Str., 9002 Varna, Bulgaria
e-mail: danailpavlov@gmail.com
ABSTRACT
PURPOSE: The Smoke tree (Cotinus coggygria) is well known medicinal plant that is used mainly external-
ly by the Balkan folk medicine for its antiseptic and anti-inflammatory properties. There are scarce reports
about the internal usage of decoctions from C. coggygria leaves against gastric ulcers. Our study was aimed
to explore the effect of aqueous infusion from Cotinus coggygria leaves (AICCL) on indomethacin-induced
gastric mucosal damage in Wistar rats and its possible effect on the gastric oxidative status.
MATERIAL AND METHODS: Three AICCL (1/100, 2/100 and 4/100) were applied by gastric gavage (volume:
10 ml/kg) as a pretreatment 3 days before a single intragastric administration of indomethacin (dose: 100
mg/kg). Gastric ulcer formation was estimated morphometrically and histopathologically 4 h after the in-
domethacin administration. Malondialdehyde (MDA) in blood serum and stomach was measured as a bio-
chemical marker of lipid oxidation. Gastric necrosis was also evaluated by alkaline phosphatase (ALP) and
uric acid (UA) assays.
RE SULTS: Morphometrical examinations of stomachs showed that the 2/100 AICCL significantly decreased
the ulcer number and area. Histopathological studies demonstrated that AICCL induced a reduction of the
depth and severity of indomethacin-induced mucosal lesions. AICCL reduced the elevated by indomethacin
gastric MDA, ALP and UA levels.
CONCLUSION: Indomethacin-induced gastric mucosal damage was accompanied by the development of ox-
idative stress. AICCL-pretreatment alleviated the gastric lesions, and reduced the indomethacin-induced el-
evation of ALP and UA. It could be suggested that the gastroprotective effect of AICCL was due to its antiox-
idant properties as evidenced by the decreased gastric MDA levels.
Key words: Cotinus coggygria, Indomethacin, Gastric mucosal damage, Oxidative stress, Lipid peroxida-
tion, Antioxidant activity
Received: September 5, 2013
Accepted: October 7, 2013
INTRODUCTION
Gastric ulcer is a recurrent chronic illness that
affects approximately 10% of the world population
(1). It is induced by several factors, including infection
by Helicobacter pylori, emotional stress, smoking,
nutritional deficiencies, alcohol consumption and
treatment with non-steroidal anti-inf lammatory
Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna 33
Danail Pavlov, Diana Ivanova, Miroslav Eftimov et al.
drugs (NSAIDs) (2, 3). Ulceration occurs when there
is an imbalance between protective (mucus secretion,
blood flow, prostaglandins, enzymatic and non-
enzymatic antioxidants) and aggressive mechanisms
in the stomach (acid-pepsin, leukotrienes and react ive
oxygen species, ROS) (4). It is well known that ROS,
especially the superoxide anion and the hydroxyl
radical, play an important role in the pathogenesis
of acute experimental gastric lesions induced by
NSAIDs (5).
Indomethacin, like other NSAIDs, is known to
induce gastric mucosal damage in humans (6) and is
considered as an appropriate agent for development
of animal models of NSAIDs-induced ulcerogenesis
(7). The inhibition of cyclooxygenase (COX) and
deficiency of endogenous prostaglandins (PGs)
is accepted as a main mechanism implicated in
indomethacin-induced gastropathy (8).
The therapy used for treating gastric ulcers
includes the control of the H. pylori infection, the
control of the H+/K+-ATPase pump and the acid
secretion, as well as the damage and inf lammation
reversal to the mucosa (9). Medications prescribed
for the treatment of gastric ulcer are not completely
effective and exhibit many adverse reactions in
addition of high economic burden (10). This has been
the basis for screening of new sources of bioactive
compounds, such as herbal extracts.
The Eurasian smoke tree (Cotinus coggygria
Scop., Anacardiaceae) is a medicinal plant species
with wide distribution from southern Europe, the
Mediterranean, Moldova, and the Caucasus to
Central China and the Himalayas (11). According to
some authors (12, 13) the whole plant is poisonous
due to the large content of gallotannins (above 25%).
However, in the Balkan folk medicine, decoctions
from leaves of C. coggygr ia are applied to treat gingival
and throat inf lammations, stomach ache, gastric
ulcer, diarrhea, nephritis, anthrax, asthma, cardiac
and urinal diseases, and even diabetes mellitus, due
to their antiseptic, anti-inflammatory, antimicrobial,
anti-hemorrhagic, and wound-healing properties
(11, 13, 14, 15).
Studies on the chemical composition of leaves
infusion report the presence of gallic acid methyl ester
and anthocyanins (16), and gallotanins, gallic acid,
flavonic glycosides, myrcen, alpha-pinene, camphen,
linalool, and alpha-terpineol (11, 17). Numerous
polyphenolic compounds have been isolated,
including quercetin, fustin, and taxifolin (18).
The antioxidant activity of extracts from C.
coggygria leaves was demonstrated in several studies,
suggesting the role of high polyphenol content (19,
20, 21, 22). It is noteworthy that the ethanol and
aqueous extracts have shown the highest antioxidant
activity and the highest content of polyphenols
among dozens of investigated Bulgarian medicinal
plants (19). Although that the plant seems to be
extremely rich in biologically active compounds,
it has been somewhat ignored by pharmacological
studies because of the traditionally reported toxicity.
The aim of the present study was to investigate
the effect of aqueous infusion from Cotinus coggygria
leaves (AICCL) on indomethacin-induced gastric
mucosal damage in rats and its possible effect on the
gastric oxidative status.
MATERIAL AND METHODS
Experimental substances
Three aqueous infusions of Cotinus coggygria
leaves (AICCL) were prepared one hour before each
treatment: 1, 2 and 4 g dried material was scalded
in 100 ml boiling distilled water for 10 min. 1/100
AICCL is commensurable to a traditional Bulgarian
recipe for treatment of gastric ulcer (13).
Chemicals
Indomethacin (Indo) was obtained from Sig-
ma-Aldrich (Germany). It was prepared as a suspen-
sion in a vehicle (2 drops of Tween 80 per 5ml of dis-
tilled water). All chemicals used for the biochemical
analyses and histopathological examinations were
of analytical grade and were obtained from Merck
(Germa ny).
Experimental design
Male albino Wistar rats (2-2.5 months old; 220-
250g) were kept under the standard conditions of the
animal house with 12-h light-dark cycle (light 7:00-
19:00) at a temperature 23-25ºC. They were fasted 24
h before the indomethacin administration but had
free access to water. The cohort comprised of five
experimental groups each of eight rats: I. Control
(C), II. Indomethacin (Indo), III. 1/100 AICCL+Indo,
IV. 2/100 AICCL+Indo, V. 4/100 AICCL+Indo.
The rats were orally pretreated by direct stomach
34 Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna
Effect of aqueous infusion from Cotinus coggygria leaves on indomethacin-induced gastric mucosal damage ...
intubation (orogastric cannula) with water (groups I
and II, volume: 10 ml/kg) or AICCL (groups III, IV,
and V, volume: 10 ml/kg). Three days later, the rats
were treated by a single intragastric administration
of indomethacin (dose: 100 mg/kg). All procedures
concerning animal treatment and experimentation
were conducted in compliance with the national laws
and policies and in conformity with the international
guidelines (EEC Council Directive 86/609, IL 358, 1,
December 12, 1987).
Blood serum and tissue preparation
The animals were anaesthetized with diethyl-
ether 4 h after the indomethacin treatment. Blood
was collected from the sublingual veins in heparin-
ized tubes. Samples were was centrifuged at 2000g
rpm for 10 min and serum was obtained and stored
at 20°C until biochemical analyses of uric acid (UA),
malondialdehyde (MDA) and sulphydryl groups
(SH-groups) concentrations. After the animals de-
capitation the stomachs were removed immediately,
opened along the great curvature, gently washed in
physiological salt solution, spread over the pad and
observed macroscopically for appearance of muco-
sal lesions. The length of each lesion was measured.
In the case of petechia, five of them were considered
as a 1 mm lesion. Mean ulcer number and area were
calculated. Stomachs were homogenized in 1:5 w/v
50mM phosphate buffer (pH 7.4) at 4000 rpm for 10
min. The homogenate was centrifuged at 800g rpm
for 15 min to discard the sediment and the super-
natant was taken for biochemical analyses: activi-
ty of alkaline phosphatase (ALP); concentrations of
UA and MDA. All manipulations were performed at
4-8ºC. MDA, ALP and UA were determined imme-
diately after thawing the samples.
Histopathological study
Pieces of the stomachs were fixed immediately
after morphometrical examination in 10% neutral
buffered formaldehyde solution. Fixed tissues were
embedded in paraffin, cut into sections and placed
on microscope slides. Staining of the slides with
hematoxylin-eosin was used for the histopathological
examination which was performed under light
microscopy and documented by microphotocamera.
Biochemical assays
Membrane lipid peroxidation was monitored by
MDA in blood serum and stomach homogenates us-
ing the method of Porter (23). Determination of SH-
groups was performed spectrophotometrically in se-
Fig. 1. Effect of AICCL-pretreatment on the number (A) and area (B) of gastric mucosal lesions in rats with indometha-
cin-induced ulceration.
***P<0.001 vs. water control; **P<0.01 vs. Indo; *P<0.05 vs. Indo
Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna 35
Danail Pavlov, Diana Ivanova, Miroslav Eftimov et al.
rum according to the method of Ellman (24). Activi-
ty of ALP in stomach homogenates was measured by
the standard kit of BioSystems S.A. (Spain). UA levels
in blood serum and homogenates were measured by
the standard kits of HUMAN liquicolor (Germany).
Statistical analyses
Data were analyzed by one-way analysis of
variance (ANOVA) followed by Dunnett’s multiple
comparison posttest. Each two independent groups
were compared also by Student’s t-test. A value of
P<0.05 was considered as statistically significant.
Data are expressed as mean ± SEM. GraphPad Prism
v 5.00 statistical software was used.
RESU LTS
Morphometric evaluation of gastric mucosal
damage
No mucosal lesions were detected in rats from
water control group. Indomethacin induced multiple
gastric mucosal lesions in the glandular part of the
stomach, most often 1-4 mm2 in size. The mean
ulcer number in the Indo-group was 11.58 (Fig.
1A), and the mean ulcer area was 22.39 mm2 (Fig.
1B). Pretreatment with 2/100 AICCL significantly
reduced the ulcer number by 87% (Fig. 1A), and the
ulcer area by 96% (Fig. 1B), respectively.
Biochemical
markers
Control
(Water)
Indomethacin
(Indo+Water)
1/100 AICCL
+ Indo
2/100 AICCL
+ Indo
4/100 AICCL
+ Indo
Stomach
МDА [μmol/L] 1.216± 0.10οοο3.285±0.32 **1.462±0.23 **1.369±0.16**1.660±0.11
UAmol/L] 225.37.9 οοο447.19.0 **210.38.6 **312 .39.5 **247.40.2
ALP [U/L] 19.17±1.53 οο47.28±5.68 **18.23±2.28 **18.31±2.53 **20.90±3.68
Blood
МDА [μmol/L] 0.507±0.02 0.541±0.03 0.483±0.02 0.530±0.02 0.441±0.02
UAmol/L] 105.4.50 94.13±5.32 89.10±4.22 83.91±4.82 83.17±3.60
SH-groupsmol/L] 225.9.08 220.7.47 230.9.55 232.14.5 4 224.12.86
Table 1. Results from biochemical analyses of stomach homogenates and blood serum from rats, treated in a model of
indomethacin-induced ulcerogenesis
Legend: οοοP<0.001 vs. Water Control; οοP<0.01 vs. Water Control; **P<0.01 vs. Indomethacin
Fig. 2. Microscopic appearance (X100) of a rat stomach following the application of water (A), water plus indomethacin
(B), and 2/100 AICCL plus indomethacin (C)
36 Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna
Effect of aqueous infusion from Cotinus coggygria leaves on indomethacin-induced gastric mucosal damage ...
Histopathological study
The microscopic appearance of the gastric
mucosa of the control rats was normal (Fig. 2A). The
experimental lesions evoked by indomethacin were
manifested by multiple erosions comprising about
2/3 of the mucosal layer thickness. The defects were
filled with hemorrhages and epithelial cell necroses
(Fig. 2B). In the rats pretreated with 2/100 AICCL
before the indomethacin administration, the gastric
erosions were more superficial and in some cases only
bleeding and focal desquamation of the epithelium
were found (Fig. 2C).
Biochemical assays
All results from biochemical measurements are
presented in Table 1. The gastric MDA levels of Indo-
group were increased by 270% versus the control. In
the groups pretreated with AICCL before the indo-
methacin administration, the concentration of MDA
decreased significantly (P<0.01) in comparison with
the Indo-group. The same tendency was observed in
UA and ALP levels in the stomach. No significant
changes were found in blood serum levels of MDA,
UA and SH-groups.
DISCUSSION
The indomethacin-induced gastric lesions
could be caused by several mechanisms. It is gener-
ally accepted that the ulcerogenic activity of NSAIDs
is related to their ability to inhibit endogenous PGs
synthesis due to the non-selective inhibition of COX
(8). Some authors (25) concluded that the complete
inhibition of COX leading to decrease in PGE2 con-
tent probably consumed a much longer time and did
not occur 6 h after a single dose. In regard to these
findings, we might suppose that in the current ex-
perimental model the inhibition of the PGs secre-
tion is not the main pathobiochemical mechanism of
ulcerogenesis.
There are data that ROS are involved in the de-
velopment of mucosal damage by NSAIDs (5), and
that they increase lipid peroxidation, an important
cause for cellular membranes damage. In our study,
the involvement of extensive lipid peroxidation in in-
domethacin-induced gastric mucosal damage was
evidenced by the accumulation of MDA in gastric
mucosa (Table 1). Similar are the results obtained
by some other authors (26), who studied the perox-
idation of lipids in the same experimental model. In
their study, the amount of MDA in the gastric muco-
sa was significantly increased 4 h after indomethacin
administration. Presented results demonstrated that
the AICCL reduced the oxidative stress and the re-
lated histomorphological signs of indomethacin-in-
duced gastric mucosal damage. One possible mech-
anism of this effect is the antioxidant potential of
AICCL (19), due to the polyphenols in the infusion,
predominantly high gallic acid content (11, 16, 17).
Another possible mechanism of the gastroprotective
effect of AICCL might be the anti-histamine activity
demonstrated for some f lavonoids (27).
ALP activity has been reported as a biochemi-
cal marker in bone, liver and gastrointestinal lumen
diseases (28). The release of this enzyme is related to
the mechanisms of tissue necrosis (29). The results
from biochemical analysis (Table 1) showed that in-
domethacin increased significantly the levels of ALP
in gastric tissue. The pretreatment with AICCL de-
creased significantly gastric ALP levels, suggesting
a strong protective effect of Cotinus coggygria infu-
sions that was confirmed histopathologically (Fig. 2).
The absence of gastric lesions in AICCL-pretreated
groups was also confirmed by the significantly low-
er gastric UA concentrations. Higher UA levels in
Indo-group could be associated with the degrada-
tion of nucleotides due to elevated necrosis caused by
indomethacin.
CONCLUSIONS
Our study demonstrated a strong protective
effect of aqueous infusion from Cotinus coggygria
leaves against indomethacin-induced gastric
ulceration. Based on results discussed above, we
suggest that the most probable mechanism of this
beneficial effect is the significant decrease of lipid
peroxidation, due to antioxidant properties of plant
investigated.
REFERENCES
1. Zapata-Colindres, J. C., S. Zepeda-Gomez, A. Mon-
tano-Loza, E. Vazquez-Ballesteros, J. Jesus-Villalo-
bos, F. Valdovinos-Andraca. The association of He-
licobacter pylori infection and non steroidal anti-
inflammatory drugs in peptic ulcer disease.-Cana-
dian -J. Gastroenterol., 20, 2006, 277-280.
2. Belaiche, J., A. Burette, M. De Vos, E. Lou-
is, M. Huybrechts, M. Deltenre. Study Group of
NSAID-GI Complications. Observational survey
Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna 37
Danail Pavlov, Diana Ivanova, Miroslav Eftimov et al.
of NSAID-related upper gastro-intestinal adverse
events in Belgium.-Acta Gastroenterol., 65, 2002,
65-73.
3. Rao, C. V., S. K. Ojha, K. Radhakrishnan, R. Go-
vindarajan, S. Rastogi, S. Mehrotra, P. Push-
pangadan. Antiulcer activity of Utleria salicifo-
lia rhizome extract.-J. Ethnopharmacol. 91, 2004,
243-249.
4. Repetto, M. G., S. F. Llesuy. 2002. Antioxidant
properties of natural compounds used in popular
medicine for gastric ulcers.-Braz. J. Med. Biol. Res.,
35, 2002, 523-534.
5. Pihan, G., C. Regillo, S. Szabo. Free radicals and
lipid peroxidation in ethanol or aspirin-induced
gastric mucosal injury.-Digestive Dis. Sci. 32, 1987,
1395-1401.
6. Arun, M., V. V. Asha. Gastroprotective effect of
Dodonaea viscosa on various experimental ulcer
models.-J.Ethnopharmacol., 118, 2008, 460-465.
7. Wallace J. L., G. W. Mc Knight. Characterization
of a simple animal model for nonsteroidal anti-in-
flammatory drug induced antral ulcer.-Canadian J.
Physiol. Pharmacol., 71, 1993, No 7, 447-452.
8. Wallace, J. L. Prostaglandins, NSAIDs, and gastric
mucosal protection: why doesn’t the stomach digest
itself ?-Physiol. Rev., 88, 2008, 1547-1565.
9. Freitas, F. F. B. P., H. B. Fernandes, C. A. Piauilino,
S. S. Pereira, K. I. M. Carvalho, M. H. Chaves, P.
M. G. Soares, L. M. C. V. Miura, J. R. S. A. Leite, R.
C. M. Oliveira, F. A. Oliveira. Gastroprotective ac-
tivity of Zanthoxylum rhoifolium Lam. in animal
models.-J. Ethnopharmacol., 137, 2011, 700-708.
10. Toma, W., J. S. Gracioso, F. D. P.Andrade, C. A. Hi-
ruma-Lima, W. Vilegas, A. R. M. S. Brito. Antiul-
cerogenic activity of four extracts from the barks
wood of Quassia amara L. (Simaroubaceae).-Biol.
Pharm. Bull., 25, 2002, 1151-1155.
11. Novakovic M., I. Vuckovic, P. Janackovic, M. So-
kolovic, A. Filipovic, V. Tesevic, S. Milosavljevic.
Chemical composition, antibacterial and antifun-
gal activity of the essential oils of Cotinus cog-
gygria from Serbia.-J Serbian Chem. Soc., 72, 20 07,
No 11, 1045-1051.
12. Vodenicharov, D., A. Petrov. Poisonous plants and
the poisoning with them. Sofia-Moscow, Pensoft
Publ., 2001 (in Bulgarian).
13. Landzhev, I. Encyclopedia of Medicinal Plants in
Bulgaria. Sofia, Trud Publ., 2010 (in Bulgarian).
14. Kültür, Ş. Medicinal plants used in Kirklareli
Province (Turkey).-J. Ethnopharmacol., 111, 20 07,
341-36 4.
15. Dulger, B., N. Hacioglu, S. Bilen. Antimicrobial ac-
tivity of Cotinus coggygria from Turkey.-Asian J.
Chem., 21, 2009, No 5, 4139-4140.
16. Oren-Shamir, M. Does anthocyanin degradation
play a significant role in determining pigment con-
centration in plants?-Plant Sci., 177, 2009, 310-316.
17. Westenburg, H., K. Lee, S. Lee, H. Fong, R. Bree-
men, J. Pezzuto, A. Kinghorn. Activity-guid-
ed isolation of antioxidative constituents of C.
coggygria.-J. Nat. Prod., 63, 20 00, 1696-1698.
18. Valianou, L., K. Stathopoulou, I. Karapanagiotis, P.
Magiatis, E. Pavlidou, A. Skaltsounis, Y. Chryssou-
lakis. Phytochemical analysis of young fustic (Co-
tinus coggygria) heartwood and identification of
isolated colourants in historical textiles.-Anal. Bio-
anal. Chem., 394, 2009, 871-882.
19. Ivanova, D., D. Gerova, T. Chervenkov, T. Yanko-
va. Polyphenols and antioxidant capacity of Bulgar-
ian medicinal plants.-J. Ethnopharmacol., 96, 2005,
145-150.
20. Katalinic, V., M. Milos, T. Kulisic, M. Jukic. Screen-
ing of 70 medicinal plant extracts for antioxidant
capacity and total phenols.-Food Chem., 94, 2006,
550-557.
21. Savikin, K., G. Zdunic, T. Jankovic, T. Stano-
jkovic, Z. Juranic, N. Menkovic. In vitro cytotox-
ic antioxidative activity of Cornus mas and Co-
tinus coggygria.-Nat. Prod. Res., 23, 2009, No 18,
1731-1739.
22. Niciforovic, N., V. Mihailovic, P. Maškovic, S. Solu-
jic, A. Stojkovic, I. Pavlovic, D. Muratspahic. Anti-
oxidant activity of selected plant species; potential
new sources of natural antioxidants.-Food Chem.
Tox i c o l ., 48, 2010, 3125-3130.
23. Porter, N., J. Norton, J. Ramdas. Cyclic peroxidase
and thiobarbituric assay.-Biochem. Biophys. Acta,
441, 1976, 596-599.
24. Ellman, G. L. Tissue sulfhydryl groups.-Arch. Bio-
chem. Biophys., 82, 1959, 70-77.
25. Saad, Q. H. M., N. M. Kassim, G. M. Top, N. M. Is-
mail. Tocotrienol-rich fraction and its effects on
parameters affecting gastric mucosal integrity af-
ter a single exposure to indomethacin.-Pakistan J.
Nutr., 1, 2002, 89-92.
38 Scripta Scientifica Medica, vol. 45, suppl. 3, 2013, pp. 32-38
Copyright © Medical University of Varna
Effect of aqueous infusion from Cotinus coggygria leaves on indomethacin-induced gastric mucosal damage ...
26. Tanaka, J., Y. Yuda. Lipid peroxidation in gastric
mucosal lesions induced by indomethacin in rat.-
Biol. Pharm. Bull., 19, 1996, 716-720.
27. Parmar, N. S. The gastric anti-ulcer activity of nar-
ingenin, specific histidine decarbohylase inhibitor.-
Int J. Tissue React., 4, 1983, 415-420.
28. Varley, H., A. H. Gowenlock, M. Bell. Practical
Clinical Biochemistry. Delhi, CBS Publ. Distrib.,
1991.
29. Ferguson, W. W., J. R. Starling, S. L. Wangensteen.
Role of lysosomal enzyme release in the pathogen-
esis of stress-induced gastric ulceration.-Surgeons
Forum, 23, 1972, 380-382.
Acknowledgments
The financial support from the European Social
Fund within the Project BG051PO001-3.3.06-0028
Enhancing of the research potential and opportu-
nities for career development in the fields of med-
icine, healthcare and biotechnology” is greatly
acknowledged.
... The intragastric administration of 10 ml 2% infusion reduced the number and area of ulcerations, as well as their depth and severity. This effect was accompanied by the decrease of malondialdehyde and uric acid levels, reducing as well the activity of alkaline phosphatase (Pavlov et al., 2013a). ...
Article
Full-text available
The smoketree ( Cotinus coggygria ) is a historically known medicinal plant from Southeast Europe. Its ethnomedicinal use in skin and mucosal lesions is commonly accepted across countries. Other utilizations reported locally include fever reduction, cardiac diseases, hypertension, urinary diseases, cough, asthma, hemorrhoids, diabetes, numbness of arm, liver disease, and cancer. Departing from the smoketree’s traditional uses, this review summarizes investigations on the phytochemistry and bioactivity of the plant. In vitro and in vivo experiments supporting wound-healing, anti-inflammatory, antibacterial, cytotoxic, antioxidative, hepatoprotective, and antidiabetic effects are presented. Metabolites from smoketree that are responsible for the main pharmacological effects of smoketree are pointed out. Furthermore, the review performs a comparison between C. coggygria and the lacquer tree ( Toxicodendron vernicifluum ). The latter is a comprehensively studied species used in Asian phytotherapy, with whom the European smoketree shares a consistent pool of secondary metabolites. The comparative approach aims to open new perspectives in the research of smoketree and anticipates an optimized use of C. coggygria in therapy. It also points out the relevance of a chemosystematic approach in the field of medicinal plants research.
... The leaves have been used as an internal infusion of 5% due to their antiseptic, constipation, blood-cutting, and antipyretic effects (Baytop, 1999(Baytop, , 2007Davis, 1967;Kultur and Bitis, 2007). Previous studies revealed that different parts of the plant possess various pharmacological activities such as antimicrobial (Tunc et al., 2013), antioxidant (Niciforovic et al., 2010), anti-inflammatory (Marcetic et al., 2013), hepatoprotective (Matic et al., 2013), antiulcerogenic (Pavlov et al., 2013), immunostimulant (Bilen et al., 2013), and wound healing (Aksoy et al., 2016). Various bioactive secondary metabolites isolated from different parts of CC were reported as flavonoids (fisetin, fustin, quercetin, apigenin, myricetin, taxifolin), aurones (sulfuretin, disulfuretin, sulfurein), chalcones (butein, isoliquiritigenin), anthocyanins (delphinidin-3-galactoside, cyanidin-3-galactoside, petunidin-3-glucoside), catechins, and other phenolics, e.g. ...
Article
Cotinus coggygria Scop. (Anacardiaceae, syn: Rhus cotinus L.) is known as “boyacı sumağı, sarı boya, duman ağacı” in Turkish and “smoke tree” in English. It is commonly grown in Southern Europe and Anatolia. The leaves have been used due to its antiseptic, hemostatic, antipyretic, and wound healing effects as a 5% infusion in traditional medicine. It has also been reported to be used against skin disorders in Russia. Based on this information, the ethanol extracts prepared from the pedicels and leaves of C. coggygria were investigated for their elastase, collagenase, and tyrosinase inhibitory effects, which are enzymes related to anti-aging, using ELISA microtiter assays. Based on our results, the ethanol extracts prepared from the leaves and pedicels of C. coggygria had low elastase (28.16% ± 2.91 and 25.76% ± 1.71, respectively), moderate collagenase (47.78% ± 4.90 and 46.51% ± 3.15, respectively), and tyrosinase (57.94% ± 0.67 and 46.20% ± 0.92, respectively) inhibition at final concentration (666 µg/mL). The ethanol extract prepared from the pedicels of C. coggygria was subjected to bioactivity-guided fractionation, which led to isolation of methyl gallate, astragalin, isoquercetin, and hyperoside from the active fractions. In addition to the enzyme assays, in order to understand the inhibition mechanisms of the compounds inside the ligand-binding domains, the interactions were simulated and the key amino acids contributing to the hydrogen bonds and non-polar interactions with the ligands were reported.
... Several parts like shoots, flowers, leaves and stem of C. coggygria contain biologically active constituents which are mainly polyphenols, flavonoids and tannins (Antal et al., 2010;Matic et al., 2016). Some scientific results showed that C. coggygria possess some significant pharmacological activities such as an antioxidant (Savikin et al., 2009;Marcetic et al., 2013), antimicrobial (Marcetic et al., 2013;Fraternale and Ricci, 2014), anti-inflammatory (Marcetic et al., 2013), anticancer (Noh et al., 2015), antigenotoxic, hepatoprotective (Matic et al., 2013), antidiabetic (Cha et al., 2009), gastroprotective (Pavlov et al., 2013a(Pavlov et al., , 2013b, wound healing (Aksoy et al., 2016) and antiviral (Jing et al., 2012) activities. ...
... Agbafor et al. (2014) have demonstrated that aqueous and ethanol extracts of fresh leaves of Zapoteca portoricensis (Jacq) HM Hern andez (Fabaceae) significantly (p < 0.05) increased GSH levels, while they decreased MDA levels significantly (p < 0.05) in the treated groups relative to the control. Pavlov et al. (2013) described the effect of aqueous infusion from C. coggygria leaves on indomethacin-induced gastric mucosal damage in Wistar rats and its possible effect on the gastric oxidative status. The infusion of C. coggygria leaves reduced the indomethacin-induced elevation of gastric malondialdehyde (MDA). ...
Article
Context: Cotinus coggygria Scop. (Anacardiaceae) leaves that were used as wound healing in traditional Balkan and Anatolian folk medicine, could be potentially effective in treating diabetic wounds. Objective: This study investigates biochemical and histological effects of ethanol extract of C. coggygria (CCE) on excision wound model in diabetic rats. Materials and methods: This study was conducted on diabetic Wistar albino rats, which were injected by a single dose (50 mg/kg i.p.) streptozotocin. Afterward an excision wound model was created in all animals; diabetic control rats were applied topically simple ointment and diabetic treatment rats were applied topically 5% (w/w) ointment with CC, once a day during the experimental period. Malondialdehyde, glutathione and hydroxyproline levels in wound tissues were investigated at the end of 3rd, 7th, and 14th days. Histopathological examination was also performed. Results: Hydroxyproline content was significantly increased in the CCE treated group versus control after the 3rd and 7th days (15.33 versus 11.83; 19.67 versus 15.67 mg/g, p < 0.05; respectively). A statistically significant elevation in glutathione at the end of 3rd, 7th, and 14th days (5.13 versus 1.58, p < 0.05; 4.72 versus 1.88, p < 0.05; 3.83 versus 1.88 μmol/g, p < 0.05, respectively) and a statistically significant decrease in malondialdehyde level at the end of 7th day (4.49 versus 1.48 nmol/g, p < 0.05) were determined in the treated group versus control group. These results were also supported by histological analyses. Discussion and conclusion: These findings indicate that CCE accelerated the cutaneous wound healing process in diabetic wounds, in confirmation of its traditional use.
Article
Full-text available
The Anacardiaceae Lindl. family comprises of many species which are used in nutrition and in traditional folk medicine for the treatment of several human diseases. Cotinus coggygria Scop. commonly known as “smoke tree”, is an commercial ornamental plant with high medicinal usages, belongs to the family Anacardiaceae. The present review provides a comprehensive report of empirical investigations on important pharmacological activities and phytochemical screening of essential oils and extracts. Relevant information was collected from scientific journals, books, and reports via library and electronic search using Medline, Pubmed, Google Scholar, ScienceDirect, Web of Science, and Scopus. The plant has been extensively investigated in a broad range of studies to provide scientific evidence for folklore claims or to find new therapeutic uses. Numerous activities namely antioxidative, antibacterial, antifungal, antiviral, anticancer, antigenotoxic, hepatoprotective and anti-inflammatory have been demonstrated for all parts of these plants by in vivo and in vitro studies. Essential oils and extracts showed various pharmacological and biological properties which make them an effective remedy for various kinds of illnesses. Considering data from the literature, it could be demonstrated that C. coggygria possesses diverse bioactive properties and immense utilization in medicine, health care, cosmetics and as health supplements.
Article
Full-text available
Ethanolic extract obtained from Cotinus coggyrw Scop. was mvestigated for its antimicrobial activity against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Micrococcus 4teus, Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, Pseudomonas aeuginosa, Pseudomonas putida, Salmonella typhimurium, Salmonella typhi, Hanseniaspora guilliermondii, Rhodotorula rubra, Kluyveromyces fragilis, Kluyveromyces marxianus, Debaryomyces hansenii, Candida utilis and Candida albicans by disc diffusion method. The extracts had strong antimicrobial activity against bacteria, but weak activity was observed against the yeast cultures used in this study.
Article
Full-text available
The effect of treatment with a tocotrienol-rich fraction (TTRF) on acute single exposure to indomethacin was investigated. Forty-eight male rats of the Sprague-Dawley (200-250g) species were randomly assigned into two groups (N and T). The N group was fed with a commercially prepared normal rat diet and the T group was fed with an identical diet enriched with TTRF 150mg/kg diet. Each group was further subdivided into two subgroups that was either challenged (NI and TI) or not challenged with indomethacin (NX and TX). After eight weeks of treatment the NX and TX rats were killed and the stomachs isolated whereas the NI and TI rats were challenged with a single dose of indomethacin (80mg/kg body weight) orally and after six hours the rats were killed. Measurements for malondialdehyde (MDA), glutathione content, PGE<sub>2</sub>, gastric acid concentration and gastric adherent mucous (GAM) were done. Gastric PGE<sub>2</sub> content and acid concentration were comparable in the NI and TI groups compared to its corresponding group that was not challenged. The gastric MDA content and GAM concentration were increased in the NI and TI compared to its corresponding group that was not challenged. This indicated that indomethacin increased MDA and treatment with TTRF could not inhibit the rise of MDA whereas TTRF has no effect on GAM concentration. The glutathione ratio was however, only elevated in the TI group compared to the TX, which indicates that in acute mucosal injury by indomethacin, TTRF is able to preserve the ratio of the endogenous antioxidant. We conclude that TTRF has beneficial effects on gastric parameters.
Article
In contrast to the detailed knowledge available on anthocyanin synthesis, very little is known about its stability and catabolism in plants. Here we review evidence supporting in planta turnover and degradation of anthocyanins. Transient anthocyanin accumulation and disappearance during plant development or changes in environmental conditions suggest that anthocyanin degradation is controlled and induced when beneficial to the plant. Several enzymes have been isolated that degrade anthocyanins in postharvest fruit that may be candidates for in vivo degradation. Three enzyme groups that control degradation rates of anthocyanins in fruit extracts and juices are polyphenol oxidases, peroxidases and β-glucosidases. Evidence supporting the involvement of peroxidases and β-glucosidases in in vivo anthocyanin degradation in Brunfelsia flowers is presented. Understanding the in vivo anthocyanin degradation process has potential for enabling increased pigmentation and prevention of color degradation in crops.
Article
The total phenolic content and related total antioxidant capacity of 70 medicinal plant infusions was analyzed. Infusions were prepared in common way in which teas are prepared for human consumption. The total phenolics were measured by Folin–Ciocalteau assay. The total antioxidant capacity was estimated by Ferric Reducing/Antioxidant Power (FRAP) assay. To make practical comparison of relative antioxidant potential of phenolics extracted from selected medicinal plants, the phenol antioxidant coefficient (PAC) was calculated for each infusion. The total phenolic content of medicinal plant infusions ranges from 9 to 2218 mg/L. The FRAP range from 0.06 to 25 mM/L. There was significant linear correlation between total phenolic content and FRAP. According to their antioxidant capacity, 70 medicinal plant extracts can be divided in five groups: (a) very low FRAP (<1 mM/L) n = 9; (b) low FRAP (1–5 mM/L), n = 37; (c) good FRAP (5–10 mM/L), n = 15; (d) high FRAP (10–20 mM/L), n = 8; and (e) very high FRAP (>20 mM/L), n = 1 medicinal plant extract. The PAC was ranging from 1.1 to 3.9 (average 2.4). The best results were obtained for Melissae folium infusions: high phenolic concentration, very high FRAP (>20 mM/L) and PAC > 3. The effect of infusion time and infusion temperature on the phenolic content, FRAP, and free radical scavenging ability was tested. DPPH radical scavenging ability of Melissae folium phenolics was similar to (+)-catechin but not as good as for quercetin. Compared to Trolox and vitamin C, Melissae folium phenolics were more efficient free ABTS radical scavengers. The results indicate that Melissae folium infusions could be an important dietary source of phenolic compounds with high antioxidant capacity comparable with red wine or beverages like tea.
Article
The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly increased the mucus production, however, the gastric secretion parameters (volume, [H(+)], pH) did not show any alteration. Our results indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The release of the nitric oxide, the opening of the K(ATP) channels, the participation of the non-protein sulfhydril groups (NP-SH), catalase and the increase of mucous secretion seem to be involved in the gastroprotection activity of the EEZR. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.
Article
The aim of this study was to examine six plants from Serbia for their potential antioxidant activity. Therefore, six antioxidant activity assays were carried out, including: total antioxidant capacity, DPPH free-radical scavenging, the inhibitory activity toward lipid peroxidation, Fe(3+)- reducing power, Fe(2+)- chelating ability and hydroxyl radical scavenging activity. Total phenolic and flavonoid contents were also determined for each alcoholic extract. Cotinus coggygria extract contained the highest amount of total phenols (413mg GAE /g dry extract), while the highest proportion of flavonoids was found in the Echium vulgare methanol extract (105 mg RU/g). Cotinus coggygria and Halacsya sendtneri alcoholic extracts showed the highest total antioxidant capacity (313 and 231 mg AA/g dry extract), as well as DPPH free-radical scavenging (IC(50)=9 and 99 μg/ml), inhibitory activity toward lipid peroxidation (IC(50)=3 and 17 μg/ml) and reducing power. Whereas, the greatest hydroxyl radical scavenging activity, as well as ferrous ion chelating ability showed Echium vulgare, Echium rubrum and Halacsya sendtneri.
Article
Young fustic (Cotinus coggygria Scop.; Anacardiaceae) has been used as a dyestuff since antiquity. Phytochemical investigation of the methanol extract of the heartwood has led to the isolation and structure elucidation by nuclear magnetic resonance and mass spectrometry (MS) of 3',4',6-trihydroxyaurone (sulfuretin) and 3',4',7-trihydroxyflavonol (fisetin) as well as 3',4',7-trihydroxyflavanol (fustin), 3',4',5,7-tetrahydroxyflavonol (quercetin), 3',4',5,7-tetrahydroxyflavanol (taxifolin), 4',7-dihydroxyflavanol, 3',4',7-trihydroxyflavanone (butin), 4',7-dihydroxyflavanone (liquiritigenin), trans-2',3,4,4'-tetrahydroxychalcone (butein), 4',5,7-trihydroxyflavanone and trans-2',4,4'-trihydroxychalcone (isoliquiritigenin). The isolated compounds were used as reference materials for the development of a high-performance liquid chromatography-diode array detector-MS method, which was then applied to analyse (1) fresh silk samples dyed with young fustic, (2) dyed silk subjected to artificially accelerated light ageing and (3) historical silk micro-samples, extracted from ecclesiastical post-Byzantine garments (fifteenth to eighteenth century), which belong to monasteries of Mount Athos. Sulfuretin and fisetin, which are usually used as markers for the identification of the yellow dye and, for the first time, some of the aforementioned flavonoid components of young fustic were identified in the historical extracts. Furthermore, preliminary experiments suggested that although the amounts of the dye components decrease with light ageing, the relative ratio of fisetin and sulfuretin, after a first step of ageing, seems to be almost unaffected by such degradation processes raised by light. The effect of the latter on the morphology of the dyed silk fibres is briefly investigated by scanning electron microscopy.