ArticlePDF Available

Ameliorative and Safety Characteristics of Argemone mexicana in Indomethacin-Induced Peptic Ulcer

Authors:
  • Federal University of Health Sciences, Otukpo, Benue State

Abstract and Figures

Argemone mexicana (A. mexicana) is a plant traditionally used in Nigeria and some African countries to treat peptic ulcer disease. In this study, the ameliorative effect of ethanolic leaf extract of A. mexicana in indomethacin-induced peptic ulcer and its safety were investigated. Phytochemical screening was performed using standard procedures. Ulcer was induced in rats by single oral administration dose of 25 mg/kg body weight (b.w.) indomethacin followed by treatment with 100, 200, and 400 mg/kg b.w. ethanolic leaf extract of A. mexicana. Ulcer-related indices such as gastric pH, acidity, pepsin, and Na+/K+-ATPase activities, glycoprotein, and mucus contents were determined. The status of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, reductase, and transferase) in the stomach and duodenum of the rats was also evaluated. Safety of the extract in the liver and kidney was investigated by chromosomal aberration. The results showed that alkaloids, flavonoids, phenolics, and saponins present in the extract as phytochemical constituents. The extract at 200 mg/kg b.w. significantly (p < 0.05) attenuated the gastric pH, volume, and acidity of the stomach. It also significantly (p < 0.05) enhanced the glycoprotein and mucus contents in the mucosal membrane of rats. The status of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, reductase, and transferase) in both tissues was also significantly improved. Study on safety evaluation revealed that the extract is relatively safe at the most active dose investigated. The study concluded that A. mexicana could serve as an alternative therapy for the development of a safer antiulcer drug.
Content may be subject to copyright.
Ameliorative and Safety Characteristics of Argemone
mexicana in Indomethacin-Induced Peptic Ulcer
Oluwafemi Ayodeji Idowu1
Rotimi Olusanya Arise2
1Department of Biochemistry, University of Ilorin, Ilorin, Kwara State,
Nigeria
2Department of Biochemistry, University of Ilorin, Ilorin Kwara State,
P.M.B 1515, Ilorin, Nigeria
Pharmaceut Fronts 2020;2:e133e142.
Address for correspondence Oluwafemi Ayodeji Idowu, PhD,
Department of Biochemistr y, College of Natural and Applied Sciences,
Oduduwa University, P.M.B 5533, Ile-Ife, Osun State, Nigeria
(e-mail: id4phemy@gmail.com;
idowu.oluwafemi@oduduwauniersity.edu.ng).
Introduction
Peptic ulcer disease (PUD) is a disease of the stomach and/or
duodenum. It is one of the gastrointestinal tract diseases
affecting a large number of the populace globally in their
everyday life.1PUD manifests as an injury in the mucosal
lining of the stomach or the duodenum. Ulcer that develops
in the duodenum of the small intestine is called duodenal
ulcer, while that which develops in the stomach is referred to
as gastric or stomach ulcer. The former largely occurs in
younger individuals a nd the latter in older age. Th e likelihood
of developing PUD is approximately 10% for males and 4% for
females.2,3 The disease usually results from an imbalance
between gastric aggressive factors (acid, pepsin, reactive
oxygen species) and defensive mucosal factors (prostaglan-
dins, bicarbonate, mucin, antioxidant enzymes) induced by
factors such as Helicobacter pylori infection, indiscriminate
consumption of nonsteroidal anti-inammatory drugs,
Keywords
Argemone mexicana
indomethacin
peptic ulcer
antioxidant
chromosomal
aberration
Abstract Argemone mexicana (A. mexicana) is a plant traditionally used in Nigeria and some
African countries to treat peptic ulcer disease. In this study, the ameliorative effect of
ethanolic leaf extract of A. mexicana in indomethacin-induced peptic ulcer and its safety
were investigated. Phytochemical screening was performed using standard proce-
dures. Ulcer was induced in rats by single oral administration dose of 25 mg/kg body
weight (b.w.) indomethacin followed by treatment with 100, 200, and 400 mg/kg b.w.
ethanolic leaf extract of A. mexicana. Ulcer-related indices such as gastric pH, acidity,
pepsin, and Na
þ
/K
þ
-ATPase activities, glycoprotein, and mucus contents were deter-
mined. The status of antioxidant enzymes (superoxide dismutase, catalase, glutathione
peroxidase, reductase, and transferase) in the stomach and duodenum of the rats was
also evaluated. Safety of the extract in the liver and kidney was investigated by
chromosomal aberration. The results showed that alkaloids, avonoids, phenolics, and
saponins present in the extract as phytochemical constituents. The extract at 200
mg/kg b.w. signicantly (p<0.05) attenuated the gastric pH, volume, and acidity of
the stomach. It also signicantly (p<0.05) enhanced the glycoprotein and mucus
contents in the mucosal membrane of rats. The status of antioxidant enzymes
(superoxide dismutase, catalase, glutathione peroxidase, reductase, and transferase)
in both tissues was also signicantly improved. Study on safety evaluation revealed that
the extract is relatively safe at the most active dose investigated. The study concluded
that A. mexicana could serve as an alternative therapy for the development of a safer
antiulcer drug.
DOI https://doi.org/
10.1055/s-0040-1722216.
ISSN 2628-5088.
© 2020. The Author(s).
This is an open access article published by Thieme under the terms of the
Creative Commons Attribution License, permitting unrestricted use,
distribution, and reproduction so long as the original work is properly cited.
(https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart,
Germany
THIEME
Original Article e133
Published online: 2020-12-24
smoking, diet, alcohol, and both physiological and physio-
logical stress.4The prevalence of PUD differs around the
globe. While the prevalence has reduced in developed coun-
tries, the disease is still a burden in underdeveloped and
developing countries like Africa.5Poor hygiene capable of
promoting the invasion of H. pylori into the gastric lumen of
the gastroin testinal tract, low socio economic status, poverty,
lack of awareness about the disease as well as ineffective
synthetic drugs in treating PUD among other reasons may
have contributed to its burden. Antacids (e.g., aluminum and
potassium hydroxides), histamine receptor blockers (e.g.,
famotidine and cimetidine), proton pump inhibitors (omep-
razole, pantoprazole, and lansoprazole), prostaglandin ana-
logues (misoprostol), and antibiotics (clarithromycin,
metronidazole, amoxicillin) are among the class of synthetic
drugs currently available for treating PUD; however, they are
reported to produce adverse effects such as headache, male
hormone disturbances,6pneumonia, osteoporosis, vitamin
B
12
malabsorption,7diarrhea, abdominal pain, nausea, vom-
iting, and constipation.8This therefore necessitated the
search for better modalities in treating PUD. Studies on
medicinal value of plants which are of natural origin have
shown that these plants not only afford gastroprotection but
are also capable of accelerating ulcer healing,9as various
plants with different compositions are used either as decoc-
tion, concoction, or as food additives to combat PUD in folk
medicine by many developing countries. In Nigeria, a West
African country with a population of above 180 million,
Argemone mexicana is one plant traditionally used to treat
PUD in this region. Argemone mexicana is part of the plant
family Papaveraceae, generally called prickly poppy in En-
glish, Mexican poppy in Mexico, Ghamoya in India, and
locally called Mafowokan-mo-mi10 or Egun-Arugbo,11
Akede,12 and Kwarko13 in Southern, Eastern, and North-
ern parts of Nigeria, respectively. Therefore the antiulcer
activity of ethanolic leaf extract of A. mexicana used as a folk
medicinal herb in Nigeria to treat PUD was studied for the
purpose of developing an effective and safer antiulcer drug.
Materials and Methods
Collection of Plant Materials and Authentication
Fresh leaves of A. mexicana were plucked in June 2015 from a
tree in Shaki town, Oyo State, South-West, Nigeria. Leaves
were identied and authenticated at the Department of
Botany, University of Ilorin, Ilorin, Kwara State, Nigeria. A
voucher number UIH0011171 was deposited in the
herbarium.
Chemicals
5-Methoxy-2-([(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]
sulnyl)-1H-benzimidazole (omeprazole) and 1-(4-chloroben-
zoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid (indo-
methacin) were purchased from Pauco Pharmaceutical
(Anambra, Nigeria). Glutathione (GSH) peroxidase (GSH-px),
GSH reductase (GSH-Red), GSH-S-transferase (GST), and
superoxide dismutase (SOD) assay kits were procured
from Randox Laboratories (Antrim, United Kingdom). All
other chemicals commercially purchased were of standard
grade.
Extraction of Plant Materials and Preparation of Test
Dose
The fresh leaves were rinsed with distilled water, air-dried
for 14 days at a temperature of 24 2°C, and were made to a
powder form with a mechanical blender (Mazeda Mill, MT
4100, Japan). An amount of 500 g of the powder was macer-
ated with absolute (99%) ethanol ( 1.2 L) for 7 2 hours using a
cold extraction method. The extract obtained was ltered
with Whatman No. 1 lter paper and concentrated in a rotar y
evaporator (RE-300B model, product of Henan Touch Science,
China). The test doses of 100, 200, and 400 mg/kg body
weight (b.w.) were adopted in this study, according to the
oral acute toxicity test performed by Das et al14 on ethanolic
extract of A. mexicana which was in accordance with Orga-
nisation for Economic Co-operation and Development guide-
lines.15 The extract at these doses was dissolved in distilled
water and administered to the experimental rats.
Phytochemical Screening
Standard methods were adopted to screen the ethanolic leaf
extract of A. mexicana for secondary metabolites.1618
Experimental Animals
A total of 36 Wistar rats of both sexes (male and female) aged
approximately 4 months weighing 162 1.4 5 g were pro-
cured from the Animal Holding Unit, Biochemistry Depart-
ment University of Ilorin, Ilorin, Kwara State, Nigeria. They
were housed in a cage under standard conditions (tempera-
ture: 22 3°C, light per iods of 12 hour light and 12 hour
darkness, and relative humidity of 45%), fed with commercial
feed (Topfeed Mills Company, Ilorin), and given tap water ad
libitum. Full committee approval guiding experimental ani-
malsuse with an ethical number UERC/ASN/2015/120 was
issued by the University of Ilorin Ethical Committee.
Experimental Procedure
The rats were randomly grouped and treated asfollows: group I:
control (un-ulcerated) rats administered distilled water only;
group II: ulcerated rats administered distilled water only; group
III: ulcerated rats administered 20mg/kg b.w. omeprazole
(reference drug); groups IVVI: ulcerated rats administered
100, 200, and 400 mg/kg b.w. of ethanolic leaf extract of A.
mexicana, respectively. Rats were fasted for 12 hours before the
commencement of the experiment with access to water but
later withdrawn 3 hours to the experiment. Rats were made
ulcerated by 25 mg/kg b.w. indomethacin administered at a
single dose orally and ulcer was conrmed on the third day by
serum pepsinogen estimation. This was followed by the admin-
istration of omeprazole and the extract and lasted for 7 days.
Preparation of Tissue Homogenates
Rats were anesthetized under diethyl ether and the stomach
ligated at both openings of the sphincter (lower esophageal
and pyloric sphincters) and the gastric juice was collected for
biochemical analysis. The stomach and duodenum were
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arisee134
excised and separately homogenized in ice-cold sucrose solu-
tion (0.25 M), and spun at 1,000 gfor 10minutes with a
centrifuge (Model SM8 B, Surgrifriend Medicals, Essex,
England). The supernatant was carefully removedwith Pasteur
pipettes into sample bottles and stored until further analysis.
Macroscopic Examination for Ulcer Index Determination
The procedure highlighted in Gregory et al19 was employed to
estimate the ulcer index (UI). The gastric juice in the stomach
was rst collected by ligation and the stomach was rinsed with
normal saline. It was stretched and pinned on a board and
examined macroscopically for gastric lesion using hand lens
(20). The UI was calculated in mm
2
using the expression:
Ulcer index (UI) ¼Length (mm) Breadth (mm) of lesion.
Determination of Ulcer Indices
The gastric juice was spun at 850 gfor 10 minutes and the
content poured into a graduated measuring cylinder; this
was taken as the volume of the gastric juice.9The pH of the
gastric juice was measured by placing a digital pH meter into
the supernatant. The gastric acidity was determined accord-
ing to a reported method.20 Briey 0.5 mL of gastric content
was titrated against 0.01 N sodium hydroxide, w ith the use of
phenolphthalein as the indicator. The gastric acidity was
expressed in milli-equivalent per liter (mEq/L).
Pepsin Activity in Gastric Juice
The procedure highlighted in Hirohashi et al21 was adopted to
determine pepsin activity in the gast ric juice. The pepsin activity
was calculated from standard protein curve extrapolation.
Determination of Glycoprotein Concentration
Glycoprotein concentration in the gastric juice was
expressed as a ratio of total carbohydrate (Tc) to total protein
(Tp) as described by Nair.22
Total Carbohydrates
The Tc content in the stomach juicewas estimated according to
Nair.22 Briey, 1 mL of 5% phenol was added to a separate test
tube containing 0.15 mL of the juice and the blank (distilled
water),respectively, and then shaken vigorously. An amount of
5 mL of 96% H
2
SO
4
was later introduced and mixed slowly.
After 10 minutes, the test tubes were again shaken thoroughly
and placed in a water bath at 30°C for 20 minutes. The absor-
bance was read at 482 nm. A standard curve with different
concentrations of glucose solution was prepared and the Tc in
the gastric juice was expressed in micrograms per milliliter.
Total Protein
The protein content was measured according to a reported
study by Lowry et al.23 Briey 1 mL of stomach juice and 9 mL
of 95% alcohol were mixed rigorously, and the mixture was
spun at 3,000 gfor 15 minutes to get a precipitate. Then to
0.1 mL of the alcohol precipitate, 1 mL of 0.1N sodium
hydroxide and 0.9 mL of distilled water were added. An
amount of 0.4 mL was taken out of the mixture into another
test tube and 4 mmof Biuret reagent was addedand allowed to
stand for 10 minutes. Then 0.4 mL of phenol reagent was later
introduced andallowed to stand for 10minutes to ensure color
development. Absorbance was measured at 610 nm against a
blank made with distilled water. The protein content was
extrapolated from a standard protein curve prepared with
bovine albumin and expressed in micrograms per milliliter.
The glycoprotein concentration was expressed as:
Determination of H
þ
/K
þ
-ATPase Activity
The activity of H
þ
/K
þ
-ATPase in the gastric mucosa was
expressed as nmol of Pi liberated/min/mg protein, which
was assayed accordingto the procedure of Reyes-Chilpa et al.24
Adherent Gastric Mucus Content
The adherent gastric mucus content in the stomach was
determined following a reported study.25 Glandular
segments of the stomach were excised and weighed. Each
segment was placed into 10 mL 0.1% w/v Alcian blue solution
(in 10 mL of 0.16 M sucrose solution, buffered with 0.05 M
sodium acetate, pH 5). Following immersionfor 2 hours, excess
dye was removed by successively rinsing twice with 10mL of
0.25 M sucrose, rst for 15 minutes then later for 45 minutes.
The dye complexed with stomach wall mucus was extracted
with 10 mL of 0.5 M MgCl
2
with intermittent shaking for
1 minute at 30-minute intervals for 2 hours. Then 4 mL of
the Alcian blue extract was added with an equal volume of
diethyl ether and shaken vigorously. The emulsion obtained
was spun at 725 gfor 10 minutes and the absorbance of an
aqueous layer formed was read at 580 nm. Values were com-
pared with the Alcian blue concentration standard curve.
Determination of Glutathione Concentration and Lipid
Peroxidation
Reduced GSH concentration and lipid peroxidation were de-
termined in the stomach and duodenum of rats by employing
the procedures of Ellman26 and Buege and Aust,27respectively.
Determination of Antioxidant Enzyme Status and
Chromosomal Aberration
SOD, catalase (CT), GSH-Red, GSH-Px, and GST activities in
the stomach and duodenum were determined following
methods reported in various studies.2832 The method de-
scribed by Krause33 was adopted for chromosomal aberra-
tion analysis in the kidney and liver of rats.
Data Analysis
Data represen t the mean of six r eplicates standard error of
mean. Data were analyzed statistically with GraphPad Prism
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arise e135
8.0 using one-way analysis of variance. Differences between
group means were considered signicant at p<0.05.
Results
Phytochemical Screening
The preliminary phytochemical screening revealed that
phenolics, avonoids, alkaloids, and saponins were present
in the ethanolic leaf extract of A. mexicana. Alkaloids was the
most predo minant (14.67 0.02 g/100 g) followed by avo-
noids (10.77 0.03 g/100 g), phenolic s (4.84 0.02), and
saponins (4.3 0 0.01 g/100 g) (Table 1). There was a signif-
icant upsurge (p<0.05) in the UI of ulcerated rats when
compared with the control (nonu lcerated). Administration of
100, 200, and 400 mg/kg b.w. of the crude extract caused a
reduction of UI in rats, with a better reduction of the ulcer
lesion in the group treated with 200 mg/kg b.w. when
compared with the untreated ulcerated group. This reduc-
tion in UI of rats treated with 200 mg/kg b.w. was not
signicantly different when compared with the reference
drug (Table 2).
The gastric volume, gastric acidity, H
þ
/K
þ
-ATPase and pep-
sin activities increased signicantly (p<0.05) while the pH
reduced signicantly in ulcerated rats compared with the
control. However, 200 mg/kg b.w. of the extract was most
effective in reducing the gastric acidity andgastric acid volume
of the rats. Also the extract at 200mg/kg b.w. signicantly
(p<0.05) increased the gastric pH of rats to pH value similar to
the omeprazole-treated group (Table 2). Similarly, it was
observed that 200 mg/kg b.w. extract of A. mexicana adminis-
tered to rats signicantly (p<0.05) attenuated the activities of
H
þ
/K
þ
-ATPase, also known as proton pump (Table 3), and
pepsin (Fig. 1) close to the values of the control and omepra-
zole-treatedgroups. Tc concentration and glycoprotein content
(Tc:Tp) signicantly (p<0.05) reduced in the stomach juice of
ulcerated rats that received no medical intervention in com-
parison with the control (Table 4). A similar reduction was
also noticed in the adherent mucus content of ulcerated rats
when compared with the control (Fig. 2); however, the
ethanolic extractof A. mexicana leaves at the investigateddoses
signicantly (p<0.05) enhanced the glycoprotein and mucus
contents upon administration in the ulcerated group with
200 mg/kg b.w., showing better efcacy in comparison with
the omeprazole-treated group, with no signicant difference
observed.
Table 1 Concentration of secondary metabolites of ethanolic
leaf extract of A. mexicana
Secondary metabolites Concentration (g/100 g)
Flavonoids 10.77 0.03
Phenolic 4.84 0.02
Saponins 4.30 0.01
Alkaloids 14.67 0.02
Note: Values a re % mea n of t hree det erminations SEM.
Table 2 Effect of administration of ethanolic leaf extract of A. mexicana on gastric juice secretory parameters of indomethacin-
induced ulcerated rats
Treatment groups Gastric juice secretory parameters
Ulcer Index
(mm
2
)
Gastric volume
(mL)
pH Gastric acidity
(mEq/L)
Control (distilled water) 1.86 0.08
a
4.25 0.10
a
3.36 0.03
a
Ulcerated rats 6.45 0.09
a
5.45 0.25
b
2.43 0.01
b
8.44 0.39
b
Ulcerated rats þ20 mg/kg b.w. omeprazole 2.79 0.04
b
1.99 0.07
a
3.77 0.19
c
3.49 0.05
a
Ulcerated rats þ100 mg/kg b.w. extract 4.20 0.14
c
3.28 0.14
c
3.58 0.12
c
5.39 0.14
c
Ulcerated rats þ200 mg/kg b.w. extract 2.81 0.12
b
1.90 0.15
a
3.85 0.27
c
3.33 0.15
a
Ulcerated rats þ400 mg/kg b.w. extract 3.07 0.07
d
2.77 0.22
d
3.49 0.08
c
4.39 0.20
c
Abbreviations: b.w., body weight; SEM, standard error of mean.
Note: Data are mean of six determinations SEM. Values having different alphabets down the columnfor each parameter show signicant difference
(p<0.05).
Table 3 Effect of administration of ethanolic leaf extract of A.
mexicana on gastric H
þ
/K
þ
-ATPase activity of indomethacin-
induced ulcerated rats
Tre atm ent gr oup s H
þ
/K
þ
-ATPase activity
(nmol/min/mg protein)
Control (distilled water) 4.60 0.19
a
Ulcerated rats 9.61 0.24
b
Ulcerated rats þ20 mg/kg b.w.
omeprazole
4.84 0.11
a
Ulcerated rats þ100 mg/kg b.w.
extract
5.24 0.42
c
Ulcerated rats þ200 mg/kg b.w.
extract
4.79 0.14
a
Ulcerated rats þ400 mg/kg b.w.
extract
7.90 0.62
d
Abbreviations: b.w., body weight; SEM, standard error of mean.
Note: Data are mean of six determinations SEM. Values having
different alphabets down the column for each parameter show signi-
cant difference (p<0.05).
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arisee136
Antioxidant Enzyme Status
The antioxidant enzyme status data in the stomach and
duodenum of ulcerated rats are presented in Tables 5
and 6and Figs. 3 and 4.SOD(Fig. 3)andCT(Fig. 4)
activities signicantly (p<0.05) decreased in the stomach
and duodenum of ulcerated rats compared with the control.
In the same vein, a signicant decrease (p<0.05) in activity
of thiol antioxidant enzymes (GSH-Red, GSH-px, and GST)
was observed in both tissues of untreated rats when com-
pared with the control (Tables 5 and 6). It was noticed that
200 mg/kg b.w. of the extract effectively ameliorated the
enzyme (CT, SOD, GSH-Red, GSH-px, and GST) activity which
was initially depleted in both tissues of the ulcerated
untreated rats and this was comparable with the reference
drug (omeprazole).
Glutathione and Malondialdehyde Concentrations
The concentration of GSH decreased signicantly (p<0.05),
whereas the concentration of the lipid peroxidation product
(malondialdehyde [MDA]) increased signicantly in the
stomach and duodenum of ulcerated rats that received no
medical attention when compared with the distilled water
group (control). The level of reduced GSH improved signi-
cantly (p<0.05) in both tissues of ulcerated rats treated with
the doses of the extract (Table 5), while the MDA concen-
tration signicantly (p<0.05) reduced after treatment
with the different doses of the extract (Fig. 5) however;
200 mg/kg b.w. of the extract was most effective in amelio-
rating the alterations in GSH and MDA concentrations.
Macroscopic View
The macroscopic view of the gastric mucosa of ulcerated rats
administered ethanolic leaf extract of A. mexicana is depicted
Fig. 6. Total ulcerationevident with severe injury was seen to
have appeared in the gastric pits of ulcerated rats without
medical attention (Fig. 6b), but a mild amelioration of the
gastric pit was observed in the gastric mucosa of rats that
Fig. 1 Effect of administration of ethanolic leaf extract of A. mexicana
on gastric pepsin activity of indomethacin-induced ulcerated rats.
Values are mean of six determinations SEM. Bars with different
alphabets are signicantly different (p<0.05) from each other. SEM,
standard error of mean.
Table 4 Effect of administration of ethanolic leaf extract of A. mexicana on glycoprotein concentration in gastric juice of
indomethacin-induced ulcerated rats
Tre atm ent gr oup s Tot al CH O ( μg/mL) Total protein (μg/mL) Total CHO:total protein
(glycoprotein) (μg/mL)
Control (distilled water) 66.33 0.61
a
31.89 0.10
a
2.08 0.02
a
Ulcerated rats 35.62 0.10
b
41.70 0.26
b
0.85 0.01
b
Ulcerated rats þ20 mg/kg b.w. omeprazole 65.04 0.21
a
32.63 0.23
a
2.01 0.02
a
Ulcerated rats þ100 mg/kg b.w. extract 58.05 0.21
c
31.10 0.01
a
1.87 0.01
c
Ulcerated rats þ200 mg/kg b.w. extract 66.93 0.01
a
32.84 0.01
a
2.04 0.01
a
Ulcerated rats þ400 mg/kg b.w. extract 62.81 0.01
d
30.32 0.14
a
2.07 0.01
a
Abbreviations: b.w., body weight; SEM, standard error of mean.
Note: Data are mean of six determinations SEM. Values having different alphabets down the columnfor each parameter show signicant difference
(p<0.05).
Fig. 2 Effect of administration of ethanolic leaf extract of A. mexicana
on adherent mucus content of indomethacin-induced ulcerated rats.
Values are mean of six determinations SEM. Bars with different
alphabets are signicantly different (p<0.05) from each other. SEM,
standard error of mean.
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arise e137
received 100mg/kg b.w. of the extract as medical intervention
(Fig. 6d) when compared with the untreated group (Fig. 6b),
whereas 200 mg/kg b.w. of the extract (Fig. 6e) effectively
ameliorated the ulcerated gastric mucosa of rats in a manner
similar to that observed for the reference-drug-treated group
(Fig. 6c>) when compared with the untreated group (Fig.
6b). The gastric mucosa of rats that received 400 mg/kg b.w. of
the extract as medical intervention also showed a promising
ulcer lesion amelioration (Fig. 6f).
Macroscopic View
Tables 7 and 8depict the rate of chromosomal aberration in
the liver and kidney of ulcerated rats respectively following
treatment of rats with the extract at the three doses investi-
gated. A signicant upsurge (p<0.05) in the frequencies of
chromosomal aberration was observed in the liver and kidney
of rats that received the highest dose (400 mg/kg b.w.) of the
extract as medical intervention when compared with the
control. This increase in frequencies of chromosomal aberra-
tion observed in this group was not signicantly (p>0.05)
different when compared with the ulcerated group that re-
ceivedno medical attention. Conversely,rats administered 100
and 200 mg/kg b.w. ethanolic leaf extract of A. mexicana
showed no signicant alteration or change (p>0.05) in the
frequencies of chromosomal aberration both in the liver
(Table 7) and kidney (Table 8) of rats when compared
with the control.
Discussion
Alkaloids, avonoids, saponins, and phenolics, which are the
phytoconstituents identied in the ethanolic leaf extract of
A. mexicana, have also been reported by Perumal et al.34
These secondary metabolites have demonstrated antiulcero-
genic activities by different mechanisms and are well docu-
mented in the literature.3538
The ulcer model used in this study has widely been
employed.39,40 Indomethacin used toinduce ulcer in this study
is a therapeutic agent whose involvement in ulcer formation is
by inducing uncontrolled gastric acid production and dimin-
ishing the gastric mucosa defense system.41 It also acts by
inhibiting cyclooxygenase II enzyme which subsequently sup-
presses prostaglandin (a key metabolite that protect the
stomach from the corrosive effect of gastric acid) synthesis
Table 5 Effect of administration of ethanolic leaf extract of A. mexicana on reduced glutathione concentration and glutathione
peroxidase activity in the stomach and duodenum of indomethacin-induced ulcerated rats
Treatment groups Reduced glutathione
(nmol/mg protein)
Glutathione peroxidase
(nmol/mg protein)
Stomach Duodenum Stomach Duodenum
Control (distilled water) 8.86 0.14
a
8.20 0.34
a
0.45 0.03
a
0.37 0.03
a
Ulcerated rats 2.47 0.19
b
1.46 0.12
b
0.20 0.01
b
0.14 0.01
b
Ulcerated rats þ20 mg/kg b.w. omeprazole 6.98 0.15
c
7.61 0.10
c
0.40 0.02
a
0.40 0.03
a
Ulcerated rats þ100 mg/kg b.w. extract 4.10 0.26
d
3.69 0.13
d
0.18 0.01
b
0.27 0.01
c
Ulcerated rats þ200 mg/kg b.w. extract 8.40 0.32
a
7.51 0.12
c
0.44 0.03
a
0.41 0.03
a
Ulcerated rats þ400 mg/kg b.w. extract 5.34 0.13
e
6.80 0.04
e
0.34 0.02
c
0.30 0.02
c
Abbreviations: b.w., body weight; SEM, standard error of mean.
Note: Data are mean of six determinations SEM. Values having different alphabets down the columnfor each parameter show signicant difference
(p<0.05).
Table 6 Effect of administration of ethanolic leaf extract of A. mexicana on glutathione reductase and glutathione-S-transferase
activities in the stomach and duodenum of indomethacin-induced ulcerated rats
Treatment groups Glutathione reductase
(nmol/mg protein)
Glutathione-s-transferase
(nmol/mg protein)
Stomach Duodenum Stomach Duodenum
Control (distilled water) 28.42 0.11
a
9.49 0.05
a
14.24 0.18
a
4.49 0.02
a
Ulcerated rats 13.76 0.28
b
4.63 0.22
b
7.45 0.25
b
2.32 0.02
b
Ulcerated rats þ20 mg/kg b.w. omeprazole 26.60 0.39
c
9.30 0.05
a
13.58 0.04
c
4.20 0.22
a
Ulcerated rats þ100 mg/kg b.w. extract 21.33 0.71
d
6.22 0.18
c
9.56 0.09
d
3.52 0.16
c
Ulcerated rats þ200 mg/kg b.w. extract 27.98 0.23
c
9.33 0.08
a
14.20 0.15
a
4.32 0.20
a
Ulcerated rats þ400 mg/kg b.w. extract 25.49 0.18
e
8.49 0.06
d
11.28 0.22
e
3.69 0.14
c
Abbreviations: b.w., body weight; SEM, standard error of mean.
Note: Data are mean of six determinations SEM. Values having different alphabets down the columnfor each parameter show signicant difference
(p<0.05).
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arisee138
and epithelial cell proliferation.42 In addition, indomethacin
has been reported to show involvement in the production of
free radicals that alter the permeability of the gastric mucus
and eventually cause its depletion in the mucosa.43,44
Gastric acidity, volume, pH, and UI are indices of ulceration.
Alteration in the concentration of theseindices (i.e., an increase
in gastric acidity, volume, UI, and low pH) usually indicates
ulceration in the gastrointestinal mucosal membrane. The
alterations observed in the concentration of these indices in
the indomethacin-induced ulcerated group that received no
medical intervention may be due tothe fact that indomethacin
caused an imbalance between gastric defensive factors and the
aggressive factors by inhibiting cyclooxygenase enzyme. Cor-
relations between gastric acidity, gastric volume, pH, and UI in
the ulcerative state have been established.45 Also UI, gastric
volume, and pH are reective of gastric acidity. The higher the
gastric acidity, thehigher are the gastric volume and UI (degree
of ulceration), and the lower the gastric pH.
Mahmoud et al46 established that gastric ulcer is usually
accompanied by an elevated level of gastric acidity, volume,
and low pH, and this is evident in this study (Table 2). The
signicant increase in UI, gastric volume, acidity, and low pH
of ulcerated rats after administering indomethacin is in
consonance with the ndings of various studies4749 where
indomethacin caused alterations in the level of these indices.
The signicant decrease in the concentration of glycopro-
tein and depletion in mucus content seen in ulcerated rats
may also be attributed to the imbalance between the defen-
sive factors and aggressive factors which resulted from
indomethacin administration. Gastric H
þ
/K
þ
-ATPase is an
enzyme or proton pump found in the apical parietal cell
membrane mainly responsible for acidication of the stom-
ach content. The increase in the activities of the pump and
pepsin may indicate that i ndomethacin caused the activation
of the proton pump enzyme leading to excessive gastric acid
output and subsequently increasing pepsin activity since
acidication is required for activation of pepsin in the
stomach.50 The ability of the extract particularly at 200
Fig. 5 Effect of administration of ethanolic leaf extract of A. mexicana
on malondialdehyde concentration in the stomach and duodenum of
indomethacin-induced ulcerated rats. Values are mean of six deter-
minations SEM. Bars with different alphabets are signicantly dif-
ferent (p<0.05) from each other. SEM, standard error of mean.
Fig. 3 Effect of administration of ethanolic leaf extract of A. mexicana
on superoxide dismutase activity in the stomach and duodenum of
indomethacin-induced ulcerated rats. Values are mean of six deter-
minations SEM. Bars with different alphabets are signicantly dif-
ferent (p<0.05) from each other. SEM, standard error of mean.
Fig. 4 Effect of administration of ethanolic leaf extract of A. mexicana
on catalase activity in the stomach and duodenum of indomethacin-
induced ulcerated rats. Values are mean of six determinations SEM.
Bars with different alphabets are signicantly dif ferent (p<0.05) from
each other. SEM, standard error of mean.
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arise e139
mg/kg b.w. to effectively attenuate the ulcer indices and
enhance the mucus content is an evidence that the extract
restored normalcy or equilibrium between the aggressive
factors and defensive factors probably facilitated by the
phytoconstituents acting either individually or synergisti-
cally. The extract was also able to lower the activities of the
proton pump and pepsin thus s uggesting its inhibitory role in
the signaling pathway that leads to the activation of the
proton pump and the release of pepsin from the acidication
process in the stomach.
Alkaloids are known to inhibit lesions in the ulcerative
state by altering acid secretion via increasing luminal gastric
discharge of basal bicarbonate and pH. Also avonoids and
saponins have been reported to stimulate mucus production
and counteract the deteriorating effects of reactive oxidants
in the gastrointestinal tract.51,52
Oxidative stress is known to be involved in the pathogen-
esis of ulcer,53,54 but antioxidant enzymes serve as the rst
line of defense against oxidative stress in the gastric mucosal
membrane, this necessitates the need in this study to check
the antioxidant status. The decrease in antioxidant enzyme
(SOD, CT, GSH-Red, GSH-px, and GST) activity in the stomach
and duodenum of rats is an indication of imbalance between
pro-oxidants and antioxidant status caused by the adminis-
tration of indomethacin since there is a correlation between
oxidative stress and ulceration caused by indomethacin,54 or
may indicate increased oxidative stress in the tissues of the
ulcerated rats. The amelioration of the depleted antioxidant
enzymes following treatment of rats with the extract, which
was particularly more pronounced in rats treated with 200
mg/kg b.w., may have been facilitated by avonoids as an
antioxidant booster. Therefore, avonoids among other com-
ponents may be responsible for the antiulcerogenic activity
exhibited by the ethanolic extract of A. mexicana.
The microscopic view of the gastric mucosal membrane of
rats treated with 200 mg/kg b.w. of the ext ract which showed
completely ameliorated injury or damage of the gastric
mucosal membrane could indicate wound healing activity
of the extract. This was consistent with Dash and Murthys
earlier suggestions of the wound healing activity of A.
mexicana.55
The concentration of MDA, a product of lipid peroxida-
tion, which increased signicantly in ulcerated rats, is also an
indicator of increased oxidative stress resulting from pro-
duction of MDA via lipid peroxidation in the gastric mucosal
membrane. It has been reported that free radicals over-
whelm antioxidant enzyme activity and activate lipid dete-
rioration, a process in the toxicity mechanism of
indomethacin.56 From this study, ethanolic leaf extract of
A. mexicana at a dose of 200 mg/kg b.w. was more efcacious
Table 7 Effect of administration of ethanolic leaf extract of A. mexicana on chromosomal aberration in the liver of indomethacin-
induced ulcerated rats
Tre atm ent gr oup s TNMA MC A MI % CA
Control (distilled water) 143.00 11.00
a
2.00 1.00
a
27.80 1.00
a
1.85 0.47
a
Ulcerated rats 143.00 12.00
a
36.55 1.50
b
29.20 0.70
a
42.10 1.20
b
Ulcerated rats þ20 mg/kg b.w. omeprazole 139.00 10.00
a
2.10 2.00
a
26.90 2.20
a
2.20 0.00
a
Ulcerated rats þ100 mg/kg b.w. extract 142.00 9.00
a
3.00 1.00
a
28.00 1.30
a
2.40 0.20
a
Ulcerated rats þ200 mg/kg b.w. extract 138.00 10.00
a
2.20 1.50
a
27.70 1.20
a
1.90 1.00
a
Ulcerated rats þ400 mg/kg b.w. extract 139.00 12.00
a
32.50 1.70
b
29.10 0.90
a
39.57 2.50
b
Abbreviations: b.w., body weight; % CA, percentage of chromosomal aberration; MCA, mitotic chromosomal aberration; MI, mitotic index; TNMA,
total number of mitotic.
Note: Data are mean of three determinations SEM. Values having different alphabets down the column for each parameter show signicant
difference (p<0.05).
Table 8 Effect of administration of ethanolic leaf extract of A. mexicana on chromosomal aberration in the kidney ofindomethacin-
induced ulcerated rats
Tre atm ent gr oup s TN MA MC A MI % CA
Control (distilled water) 156.00 2.00
a
2.00 1.20
a
17.20 0.20
a
2.24 1.20
a
Ulcerated rats 149.00 4.00
a
34.45 2.20
b
15.17 0.60
a
41.26 0.40
b
Ulcerated rats þ20 mg/kg b.w. omeprazole 151.00 2.50
a
3.00 2.00
a
16.58 0.35
a
3.02 0.68
a
Ulcerated rats þ100 mg/kg b.w. extract 153.00 2.50
a
3.00 2.00
a
16.60 0.20
a
3.00 0.72
a
Ulcerated rats þ200 mg/kg b.w. extract 146.50 4.00
a
2.00 1.20
a
15.58 1.54
a
2.20 0.98
a
Ulcerated rats þ400 mg/kg b.w. extract 157.00 2.00
a
32.20 2.50
b
17.10 0.40
a
39.55 4.50
b
Abbreviations: b.w., body weight; % CA, percentage of chromosomal aberration; MCA, mitotic chromosomal aberration; MI, mitotic index; TNMA,
total number of mitotic.
Note: Data are mean of three determinations SEM. Values having different alphabets down the column for each parameter show signicant
difference (p<0.05).
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arisee140
against indomethacin-induced ulceration in rats than the
other two doses (100 and 400 mg/kg b.w.), investigated by
attenuating the gastric acidity, gastric volume, pepsin, and
H
þ
/K
þ
-ATPase activities, improved the gastric mucus and
glycoprotein concentrations, and ameliorated the depleted
antioxidant enzyme activities (SOD, CT, GR, GPx, GST) of
ulcerated rats to values relatively close to those of the
omeprazole group used as the reference antiulcer drug.
This efcacy exhibited by the extract at 200 mg/kg b.w.
may be attributed to the interaction effects of the chemical
constituents present in the extract which could be synergis-
tic, additive, or antagonistic.
Chromosomal aberration assays are used to detect agents
(i.e., clastogens) that cause chromosome damage, which may
be chromatid, chromosome breaks, and complex chromo-
some changes in the form of exchanges, rings, and dicentrics.
The induction of chromosomal aberrations in cells may play
an essential role in the development of certain tumor and it is
believed to be a relevant biomarker for cancer risk in
humans.57 An increase in frequencies of mitotic chromo-
some breakage may indicate that a chemica l has the potential
to induce numerical a berrations.57 In this study, there was no
increase in the frequencies of chromosomal aberration in the
kidney and liver of rats following the administration of 100
and 200 mg/kg b.w. of the extract, this means that the extract
may be considered safe at these doses. On the contrary, the
increase observed in the frequencies of chromosomal aber-
ration in the liver and kidney of rats that received 400 mg/kg
b.w. of the extract could indicate that at a much higher dose
of 4 00 mg/kg b.w., the extract may not be safe for consump-
tion. This observation may be in connection with the high
amount of alkaloids present in the extract. Dalvi58 and El-
Gamal59 have reported the DNA damage and cytotoxicity
associated with alkaloids found in different extracts of A.
mexicana. Also, Manjamalai et al60 in their study reported
the deoxyribonucleic acid damage of blood cells and bone
marrow in mice administered extract of A. mexicana.In
addition, sanguinarine, an alkaloid isolated from A. mexicana
oil, has been reported to cause in vivo damage to the DNA in
mice as the rate of chromosomal aberration; micronuclei
formation and development of comets were seen to be
increased.61
Conclusion
The study concluded that A. mexicana exhibits antiulcer
activity in rats and is considered safe at a low dose. Therefore,
it may be employed as an alternative source for development
of new and safer antiulcer drugs. Further work is ongoing to
isolate the bioact ive principle(s) responsible for the a ntiulcer
activity of the plant.
Funding
This research did not receive any funding.
Conict of Interest
The authors declare that they have no conicts of interest.
References
1Garg S, Pal K, Sharma A, Garg K. Ethn opharmacological evaluation
of antiulcer activity of Caralluma attenuta. IJPLS 2014;5(06):
35853589
2Kumar V, Abbas A, Fausto N, Aster J. Robbins and Cotran Patho-
logic Basis of Disease. The gastrointestinal tract, 8th ed. Amster-
dam: Elsevier Publisher; 2009;14:798847
3Lozano R, Naghavi M, Foreman K, et al. Global and regional
mortality from 235 causes of death for 20 age groups in 1990
and 2010: a systematic analysis for the Global Burden of Disease
Study 2010. Lancet 2012;380(9859):20952128
4Søreide K, Thorsen K, Harrison EM, et al. Perforated peptic ulcer.
Lancet 2015;386(10000):12881298
5Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter
pylori infection: systematic review and meta-analysis. Gastroen-
terology 2017;153(02):420429
6Das AK, Bigoniya P, Verma NK, Rana AC. Gastroprotective effect of
Achyranthes aspera Linn. leaf on rats. Asian Pac J Trop Med 2012;5
(03):197201
7Maes ML, Fixen DR, Linnebur SA. Adverse effects of proton-pump
inhibitor use in older adults: a review of the evidence. Ther Adv
Drug Saf 2017;8(09):273297
8Mössner J. The indications, applicat ions, and risks of proton pump
inhibitors. Dtsch Arztebl Int 2016;113(2728):477483
9Magaji RA, Okasha MAM,Abubakar MS, Fatihu MY. Anti-ulcerogen-
ic and andti-secretory activity of the n-butanol portion of Syzygium
aromaticum in rat. Niger J Pharm Sci 2007;6(02):119126
10 Sonibare MA, Moody JO, Adesanya EO. Use of medicinal plants for
the treatment of measles in Nigeria. J Ethnopharmacol 2009;122
(02):268272
11 Kayode J, Kayode GM. Ethnomedicinal survey of botanicals used in
treating sexually transmitted diseases in Ekiti State, Nigeria.
Ethnobotanical Leaets 2008;12:4455
12 Aiyeloja AA, Bello OA. Ethnobotanical potentials of some herbs in
Nigeria. A case study of Enugu State. Educ Res Rev 2006;1(01):
1622
13 Bhat RB, Etejere EO, Oladipo VT. Ethnobotanical studies from
central Nigeria. Econ Bot 1990;44(03):382390
14 Das PK, Seth R, Panda P, Pani SM. Hepatoprotective activity of plant
Argemone mexicana (linn).against carbon tetrachloride (CCl
4
)in-
duced hepatoxicity in rats. Int J Pharm Res Dev 2009;8(02):120
15 Organization for Economic Co-operation and Development Acute
oral toxicity-Acute oral toxic class method, guideline 423,
adopted December 17, 2001:114
16 Harbone JB. Phytochemical Methods: A guide to modern techni-
ques of plant analysis. 2nd ed. London: Chapman & Hall; 1984;
49:414
17 Sofowora A. Medicinal plants and traditional medicines in Africa.
2nd ed. Ibadan: Spectrum; 1993:134156
18 Trease GE, Evans WC. A textbook of pharmacognosy. 13th ed.
Philadelphia: Bailleire-Tindall; 1989:824832
19 Gregory M, Vithalrao KP, Franklin G, Kalaichelavan V. Anti-ulcer
(Ulcer-preventive) activity of Ficus arnottiana Miq. (Moraceae) leaf
methanolic extract. Am J Pharmacol Toxicol 2009;4(03):8993
20 Parmar NS, Hennings G. The gastric antisecretory activity of 3-
methoxy-5,7,3,4tetrahydroavin (ME) - a specic histidine decar-
boxylase inhibitor in rats. Agents Actions 1984;15(34):143145
21 Hirohashi M, Takasuna K, Kasi Y, Usui C, Tamura K, Kojima H.
General pharmacological prole of the new anti-ulcer drug 3-[[[2-
(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]-amino-N -meth-
ylbenzamide. Arzneimittelforschung 1993;43(05):569577
22 Nair BR. Investigations on the Neuron of South Indian Scorpion
Hetrometrus Scaber [PhD dissertation]. Trivendrum (Kerala):
University of Kerala; 1976
23 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measure-
ment with the Folin phenol reagent. J Biol Chem 1951;193(01):
265275
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arise e141
24 Reyes-Chilpa R, Baggio CH, Alavez-Solano D, et al. Inhibition of
gastric H
þ
,K
þ
-ATPase activity by avonoids, coumarins and xan-
thones isolated from Mexican me dicinal plants. J Ethnopharmacol
2006;105(12):167172
25 Corne SJ, Morrissey SM, Woods RJ. Proceedings: a method for the
quantitative estimation of gastric barrier mucus. J Physiol 1974;
242(02):116P117P
26 Ellman GL. Tissu e sulfhydryl groups. Arch Biochem Bi ophys 1959;
82(01):7077
27 Buege JA, Aust SD. Microsomal lipid peroxidation. Methods
Enzymol 1978;52:302310
28 Mistra HP, Fridovich I. The role of superoxide anion in the auto-
oxidation of epinephrine and simple assay for superoxide dis-
mutase. J Biochem 1972;247(10):31703175
29 Beers RF Jr, Sizer IW. A spec trophotometric method for measuring
the breakdown of hydrogen peroxide by catalase. J Biol Chem
1952;195(01):133140
30 Goldberg DM, Spooner R, Bergmeyen HV. Assay of glutathione
reductase. In: Bergmeyen HV , ed. Methods of Enzymatic Analysis.
3rd ed. Florida: Verlog Chemie; 1983:258265
31 Paglia DE, Valentine WN. Studies on the quantitative and qualita-
tive characterization of erythrocyte glutathione peroxidase. J Lab
Clin Med 1967;70(01):158169
32 Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The
rst enzymatic step in mercapturic acid formation. J Biol Chem
1974;249(22):71307139
33 Krause WJ. The art of examining and interprinting histologic
preparations. A laboratory manual and study guide. USA: Univer-
sal Publishers; 2004;89:910
34 Perumal P, Sekar V, Rajesh V, Gandhimethi S, Sampathkumar R,
Shuja-Nazimudin KH. In vitro antioxidant activity of A. mexicana
roots. Int J Pharm Tech Res 2010;2(02):14771482
35 Wan YJ. Effect of anisodamine on gastric ulcer induced by
restraint water-immersion in rats. Exp Clin Gastroenterol 1993;
3:154158
36 Cook NC, Samman S. Flavonoids-chemistry, metabolism, cardiopro-
tective effects and dietary sources. J NutrBiochem 1996;7(02):6674
37 Galati EM, Monforte MT, Tripodo MM, dAquino A, Mondello MR.
Antiulcer activity of Opuntia cus indica (L.) Mill. (Cactaceae):
ultrastructural study. J Ethnopharmacol 2001;76(01):19
38 Fan TY, Feng QQ, Jia CR, Fan Q, Li CA, Bai XL. Protective effect of
Weikang decoction and partialingredients on modelrat with gastric
mucosa ulcer. World J Gastroenterol 2005;11(08):12041209
39 Balogun ME, Oji JO, Besong EE, Ajah AA, Michael EM. Anti-ulcer
activity of aqueous leaf extract of Nauclea latifolia (Rubiaceae) on
indomethacin-induced gast ric ulcer in rats. Afr J Biotechnol 2013;
12(32):50805086
40 Saheed S, Sulyman AO, Garuba T, Sunmonu TO, Abdulrahaman
AA. Combined administration of Spondias mombin and Fic us
exasperata leaf extracts stall indomethacin-mediated gastric
mucosal onslaught in rats. Afr J Tradit Complement Altern Med
2015;12(01):4551
41 Lichtenberger LM. The hydrophobic barrier properties of gastro-
intestinal mucus. Annu Rev Physiol 1995;57(01):565583
42 Wada K, Kamisaki Y, Nakamoto K, Kishimoto Y, Ashida K, Itoh T.
Effect of plaunotol on gastric injury induced by ischaemia-reper-
fusion in rats. J Pharm Pharmacol 1997;49(09):903907
43 Cheung DY, Kim JI, Park SH, Kim JK. Proanthocyanidin from grape
seed extracts protects indomethacin-induced small intestinal
mucosal injury. Gastroenterol Res Pract 2014;2014(01):618068
44 Yin H, Pan X, Song Z, Wang S, Yang L, Sun G. Protective effect of
wheat peptides against i ndomethacin-induced oxidative stress in
IEC-6 cells. Nutrients 2014;6(02):564574
45 Selvamathy SMKN, Geetha A, Sara nya P. Gastroprotective effect of
Swertia chirayita- a study with ulcer induced rats. Pharmacolo-
gyonline 2010;1:332355
46 Mahmoud AH, Farrag EM, Fayed DB. Antiulcer activity Citharex-
ylum quadrangular JACQ leaves (ethanolic ext ract) on experimen-
tally induced gastric ulceration rats. World J Pharm Pharm Sci
2016;5(02):145159
47 Beck PL, Xavier R, Lu N, et al. Mechanisms of NSAID-induced
gastrointestinal injury dened using mutant mice. Gastroenter-
ology 2000;119(03):699705
48 Adhikary B, Yadav SK, Roy K, Bandyopadhyay SK, Chattopadhyay S.
Black tea and theaavins assist healing of indomethacin-induced
gastric ulceration in mice by antioxidative action. Evid Based
Complement Alternat Med 2011;2011:546560
49 Muhammed AVK, Thamotharan G, Sengottuvelu S, Haja-Sherief S,
Sivakumar T. Evaluation of antiulcer activity of Ficus pumila L. leaf
extract in albino rats . Glob J Res Med Plants Indig Med 2012;1(08):
340351
50 Berg JM, Tymoczko JL, Stryer L, Gatto GJ. Biochemistry. 7th ed.
Basingstoke: W.H. Freeman; 2012;32:234247
51 Lewis DA, Hanson PJ. Anti-ulcer drugs of plant origin. Prog Med
Chem 1991;28:201231
52 Pandian RS, Anuradha CV, Viswanathan P. Gastroprotective effect
of fenugreek seeds (Trigonella foenum graecum) on experimental
gastric ulcer in rats. J Ethnopharmacol 2002;81(03):393397
53 Salim AS. The relationship between Helicobacter pylori and
oxygen-derived free radicals in the mechanism of duodenal
ulceration. Intern Med 1993;32(05):359364
54 Dash GK, Murthy PN. Evaluation of Argemone mexicana Linn.
Leaves for wound healing activity. J Nat Prod Plant Resour
2011;1(01):4656
55 MaityP,BinduS,DeyS,etal.Indomethacin,anon-steroidal
anti-inammatory drug, develops gastropathy by inducing
reactive oxygen species-mediated mitochondrial pathology
and associated apoptosis in gastric mucosa: a novel role of
mitochondrial aconitase oxidation. J Biol Chem 2009;284(05):
30583068
56 Halici M, Odabasoglu F, Suleyman H, Cakir A, Aslan A, Bayir Y.
Effects of water extract of Usnea longissima on antioxidant
enzyme activity and mucosal damage caused by indomethacin
in rats. Phytomedicine 2005;12(09):656662
57 Bonassi S, Hagmar L, Strömberg U, et al;European Study Group on
Cytogenetic Biomarkers and Health. Chromosomal aberrations in
lymphocytes predict human cancer indepen dently of exposure to
carcinogens. Cancer Res 2000;60(06):16191625
58 Dalvi RR. Sanguinarine: its potential as a liver toxic alkaloid
present in the seeds of Argemone mexicana. Experientia 1985;
41(01):7778
59 El-Gamal AA. Phytochemistry, Pharmacology and Toxicology of
Argemone mexicana L. [PhD Thesis]. Khartoum: University of
Khartoum; 1995
60 Manjamalai A, Sardar-Sathyajith-Singh R, Guruvayoorappan C,
Berlin-Grace VM. Analysis of phytochemical constituents and
anti-microbial activity of some medicinal plants in Tamil Naidu,
India. Global J Biotech Biochem 2010;5(02):120128
61 Anartha S, Chaudhari S. Neuropharmacological study of Argemon
mexicana Linn. J Appl Pharm Sci 2011;1(04):121126
Pharmaceutical Fronts Vol. 2 No. 3/2020 © 2020. The Author(s).
Argemone mexicana, Indomethacin, Peptic Ulcer, Antioxidants, Chromosomal Aberration Idowu, Arisee142
Article
Full-text available
Proton-pump inhibitors (PPIs) are a widely prescribed class of medications used to treat acid-related disorders and use has significantly increased over the last few decades. PPIs are often inappropriately prescribed and since they have been on the market, a number of post-marketing studies have been published demonstrating associations between longer duration of PPI therapy and a number of adverse effects that are a concern in older adults. The objective of this review is to discuss the existing literature of potential adverse effects with long-term PPI use in older adults and to summarize the implications in clinical practice. A PubMed search was conducted to identify studies evaluating the potential long-term adverse effects of PPI therapy in older adults, and publications were selected based on relevant criteria. PPIs have been associated with an increased risk of a number of adverse effects including osteoporotic-related fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin B12 deficiency, kidney disease, and dementia, demonstrated by a number of case-control, cohort studies, and meta-analyses. Older adults should be periodically evaluated for the need for continued use of PPI therapy given the number of potential adverse effects associated with long-term use.
Article
Full-text available
Background & aims: The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to evaluate changes in the global prevalence of H pylori infection. Methods: We performed a systematic search of the MEDLINE and EMBASE databases for studies of the prevalence of H pylori infection published from January 1, 1970 through January 1, 2016. We analyzed data based on United Nations geoscheme regions and individual countries. We used a random effects model to calculate pooled prevalence estimates with 95% CIs, weighted by study size. We extrapolated 2015 prevalence estimates to obtain the estimated number of individuals with H pylori infection. Results: Among 14,006 reports screened, we identified 263 full-text articles on the prevalence of H pylori infection; 184 were included in the final analysis, comprising data from 62 countries. Africa had the highest pooled prevalence of H pylori infection (70.1%; 95% CI 62.6-77.7), whereas Oceania had the lowest prevalence (24.4%; 95% CI 18.5-30.4). Among individual countries, the prevalence of H pylori infection varied from as low as 18.9% in Switzerland (95% CI 13.1-24.7) to 87.7% in Nigeria (95% CI 83.1-92.2). Based on regional prevalence estimates, there were approximately 4.4 billion individuals with H pylori infection worldwide in 2015. Conclusions: In a systematic review and meta-analysis to assess the prevalence of H pylori infection worldwide, we observed large amounts of variation among regions-more than half the world's population is infected. These data can be used in development of customized strategies for the global eradication.