HERBAL TREATMENT ALTERNATIVES FOR PEPTIC ULCER DISEASE

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DOI: 10.22270/jddt.v6i3.1210
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Abstract
From the ancient times, plants have afforded themselves for the treatment of wide variety of diseases. This herbal basket of the nature has been explored in this review to highlight some of its potential herbs for the cure of Peptic Ulcer Disease (PUD). The motto behind the review on PUD was due to the wide spreading nature of peptic ulcer in all class of population, which may be due to the rapidly changing food habits and stress, causing an imbalance between the gastric offensive and defensive factors. Plants are getting more reliability in current days, because they lack significant side effects and are safe. On the other hand, the synthetic antiulcer drugs are constantly reported to possess critical adverse effects like arrhythmia, gynaecomastia, impotency, arthralgia etc. The relapse rate of ulcer has also been reported to be high in such molecules. A few plants have been reviewed to bring their mechanism of anti-ulcerogenic properties to the front, to promote more research on them. Some phytoconstituents have been discussed along with the research conducted by researchers in different ulcer models for better understanding the activity of the plants. The review may hopefully put some light on this particular section of research oriented towards searching new herbal moieties to treat the PUD. Keywords: Ulcerogenic, H. pylori, Defensive factors, ethnomedicinal, phytoconstituents, gastroprotective.
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Tripathy et al Journal of Drug Delivery & Therapeutics. 2016; 6(3):27-33 27
© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO
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REVIEW ARTICLE
HERBAL TREATMENT ALTERNATIVES FOR PEPTIC ULCER DISEASE
Tripathy Surendra*, Afrin Rafat
Varanasi College of Pharmacy, Varanasi-221006, India
*Corresponding Author’s Email: surendratripathy210@gmail.com
Received 02 April 2016; Review Completed 28 April 2016; Accepted 29 April 2016, Available online 15 May 2016
INTRODUCTION
Peptic ulcer disease (PUD), which includes gastric and
duodenal ulcers, is the most common gastrointestinal
problem and demands a well targeted therapeutic
strategy. The most common sites for ulcers are the
stomach and the first few centimeters of the duodenum.
Peptic ulcer causes break off in the continuity of the
mucosa of stomach or duodenum as a consequence of
some medications like non-steroidal anti-inflammatory
drugs (NSAIDS), gastric acids and pepsin, finally
causing lesions1. Basically, word ‘peptic’ is derived
from Greek term ‘peptikos’ whose meaning is related to
digestion .Various reports indicate that old age group
patients are more susceptible to gastric ulcer. Younger
individuals have higher risk of duodenal ulcers2,3,4. The
pathogenesis of peptic ulcer disease shows a complex
imbalance between gastric offensive factors like acid,
pepsin secretion, Helicobacter pylori (H.pylori), bile
salts, ethanol, some medications like NSAIDS, lipid
peroxidation, Zollinger-Ellison syndrome and defensive
mucosal factors like prostaglandins, nitric oxide, gastric
mucus, cellular renovation, blood flow, mucosal cell
shedding, glycoproteins, mucin secretion, proliferation
and antioxidant enzymes like catalase , superoxide
dismutase and glutathione levels5.
Acute peptic ulcers involve tissues down to the depth of
the submucosa, and the lesions may be single or
multiple. Reasons for the development of acute ulcers
include severe illness, shock, burns, severe emotional
disturbance, and postsurgical complications. Chronic
peptic ulcers penetrate through the epithelial and muscle
layers of the stomach wall. There are several symptoms
of ulcer like changes in appetite, nausea, bloody or dark
stools, weight loss, indigestion, vomiting, and chest
pain. Complications of peptic ulcers include
haemorrhage, perforation, pyloric stenosis and the
development of malignant tumors. Poor digestion and
elimination, improper metabolism, mental and physical
stress, and difficult to digest food enhance the
development of ulcers. Peptic ulcer can be categorized
on the basis of location and on the severity of disease.
Numerous other factors are also responsible for
progression of peptic ulcers like Tumor Necrosis Factor-
α (TNF α), Reactive Oxygen Species (ROS), release of
histamine, incidence of apoptosis and bile acids
secretion6,7.
A number of drugs are available for the cure of peptic
ulcers, but clinical evaluation of these drugs indicates
high relapse rate, side effects and drug interactions.
These complications enforces for the development of
new antiulcer drugs and the search for novel molecules
from the drug basket of nature, which is the herbal
resources. Plants have been a valuable source of new
ABSTRACT
From the ancient times, plants have afforded themselves for the treatment of wide variety of diseases. This herbal basket of
the nature has been explored in this review to highlight some of its potential herbs for the cure of Peptic Ulcer Disease
(PUD). The motto behind the review on PUD was due to the wide spreading nature of peptic ulcer in all class of population,
which may be due to the rapidly changing food habits and stress, causing an imbalance between the gastric offensive and
defensive factors. Plants are getting more reliability in current days, because they lack significant side effects and are safe.
On the other hand, the synthetic antiulcer drugs are constantly reported to possess critical adverse effects like arrhythmia,
gynaecomastia, impotency, arthralgia etc. The relapse rate of ulcer has also been reported to be high in such molecules. A
few plants have been reviewed to bring their mechanism of anti-ulcerogenic properties to the front, to promote more
research on them. Some phytoconstituents have been discussed along with the research conducted by researchers in different
ulcer models for better understanding the activity of the plants. The review may hopefully put some light on this particular
section of research oriented towards searching new herbal moieties to treat the PUD.
Keywords: Ulcerogenic, H. pylori, Defensive factors, ethnomedicinal, phytoconstituents, gastroprotective.
Tripathy et al Journal of Drug Delivery & Therapeutics. 2016; 6(3):27-33 28
© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO
molecules and considered as an alternative strategy in
search for new drugs for numerous ailments. There are a
number of plants used in traditional medicine known to
possess antiulcer properties that may, after a few
possible chemical modifications, provide new and
improved antiulcer agents8.
EMERGENCE OF HERBAL DRUGS TO TREAT
ULCER
From ancient times, herbs have been used to treat all
types of ailment. The herbal medicines are advantageous
than synthetic drugs as they are much safer than
synthetic drugs. Synthetic medications are less stable
than herbal medicines. Compared to synthetic medicines
herbal medicines are less expensive. The use of herbal
medicine can reduce toxicities and improve remedial
outcomes. Synthetic drugs also lead to many deaths each
year and are quickly becoming a major public health
concern. In short we can say that natural therapies are
less expensive, more valuable, and much safer. The plant
drugs possessing the active principles such as flavonoid,
tannins, terpenoids are found to show the antiulcer
activity9 (Table: 1). The different classes of synthetic
drugs are used in the treatment of peptic ulcer but many
of these drugs exhibit serious side effects like
arrhythmias, gynaecomastia, impotence, arthralgia,
hypergastrinemia and haemopoeitic changes.
Alternative approach in recent days is the research of
medicaments from ayurvedic or traditional medicinal
system. The use of phytoconstituents as drug therapy to
treat major ailments has proved to be clinically effective
and less relatively toxic than the existing drugs and also
reduces the offensive factors serving as a tool in the
prevention of peptic ulcer. In this modern era also
majority of the world populations still use herbal
medicine mainly in developing countries, for primary
health care because of better acceptability, compatibility
with the human body and lesser side effects. The
chemical constituents present in the herbal medicine or
plant are a part of the physiological functions of living
flora and hence they are believed to have better
compatibility with human body. This review outlines the
properties of some medicinal plants that exhibit antiulcer
activity.
Table 1: Some ulcer protective phytoconstituents10
Name of the Plant
Phytoconstituents
Mangifera indica
Mangiferin
Azadirachta indica
Nimbidin
Ocimum sanctum
Fixed oil eugenol
Annona squamosa
Tannic acid
Mimosa pudica
Alkaloid mimosine
Terminalia chebula
Tannins, Gallic acid, chebullinic acid, sorbitol
Ficus religiosa
Flavonoids- Naringenin
Carica papaya
Chymopapain, papain
Aegel marmelos
Luvangetin
Moringa loeifera
Quercetin, beta setosterol, beta carotene
Psidium guajava
Quercetin, guaijaverin, flavonoids
Sesbania grandiflora
Tannins, saponins
Shorea robusta
Ursolic acid, amyrin
Allium sativum
Alliin, allicin
Aloe vera
Barbaloin, isobarbaloin, saponins
Bacopa moniera
Bacoside A
MECHANISM BASED STUDY OF SOME
HERBAL ANTIULCER DRUGS
For the development of a successful antiulcer herbal
agent, it is quite necessary to understand the possible
mechanisms of the plant extract. Correlating the
chemical nature of the constituents and their
mechanisms may provide crucial information for the
development of newer herbal drugs as potential antiulcer
agent. Some herbal drugs reported to have antiulcer
activity are described below with a special concern to
their mechanism of action.
Azadirachta indica A.
It is commonly known as Neem and belongs to family
Meliaceae. It has been identified to have potent
gastroprotective and antiulcer effects. This was
experimented in rats at a dose of 2.5 g/kg. It was studied
on various parameters of possible mechanism for
treating ulcer. The main mechanism is to prevent acid-
pepsin secretion. Neem did not show any effect on
mucin secretion though it improved life span of mucosal
cells as evidenced by a decrease in cell shedding in the
gastric juice. Thus the ulcer protective activity is due to
its anti-secretory and proton pump inhibitory activity
rather than on defensive mucin secretion. Bark extract of
Azadirachta indica inhibits H+-K+-ATPase activity in
vitro. It stops oxidative damage of the gastric mucosa by
blocking lipid peroxidation and by scavenging the
endogenous hydroxyl radical (OH), the major causative
factor for ulcer11,12,13.
Momordica charantia L.
Tripathy et al Journal of Drug Delivery & Therapeutics. 2016; 6(3):27-33 29
© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO
It is commonly known as bitter gourd and karela and
belongs to family Cucurbitaceae. The methanolic extract
of Momordica charantia fruits is effective on gastric and
duodenal ulcers. The extract was administered orally at
two different doses of 100 mg/kg and 500 mg/kg. The
antiulcer activity was suggested to be due to the
increased secretion of mucus and anti-stress activity of
its constituent. The olive oil extract of M. charantia fruit
did show a healing effect in peptic ulcers14,15.
Bacopa monniera
It is commonly known as Brahmi, belonging to family
Scrophulariaceae. It is effective in treating various
gastric ulcer models of rats. The main chemical
constituent for curing the ulcer is bacoside A. It shows
anti-ulcer and ulcer-healing activities. There are multiple
possible mechanisms of bacoside A, which has been
suggested. The first one is for treating ulcer is anti-H.
pylori activity in the dose of 1000 mg/ml and increasing
prostanoids (PGE and PGI2) in the dose of 10 mg/ml. Its
other possible mechanism are mucosal offensive acid-
pepsin secretion and defensive factors like mucin
secretion, mucosal cell shedding, cell proliferation and
antioxidant activity in rats16,17,18.
Aloe barbadencis
It is commonly known as Aloe vera. It belongs to family
Asphodelaceae (Lilliaceae). Aloe vera gel posses
gastroprotective properties. The existing mucilage tissue
at the center of leaves in this plant called aloe gel is used
for various medicinal purposes. Its healing property is
due to a compound called glucomannan, which is
enriched with polysaccharides like mannose. The
glucomannan affects fibroblast growth factor and
stimulates the activity and proliferation of these cells.
The mucilage of aloe vera not only increases amount of
collagen on wound site, but also increases transversal
connections among these bands rather than changing
collagen structure fastening wound healing19,20.
Ficus religiosa
It is commonly known as “peepal tree”. It belongs to
family Moraceae. The alcoholic extract of F. religiosa
has been reported for antiulcer activity against pylorus
ligation induced ulcers, ethanol induced ulcers and
asprin-induced ulcers at dose level of 250 mg\kg and
560 mg\kg in swiss albino rats. The stem bark ethanolic
extract possesses antiulcer activity due to endogenous
production of prostaglandins, which in turn promotes
mucus secretion, apart from this, the plant also possesses
anti-inflammatory and anti-oxidant properties, which
comes together to make the plant as a potential antiulcer
drug21,22.
Carica papaya
It is commonly known as Papaya, belonging to family
Caricaceae. The methanolic extract of the seed of the
plant shows gastroprotective and healing effects on ulcer
in rats at a dose of 125, 250, and 500 mg/kg. It
significantly reduced the gastric lesion with 56, 76, and
82 % inhibition. The cytoprotective effect of papaya is
responsible for its Anti-ulcerogenic activity. The enzyme
P1G10 present in papaya has shown healing activity of
chemically induced gastric ulcer23,24,25.
Ananas comosus
It is commonly known as Pineapple, belonging to family
Bromeliaceae. The dichloromethane extract of pineapple
has been found with the ability to protect the gastric
mucosa against injuries caused by 0.3 M HCl, absolute
ethanol, non-steroidal anti-inflammatory drugs, and
pylorus ligation, in mice and rats. The mechanism of
action of the DCM extract suggested that the effective
gastroprotective action is due to the sulfhydryl group.
Vianain, present in pineapple has also shown wound
healing property in a guinea pig ischemic ulcer
model26,27.
Cynodon dactylon
It is commonly known as Durva grass or Doob ghas,
belonging to family Poaceae. Doob ghas was proved for
antiulcer activity in albino rats at a dose level of 200,
400 and 600 mg per kg. Doob grass herb contains
flavonoids. The alcoholic extract showed the presence of
flavanoids, which is supposed to be responsible for
antiulcer property28,29,30.
Glycyrrhiza glabra
It is commonly known as licorice, belonging to family
Leguminosae. It showed effective healing on ethanol-
induced ulcers. It reduces stomach secretions and also
produces thick protective mucus which covers the lining
of stomach, therefore protects from peptic ulcers.
Further it has been reported to increasing the local
concentration of prostaglandins which promotes mucous
secretion and cell proliferation in the stomach31,32.
Ocimum sanctum
It is commonly known as Tulsi and belongs to family
Lamiacae. It is considered as a sacred plant by the
Hindus in India. Advanced studies on this plant have
been reported that it has antiulcer activity. The fixed oil
has proved to show antiulcer activity because of its
lipoxygenase inhibitory activity, histamine antagonistic
and anti-secretory effects33,34,35.
Panax ginseng (Korean red ginseng)
It is a species of ginseng. It belongs to family
Araliaceae. Korean red ginseng gives healing effect on
gastric ulcer at a dose of 30, 100, and 300 mg/kg,
peroral, occurred 1 hr before the ulcer induction in mice.
The supposed mechanism of Ginseng species are
significant increase in mucin secretion and inhibited
malondialdehyde (MDA) and H+/ K+ ATPase activity
in the stomach36,37.
Musa sapientum
It is commonly known as Kela, belonging to Musaceae
family. Musa at a dose of 100 mg/kg was studied for its
antiulcer and mucosal defensive factors in NIDDM rats .
Anti-ulcerogenic effect of Musa may be due to its anti-
secretory and cyto-protective activity. This is a
mucoadhesive agent that form lining in stomach and
Tripathy et al Journal of Drug Delivery & Therapeutics. 2016; 6(3):27-33 30
© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO
duodenum and protect it from the corrosion of acid and
pepsin38,39.
Brassica oleraceae
It is commonly known as cabbage, belonging to family
Brassicaceae. The aqueous extract of Brassica oleracea
var. capitata plant was used in the gastric disorders like
ulcer at a dose of 0.250, 0.50 and 1.0 mg/kg on Wistar
rat. There is a chemical Lysophosphatidic acid (LPA),
present in cabbage. It is a lipid mediator involved in a
variety of physiological responses, like wound healing.
This phospholipid shows an antiulcerogenic activity40,41.
Solanum nigrum
It is commonly known as Potato, belonging to family
Solanaceae. It has gastric antiulcerogenic effects.
Solanum nigrum was found to possess antiulcerogenic as
well as ulcer healing activities. Antiulcer activity was by
blocking acid secretion through inhibition of H+
K+ATPase and decreasing secretion of gastrin
hormone42.
Commiphora molmol
It is commonly known as Guggul, belonging to family
Burseraceae. It is widely used as an anti-inflammatory
and wound healing agent. Its gastric ulcer activity at a
dose of 500 mg/kg in rats was evaluated. The protective
effect of Commiphora molmol has shown its effect on
mucus production, increase in nucleic acid and non-
protein sulfhydryl concentration. It has been also
diagnosed for free radical-scavenging properties43,44.
Vaccinium oxycoccos
It is commonly known as Cranberry, belonging to family
Ericaceae. Cranberry juice is effective in peptic ulcer.
Several H. pylori bacteria shows antibiotic resistance but
can be treated well by cranberry juice. Regular
consumption of cranberry juice could suppress H. pylori
infection in endemically afflicted populations. The
possible mechanism behind the antiulcer activity may be
that, it causes immobilization of H. pylori strains in
human mucus, erythrocytes, and cultured gastric
epithelial cells45,46,47.
Ceratonia siliqua
It is commonly known as Carob, belonging to Fabaceae
(Leguminoceae) family. Carob has shown to reduce the
effect of gastroesophageal reflux and vomiting in
infants. It works by several activities of its constituents
mainly the Flavonoid content. It possesses demulcent
property and the flavonoid content imparts
gastroprotective and antioxidant properties, which
together lend the drug to exhibit antiulcerogenic
potential.
A number of researches have been conducted on
different plants for their antiulcer activity. A few
pharmacologically tested Antiulcer plant drugs were
studied and summarized in Table 2.
Table 2: Some pharmacologically tested Antiulcer plants.
Name of Plants
(Family)
Solvent of
Extraction
(Plant part)
Ulcer induction method
Researcher
Emblica officinalis
(Euphorbiaceae)
Methanol
(Leaves)
Ethanol, Aspirin, Cold
Restraint Stress(CRS)
Goel et al, 200249
Asparagus racemosus
(Liliaceae)
Methanol
(Roots)
CRS, Pyloric ligation,
Aspirin, Cysteamine
Goel et al, 200350
Bambusa arundinaceae
(Poaceae)
Methanol
(Leaves)
Aspirin
Muniappan et al, 200351
Urtica dioica L.
(Urticaceae)
Water
(Nettle)
Ethanol
Kufrevioglu et al, 200452
Utleria salicifolia
(Asclepiadaceae)
Ethanol
(Rhizome)
CRS, Pyloric ligation,
Aspirin, Ethanol
Rao et al, 200453
Elettaria cardamomum
(Zingiberaceae)
Methanol
(Fruits)
Pyloric ligation, Aspirin
Jafri et al, 200454
Bauhinia purpurea
(Fabaceae)
Water
(Leaves)
Absolute ethanol,
Indomethacin
Zakaria et al, 201155
Zingiber montanum
(Zingiberaceae)
Methanol
(Rhizomes)
1N HCl
Hossain et al, 201256
Aerva persica Merrill
(Amaranthaceae)
Ethanol
(Root)
Ethanol, Pyloric ligation
Vasudeva et al, 201257
Toona ciliate
(Meliaceae)
Ethanol
(Heart wood)
HCl-Ethanol, Pyloric
ligation
Malairajan et al, 200758
Excoecaria agallocha
(Euphorbiaceae)
Water
(Bark)
Diclofenac
Thirunavukkarasu et al,
200959
Abutilon indicum L.
(Malvaceae)
Methanol
(Leaves)
Ethanol, Pyloric ligation
Dashputre et al, 201160
Heliotropium indicum
(Boraginaceae)
Ethanol
(Leaves)
Pyloric ligation, Aspirin
Shenoy et al, 201161
Tripathy et al Journal of Drug Delivery & Therapeutics. 2016; 6(3):27-33 31
© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO
Nigella sativa L.
(Ranunculaceae)
Ethanol
(Seeds)
Pyloric ligation, Aspirin
Rajkapoor et al, 200262
Centella asiatica
(Apiaceae)
Water
(Leaves)
Ethanol
Al-Bayati et al, 201063
Buchanania lanzan
(Anacardiaceae)
Ethanol
(Root)
Ethanol, Pyloric ligation
Pareta et al, 201064
Terminalia chebula
(Combretaceae)
Methanol
(Fruits)
Ethanol, Pyloric ligation
Raju et al, 200965
Piper aleyreanum
(Piperaceae)
Essential oil,
(Aerial part)
Ethanol
Santos et al, 201266
Scoparia dulcis
(Scrophulariaceae)
Water
(Aerial part)
Indomethacin
Babincova et al, 200867
Pithecellobium dulce
(Fabaceae )
Hydroalcoholic,
(fruit)
Ethanol, Aspirin, CRS
Megala et al, 201268
Lafoensia pacari)
(Lytraceae)
Methanol
(Stem bark)
Ethanol, Indomethacin,
CRS, Acetic acid
Martins et al, 201269
Albizia lebbeck
(Mimoceae)
Ethanol
(Bark, Leaves)
Ethanol, Indomethacin,
CRS, Acetic acid
Lawande et al, 201270
Andrographis paniculata
(Acanthaceae)
Hydroalcoholic
(Aerial part)
Cysteamine
Gupta et al, 201171
Picralima nitida
(Apocyanaceae)
Methanol
(Seeds)
Pyloric ligation, Aspirin
Ogochukwu et al, 201172
Cordial sebestena L.
(Boraginaceae)
Methanol
(Root)
Ethanol
Trivedi et al, 201573
CONCLUSION
Research on natural products often is guided by
ethnomedicinal knowledge, and their contribution to
drug innovation by providing novel chemical structures
and mechanisms of action is substantial. Large number
of herbal extracts is used in folk medicine to treat
various types of disorders. The synthetic drugs used to
treat it are having side effects and it has been seen that
some synthetic drugs have ulcer as their adverse effect.
In that case, the herbal natural remedy is the obvious
alternative, which is safe and equally effective as the
synthetic drug. Several plant sources have been
highlighted in this article on the basis of traditional
knowledge and reports of different researchers. Apart
from this, searching for new pathways to treat ulcer can
be developed only by understanding the mechanism of
ulcerogenesis, by which it can be targeted. The
investigative parameters which are the major aspects for
herbal drug screening has also been mentioned at
required places in the paper, which will hopefully help
the researchers working in this area.
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How to cite this article:
Tripathy S, Afrin R, Herbal treatment alternatives for peptic ulcer
disease, Journal of Drug Delivery & Therapeutics. 2016; 6(3): 27-33
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