FOCUS ON CURRENT TRENDS IN THE TREATMENT OF HELICOBACTER PYLORI INFECTION

Volume 9, Issue 1, July – August 2011; Article-009 ISSN 0976 – 044X
International Journal of Pharmaceutical Sciences Review and Research Page 42
Available online at www.globalresearchonline.net
CH. Prasanthi, N.L. Prasanthi
*
, S.S. Manikiran, N. Rama Rao
Department of Pharmaceutics, Chalapathi Institute of Pharmaceutical Sciences, Lam, Guntur- 522034, Andhra Pradesh, India.
*Corresponding author’s E-mail: prasanthi_pharm@yahoo.com
Accepted on: 23-03-2011; Finalized on: 01-07-2011.
ABSTRACT
One of the most vulnerable gastro intestinal tract infections affecting the human population worldwide are H pylori infections. It
causes complicated gastric problems such as gastritis, gastro duodenal ulcers, gastric cancer and primary B-cell gastric lymphoma.
The current dosage regimens proposed by the international guidelines which are in practice to abate this chronic destructive
bacterial infection (combination of two antibiotics (clarithromycin plus amoxicillin or metronidazole) with a PPI for at least 7 days for
the eradication of H pylori) were still found to be unsatisfactory. So there is a need of hour to design and develop alternative drug
delivery systems viz. gastro retentive delivery systems, site specific delivery systems and probiotics. This review focuses the issues
related to the diagnosis and treatment of H pylori infection including herbal formulations.
Keywords: Gastric lymphoma, diagnostic tests, bismuth salts, herbal formulations, gastrorententive systems, lipobeads.
INTRODUCTION
Helicobacter pylori were the first isolated microaerophilic
gram-negative bacteria from the gastric mucosa of
gastritis patients by Marshall and Warren in 1980s. It is a
spiral-shaped, highly motile organism with a unipolar
flagellum that harbors within and beneath the mucous
layer of the stomach and often found attached to gastric
mucosa. It is a worldwide common infection with
prevalence rates in the general population ranges from
not only 30-40% in United States, 80-90% in South
America and 70-90% in Africa but also in developing
countries like India, China from the age of teenagers 20%
to 50-60% of elderly subjects
1, 2
. The infection is usually
acquired in early childhood, either through the fecal to
oral / oral to oral route. Acute infection with H pylori
during childhood can be accompanied by diarrhea and
slowing of weight gain. In adults, however, acute infection
usually passes unnoticed except for transient and mild
dyspepsia, nausea and vomiting3
. According to the
statistics, it causes peptic ulcer disease approximately one
in six (17%) persons and each year 1% to 2% of these will
experience a major or life threatening complication, such
as bleeding or gastric outlet obstruction
4
. H pylori is such
a threat that the World Health Organization's (WHO)
International Agency for Research into Cancer (IARC) in
1994 has classified as a “Class-I-Carcinogen”5
.
The location of H pylori in stomach is shown in Figure 1.
The series of steps or pathogenic mechanisms of H pylori
in the stomach are6
,
 Attachment - The H pylori bacteria enter into the
stomach and attach themselves to the lining of the
stomach to establish an environment in which to
grow.
 Toxin production - H pylori produce poisonous
substances to increase the secretion of water and
electrolytes in the stomach and cause cell death in
the cells of the stomach lining. This will help the
bacteria take over the stomach environment and will
lessen the competition for required nutrients.
 Cell invasion - The bacteria will enter into the
stomach lining cells for protection and then kill the
cells they are in (their host cells) so that they can
move on to invade more stomach-lining cells. This
process will continue, thus creating tissue damage.
This tissue damage will become the ulcer formation
in the stomach.
 Loss of microvilli/villi – The substances released into
the host cell during the ‘Cell Invasion’ step cause a
change in the stomach-lining cells. This change
results in fewer calories getting absorbed by the
stomach. The body will get fewer nutrients from the
food eaten at every meal.
Figure 1: H pylori location within the stomach
FOCUS ON CURRENT TRENDS IN THE TREATMENT OF HELICOBACTER PYLORI INFECTION: AN UPDATE
Review Article

The situations provoking for the growth of H pylori are,
1. H pylorus is a curable chronic destructive bacterial
infection. Once H pylori acquired, it penetrates the
gastric mucus layer and fixes itself to various
phospholipids and glycolipids on the epithelial
surface including phosphatidyl ethanolamine, GM3
ganglioside and Lews antigen. Therefore the
organism exclusively resides on the luminal surface of
the gastric mucosa under the mucus gel layer in the
acidic environment of the stomach.
2. Bitterly violent factors exhibited by H pylori are
motility (help to swim in mucosa), adherence
(increases mucosal contact), CagA (antigenic protein-
increases the mucosal inflammatory response),
Urease (urea is broken down into bicarbonate and
ammonia; this protects the bacterium in the acid
milieu of stomach). These special factors of H pylori
promote the colonization and tissue injury in the
stomach.
3. H pylori cause physiological changes in the stomach
by decreases or inhibit mucin synthesis via inhibition
of UDP-galactosyltransferase. This effect may
certainly impair the gastric mucosal barrier and
contribute to the mucosal injury which leads to
interaction between H pylori and phagocyte cells and
activation of the mast cells, which shows the acute
and chronic inflammatory response associated with H
pylori infection
7
. Inflammation caused by H Pylori was
depicted in Figure 2.
Figure 2: Survival of H pylori in the stomach (Acidic Environment)
DISEASES CAUSED BY H PYLORI
8
H pylori infection not only causes the physiological
changes in the stomach but also causes several diseases
depending on progression of infection; the process is
depicted in Figure 3 and 4.
Figure 3: Sequential diseases caused by long term H pylori
infection
Figure 4: Ulcerogenic and carcinogenic effects of H pylori
1. Gastritis
H pylori infected gastric mucosa causes epithelial cell
damage due to polymorpho nuclear and mononuclear
inflammatory cells; and lymphoid follicles. The
lymphocytic component of the inflammatory response is
known as mucosa-associated lymphoid tissue (MALT).
Inflammation tends to spread upwards from the gastric
antrum to corpus, thereby causing a reduction in acid
secretion and eventual loss of parietal cells, leading to
gastric atrophy. Chronic gastritis is the precursor lesion
for the development of gastric atrophy, which in turn can
progress to gastric carcinoma.

2. Peptic ulcer Disease
H pylori infection is responsible for nearly all duodenal
ulcers and approximately 70% of gastric ulcers. These
ulcers are occurring due to imbalance caused by H pylori
between aggressive factors (gastric acid and pepsin) and
protective factors (gastric mucus, bicarbonate,
prostaglandins). When H pylori causes inflammation in
the antrum results in constant stimulation of gastrin
secretion there by increases the acid secretion. It leads to
the lowering of the pH in the duodenum, causes the
removal of bile acids (which inhibit growth of H pylori in
the small intestine). Due to this colonization of H pylori
occurs. Sometimes the infection spreads to proximal part
of stomach and invades the mucosa by binding to class II
major-histocompatibility-complex (MHC) molecules on
the surface of the epithelia, inducing apoptosis of the
gastric epithelial cells. The produced antibodies cross-
react with surface antigens on the gastric parietal cells,
enhancing the inflammatory injury to the mucosa lead to
gastric ulcer.
3. Gastric Cancer
The risk for developing gastric cancer is most closely
related to the degree of damage of gastric mucosa by H
pylori. The risk is highest in case of pangastritis with
intestinal metaplasia, hypochlorhydria and lowest in
predominantly antral gastritis. The mechanism for the
development of gastric carcinoma is multifactorial such as
development auto antibodies that cross-react with gastric
antigens. Patients with these auto antibodies have a
higher frequency of glandular atypia and neoplastic
transformation, which may explain progression of
gastritis to atrophy and metaplastic changes in some
patients. Once the precursor lesion has developed
(atrophic pangastritis), the risk of gastric cancer appears
to be relatively constant across age groups and
populations.
4. Gastric (MALT) Lymphoma
The normal stomach lacks organized lymphoid tissue.
Chronic H pylori infection prolonging the antigen
stimulation due to this lymphocytes form MALT. Over
time, MALT can develop into lymphoma. Gastric MALT
lymphomas are typically low grade, T cell dependent, B
cell lymphomas whose antigenic stimulus is thought to be
H pylori. Complete resolution of MALT lymphomas usually
occurs following cure of the H pylori infection, provided
that the lymphoma is localized to the stomach. MALT
lymphomas may exist in apparently normal mucosa and
therefore require histological examination.
Diagnostic tests for H pylori 9, 10
H pylori easily spread through the fecal-oral, oral-oral
route by contaminated sources, poor sanitation and
crowded living condition. Immediate diagnosis is
necessary for identification of infection and for
treatment. The list of diagnosis tests were given in Table
1.
TREATMENT FOR H PYLORI INFECTION
10, 11
Eradication of H pylori is difficult because of the
organism’s habitat in the stomach under the mucus layer.
For effective H pylori eradication therapeutic agents have
to penetrate the gastric mucus layer to disrupt and inhibit
the mechanism of colonization. The agents used for
eradication of H pylori infection are
1. Antimicrobial agents
The antimicrobial agents are act topically and systemically
to eradicate the H pylori.
Metronidazole: H pylori are highly sensitive to
metronidazole. It is a prodrug that undergoes activation
by nitro reductase of bacteria, then acting on helical
structure of bacterial DNA, break strand, which causes
impairment of bacterial function and it has a pH
independent activity. Unfortunately, H pylori rapidly
developed resistance to this drug.
Clarithromycin: It is very effective for treatment of H
Pylori. It is a 14-membered ring macrolide antibiotic,
binds to bacterial ribosome and disrupts protein
synthesis, leading to cell death. It is relatively stable in the
acid environment, it having lowest minimum inhibitory
concentration (MIC). When given in conjunction with a
PPI, its concentration in the mucous layer increases
markedly.
Amoxicillin: It inhibits the synthesis of the bacterial cell
wall by acting topically and systemically. It is more stable
in acidic environment .It has significant effect against
bacteria along with anti secretary agent. Resistance to
amoxicillin is uncommon but has been reported.
Tetracycline: It is a derivative of the polycyclic
naphtacenecarboxamides and acting on bacterial cell. It
inhibits protein synthesis by specifically binding to the 30-
S ribosomal subunit there by prevents the addition of
amino acids to the growing peptide chain. It is active at
low pH.
2. Anti secretary Agents
These shows indirect action on H pylori i.e. they increase
the antibiotic concentration in stomach by decrease
gastric juice volume. The anti secretary agents are proton
pump inhibitors (blocks the H
+
, K
+
ATPase pump on the
gastric parietal cell. e.g. omeprazole and lansoprazole)
and H2 receptor antagonists (Cimetidine, ranitidine,
famotidine).
3. Bismuth
It is directly acting on bacterial cell walls and disrupt their
integrity by accumulating in the periplasmic space and
leads to bacterial lysis. H pylorus is unable to develop
resistance to the various bismuth salts, but the drawbacks
are discoloration of tongue and black stool. e.g.: bismuth
subsalicylate, ranitidine bismuth citrate.
Most antibiotics have very low in vitro minimum
inhibitory concentrations (MIC) against H pylori (MIC 90 ≤

1mg/L), no single antibiotics was able to eradicate this
organism effectively. Currently, drug combination
therapies are using to increase healing rates of H pylori by
acting luminally as well as systemically.
Dual Therapies (approved but not recommended): A PPI or
bismuth plus any one of the antibiotic (Amoxicillin or
Clarithromycin). The cure rate after completion of course
is only 70%.
Triple Therapies: A PPI or bismuth plus any 2 of the
antibiotics (Amoxicillin, Clarithromycin, Metronidazole
and Tetracycline). The course of the therapy is 10 days to
2 weeks and cure rate is 85%.This treatment is fairly
complicated (20 pills/day). The options for triple therapy
are given in Table 2.
BMT Quadruple Therapy Includes (all given for 2 weeks):
This therapy consisting Bismuth subsalicylate 2 tablets
QID, Metronidazole 500 mg TID, Tetracycline 500 mg QID,
proton pump inhibitor (Omeprazole 20 mg BID or
lansoprazole 30 mg BID). The cure rate is only 66.7% and
side effects were more than above therapies. FDA
approved regimens for H pylori infection are listed in
Table 3.
Main drawback of above therapies is expensive, poor
patient compliance and developed resistance power for
antibiotics to H pylori.
Table 1: Diagnostic tests for H. pylori
Test What does it measure Sensitivity Comments
Invasive (requiring endoscopic biopsy)
1. Steiner’s stain of gastric biopsy
specimen
Histological identification of
organism
82 to 95% Considered the “gold standard.
2.Rapid Urease test (CLO test,
Delta Wenst, Bently, Western
Australia)
Urease activity of biopsy
specimen
85-90% Sensitivity decreased by acid suppression
and acid bleeding.
3.Culture Presence of organisms;
antimicrobial sensitivities
70-80% Especially useful for the research and to
guide management in treatment failure;
requires experienced laboratory.
Noninvasive
1.Serology:
laboratory based ELISA
IgG 90-96% Accurate, convenient for initial infection,
titers diminishes slowly after eradication
and may remain positive after one year.
2. Whole blood:
office based ELISA
IgG 50-85% Less accurate, but fast, convenient and
inexpensive.
3. Stool: HpSA H. pylori antigens 95-98% Relatively convenient and available.
4. Urease breath test Urease activity 95-100% Sensitivity reduced by acid suppression.
5.String Test (swallowed and
recovered polymeric string)
Culture or polymerase chain
reaction on gastric mucosa
75-80% Minimally invasive method to obtain
viable organisms, but retrieval rate less
than with endoscopy.
6.Urine ELISA IgG 70-96% Greater patient acceptance and
convenience than stool test; not yet
readily available.
7.Saliva ELISA 82-91% Greater patient acceptance and
convenience than stool test; not yet
readily available.
CLO=Campylobacter-like organism; ELISA=enzyme –linked immunosorbent assay; HpSA =H. pylori stool antigen
Table 2: Options for triple therapy
Option 1 Option 2 Option 3
Proton-Pump Inhibitors
E.g, Omeprazole, Pantoprazole,
Lansoprazole
Proton-Pump Inhibitors
E.g, Omeprazole, Pantoprazole,
Lansoprazole
Bismuth compounds
e.g., Bismuth subsalicylate
Clathromycin
Brand names : Biaxin, Klaricid, Klabax,
Claripen, Calidar, Fromilid, Calcid
Clathromycin
Brand names: Biaxin, Klaricid, Klabax,
Claripen, Calidar, Fromilid, Calcid
Metranidazole
Brand name: Flagyl
Amoxicillin
Brand names: Amoxil, Dispermox,
Trimox
Metranidazole
Brand name: Flagyl
Tetracycline
Brand names : Sumycin, Terramycin,
Tetracyn, Panmycin

Table 3: FDA approved regimens for treatment of H pylori infection
4
ABRREVATION DRUG DESIGN EFFICIENCY DURATION
OC
Omeprazole
Clarithromycin
40mgqAM
500mg TID
70-80 14
RBC+C
Ranitidine bismuth citrate
Clarithromycin
400mg BID
500mg TID
70-85 14
BMT+H2 ANTAGONIST
Bismuth subsalicylate
Metronidazole
Tetracycline HCI
2 tabs QID
250mg QID
500mg QID
70-90 14
LAC
Lansoprazole
Amoxicillin
Clarithromycin
30mg BID
1mg BID
500mg BID
80-95 14
LA
Lansoprazole
Amoxicillin
30mg BID
1mg BID
70 14
OAC
Omeprazole
Amoxicillin
Clarithromycin
20mg BID
1mg BID
500mg BID
80-95 10
Gastro retentive drug delivery systems against H pylori
GRDDS are designed to localize the action of drug on
gastric region and prolong the gastric residence time of
the drugs. Now a day’s research is going on these dosage
forms for effective treatment of H pylori. Drug delivery to
the site of infection i.e. gastric mucosa may help to solve
the problems associated with the above therapies. The
major gastro retentive drug delivery formulations for
eradication of H pylori are
1. Floating drug delivery systems
These systems have a bulk density lower than the gastric
content. They remain buoyant in the stomach for a
prolonged period of time and localize the drug activity.
Various floating drug delivery systems for eradication of H
pylori infection are listed in Table 4 and represented
diagrammatically in Figure 5. They are,
a) Hydrodynamically balanced systems
Figure 5a: Floating drug delivery systems -
Hydrodynamically balanced
These are single unit dosage forms containing
hydrocolloid (HEC, HPMC, NaCMC, Poly saccharides) and
matrix forming polymer (polycarbophil, polyacrylates and
polystyrene) incorporated either in tablets or in capsules.
Up on oral administration hydrocolloid starts to hydrate
due to gastric fluid and forming a gel surface and
maintains a relative integrity of shape and a bulk density
of less than one. The resultant gel structure then controls
the rate of diffusion of solvent in and drug out of the
dosage form. As the exterior surface of the dosage form
goes into solution, the gel layer is maintained by the
immediate adjacent hydrocolloid layer becoming
hydrated. As a result the drug dissolves in and diffuses
out with the diffusing solvent creating a ‘receding
boundary’
12
.
b) Gas-Generating Systems
Figure 5b: Floating drug delivery systems - Gas generating
system
Floatability of this type system can be achieved by
generating gas bubbles. This system formulated as
matrices by a swellable polymer such as HPMC or
polysaccharides (Chitosan) and carbonates or
bicarbonates which reacts with acid either natural gastric
acid or co-formulated ingredients such as citric and
tartaric acid. When the matrices are in contact with the
acidic environment CO2 was librated and entrapped in
swellable hydrogels, produces upward motion by
decreasing specific gravity13
.

c) Low density systems (hallow microspheres)
Figure 5c: Floating drug delivery systems - Raft forming
system
Low density systems are globular shells apparently having
lower density than that of gastric fluids. The buoyancy of
this system achieved by low-density carriers like popcorn,
poprice, polystrol, polypropylene .The surface of the
empty shells is coated with sugar or with polymeric
materials such as methacrylic polymer and cellulose
acetate phthalate. The under coated shell is then coated
by mixture of drug with polymers such as Ethyl cellulose
or HPMC, on contact with GI fluid the tablet forms a
water impermeable colloid gel barrier around its surface
and maintains the bulk density lees than one. Due to that
it shows good buoyancy and target action.
d) Raft Forming System
This system has received much attention in drug delivery
for GI infections mainly for H pylori. It contains a gel
forming agent (alginic acid), sodium bicarbonate and acid
neutralizer, which forms a foaming sodium alginate gel
(raft), when in contact with gastric fluids. The raft thus
formed floats on the gastric fluids because low bulk
density created by the formation of CO2 and prevents the
reflux of the gastric contents (i.e. gastric acid) into the
esophagus by acting as a barrier between the stomach
and esophagus
14
.
Figure 5d: Floating drug delivery systems - Low density
system
2. Mucoadhesive drug delivery systems
Mucoadhesive drug delivery systems prolong the
residence time of the dosage form at the site of
application and improved therapeutic performance of the
drug. The absorption of an antibiotic into the mucus
through the mucus layer (from the gastric lumen) is
believed to be more effective for H pylori eradication than
absorption through the basolateral membrane (from
blood). A preparation that spreads out adheres to the
gastric mucosal surface and continuously releases
antibiotic should be highly effective against H pylori.
Various mucoadhesive drug delivery systems have been
proposed for H pylori eradication is listed in Table 5 and
system was depicted in Figure 6.
Figure 6: Mucoadhesive drug delivery system
Table 4: Floating drug delivery system15-18
Drug delivery system Method Materials Results
Hydrodynamically
balanced system (HBS)
Direct compression
technique
HPMCK4M, HPMCK125M,
sodium bicarbonate
Buoyancy duration less than 12hr, and
buoyancy lag time 49sec.
Gas generating system Expendable asymmetric
triple layer tablet
Tetracycline HCL,
Metronidazole
Buoyancy duration (0.1NHCL),6-8hr Buoyancy
lag time 17-28min.
Raft forming system Compressed tablet Triclosan,Alginic acid, Sodium
bicarbonate, Calcium
carbonate and Mannitol
In acidic conditions bicarbonate salts
produced effervescent causes the buoyancy of
raft structure formed by alginate.
Low density system Polycarbonate micro
balloons by Emulsion
(o/w) solvent
evaporation technique
Antiurease drug
(acetohydroxamic acid (AHA),
poly carbonate
Buoyancy duration (stimulated gastric-fluid) is
12hrs and shows sustain release.

Table 5: Mucoadhesive drug delivery system
19-22
Formulation Method Materials Results
Microsphere
(250-335µm)
Spray chilling method Amoxicillin(drug), carboxyvinly
(Bioadhesive polymer), Curdlan
(Polysaccharide)
Microspheres adhesion on Mongolian
gerbil’s stomach wall after 4hr is 20%
and having 10 times greater activity
than suspension.
Microspheres Emulsion/evaporation
method
Amoxicillin, polymer (carpobol
934P)
The remained amount of drug in rat
stomach after 4hr is 63.6+ 21.9% and
higher effectiveness than powder.
Sustain release
liquid preparation
Sodium alginate form a firm
gel contact with acid or di or
trivalent metal ions
Ampicillin, sodium alginate The remained amount of drug in rat
stomach is 87% after 60min.
Chitosan microspheres Chemical(glyxal) crosslinking
method
Tetracycline, glyxal It fasted gerbils the cross linked
chitosan microspheres in stomach is
17% and 10% at 2 , 10 hr respectively
1. Drug delivery systems with specific interaction
a) Some strains of H. pylori express an adhesin, BabA2, it
interact with the fucosylated histo-blood antigen Lewis b
(Le
b
) in the stomach. Therefore, formulations having
fucose as ligand is suitable for targeting to H pylori.
e.g.: Umamaheshwari et al. developed chitosan-
glutamate nanoparticles by ionotropic gelation method
and covalently bind the L-fucose. A ‘‘plug and seal’’ effect
between H pylori and nanoparticles was observed. In vitro
growth inhibition studies showed that L-fucose-
conjugated chitosan-glutamate nanoparticles exhibited 2-
fold inhibitory efficacy compared to chitosan-glutamate
nanoparticles and the plain drug23
.
b) Receptor-mediated drug delivery system: PE is a
predominant lipid in the antrum of the human stomach
and function as a receptor for H pylori adhesion24
.
e.g.: Anti Urease drug, acetohydroxamic acid (AHA) was
formulated into lipobeads. The system consists of a lipid
bilayer shell (PE) that is anchored on the surface of a
hydrogel polymer (polyvinyl alcohol xerogel) core. The
specific binding between lipobeads and PE specific
surface receptor of H pylori was confirmed by in situ
adherence and radiolabelling assays with human stomach
cells and KATO-III cells respectively. The in vitro growth
inhibition studies showed a better efficacy of PE-
lipobeads than polyvinyl alcohol (PVA) bare beads and
plain AHA (the three formulations containing the same
amount of AHA). The % growth inhibition rate of
lipobeads, PVA-bare beads and plain AHA are 100%, 25%
and 35% respectively25, 26
. The system was depicted in
Figure 7.
Herbal formulations for H pylori eradication
The widespread use of antibiotics not only causes the side
effects but also increases the resistance power of all
pathogenic bacteria. Therefore, need a non-antibiotic
agent which is both effective and free from side effects.
For centuries, herbals have been used as traditional
medicine to treat a wide range of ailments including
gastrointestinal (GI) disorders such as dyspepsia, gastritis
and peptic ulcer disease (PUD). Commonly used medical
plants for treatment of H pylori are
1. Black myrobalan: The aqueous extract of black
myrobalan (Terminalia chebula Retz) has uniform
antibacterial activity against ten clinical strains of H
pylori. The antibacterial activity of aqueous extracts
of black myrobalan against H pylori was significantly
higher than that of ether and alcoholic extracts. The
minimum inhibitory concentration and minimum
antibacterial activity of the extract is 150 and
175mg/L respectively
27
.
2. Ginger: Ginger root (Zingiber officinale Rosc)
traditionally used for the treatment of gastrointestinal
ailments such as motion sickness and dyspepsia .The
constituents such as 6-, 8- and 10-gingerol and 6-
shogoal were isolated from Ginger rhizome in
menthol. The isolated compounds eradicate 19 strains
of H pylori, including 5Cag A-positive .The methanol
extract of ginger rhizome inhibited growth of all
strains in vitro with MIC range of 6.25-50µg/mL. One
fraction of the crude extract containing gingerol
inhibited all strains of H pylori including CagA-positive
strain with an MIC 0.78 to12.5µg/mL28
.
3. Turmeric: The derived chemical constituents of
turmeric (Curcuma longa L) are curcumin, a
polyphenolic which prevent gastric and colon cancer in
rodents. A methanol extract of the dried powered
turmeric rhizome and curcumin inhibited growth of 19
strains of H pylori, including 5 Cag A–positive in vitro
with MIC range of 6.25 to50µg/ml 29, 30
.
4. Thyme: It is a popular herbal remedy in ancient Egypt,
Greece and Rome. Thyme was mainly used for
headaches, digestive problems, respiratory illness,
and as a mood-enhancer. Researcher who
investigated the antimicrobial properties of 21
essential oils against five important food-borne
pathogens, including H pylori noted that thyme was
very effective at inhibition activity
31.
5. Liquorice: In a recent study at the Institute of Medical
Microbiology and Virology, Germany, researchers
found that liquorice extract produced a potent effect
against strains of H pylori that are resistant against
Clarithromycin32
.

6. Berberine: Berberine is a plant alkaloid isolated from
the roots and bark of several plants including golden
seal, barberry, Coptis chinensis Franch and Yerba
mansa. Berberine-containing plants have been used
medicinally in ayurvedic medicine, and are known to
have antimicrobial activity against a variety of
organisms including bacteria, viruses, fungi,
protozoans, helminthes, and Chlamydia. More
recently, berberine had been demonstrated to be
effective against H pylori
33
.
Probiotics34,35
Probiotics are defined as live, non-pathogenic microbial
feed or food supplements that exert a positive influence
on the host by altering the host's microbial balance.
Currently, probiotics are accepted as being useful in the
prevention and/or treatment of certain pathological
conditions, mainly (but by no means exclusively)
infections of GI track. Several in vitro studies show that
lactobacilli or their cell-free cultures having a inhibitory
effect on H pylori and increases the eradication rate of H
pylori. In vivo models demonstrate that pre-treatment
with a probiotic can prevent H. pylori infections and/or
that administration of probiotics markedly reduced an
existing infection. The mechanisms of probiotics to
counteract H. pylori induced functional effects are shown
in Figure 8.
1. Inducing aggregation.
2. Competing with host-cell binding sites.
3. They could modulate inflammatory responses.
4. Strengthen the mucosal barrier.
5. Probiotics with a high fraction of CpG sequences can
possibly reduce H. pylori colonization.
6. Differential modulation of cytokine production
recognized by Toll-like receptors (TLR) .
7. Enhancement of secretary immunoglobulin A (Ig) A
production.
8. Decreases tumor necrosis factor (TNF)-α production by
macrophages could have a role in H. pylori infection.
9. Probiotics could down-regulate the production of
virulence factors of H pylori.
10. Induce mucin release from epithelial cells.
11. They could compete with H. pylori in binding to
dendritic cell (DC) receptor specific intercellular adhesion
molecule 3-grabbing nonintegrin (SIGN).
12. Modulate DC function and regulatory T (Tr) cell
development.
Probiotics are a promising alternative among individuals
who have adverse reactions to antibiotics because they
help the gastrointestinal flora resist gastrointestinal
aggression brought on by antibiotics.
Figure 7: Site specific drug delivery system
Figure 8: Mechanisms of probiotics to counteract H pylori induced functional effects

CONCLUSION
Eventually, the need for the design and development of
GRDDS or site specific drug delivery systems to eradicate
H pylori infection is immense. But high mucous turnover
rate and low retention time of dosage form in stomach
and guaranteed clearance of swellable systems after
appropriate time are the most challenging aspects of
designing GDDS. In addition, much more knowledge
about the pathogen in terms of identification of certain
specific receptors on the surface of the bacterium will be
possible for ligand targeted action. However, further
investigation on the coccoid form of the bacterium H
pylori existing either as degenerative type or resistant
type along with its virulence factors will certainly gain an
advantage to understand its physiology. Moreover, the
recent advent of herbal drugs in conjunction with novel
drug delivery systems can be a fruitful alternative option.
Thereby, a more effective therapy can be rendered to
protect from the diseases caused by H pylori infection.
Acknowledgements: The authors are thankful to
Chalapathi Educational Society, Guntur for providing the
necessary facilities.
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