| |

Received: 4 December 2018    Revised: 25 March 2019    Accepted: 26 March 2019

DOI: 10.1111/1440-1681.13092

REVIEW ARTICLE

Therapeutic potential of medicinal plants for the management

of urinary tract infection: A systematic review

Ghazala Shaheen1 | Muhammad Akram2 | Farhat Jabeen3 | Syed Muhammad Ali Shah2 |

Naveed Munir4,5 | Muhammad Daniyal6 | Muhammad Riaz7 | Imtiaz Mahmood Tahir4 |
Aymen Owais Ghauri8 | Sabira Sultana2 | Rida Zainab2  | Muslim Khan9

1
University College of Conventional
Medicine, Islamia University of Bahawalpur, Abstract
Bahawalpur, Pakistan Urinary tract infection (UTI) is one of the most severe public health problem affecting
2
Department of Eastern
both sexes but females are more susceptible due to the differences in urogenital and
Medicine, Directorate of Medical
Sciences, Government College University‐ reproductive anatomy, physiology and lifestyle. As in UTI, different parts of the uri-
Faisalabad, Faisalabad, Pakistan
nary tract are affected and morbidity due to UTI is more common in women of all
3
Department of Zoology, Government
College University‐Faisalabad, Faisalabad,
ages and older men. Due to multi‐drug resistant strains and high recurrence rate, UTI
Pakistan has become a major socioeconomic burden. The current review article was aimed to
4
College of Allied Health describe the natural therapeutic strategies to manage and cure the UTI. For this pur-
Professional, Directorate of Medical
Sciences, Government College University‐ pose, different databases including Google Scholar, Cochrane database, and PubMed
Faisalabad, Faisalabad, Pakistan etc. were explored. Inclusion criteria were any research article investigating the cur-
5
Department of Biochemistry, Government
rent therapy of UTI. It was found that microbial infections including Escherichia coli,
College University Faisalabad, Faisalabad,
Pakistan Enterococcus faecalis and Klebsiella species are the major causes of UTI with different
6
TCM and Ethnomedicine Innovation signs and symptoms including painful urination or dysuria, hematuria, urinary ur-
& Development International
Laboratory, Innovative Materia gency, burning micturition, frequent urination, nausea, and vomiting. Antibiotics like
Medica Research Institute, School of trimethoprim, sulfamethoxazole, quinolone etc. as the first choice of the drug are
Pharmacy, Hunan University of Chinese
Medicine, Changsha, China used worldwide. However, due to microbial resistance, several life‐threatening side
7
Department of Allied Health effects, repeated high doses, high cost and low efficacy of these antibiotics moti-
Sciences, Sargodha Medical
vated the researchers to explore natural remedies for the treatment of UTI. Herbal
College, University of Sargodha, Sargodha,
Pakistan medicines are effective to combat bacterial resistance with high efficacy, and easy
8
Faculty of pharmacy, Rayaz College of availability with minimal or no side effects. For these reasons it has attained the at-
Eastern Medicine, Jinnah University for
Women, Karachi, Pakistan
tention of researchers wanting to explore the herbal treatment of UTI. Vaccinium
9
Department of Chemistry, Kohat University macrocarpon, Tribulus terrestris, Trachyspermum copticum, Cinnamomum verum and
of Science and Technology, Kohat, Pakistan Hybanthusenn easpermus are some common medicinal plants reported to have thera-
Correspondence peutic potential for the management and cure of the UTI. Although herbal medicines
Muhammad Akram, Department of Eastern have more potential over conventional medicine but more discoveries are required to
Medicine, Directorate of Medical Sciences,
Government College University‐Faisalabad, explore the phytoconstituents and their mechanism of action responsible for the
Faisalabad, Pakistan. management and cure of UTI.
Email: upr2014@yahoo.com

KEYWORDS
chemical constituents, Escherichia coli, herbal medicines, microbes, natural remedy,
nutraceuticals, safety, uropathogens, UTI

Clin Exp Pharmacol Physiol. 2019;46:613–624. © 2019 John Wiley & Sons Australia, Ltd |  613
wileyonlinelibrary.com/journal/cep  
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614       SHAHEEN et al.
1 |  I NTRO D U C TI O N
Urinary tract infection (UTI) is a contagious infection among male
and female and may affect different parts of the urinary tract
system like kidneys, urinary bladder, ureter and urethra espe-
cially lower urinary tract system including the urinary bladder and
urethra. The chances of UTI are very high when the number of
causative agent increases above 10 000 CFU/mL in a urine culture
1
or urine analysis. Approximately, 3%–8% girls and 1% of boys
are clinically diagnosed with UTI in developed countries like the
United States and Europe, with approximately seven million cases
of UTI reported annually. 2,3
Healthcare‐associated UTI (HAUTI)
prevalence among different healthcare professionals was reported
as 12.9% in the United States, 19.6% in Europe and 24% in devel-
oping countries like India, Pakistan and Bangladesh. Further, it was
found that the prevalence of UTI in urology departments is 5.1%.4
The main predisposing factors are sex, age, history of UTI, sexual
activity and diabetes. Urinary tract infection is more common in
diabetic patients and older people that are more prone to infection
than the young. Prevalence of UTI is greater in female as compared
to male, however, the prevalence of UTI is greater in uncircum-
cised males than in circumcised males. Sexually active females are
more prone to UTI particularly those using spermicidal agents and
diaphragms for contraception because of immune suppression in
such females. UTI in pregnant women may cause premature de-
livery and high blood pressure. Spread of infection to the kidney
is more common in pregnant women due to their weakened im-
mune system during pregnancy. UTIs are one of the most com-
mon bacterial infections in women accounting for nearly 25% of
all infections with around 50%–60% of women experiencing UTI in
their lifetime. Higher rates of UTIs are found in post‐menopausal
women due to the lack of oestrogen, pelvic prolapse, increased
peri‐urethral colonization by Escherichia coli, loss of Lactobacilli sp.
in the vaginal flora and diabetes mellitus. 5 tose the microbes. However, some microbes multiply and make bio-
It has been observed that childbearing age women are more
prone to recurrent UTI; the other factors are frequent coitus act and
spermicidal usage. Childbearing females also act as the source of in-
6
fection for infants and children. Urinary catheterization increases
the chances of UTI. Some chronic diseases also act as risk factors
for UTI such as diabetes, kidney failure, prolonged corticosteroid
therapy, and intake of immune‐suppressive drugs for autoimmune
diseases. Obstructions in the urinary tract system due to prostate
enlargement, repeated pregnancies, tumour, stone in the kidneys,
ureter, urinary bladder and catheterization of the bladder are the
other predisposing factors.
The major causative agents are E. coli, Enterococcus faecalis
and Klebsiella species. Pseudomonas spp., Stapylococcus spp. and
7
Proteus vulgaris are rare bacteria responsible for UTI. E. coli origi-
nating from the intestine is generally harmless, but if it reaches the
opening of the vagina during washing or after sexual intercourse,
then it may enter and colonizes the urinary bladder to cause in-
fection. In younger girls, the causative agent is Staphylococcus
saprophyticus subsp. saprophyticus (ATCC 15305), while in elderly
age women, the causative organisms of UTI in most of the cases
are E. faecalis (ATCC 49532) and Proteus mirabilis Hauser (ATCC
29906). Ureaplasma urealyticum (ATCC 27618) and Mycoplasma
hominis (ATCC 27545TTR) rarely cause UTI and these are less
hazardous microorganisms. Clinical manifestations of UTI include
strong and persistent urge to urinate, burning sensation when uri-
nating, passing frequent and small urinary volume. Other clinical
manifestations include urine appearance as cloudy, red, bright
pink, bloody and strong foul‐smelling urine. Pelvic pain occurs
in women especially in the center of the pelvis and around the
area of the pubic bone. There may be fever depending upon the
severity of the infection. Nausea and vomiting can present as an
associated feature. 8
Antibiotics are generally preferred for the treatment of patients
of symptomatic UTI which result in long‐term alteration of the nor-
mal microbial flora of gastrointestinal tract and female vagina and
ultimately resistance development in microorganisms.9 Altered mi-
crobiota do not colonize the niches which increased the risk of mul-
tidrug‐resistant uropathogens to infect. So, it can be argued that the
‘golden era’ of antibiotics is waning. Therefore, the need for rational
and alternative treatments is increasing.10,11 The main objective of
this systematic review is to describe the UTI with its different types,
pathogenesis, investigation and herbal medicine as alternative strat-
egies for its management.
1.1 | Pathogenesis
Uropathogens are pathogens which are present in the gut and con-
taminate the peri‐urethral area during uncomplicated UTIs. Such
pathogens present in urethra move to the bladder where adhesion
molecules and pilli help them to invade and colonize the superficial
umbrella cells. Host immune response in the form of inflammation
and neutrophilic infiltration in the infected area helps to phagocy-
films in the urinary bladder upon the evasion of the immune system.
Different types of toxins and proteases from bacteria stimulate the
host cell damage, and survival of bacteria during the release of vital
nutrients which promote the movement of microbes to the kidneys.
Colonized bacteria in the kidneys cause host tissue destruction due
to the release of toxins from bacteria and bacteremia might occur
if the pathogen crosses the tubular epithelial barrier in the kidneys.
On the other hand, in complicated UTIs, uropathogens reach the
bladder as in uncomplicated UTI. But during complicated UTI, the
bladder defensive environment must be compromised to cause the
infection. Catheterization is the most common reason for a compro-
mised bladder. In catheterization, fibrinogen makes a house on the
catheter and acts as the source of pathogen attachment. Then, mi-
crobes multiply and promote epithelial damage infecting the kidneys
by bacteria resulting in bacteremia.11,12 The infecting bacteria in UTI
may enter the urinary tract from the rectum during sexual activity
and then ascend towards the urinary bladder. Literature reports in-
dicated that vaginal environment, when changed due to any cause
or especially the loss of H2O2‐producing Lactobacilli, then females
SHAHEEN et al.
become prone to developing E. coli related UTI which causes 80% of
13
infections in healthy individuals. However the Escherichia coli may
have entered the body through the urethra, it is cleared naturally by
the body defense system after a few months but in individuals with
low immunity, it may persist for some months and can cause infec-
tion in individuals with low immunity.14
2 | C L A S S I FI C ATI O N
Urinary tract infections are divided into two types; complicated and
uncomplicated.
In uncomplicated cases of UTI, the urinary tract system function
is normal.
In complicated UTI, urinary tract is not normal systematically.
Infections are further categorized as follows.
2.1 | Isolated infection
An isolated infection means that there is a gap of 6 months be-
tween two episodes of infection. It mostly involves women under
30–40 years age.
2.2 | Unresolved infection
Unresolved infections mean one attempt has been made to kill mi-
croorganism, but the microorganisms did not respond to therapy.
2.3 | Re‐infection
As indicated that in this type, re‐infection is common in patients who
have cleared the previous infection with different types of antibiot-
ics but again suffered from infection.14
3 | U TI R E L ATE D CO N D ITI O N S
3.1 | Cystitis
It is the inflammation of the urinary bladder. Cystitis is caused by bac-
teria present in the faecal flora that colonize the vaginal and peri‐ure-
thral openings and ascend towards the bladder. Many microorganisms
become dead in urine because urine is naturally acidic, and it has high
urea concentration.15,16 E. Coli binds to α d‐Mannose, a monosaccha-
ride (sugar) that is present in the bladder.17 Enterococci and non‐E. coli
aerobic Gram‐negative rods account for 5%–10% of UTI.
3.2 | Pyelonephritis
Pyelonephritis denotes the infection that spread to the kidneys and
this involves the upper urinary tract. The clinical features of pyelo-
nephritis are more complicated than the lower UTIs. When bacteria
from bladder moves upward and causes infection in the kidneys,
then it is known as pyelonephritis. In some cases, the bacteria may
|
      615
reach the kidney through the bloodstream, but this is rather a rare
cause of pyelonephritis.18,19
3.3 | Complicated and uncomplicated infections
Most urinary infections occur in women who are otherwise healthy;
these are termed as uncomplicated infections. Complicated pyelone-
phritis (or cystitis) occurs when upper (or lower) UTI are associated
with urinary tract malfunctioning, and conditions causing long‐term
inflammation. They include anatomical or functional defects of the
urinary tract, recent urinary tract catheterization and are associated
with a wider range of infecting organisms than in uncomplicated in-
fections. However, Klebsiella and Proteus appear with increased fre-
quency in complicated UTI. 20
3.4 | Asymptomatic bacteriuria
In this, bacteria appear in two consecutive urine samples in the ab-
sence of typical symptoms. It appears in women of all ages but is
more common in elderly women with diabetes. Asymptomatic bac-
teriuria is universal in catheterized patients. 21
3.5 | Recurrent cystitis
A recent Cochrane systematic review has described by Albert et al22
that recurrent UTI (RUTI) is defined as 2–3 episodes of UTI during
1 year. According to literature reports about UTI, the two episodes
of infections may occur during the last 6 months. The recurrent UTI
is much more difficult to differentiate from the relapse, but the dif-
ference is that the causative organisms may be different in case of
recurrent infection, but they are the same in case of relapse. 23
3.6 | Urethral syndrome
When the clinical features of UTI are present, but the urine is not
positive for the bacteria, this condition is known as a urethral syn-
drome. 24 Between a quarter and a half of the patients come to the
hospital with the complaints of lower urinary tract bacterial infec-
tion. 25 It may either be due to microorganisms, transmitted during
sexual activity or there may be another cause such as trauma, medi-
cations, or chronic diseases such as diabetes. 26
3.7 | Interstitial cystitis
Interstitial cystitis can provoke UTI. In this case, the bladder wall
is inflamed and irritated, accompanied by the frequency and ur-
gency of at least 6 months duration. It occurs more commonly in
young to middle aged women due to unknown cause. In the United
States, over one million people are affected by interstitial cystitis.
According to an official survey conducted by Grover et al27, 575 in
every 100 000 women have interstitial cystitis. The prevalence of
bladder problems is 10 times higher in children than in the general
population of interstitial cystitis patients. 27
 |
616       SHAHEEN et al.

and a specificity of 41%–86%. Other advanced techniques including

3.8 | Investigations
ultrasound, intravenous pyelogram, cystoscopy, and computerized
It could be investigated that which type of organism causes UTI tomography could be used in detecting congenital structural uro-
and which type of corresponding treatment is required as a result genital anomalies.31
28,29
of urine culture and sensitivity testing. Based on positive urine
culture, UTI could be defined as urine culture having more than 105 
4 | M A N AG E M E NT O F U TI
CFU/mL and in symptomatic patients urine culture with 103 CFU/
mL for diagnosis of acute cystitis and urine culture with 10 4 CFU/
4.1 | Prevention of UTI
mL for acute pyelonephritis diagnosis might be enough.15 Lifshitz
et al30 reported that urine culture remained positive up to 2 weeks Recurrent UTI may be prevented by identifying the causes and its
even after treatment in cases of chronic UTI or recurrent UTI (mid- prompt treatment (Figure 1). According to The National Institute for
stream or ‘clean‐catch’ technique is used for culture). Urine complete Health and Clinical Excellence guidelines, recurrent UTI may be pre-
examination especially for the investigation of pus cell and nitrate vented by curing constipation, improving the dysfunctional elimina-
is a method with great specificity (50%) and very high sensitivity tion syndromes and guiding the patients to drink more fluid so that
(80%–90%), by either the dipstick or microscopy. But some non‐ni- bladder remains clean from the microorganisms.32
trate producing bacteria like Staphylococcus saprophyticus might give
false results with the dipstick method for UTI diagnosis. Dipstick test
4.2 | Prophylaxis
could also be beneficial for the determination of leukocyte esterase,
an enzyme produced by neutrophils with a sensitivity of 72%–97% Urinary tract infection can be prevented in the following ways.

Methenamine Hippurate (as prodrug)

1- Kidney A

Herbal Medicines B
Urinary Alkalization
C
H Oral Immunomodulators
(Phytoconstituents)
E G J D-Mannos (also Derived from some medicinal plants)

Vaginal Vaccination

Cranberry H
F
Topical Estrogen/ Phytochemicals E G J I
as stimulants or pro-hormones
F
F D
Intravesical hyaluronic acid D
Chondroitin sulfate D
(Use Both in male and female but frequently in female)
D
Probiotics (From Natural/ Prescribed Microbial flora)
2- Male Urinary and Reproductive organs 3- Female Urinary and Reproductive organs

F I G U R E 1   Alternative strategies to manage UTIs both in males and females. Data to reconstruct the figure were adopted and modified
from different sources79-83
TA B L E 1   Commonly used herbs for urinary tract infection

Serial no. Botanical name Local name Family to belong Parts used Method of use Active phytochemicals References
84
1 Prunella Vulgaris Self‐heal Lamiaceae Leaves, Stems Salads Phytosteroids, tannins, lupeol, D‐camphor
SHAHEEN et al.

and fenchone, cyanidin, delphinidin,

beta‐sitosterol,
85
2 Camellia sinensis L. Green Tea Theaceae Leaves Dry unprocessed leaves, spray‐dried Phenolic compounds, glycosides, alkaloids
aqueous extract
86
3 Cichorium intybus L. Chicory Asteraceae Leaves Powder of leaves is taken Flavonoids, Terpenoids, Tannins, Saponins,
Cardiac glycosides,
87
4 Caesalpinia nuga (L.) Lata Fabaceae Leaves, roots Powder of root and leaves Flavonoids, Carbohydrates, Glycosides,
Aiton Phenols, Saponins, Tannins
88
5 Brassica nigra L. Left Sorsa Brassicaceae Seed Seeds are grinded to take Flavonoids, alkaloids, Sterols, Saponins,
Glycosides, Steroids, Tannins,
89
6 Bidens pilosa L. Hairy Asteraceae Whole herb Extract of entire plants is taken Alkaloids, Flavonoids, Steroids,
Beggartides Anthraquinones, Tannins, Glycosides,
Saponins,
90,91
7 Azadirachta indica A. Neem Meliaceae Fruit, leaves, Powder of bark and leaves, fresh Alkaloids, Polyphenols, Saponins, Flavonoid,
Juss. Bark fruits are taken Anthraquinones, Cardiac glycosides,
Terpenoids, Terpenes, Steroids, Tannins,
92
8 Apium graveolens L. Apium Apiaceae Aerial part Extract of fresh leaves and fruits Alkaloids, Tannins, Steroids, Flavonoids,
taken Terpenoids, Phenols,
93
9 Andrographis Kalmegh Acanthaceae Leaves Extract of Fresh leaves Alkaloids, Anthracene, Steroids, Glycosides,
paniculata Quinines, Flavonoids, Phenols, Tannins
Wall. ex. Nees.
94
10 Pimpinella anisum L. Mithazira Apiaceae Seed Seeds as such are taken Alkaloids, Flavonoids, Cardiac Glycosides,
Terpenoids, Carbohydrate, Phytosterols
95
11 Malva sylvestris L Mallow Malvaceae Leaves Used in salad Alkaloids, Tannins, Phenols, Flavonoides,
Saponins,
96
12 Hibiscus rosa‐sinensis Jaba Malvaceae Flower Decoction of flower is performed Flavonoides, Steroids, Tannins, Glycosides,
L. before taken Phenols, Saponins, Phlobatannins,
Terpenoids,
97
13 Cucumis sativus L. Sasa Cucurbitaceae Seeds Grinded seeds with rock salt are Cardiac glycosides, Tannins, Phytosterol,
taken Terpenoids, Saponins,
98
14 Clitoria ternatea L. Aparajita Fabaceae Root Special preparation with rice water is Phenols, Flavonoids, Saponins
made to take its roots
99
15 Ananus comosus (L.) Anarus Bromeliaceae Leaves, fruit Leaves and fruit juice in combined Alkaloids, Phenols, Flavonoids, Glycosides,
Merr. form Tannin, Phytosterols,
100
16 Acacia nilotica Delile Babool Fabaceae Leaves, Gum, Gum Paste and leaves with cow's Flavonoids, Cardiac Glycosides,
Bark milk are taken orally. Powder of Anthraquinones, Tannins, Saponins
|

Bark
      617

(Continues)
 618       | SHAHEEN et al.

4.3 | Post intercourse regimen

References
Some studies showed that only prophylactic antibiotics alone are

104,105
not enough for the prevention of UTI in sexually active people. It

103

106
102
101

is reported that if they use some drugs after intercourse, the infec-

Alkaloids, Glycosides, Flavonoids, Saponins,

Terpenoids, Phenols, Glycosides, Saponins
tion may be prevented. The use of spermicidal cream containing

alkaloids, Amino acid, Cardiac glycosides,

Saponins, Phenols, Tannins, Terpenoids,
Flavonoids, Alkaloids, Phenols, Ascorbic

Alkaloids, Steroids, Flavonoids, Sterols,

nonoxynol‐9 in combination with antibiotics is prescribed to prevent

Flavonoids, Phytosterols, Steroids, infection.33,34

Glycosides, Terpenoids, Tannins

4.4 | Topical treatment
acid, Steroids, Tannins
Active phytochemicals

Glycosides, Saponins

Phenolic, Terpenoids
Some topical creams are also used for the prevention of UTI espe-
cially the creams that contain povidone and iodine. These creams are
antiseptic and used to suppress the inflammatory processes locally.
Topical vaginal estriol prevents UTI in post‐menopausal women by
modifying the vaginal flora.35

4.5 | Functional foods
Powder of leaves and roots taken

With sugar seedless fruits taken

Some foods can also play a preventive role in UTI such as cran-
Extract of the fruit is taken

berry juice; it has anti‐adhering activity that inhibits E. coli

Extract of Bark is taken

from adhering the bladder walls. 36 Meta‐analysis showed that

35% decrease in infection had been found in females with re-
Seeds are taken
Method of use

current UTI using cranberry for 12 months. McMurdo et al 37

reported that cranberry extract (500 mg/kg) administered for
orally

orally

6 months decreased the UTI to the same level as the trimetho-

prim (100 mg). Sialic acid is found in cranberry extract that has
anti‐inflammatory and painkilling effect. It can assist in alleviat-
ing manifestations of UTI. Cranberry is not suggested in active
Root, leaves
Parts used

UTI but is effective in decreasing the rate of recurrent UTI 37

(Figure 1).
Seed

Fruit

Fruit
Bark

4.6 | Vaccines
Family to belong

Rhamnaceae

Vaccines for UTI have not been discovered properly until now. In
Myrtaceae
Malvaceae

Malvaceae
Fabaceae

some people, extracts of bacterial antigens were given orally for

immunization against microorganism and the study results showed
that it is good in stimulating the immune system and decreases
the severity of infection. 38 Some researchers used the extract of
Local name

FimH to stimulate the immune system through vaginal application,

but the results are not encouraging. 39 No research on vaccines for
Bhendi
Jamun

Takkul
Paatri
Mung

UTI has reported reaching to phase III trials. No vaccine is more

effective than antibiotic prophylaxis. Studies reported that the
Zizyphus jujuba Mill.
Syzygium cumini (L.)

innate and adaptive immune responses to the microorganisms of

Abutilon indicum L.
Botanical name

UTI are responsible for the inflammatory action causing UTI by

Vigna mungo L.

esculentus (L.)
Abelmoschus

suppressing the innate immune system leading to the reduced cy-

TA B L E 1   (Continued)

Moench

tokine production and neutrophils.40 Re‐infection stimulates the

Skeels

specific T cells which are responsible for the immunity.41 A number

of studies have been conducted to discover a vaccine for UTI but
no valuable results have been achieved so far.42,43 There is a dire
Serial no.

need to conduct more studies for the development of the vaccine

for UTI.
20

21
18
17

19
SHAHEEN et al.
4.7 | Immunoprophylaxis
Immunoprophylaxis plays an important role in the prevention of re-
current UTI, and these are taken through the oral route as an al-
ternative to antibiotics. It was investigated that Uro‐Vaxom E. coli
extract (Terra‐Laba, Zagreb, Croatia) as oral immune prophylaxis
significantly prevents the UTI throughout more than 6 months.44
Furthermore, Schulman et al45 reported that the plants extracts are
efficient; effective and tolerable for UTI treatment as well as de-
crease the use of antibiotic resulting in reduced rate of recurrent
UTI.
4.8 | Probiotics
Lactobacillus is a probiotic, well reported for the prevention of UTI
and it may be given orally or vaginally. Lactobacilli create an unfa-
vorable environment so that the urinary microorganisms cannot
46
survive in urine. Scientists are now focusing on the role of pro-
biotics in the management of UTI and have proven that it is benefi-
cial against different microorganisms. It is observed that probiotics
have a protective role in the UTI.47 Reid et al48 reported that pro-
biotic Lactobacilli prevent the UTI by strengthening the immune
system and decreasing the ascending rate of microorganisms from
the rectum, therefore, can interact with colonization and survival
of pathogens. Lactobacillus plantarum and Lactobacillus rhamnosus
showed the anti‐adherence activity of E. coli to gastrointestinal tract
in vitro. This may be due to an increase in the production of mucin,
which has a protective action on the epithelial cells, and it inhibits
the adhesion of microorganisms. Another study showed that oral
Lactobacillus rhamnosus (1 × 109 CFU/1 billion) and a Lactobacillus
reuteri (1 × 109 CFU/1 billion) could recover the vaginal Lactobacillus
49-53
96% compared to 53% in controls (Figure 1).
4.9 | Antibiotic treatments
The standard treatment of lower UTI is comprised of cotrimoxazole,
amoxicillin, and nitrofurantoin. These drugs are prescribed for a sin-
gle dose or a short course of 7–14 days. For upper UTI cotrimoxazole
or amoxicillin are used for the short course of 7–14 days. For UTIs,
the first treatment choice is antibiotics, but now the E. coli strains
have become resistant to antibiotics worldwide. Currently, the com-
bination of trimethoprim and sulfamethoxazole (TMP‐SMX) is the
standard treatment of UTI but the bacteria have become resistant
to these drugs also, so quinolone antibiotics have now overtaken
TMP‐SMX as the choice to treat UTIs. Researchers predicted that
resistance might develop to these drugs as well.54
Many studies have been conducted which showed that antibiotic
prophylaxes greatly decreased the chances of infection. Antibiotics
suppress the activity of microorganisms. Nitrofurantoin is a very
effective antibiotic used for the prophylaxis of UTI because it sup-
presses the rectal flora. The results of this therapy are variable; some-
times it showed 100% results, but sometimes the patients suffered
|
      619
from UTI while having the antibiotic prophylaxis. The reason may
be that some microorganisms are resistant to some antibiotics. 55,56
4.10 | Medicinal plants
Medicinal plants have been used since ancient times, because they
have beneficial effects, to treat and control various disorders.57 Due
to fewer reported side effects, cost effectiveness, easy availabil-
ity, lack of bacterial resistance and tolerance towards the patients
with UTI even at the start of the 21st century, medicinal plants have
gained more and more popularity as well as reliability worldwide.57
Moreover, 80% of the world population and more than 30% of phar-
maceutical formulations are dependent upon medicinal plants, as
reported by WHO.58 The exact mechanism of herbal medicines used
to treat UTI is still not well understood due to lack of research, but it
was reported that phytochemical constituents acted as nutraceuti-
cals and immunomodulators, boost body oxidant status or provided
antioxidant compounds, prevent attachment of microbes as well as
halt the proliferation or multiplication of microorganisms and some
might act as microcidal (Figure 1). These diverse properties of me-
dicinal plants are due to the presence of various phytochemical con-
stituents including alkaloids, anthraquinones, flavonoids, glycosides,
phenols, saponins, steroids, sterols, tannins, terpenoids, triterpe-
noids, phytosterols, hydrocarbons, mono and sesquiterpenes, phlo-
batannins and many others medicinal plant secondary metabolites.
Flowers, leaves, bark, fruit, seeds and even whole parts of medicinal
plants were ingested to treat UTI and these parts or their extracts
are consumed orally as sole preparation or might be mixed with dif-
ferent other foods or drinks like water, honey, milk, juices and black
pepper etc. The dose of herbal preparations also depends upon sex,
age and current health status of the patient.59 So, this review article
will be helpful to find out natural remedies effective in the manage-
ment and treatment of UTI. Some of the commonly used herbs with
the main phytochemical constituents responsible for their effect are
described below with their common name, family, botanical origin
and functional use for the treatment of UTI and their mode of ac-
tions are given in Table 1.
4.10.1 | Vaccinium macrocarpon
Belongs to family Ericaceae. The common name is cranberry. It pre-
vents the attachment of bacteria to uroepithelial cells. It contains
catechin, anthocyanidin, flavanols, quercetin, myricetin and pheno-
lics that are supposed to be responsible for such activities. 23
4.10.2 | Tribulus terrestris
It belongs to the family Zygophyllaceae. The common name is
Kharkhasak, Gokhru. It is diuretic, anti‐cancer, anthelmintic, antibac-
terial and aphrodisiac. It contains active constituents for therapeu-
tic values such as gitogenin, chlorogenin, tribuloside, kaempferol,
 |
620       SHAHEEN et al.
rhamnose, saponins, stigmasterol, β‐sitosterol, neo‐tigogenin, heco-
60
genin, tribulosin, neohecogeninglucoside and cinnamic amide.
4.10.3 | Trachyspermum copticum
It belongs to family Apiaceae. The common name is Ajwain. It is an-
timicrobial due to terpinene, p‐cymene, beta pinene, thymol, xylene,
palmitic acid and oleic acid.61
4.10.4 | Cinnamomum verum
It belongs to family Lauraceae. The common name is Dar chini,
Cinnamon. It is antioxidant and antibacterial. It contains phytochem-
icals such as camphor, cinnamaldehyde, eugenol, trans‐cinnamyl ac-
etate and proanthocyanidins.62
4.10.5 | Hybanthus enneaspermus
It belongs to family Violaceae. The common name is spade flower. It
is antioxidant, antidiabetic and antibacterial. It contains flavonoids,
phenolic, terpenes, alkaloids, phenols, saponins, anthraquinones,
glycosides and tannins that possess therapeutic values.63
4.10.6 | Phyllanthus amarus
It belongs to family Phyllanthaceae. The common name is Jangli
Amli. It is hypoglycemic, hypotensive, diuretic and antibacterial. It
contains tannins, flavonoids, triterpenoids, lignins, gallic acid, gera-
niin, corilagin, niranthin and phyllanthin.64
4.10.7 | Moringa oleifera
It belongs to family Moringaceae. The common name is Sohanjna. It
is antipyretic, anti‐inflammatory, and antibacterial. It contains thio-
carbamate glycoside, acetylated carbamate, amino acids, tocoph-
erol, moringine, spirochin and kaempferol.65
4.10.8 | Terminalia chebula
It belongs to family Combretaceae. The common name is Hareer, har.
It is hypolipidemic, antibacterial. It contains chebulin, tannic acid,
gallic acid, beta sitosterol, fatty acids and betulinic acid.66
4.10.9 | Allium sativum
It belongs to family Amaryllidaceae. The common name is Lehsan.
It is hypolipidemic and antimicrobial. It contains volatile oil, allicin,
alliin, acrolein, phytocidin, diallyl‐disulphide and diallyl‐trisulfide.67
4.10.10 | Ocimum sanctum
It belongs to family Lamiaceae. The common name is Tulsi. It is antibacte-
rial, antipyretic, anti‐inflammatory, analgesic and antipyretic. It contains
flavonoids, polyphenol, flavonols, flavones, carnosic acid, beta sitos-
terol, luteolin, myrtenal, apigenin, rosmarinic acid, eugenol, vicenin and
orintin.68
4.10.11 | Zingiber officinale
It belongs to family Zingiberaceae. The common name is Adrak,
Sondh. It is antibacterial, digestive and anti‐inflammatory. It con-
tains zingiberene, zingiberol, α‐zingiberene, shogaols, gingerols and
dihydroparadols.69
4.10.12 | Boerhavia diffusa
It belongs to family Nyctaginaceae. The common name is Biskhapra.
It is antibacterial, antioxidant and antidiabetic. It contains arachidic
acid, behenic acid, saturated fatty acids, vitamins C, lignin, phenolics,
steroids, glycosides and boeravinone B.70
4.10.13 | Apium graveolens
It belongs to family Apiaceae. The common name is Celery seed. It is
diuretic, antioxidant and anti‐inflammatory. It contains succinic acid,
beta sitosterol, falcarindiol, oplopandiol, lunularic acid, lunularin,
5,8‐dimethoxy psoralen, trans‐cinnamic acid, isofraxidin, trans‐feru-
lic acid and eugenic acid.71
4.10.14 | Arctium lappa
It belongs to family Asteraceae. The common name is Burdock. It is
antimicrobial and diuretic. It contains arctigenin, arctiin, lignins, fla-
vonoids, caffeoylquinic acid, cynarin, chlorogenic acid, caffeic acid,
quercetin, quercitrin, luteolin and rhamnoside.72
4.10.15 | Juniperus communis
It belongs to family Cupressaceae. The common name is Juniper. It
is diuretic and antibacterial. It contains oxygenated sesquiterpene,
monoterpene hydrocarbons, β‐pinene, limonene, sabinene and
myrcene.73
4.10.16 | Mentha piperita
It belongs to family Lamiaceae. The common name is Peppermint. It
is antispasmodic and antibacterial. It contains menthone, menthol,
limone, menthofuran and pulegone.74
4.10.17 | Taraxacum officinale
It belongs to family Asteraceae. The common name is Dandelion.
It is diuretic and antibacterial. It contains nitriles, norisopre-
noids, methyl branched aliphatic acids, phenylacetic acid and
dehydrovomifoliol.73
SHAHEEN et al.
5 | D I S CU S S I O N
In UTI, the bacterium may grow in any part of the urinary tract sys-
tem including kidneys, urinary bladder, ureter and urethra.74,75 In the
developing world like India, Afghanistan, Pakistan, Bangladesh etc.,
especially in the tropical world, UTI is the main cause of childhood
morbidity and mortality.76 Approximately, 3%–8% girls and 1% of
boys are diagnosed with UTI in developed countries like America,
Japan and Europe.77 In developing countries, the most common
infection reported by physicians is UTI. Some chronic diseases act
as risk factors for UTI such as diabetes, kidney failure, prolonged
corticosteroid therapy, intake of immune‐suppressive drugs for au-
toimmune diseases. Obstruction in the urinary tract due to prostatic
enlargement, pregnancy, tumour, catheterization of the bladder is
another predisposing factor. The major causative agents are E. coli,
E. faecalis and Klebsiella species. Pseudomonas, Staphylococcus, and
Proteus vulgaris are rare bacteria responsible for UTI in subtropical
78
areas.
Herbal drugs are safe, economical, and easy to use. The major
advantage of these herbal drugs is that bacteria have not developed
resistance against them. The major herbs used in the treatment
of UTI are listed in Table 1. The problem of resistance that occurs
due to the use of conventional medicine can be overcome by using
these herbal medicines. Microbial resistance to herbal medicine is
not reported yet because medicinal plants contained a wide range of
phytochemical constituents which are mostly responsible for their
beneficial effects as well as the synergetic effects (Figure 1). The
current research paper only enlisted the phytochemicals responsi-
ble for the treatment of UTI. The exact mechanisms of these herbs
and their phytochemical constituents that are responsible for the
effect on UTI are still to be investigated. Further research is needed
to elucidate clearly the mode of action of these phytochemicals.
Additional studies are needed to confirm the phytoconstituents
that are responsible for the treatment of UTI. That is why further
studies at molecular levels and tools to identify the mechanism of
actions of phytoconstituents to eradicate the pathogenic microbes
are required.
6 | CO N C LU S I O N
Urinary tract infection among the most common diseases in devel-
oping, as well as in the developed, world with a higher incidence rate
in females. A variety of antibiotics are being employed to treat UTI
according to the severity of the disease. But antibiotic drug resist-
ance has become an emerging challenge for clinicians to overcome
the UTI associated uropathogens. Alternatively, some remedial for-
mulations such as herbal preparations proved to be the best thera-
peutic modality and considered as the supernatural blessing for the
treatment of UTI. However, advanced tools like RNA sequencing to
directly analyze uropathogens for the diagnosis of UTI, proper docu-
mentation of medicinal plants by using barcoding methodology and
their bioactive ingredients responsible for antimicrobial activities
|
      621
required greater attention. In the end, we could hope that exten-
sive studies on highlighted problems may open a new vista for the
preparation of novel herbal formulations in alternative medicine for
the treatment of UTI.
7 | FU T U R E PROS PEC T S
Screening of medicinal plants should be done to explore the specific
anti‐UTI therapeutic potential. Furthermore, structural elucidation
and stereochemistry from isolated compounds from potent plants
may be significantly helpful for novel drug designing for treatment
of UTI.
C O N FL I C T O F I N T E R E S T
Authors declare that there is no competing interest for authorship
of this review.
ORCID
Rida Zainab  https://orcid.org/0000-0002-3335-5436
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How to cite this article: Shaheen G, Akram M, Jabeen F, et al.
Therapeutic potential of medicinal plants for the management
of urinary tract infection: A systematic review. Clin Exp
Pharmacol Physiol. 2019;46:613–624. https://doi.
org/10.1111/1440-1681.13092