Western herbal remedies for Urinary Tract infections

Urinary Tract Infections (UTIs) are one of the most common bacterial infections, with a frequency of 50%-60% in mature females [1] Urinary tract infections could be uncomplicated or complicated. Uncomplicated UTIs affects individuals with no neurological or structural deformities in urinary tract . Uncomplicated UTIs could be separated into infection of lower UTIs (cystitis) and upper UTIs (Pyelonephritis) [2]. Underlying factor for cystitis are gender, former UTI infection, genetic susceptibility, vaginal infection, sexual activeness, overweight and diabetes [3], whereas uncomplicated UTIs arises from presence of factors debilitates host immune defenses including renal transplantation, renal failure, urine retention due to neurological disorders, immunosuppression, presence of foreign bodies with urinary tract like indwelling catheters [4]. In the United states, the indwelling catheters results in 70-80% of complicated UTIs [5] with a total of one million cases per year [6]. Etiology of UTIs includes Gramnegative , grampositive and fungi. Uropathogenic Escherichia Coli (UPEC) is the most common bacterial of all types of UTIs. In the cases of Uncomplicated UTIs, UPEC is followed in frequency by K. pneumoniae, S. saprophyticus, Enterococcus faecalis, Group B Streptococcus (GBS), Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida spp. [7], whereas in complicated UTIs, UPEC is followed in frequency by Enterococcus spp., K. pneumoniae, Candida spp., S. aureus, P. mirabilis, P. aeruginosa and GBS [8].

women suffering from UTIs that those used Uvacin (an over-the-counter product including uva-ursi) showed faster recovery duration comparing with non-users of this product.
Only 14% of women was taken Uvacin under an advice, whereas only 1% without an advice [32]. Also, results for clinical trial on 57 women suffering from recurrent UTI that UVA-E product, which composed of water and alcohol extracts of leaves of A. uva-ursi and root extract of dandelion (Taraxacum offi cinale) showed that this product was effective in prevention of recurrent UTIs [33].
Leaf extract of this plant includes set of compounds as hydroquinone glycosides (mainly arbutin), fl avonoids, tanins and terpenoids, and iridoids, but the antibacterial activity towards variety of pathogens including E. coli, the most causative agent of UTIs, was attributed to Arbutin Figure 1 [31].     [64].
The aqueous extract of whole plant found to have diuretic and natriuretic activity in rabbits [65]. Aqueous extracts of areal parts of this plant given orally at small dose (4 mg/kg/h) and big dose (24 mg/kg/h) resulted in an elevation of diuresis of 11 and 84% , respectively, and natriuresis of 28 and 143%, respectively, which indicated for potential diuretic activity [66].
The ethanolic extracts of this plant at dose 1 1 g/kg (p.o) had no diuretic activity , but in dose of 500 mg/kg (i.p), it resulted in increased urine output [67]. In rat model , an increase of 20% in urine production was reported after administration of oral dose of 1g/kg of 10% decoction of leaves powder [67]. The diuretic activity of nettle leaf is approximately equal to 25% of that achieved by hydrochlorothiazine (25 mg/kg) [68]. showed strongest activity against S. aureus and B. subtilis [73].
Dandelion leaf extract has potent diuretic activity as those of furosemide [74]. Dandelion exhibits high diuretic activity much more than those of other herbs as equisetum and juniper berry [75,76].
A clinical trial study on human for confi rmation of diuretic activity of dandelion leaves showed that ethanol extracts of dandelion exerted diuretic action on sample size of 17 volunteers [77].
Cranberry. Vaccinium macrocarpon known as large Cranberry or American cranberry belongs to the family Ericaceae. it is an evergreen groundcover shrubs that grow up to four meters. Cranberry is native to North America. Its fl ower is pink colored and berries are reddish black in color. This plant is widespread throughout cool temperature northern hemisphere [78].
Cranberry used by native American indians for treatment of UTIs [79]. Chemical composition of cranberry fruit is water (Up to 88%), Catechins, anthocynidins, Flovonoids, Triterpinoids, in addition to high concentration of Vitamin C of about 200 mg / kg of fresh fruit [79]. The anthocyanidins and proanthocyanidins (PAC) are responsible for plant defense against microbes [79,80]. Numerous studies reported a connection between administration of Cranberry and prevention of UTIs [80][81][82][83][84]. The underlying mechanism of ability of cranberry in prevention and treatment of UTIs is based on prevention of bacterial adherence to uroepithelial cell, hence, stop colonization and invasion of bacterial pathogens.
This property is attributed to two components of cranberry, Native to central parts of America and distributed along parts of North America, and distributed to all over the world [87].

Fructose and proanthocyanidins (PACs
Corn silk (CS) or stigmas is the yellowish threads extends from female fl ower of Z. mays [88]. Historically, the native Indian   pain related with such complaints [107].
Animal Rat model confi rmed the diuretic activity of couch after oral and intra-peritoneal administration of aqueous extracts of this plant [108]. Two uncontrolled clinical studies showed positive effects of hydrochloric extracts of couch on cases of cystitis, irritable bladder, urethritis and prostatitis [109] in addition to cystitis and prostatic adenoma [110].
The diuretic activity of couch is attributed to sugar " Mannitol " present in high percentage of chemical constituents in this herb, and it is called as an 'osmotic diuretic' as it is     and In Vivo [138][139][140][141][142]. The antibacterial activity of H. canadensis is attributed to the alkaloid compounds, berberine [142,143], that has antibacterial activity against Gram-positive pathogens, including MRSA [144]. Root extract are rich in alkaloids as berberine, hydrastine and canadine. Figure 7. [145]. Root/leaf extract of goldenseal showed anti-bacterial activity towards S. aureus and Campylobacter jejuni, whereas showed minimum impact towards benefi cial bacterium Lactobacillus acidophilus [146]. The effl ux pump inhibitory activity in H. candensis is associated with areal part extracts [145]. Five bands in thin layer chromatogarapy and Bio-autographic studies were related to the effl ux pump inhibition activity. The chemical identity of those bands could not be diagnosed with GC/MS due to its volatility, but LC/MS analysis revealed a list of possible compounds in those bands [146].
Inhibition of effl ux pumps is very important to overcome the drug-resistance problem of bacterial pathogens. Effl ux pumps work to pumps out the antibiotic and increases the minimum inhibitory concentration (MIC) of the antibiotic. Thus, the inhibition of effl ux pumps would render bacterial cell sensitive to antibiotic and decrease its MIC to be more effective towards bacterial pathogens [147].
Leaf extracts of showed potent effl ux pumps inhibition activity towards different pump superfamilies in both S. aureus and C. jejuni. These extracts resulted in reduction in MICs of antimicrobials at least 2 fold reduction for antimicrobials against S. aureus, and 16 folds reduction in MICs for antimicrobials directed against C. jejuni by combining antimicrobials agents.
Leaf extracts works to inhibit MDR effl ux pumps via repressing genes coding for these pumps [146].  [148]. Traditionally, buch used as a herbal medicine for treatment of different disease and to achieve different activities as a diuretic and treatment of urinary disorders, respiratory and gastrointestinal disorder [148]. The primary use of buchu leaves in western herbal medicine is for treatment of genitourinary diseases like infections of kidney , bladder, urethra and prostate in addition of kidney stones and incontinence linked to prostate [149].
The antibacterial activity of buchu leaves have been attributed to essential oil of the oil glands located on underside of leaves. These oils consists of monoterpene, diosphenol.
These oil absorbed by the stomach and excreted in kidney to pass through genito-urinary tract and exert its antibacterial effects towards bacterial pathogens [149].
The GC-MS reference analysis for structure of essential oil of buchu showed that EO of Agathosoma crenulata had high content of pulegone of 50-66%, whereas those of A. betulina has a percentage of 15-35% of diosphenol, 12-30% of pseudodiosphenol, 4-26% of isomenthone and 5-24% of limonene. urinary bladder. The anti-spasmodic drugs acts on smooth muscles of bladder, thus, increasing the capacity of bladder and effectively decrease or evenly eliminate urge incontinence [153]. The spasmolytic action of essential oil of A. betulina may be attributed to healing effects of the plant for UTIs.
Oregon grape (Mahonia aquifolium). Mahonia is the second largest genus of family Berberidaceae and composed of nearly 70 species that are native to central and north of America and eastern parts of Asia [154]. M. aquifolium is native to Pacifi c Northwest of the United States of America. Owing to its yellow fl ower and red fruit, it spread to other parts of the world to be used as an ornamental plant in gardens [155].
The anti-bacterial activity of M. aquifolium is attributed to two of major alkaloids, of stem bark, berberine chloride and oxyacanthine sulphate and shown to have bactericidal bactericidal activity towards nice species of oral pathogens. Figure 9. [155]. The antimicrobial activity of berberine extract was evaluated towards 17 bacterial and fungal species. Bacterial species were E. coli , P. aeruginosa, S. aureus and B. subtilis, whereas fungal species were Aspergillus niger, Penicilium chrysogenum, Trichoderma viride, Aureobasidium pullulans, Mycrosporum gypseum ,Fusarium nivale, Trichoderma viride, Saccharomyces cerevisiae and Candida albicans. All extracts showed antimicrobial activity against all test microbes [163].
Berberine is responsible for the golden yellow appearance of Oregon grape root. Berberine is also found in few other plants as Chinese goldenthread, goldenseal and desert berberry. Berberine acts to prevent attachment of E. coli to uro-epithelial cells through reduction of expression of genes encoding Fimbriae. The anti-infectious activity of Berberine in is attributed to suppressive activity of this compound for genes responsible for synthesis and assembly of fi mbrial subuints that is results in prevention of adhesion and colonization of E. coli associated UTIs Figure 10 [163].

Conclusions and recommendations
The fourteen medicinal plants illustrated in details above showed various pharmaceutical activities as Anti-microbial, Anti-infl ammatory, anti-oxidant, anti-adhesive, diuretic activities associated with treatment of UTIs, and other activities related with treatment of other human diseases. It highly recommended to study the therapeutic activities of all medicinal plants alone and in combination with each other to obtain highest pharmaceutical activities for treatment of UTIs In Vitro and In Vivo. Further phytochemical studies are required to reveal the chemical composition for all potential compounds responsible for all pharmaceutical activities of the fourteen medicinal plants. Toxicological and genetical studies concerning all potential adverse effects, mutagenic and carcinogenic activities of those medicinal plants are highly recommended to complete the picture of pharmaceutical importance of those medicinal plants.  [148].
Others found that essential oils of A. betulina and A. crenulata had antibacterial action towards Enterococcus hirae and P. aeruginosa and very low activity against E. coli , S. aureus and Saccharomyces cerevisiae [151]. O'Brien (2005) confi rmed that essential oils of A. betulina had no antimicrobial activity towards urinary tract pathogens, but only anti-oxidant activity [152].
Lis-Balchin reported that extract of A. betulina acts on cyclic adenosine monophosphate and exerts spasmolytic action [151]. Antispasmodic drugs relax the smooth muscles of the