# Novel Insights on Plant Extracts to Prevent and Treat Recurrent Urinary Tract Infections
## 6 Plants Commonly Used in the Treatment of rUTI
### Promising Medicinal Plants to Treat rUTI  
#### 6.2.1 P. granatum  
Pomegranate  
Pomegranate (_P. granatum_ L.) is a fruit-bearing shrub in the _Punicacea_ family, described initially throughout the Mediterranean region but widely cultivated in the present [45]. Pomegranate has been known for centuries for its multiple health benefits, including antimicrobial activities, due to various biologically active substances from all plant parts, including the fruit juice, peel, arils, flowers, and bark [45; 46]. Different parts of the pomegranate (fruit, horns, skin, and seed) have been extracted utilizing an extraction procedure based on maceration with various extraction solvents (water, ethanol, methanol, ethyl acetate, etc.). Aqueous and organic extracts from the fruits and by-products have antibacterial constituents, such as hydrolyzable tannins (punicalagin and penicillins, ellagic acid, and gallic acid) synergized with bioactive flavonoids, i.e., myricetin, quercetin, and anthocyanins, e.g., cyanidin-3-glucose and pelargonidin-3-galactose [47; 48]. Seed extracts have uroobacterial activity against different _E. coli_ clinically isolated from patients suffering from urinary tract infections [49]. The researchers suggested that therapeutic antioxidants and natural glycosides are supposed to act as molecular decoys to prevent the adhesion of pathogenic bacteria from hosting cells, thereby inhibiting future pathogenesis, but further studies are required to confirm it [49]. Pomegranate peel is a waste obtained through juice processing. It contains significant amounts of bioactive compounds (total phenols, flavonoids, anthocyanins, tannins, and proanthocyanidins) with variations between different cultivars and drying processes [50]. The primary polyphenols in pomegranate that have been shown to have antimicrobial, antioxidant, and anti-inflammatory bioactivities are ellagitannins and anthocyanins, which are concentrated in the fruit's peel and kernels. Aqueous pomegranate peel extract's antimicrobial and antioxidant effect againstropathogenic _E. coli_ has recently been reported [51]. The inhibitory activity was dose- and pH-dependent, with a minimum inhibitory concentration value of 0.6 mg/mL that produced a reduction of up to 80% of the adhesion index, accompanied by a decrease in motility and ornithine decarboxylation. In comparison, total inhibition was reported at a 1.2 mg/mL value. Thus, the peel extract inhibits the biofilm formation and cellular adherence of _E. coli_ and reduces bacterial motility and the polyamine production that helps bacteria to survive during the oxidative stress produced by some antibiotics (fluoroquinolones, aminoglycos, and cephalosporions) [51]. Different parts of _P. granatum_ (pericarp, leaves, flowers, and seeds) have antibacterial activities against antibiotic-resistant _E. coli_ strains, but the ethanol extract of pericarp has a significant effect on animal _E. coli_ isolates [52]. Another significant result showed by this study is that water extracts were not as active as organic extracts against tested _E. coli_. In another study, a methanolic section of pomegranate fruit pericarp tested with ciprofloxacin against extended-spectrum \(\beta\)-lactamase (ESBL)-producing _E. coli_ showed an enhancement of ciprofloxacin activity, probably due to the bacterial efflux pump inhibitor activity of the polyphenic constituents from the extract [53]. However, the isolates exhibiting a high level of ciprofloxacin resistance did not respond to ciprofloxacin-extract combinations, and the authors consider that this result is due to target site modification that is not influenced by plant inhibitor molecules [38]. An aqueous extract of pomegranate leathery exocarp showed antifungal and antibacterial effects, including on _E. coli_, related to an anti-acetylcholinesteraseerase inhibitory effect and antioxidant activities. This promising antimicrobial effect was compared to the synthetic drug activity. At an extract concentration of 10 mg/mL, the result against _E. coli_ was equal to kanamycin.