INTRODUCTION:

A urinary tract infection (UTI) occurs by bacteria. An infection arises when pathogens from the rectal area migrate into the urethra to the bladder and multiply there. Bacteria tend to begin their journey at the urethra. Bacteria may develop and produce an infection. Urethritis is a term for an infection that merely impacts the urethra. A bladder infection is called "cystitis" which occurs due to bacteria migrating to the bladder and multiplying there. Pyelonephritis is an infection of the kidneys caused by bacteria that may travel up the ureterif the infection is not addressed rapidly¹. Infections of the urine tract are infections in any of the structures that make up the urinary system that have been transmitted by pathogenic organisms (which may involve bacteria, fungus, or parasites). The clinical symptoms of UTIs are linked to the urinary tract segment damaged by the pathological organism (s), the severity of the infection, and the patient's capacity to develop an immunological response to it². The discussion of UTIs sometimes involves other structures, such as the prostate, epididymis, and vagina, that eventually link with or share intimate anatomical proximity to the urinary tract since they may either promote or end up in UTIs. Since they are not UTIs in concept, this article will concentrate on them very briefly³. It serves as an indicator of the inflammatory reaction to an infection with bacteria⁴. The majority of individuals agree that having sex might give rise to a urinary tract infection. Many individuals believe that during a sexual act, microbes are mechanically transmitted into the urinary system. There is no doubt that sexually transmitted infections (STDs) are the root cause of UTI organisms; several diseases, like gonorrhoea and chlamydia, are extremely contagious and can be readily transmitted between partners in sexual activity⁵. In addition, we planned the advancements in our comprehension of this disorder throughout the past fifty years⁶. The research report titled "Childhood "Urinary tract Infections" was predicated on research done at LLR Hospital in Kanpur by Garg, et al. The goals were to research the treatment outcomes for children with UTIs, as well asthe isolated organisms’ clinical features, bacteriological features, and trend of antibiotic susceptibility. There was a total of 186 children in the research group, including 61 babies, who had UTIs. In all age groups, notably among the youngest, girls exceeded boys in number⁷. There was debate in the 1960s about the concept of "serious" pyuria, even though it was previously understood that pyuria might also occur in other circumstances, notably severe dehydration, trauma, instrumentation, and calculi. As far as UTI detection states, it was believed that a quantitative bacterial count was the most precise approach⁸.

Women are more inclined than men to get a UTI (81% of cases), with a peak incidence in the 16–35 age range. After the first UTI episode, around 27 percent of women suffer another infection within six months and 48% within a year. Each episode of this medical condition results in approximately six days of impairment, and the morbidity is increasing in the United States. Approximately 15% of community antibiotic prescriptions are for UTIs, with over 1.6 billion dollars being spent on them annually⁹. Women are diagnosed with urinary tract infections much more often than males, and the expense of treatment is high. By figures, a minimum of one-third of allIn the US, women are diagnosed with UTIs by the time they turn 24. 10.8% of women that were 18 years of age or beyond claimed to have a minimum of one UTI in the preceding 12 months, according to research by Foxman and colleagues in a telephone survey that involved random digit dialing and 2,000 womenWomen are more likely to get urinary tract infections. 50% of women will experience a recurrent UTI within a year, while 12% of Women who previously suffered from an infection will ultimately get another one¹⁰. Infections of the urinary tract are among the most common justifications for GP visits; as reported by to data from Sweden, it stands as the ninth most frequently occurring reason (or 1.6% of all outpatient consultations) for this reason¹².

Urine is often sterile. It does contain fluids, salts, and debris but is generally free of bacteria, viruses, and fungi. When microscopic organisms-typically bacteria from the digestive system-stick to the urethral opening and start to grow, an infection results. most illnesses originate from the E. coli bacteria, that are often found in the colon. Infections of the urine tract(UTIs) associated with catheter use are usually caused by Streptococcus faecalis, E. coli, Proteus mirabilis, P. aeruginosa, and Klebsiella pneumoniae, among others. Other species that can cause UTIs include Actinomycetes, Nocardia, Candida, and Mycobacterium tuberculosis. Furthermore, chlamydia and mycoplasma may be linked to sexually transmitted infections (UTIs)¹³. Urinary tract infections were most frequently caused by Escherichia coli (62.88%), with Klebsiella coming in second. (23.18%), In order of prevalence, Proteus mirabilis accounted for 7.02%, followed by Citrobacter (5.35%), Staphylococcus saprophyticus (1.34%), and Candida albicans (0.33%). E. coli was the most prominent cause of UTI in kids of all ages. In 57.14% of cases in the neonatal age group, E. coli was determined to be the etiological cause of UTI. E. coli was the most frequent cause of UTI in kids of all ages¹⁴.

Females suffering from a UTIs usually have the following symptoms:

1. Frequent, often small-volume urination

2. Urinating while burning

3. Cloudy or red urine

4. Pelvic discomfort

5. Vaginal discharge^15,16.

The female genital and urinary tracts are affected by two main hormones during the development cycle: progesterone and estrogen. Although the two tracts originate from the same embryonic tissues, they vary during human development. As a result, both systems are subject to steroid and sexual hormone consequences¹⁷. Hormones from both genders affect UTI among different species; progesterone is the most prevalent hormone during the follicular period. In contrast to the luteal stage, this results in a spike in bladder oscillation in adult females, which can be detected by a reduction in bladder expansion¹⁸.

The clumping bamboo species Bambusabambos, also referred to as Indian thorny bamboo, is indigenous to a number of South and East Asian nations¹⁹. Corn, sugarcane, and other grasses constitute a part of the Graminae (Poaceae) family, which also includes bamboos. The entire plant is utilized in Ayurveda as a diuretic, astringent, and laxative for inflammatory diseases²⁰. Tall, woody bamboo with multiple, prickly stems that are tufted on a sturdy root stock is how it is defined. It curves at the top and reaches a height of thirty to forty meters. Fruit and flowering only happen once in a lifetime, usually between September and May^21,22. Bamboo shavings water phase extract (WEBS). Aspergillus niger, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, Penicillium citrinium, and Saccharomyces cerevisiae were all susceptible to theantibacterial activity of WEBS in concentration-dependent manner²³. The plant's antibacterial properties can be referred to the existence of α-amyrin and phenolic chemicals²⁴.

Biological Species Plant: Bambusa Bambos

Kingdom: Plantae

Family: Poaceae

Group: Angiosperms

Synonymous names: Bambusaarundinacea, Bambusabambos, Bambusaorientalis,

Significant levels of Stigmast-5, 22-dien-3β-ol, and Stigmast-5-en-3β-ol-β-D glucopyranoside were recovered from Bambusa during the phytochemical examination. The two medications' synergistic hypoglycemic impact is well-supported by data. This plant has yielded two newly identified compounds, namely 17, 20, and 20-tri dimethyl-20α-isoprenyl oleanane, and one unique acid, eicosanoid dicarboxylic acid, along with two previously identified compounds, namely αamyrin acetate and urs-12-en-3β-ol-β-D-glucopyranosid. Benzoic acid, hydrogen chloride, reducing sugar, resins, and waxes are among the active components of shoots^25,26.

Urease is a component of the pathogenicity of many pathogenic bacteria. It is necessary for both the growth of a host species and the maintenance of bacterial cells in tissues^27,28. Urease's enzymatic action damages human cells. A key marker for several bacterial infections is the presence of ureolytic activity. Antibodies found in human serum identify urease, another immunogenic protein²⁹.

MATERIALS AND METHODS:

Ligand Curation and Preparation:

The proposed derivatives were drawn using PyRx's Pub Chem ID, while the structures of the Bambusabambos compounds employed for urinary tract infection activity were retrieved from PubChem. The structures were then docked using the structures that satisfied Veber's Law, the ADME threshold, and the Lipinski rule of five after being compressed into a single SDF file using the Open Babel Program. Moreover, the structures were confirmed online for ADME and according to the Lipinski scale of five. programs like SwissADME. Molecular weight, MlogP value, number of rotatable bonds, number of donors of hydrogen bonds and acceptors, topological surface area, and bioavailability score were all reported by the SwissADME.

Protein Preparation:

The Protein Data Bank [PDB] provided the structure of urease, which was downloaded in PDB format. The protein's active site, ligand site, and amino acid sequence were all determined using the BIOVIA Discovery Studio Visualiser 2021 v21.1.0.20298. In addition, To the protein structure, polar hydrogens were added, which was preserved in PDB format for docking analysis, while water and other heteroatoms were eliminated.

Active Site Preparation:

It is anticipated that the PDB, Discovery Studio, and literature will contain the active site for 5LXX. To make sure that the target protein binding site is covered by the grid box configuration of the PyRx software, the right predicted amino acid residue needs to be selected. Every protein's ligand-binding affinity was shown and recorded.

Molecular Docking Studies:

PyRx, a virtual screening software interface, received the uploaded chemical compounds and protein structures that were chosen. Using PyRx's Open Babel tool, chemical compounds and protein structures were saved in the'. pdbqt' format. The forward option in PyRx was used to build the grid box for the active binding site. The size and coordinates of the grid box were altered by adhering to the box's border line or by entering values into the appropriate box. Using Autodock Vina, PyRx findings are separated into distinct conformers. The docking output files were then analyzed using Discovery Studio Visualizer to look for interactions between chemical compounds and protein amino acids. Based on non-covalent bond interaction and a higher docking result, the most effective conformer was chosen. While collecting pictures of the docking location and interactions, an amino acid label was applied, the background color was changed to white, and the images were stored as 2D and 3D files. Their synthetic accessibility and ADME properties were also determined using the online SWISSADME tool.

Therotical Prediction of ADMET Parameters:

The compounds with the highest scores were sent from the docking simulation to SwissADME and the pkCSM web server in SMILES format. Following that, these substances were exposed to toxicity and bioavailability prediction techniques including Lipinski's rule of five. The SwissADME online program was used to calculate the properties of compounds, absorption, distribution, metabolism, and excretion (ADME). The resulting calculation served as a prediction for the drug-likeness of the BambusaBambos compounds used in the docking analysis. All that is done to compare the expected drug features with the established drug ADME features.

RESULT AND DISCUSSION:

To clarify the interactions between the chosen phytochemicals and important UTI-related targets, such as bacterial enzymes implicated in virulence and disease, molecular docking simulations were carried out. The compounds' binding affinities and ways of interaction with their individual protein targets were revealed by the docking studies. Numerous compounds from Bambusabambos shown substantial binding affinities to the active sites of the chosen targets, according to the docking experiments. The stabilization of ligand-protein complexes is dependent on hydrogen bonding, hydrophobic contacts, and It-Tt stacking interactions, which were the characteristics of these interactions. These interactions point to possible inhibitory effects on the enzymatic processes that are essential to the pathophysiology of UTIs. The likelihood of utilizing Bambusabambos to generate UTI inhibitors is highlighted by the combined results of molecular docking and ADMET prediction. The compounds found by computational screening exhibit intriguing interactions with targets linked to urinary tract infections (UTIs) in addition to good drug-like characteristics. These drugs are good prospects for more preclinical and clinical research, according to the positive ADMET profiles. It is possible to successfully give and maintain them in therapeutic concentrations in vivo based on their projected pharmacokinetic properties.

Table No. 02: ADMETproperties ofphytochemicals byPkCSM

Sr. No.	Pub-ChemId	Absorption				Distribution
		Intestinal-Absorption (Human)	P-Glyco-protein Substrate	P-Glycoprotein Substrate I Inhibitor	P-Glycoprotein Substrate II Inhibitor	VDss -(Human)	BBB Per- meability	CNS Per- meability


		Numeric (%absorbed)	Categorial (Yes/No)	Categorial (Yes/No)	Categorial (Yes/No)	Numeric (logLkg^-1)	Numeric (Log BB)	Numeric (logPS)
1	493570	36.107	No	No	No	-0.196	-1.552	-4.144
2	1794427	36.377	Yes	No	No	0.581	-1.407	-3.856
3	445858	93.685	No	No	No	-1.367	-0.239	-2.612
4	637542	93.494	No	No	No	-1.151	-0.225	-2.418
5	72	71.174	No	No	No	-1.298	-0.683	-3.305
6	8468	78.152	No	No	No	-1.739	-0.38	-2.628
7	107721	43.382	No	No	No	-0.26	-1.021	-3.572
8	1130	100	Yes	No	No	0.565	-0.368	-2.969
9	243	100	No	No	No	-1.64	-0.22	-2.002
10	126	87.261	No	No	No	-.101	-0.217	-2.002
11	204	51.948	No	No	No	-0.387	-0.566	-3.679
12	938	94.099	No	No	No	-1.015	-0.323	-2.869
13	68262	100	No	No	No	-0.177	-0.269	-2.94
14	971	79.42	No	No	No	-0.62	0.017	-3.415
15	247	100	Yes	No	No	-0.304	-0.214	-2.804
16	6540685	0	No	No	No	-1.341	-1.847	-4.742

Continue Table No. 02

Sr. No.	Pub-ChemId	Metabolism							Excretion	Toxicity
		Substrate		Inhibitors					Total Clearance	AMES Toxicity
		CYP							Total Clearance	AMES Toxicity
		2D6	3A4	1A2	2C19	2C9	2D6	3A4	Numeric (log mLmin^-1kg^-1)	Categorial (Yes/No)
		Categorial (Yes/No)							Numeric (log mLmin^-1kg^-1)	Categorial (Yes/No)
1	493570	No	No	No	No	No	No	No	0.7	Yes
2	1794427	No	No	No	No	No	No	No	0.307	No
3	445858	No	No	No	No	No	No	No	0.623	No
4	637542	No	No	No	No	No	No	No	0.662	No
5	72	No	No	No	No	No	No	No	0.551	No
6	8468	No	No	No	No	No	No	No	0.628	No
7	107721	No	No	No	No	No	No	No	0.194	No
8	1130	No	No	Yes	No	No	No	No	1.056	No
9	243	No	No	No	No	No	No	No	0.707	No
10	126	No	No	No	No	No	No	No	0.565	No
11	204	No	No	No	No	No	No	No	0.559	No
12	938	No	No	No	No	No	No	No	0.652	No
13	68262	No	No	No	No	No	No	No	0.627	No
14	971	No	No	No	No	No	No	No	0.766	No
15	247	No	No	No	No	No	No	No	0.326	No
16	6540685	No	No	No	No	No	No	No	0.46	No

Table 3:Drug-Likeness properties of phytochemicals bySwissADME

Srno.	PubChem ID	MW (g/mol)	mLogP	HBA	HBD	MR	TPSA	nRot	Lipinski’s Rule (Ro5)	Veber's Rule	Ghose's Rule	Egan’s Rule	Muegge'sRule
1	493570	376.36	-0.54	8	5	96.99	161.56	5	1	1	1	1	1
2	1794427	354.31	-1.05	9	6	83.5	164.75	5	1	1	1	1	2
3	445858	194.18	1	4	2	51.63	66.76	3	0	0	0	0	1
4	637542	164.16	1.28	3	2	45.13	57.53	2	0	0	0	0	1
5	72	154.12	0.4	4	3	37.45	77.76	1	0	0	3	0	1
6	8468	168.15	0.74	4	2	41.92	66.76	2	0	0	0	0	1
7	107721	311.29	-2.1	8	5	71.53	143.4	4	0	1	1	1	0
8	1130	265.35	0.05	3	2	73.26	104.15	4	0	0	0	0	0
9	243	122.12	1.6	2	1	33.4	37.3	1	0	0	3	0	1
10	126	122.12	0.79	2	1	33.85	37.3	1	0	0	3	0	1
11	204	158.12	-1.85	3	4	39.55	113.32	2	0	0	4	0	3
12	938	123.11	-1.13	3	1	31.2	50.19	1	0	0	3	0	1
13	68262	168.15	-1.27	4	0	40.08	52.6	2	0	0	0	0	1
14	971	90.03	-1.51	4	2	15.27	74.6	1	0	0	4	0	2
15	247	117.15	-3.67	2	0	28.35	40.13	2	0	0	4	0	1
16	6540685	550.47	-2.51	14	8	135.13	247.11	8	3	1	3	1	3

CONCLUSION:

This study investigated the potential of phytochemicals from Bambusabambos as urinary tract infection (UTI) inhibitors using in silico ADMET prediction and molecular docking simulations. Understanding the pharmacokinetic characteristics, safety profiles, and inhibitory actions of these drugs against important UTI-related targets was made possible by the integrated computational method. The ADMET predictions indicated that several phytochemicals from Bambusabambos exhibit favorable drug-like properties. Molecular docking simulations elucidated the binding interactions between the identified phytochemicals and bacterial enzymes crucial for UTI pathogenesis. Continued research efforts are essential to validate these findings experimentally and advance them towards clinical applications, addressing the critical need for new treatments against UTIs in clinical practice.

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Received on 01.07.2024 Revised on 07.12.2024

Accepted on 10.04.2025 Published on 03.05.2025

Available online from May 05, 2025

Asian J. Pharm. Res. 2025; 15(2):114-120.

DOI: 10.52711/2231-5691.2025.00019

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Sr No.	PubChem ID	Binding Affinity (kcal/mol)	Interacting Residue	Type of Interaction
1	493570	-8.4	LYSA:390, ASPA:28, PHEA:477, ASNA:387, SERA:322 ARGB:268, CYSA:323, GLNB:327, ARGB:481, TYRB:275, ASPB:28	Van Der Waals
			ASPA:27, ASPB:27, GLNA:379, LYSB:390	Conventional Hydrogen Bond
			ASPA:28, PHEA:477	Carbon Hydrogen Bond
			GLYA:324	Pi Donor Hydrogen Bond
			PHEB:477	Pi-Sigma
2	1794427	-8.2	GLYB:324, GLYA:324, GLNA:327, PHEA:477, GLNA:379, ASPA:28, ALAA:382, ASNA:378	Van Der Waals
			ARGB:268, GLNB:327, CYSB:323, ASNA:387, LYSB:390, ASPA:27	Conventional Hydrogen Bond
			PHEB:477	Pi-Pi T Shaped
3	445858	-7.8	ASPB:27, ASPB:28, GLNB:29, SERB:30, LYSA:480	Van Der Waals
			ASPA:476, PHEA:477	Carbon Hydrogen Bond
			ASPB:376, ASNB:378, ASNA:393	Conventional Hydrogen Bond
			LYSA:390	Pi-Alkyl
			TYRA:395	Pi-Pi T Shaped
4	637542	-7.7	ASPB:27, ASPB:28, GLNB:29, SERB:30, ASNB:378, ASNA:393, ASPA:476, PHEA:477	Van Der Waals
			ASPB:376	Conventional Hydrogen Bond
			TYRA:395	Pi-Pi T Shaped
			LYSA:390	Pi-Alkyl
5	72	-7.1	ASPA:27, SERA:30, ASNA:378, ASNB:393, TYRB:395, PHEB: 477.LYSB:480	Van Der Waals
			ASPA:376, ASPB:476	Conventional Hydrogen Bond
			GLNA:29	Pi-Cation
			LYSB:390	Pi-Alkyl


Fig No. 01: 2D and 3D interaction of Riboflavin	Fig No. 02: 2D and 3D interaction of Chlorogenic Acid

Fig No. 03: 2D and 3D interaction of Ferulic Acid	Fig No. 04: 2D and 3D interaction of 4-Hydroxycinnamic Acid