Shraddha Institute of Pharmacy, Washim.
These days, urinary tract infections are rather common. Every year, about 150 million people suffer from urinary tract infections (UTIs). In contrast to males, women are more likely than men to suffer from urinary tract infections. It coexists with high rates of both morbidity and mortality. Any section of the system, including the kidneys, ureters, and urethra, can be affected by urinary tract infections. Unrestricted use of synthetic medications to treat these illnesses has resulted in numerous obstacles. Regular use of antibiotics damages the body's beneficial flora and has negative side effects. Traditional herbs have emerged as an effective alternative therapy in these situations and are now playing a major role. Pathogen bacteria, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus species, are the cause of urinary tract infections (UTIs). In certain situations, the development of antibiotic resistance results in therapeutic failure. Alternative remedies, such as the use of herbal plants like garlic (Allium sativum), which has antibacterial properties, are one way to get around this. The antibacterial, anti-biofilm, and anti-inflammatory qualities of the herbal remedies garlic (Allium sativum) and curcumin (Curcuma longa) have been investigated in relation to urinary tract infections (UTIs). Clinical evidence is sparse and inconsistent, however preclinical studies (in vitro, animal) show antibacterial efficacy against major uropathogens and reduction of virulence factors/biofilm production. Due to garlic's heat-labile bioactive and curcumin's limited aqueous solubility, formulation techniques (aqueous suspensions, nano formulations, complexes) have a significant impact on activity.
Any contamination in which germs are present and multiply inside any portion of the urogenital device, such as the kidneys, ureters, bladder, or urethra, is known as a tract infection (UTI). Tract infections were also explained by the irritation of the urinary transition epithelium caused by the presence of microorganisms in the tract. Bladder infections are another name for UTIs. These contaminants can affect the lower and upper urinary tracts, as well as the decreasing tractor now. The symptoms of cystitis, which characterize lower urinary tract infections, include dysuria (difficulty urinating), suprapubic pain (reduction in stomachache), and urgency and frequency of urination [1].
The bacteria that cause infections of the gastrointestinal system are basically Gram-poor germs. Escherichia coli, or E. Coli, is the most common type of vital. Antimicrobials are a common topic and part of the treatment for tract diseases. Sexual activity, the use of antibiotic resistance, the length of the monthly cycle, inherited traits, and bacterial pathogenicity are among the risk factors that are frequently present in UTIs [2]. Allium sativum, or garlic, is a member of the Liliaceous family. Garlic's antibacterial properties have been known for a number of years, and as a result, allicin, also known as daily thiosulfinate (2-propenyl-2-propanediol sulfonate), is the active ingredient Curcuma longa (family Zingiberaceae) contain curcuminoids, chieflycurcumin, known for anti-inflammatory and antimicrobial activities [3]. Combining Curcuma longa (turmeric) and Allium sativum (garlic) makes sense because of their broad antibacterial range, complimentary processes, and possible synergistic pharmacological activities that improve efficacy against urinary tract infections (UTIs). Allicin, ajoene, and diallyl disulfide are examples of organosulfur compounds found in garlic, whereas curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) are abundant in turmeric. By interfering with thiol-containing enzymes that are necessary for bacterial metabolism and by rupturing microbial cell walls, allicin directly kills bacteria. Curcumin suppresses host tissue inflammation and bacterial virulence through its anti-inflammatory, antioxidant, and anti-biofilm qualities. Together, these substances target distinct microbial pathways; curcumin reduces host inflammation and stops pathogen adherence, while allicin inhibits bacterial growth, creating a dual-action defense that is advantageous for the treatment of urinary tract infections [4]. ((1E,6E)-1,7-bis-(4-hydroxy-3-methoxyphenyl) curcumin One of the main active compounds in turmeric extract, which comes from Curcuma longa, a herb that belongs to the ginger family and is often grown in southern and south-western tropical Asia, is -hepta-1,6-diene-3,5-dione [5]. It has been demonstrated that curcumin exhibits direct broad spectrum antibacterial properties against both Gram-positive and Gram-negative bacteria [6–9]. By inhibiting the pathogen's virulence factors and enhancing host-mediated immunity, curcumin also functions as an immunomodulator, thereby reducing bacterial infections [10]. When used with certain conventional antibacterial medications, curcumin exhibits a strong synergistic or additive antibacterial effect, making it a promising broad-spectrum antibacterial adjuvant to permeabilize the bacterial membrane[11].
Table 1: Phytochemical Profile of the Selected Herbs [11].
|
Plant |
Major Active Constituents |
Pharmacological Actions |
|
Curcuma longa |
Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin |
Antimicrobial, anti-inflammatory, antioxidant, anti-biofilm |
|
Allium sativum |
Allicin, Ajoene, Diallyl disulfide, S-allyl cysteine |
Antimicrobial, antifungal, anti-biofilm, immunomodulatory |
Pathophysiology of Urinary Tract Infection
Over the past ten years, we have gained a great deal of knowledge on urinary tract colonization and infection, and significant new data has brought to light the intricate interactions between pathogen virulence factors and protective host variables that affect the risk of infection. The urethral mucosa serves as a barrier to prevent infectious attacks when the disease is absent. By attaching to particular mucosal receptors, some bacteria can circumvent this defense mechanism, potentially triggering a rapid inflammatory reaction in the host. As an illustration, P-fimbriated E. coli, which cause most symptomatic UTIs, attach to a glycosphingolipid receptor on the mucosal surface, initiating a number of inflammatory cascades, interacting with submucosal tissue, and occasionally causing direct invasion of deeper tissues and the bloodstream. [12]
Fig 1: Urinary Tract Infection
When gut-dwelling uropathogens pollute the periurethral region (step 1) and have the ability to colonize the urethra, simple UTIs start. The superficial umbrella cells are colonized and invaded (step 3) as a result of subsequent migration to the bladder (step 2) and pili and adhesin expression. Extracellular bacteria are cleared by host inflammatory responses, such as neutrophil infiltration (step 4). Some bacteria multiply (step 5) and create biofilms (step 6) in order to elude the immune system, either by invading host cells or by changing their morphology to make them resistant to neutrophils. These bacteria release vital nutrients that support bacterial survival and ascend to the kidneys (step 8) after producing toxins and proteases that destroy host cells (step 7) [13]Bacterial toxin generation and host tissue damage are the outcomes of kidney colonization (step 9). If the infection penetrates the kidneys' tubular epithelial barrier, UTIs may eventually develop into bacteraemia if treatment is not received (step 11) [14]The optimal medium for bacterial growth is urine; the presence of organic acids, high urea levels, and a pH below 5 render urine unsuitable for bacterial development. It is also recognized that frequent urinating lowers the risk of UTI.[15] Adhesins on the surface of bacteria that cause UTIs enable the organism to adhere to the mucosal surface. Furthermore, a small urethra facilitates the uropathogen's entry into the urinary tract. Premenopausal women have high levels of lactobacilli in their vagina, which inhibit uropathogen colonization. Antibiotic usage, however, can negate this protective effect.[16]
Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterococcus faecalis are the main culprits behind urinary tract infections (UTIs), which are among the most prevalent bacterial illnesses that impact the bladder, urethra, and kidneys. Bacterial adhesion, colonization, biofilm formation, epithelial invasion, inflammation, and oxidative stress are some of the pathogenic events that make up the pathophysiology of UTIs. Phytoconstituents from medicinal plants like Curcuma longa and Allium sativum can be used to therapeutically target these events.[17] Stretch receptors in bladder tissue allow a person to know when their bladder is full and transmit an impulse to the sacral region of the spinal cord. A person feels the need to urinate once the bladder contracts and the internal urethral sphincter muscle relaxes after around 300 milliliters of urine have accumulated (McCance & Huether, 2019).
Mechanistic Insights : How Turmeric and Garlic Work Against UTI
Mechanism of the Antibacterial Action of Curcumin
Fig 2: Curcumin
Turmeric is a member of the Zingiberaceae family of ginger. Since ancient times, it has been utilized as a spice and medicinal, and in more recent years, its potential in other disciplines has been realized. Sugars, proteins, resins, traces of volatile oils, and a substance known as curcuminoids—which contains curcumin (diferuloylmethane), demethoxycurcumin, and bisdemethoxycurcumin—are among the phytochemical components of turmeric. Curcumin, the most bioactive component of turmeric, is responsible for the main documented pharmacological effects of turmeric, which include anti-inflammatory, anti-tumor, anti-cancer, and antioxidant properties. The US Food and Drug Administration (FDA) has classified curcumin as generally regarded as safe (GRAS) because of its low toxicity, even at quite high doses.[19]It has been demonstrated that curcumin and its two analogs, DMC and BDMC, exhibit antibacterial action against a variety of microorganisms [20]. Research has indicated that curcumin cancause bacterial cell death by impairing the permeability and integrity of bacterial cell membranes in both Gram-positive and -negative bacteria [21]. Curcumin can directly insert into liposome bilayers thanks to its lipophilic nature, which increases the permeability of the bilayer [22]. Curcumin can insert deeply into the membrane in a trans-bilayer orientation, according to solid-state nuclear magnetic resonance (NMR) spectroscopy studies. This makes 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes disordered and affects exocytotic and membrane fusion processes [23]. At a 100 µM concentration, Tyagi et al. showed that curcumin might cause the cell walls of S. aureus and E. coli to permeate . The direct bacterial killing activity of curcumin against both Gram-positive and -negative bacteria may be explained by this membrane permeabilization feature [24,25]
Fig 3: Impact of turmeric and its principal bioactive
Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus epidermidis were among the several antimicrobial strains that were tested. Indium curcumin was found to have significant antibacterial potential against all tested strains, while curcumin showed potential antibacterial activity against all tested species. Indium diacetyl-curcumin was found to have an antibacterial effect against Staphylococcus aureus and Staphylococcus epidermidis, while diacetyl-curcumin had no antibacterial effect on any species. The MIC of curcumin against Staphylococcus aureus and Staphylococcus epidermidis was 187.5 µg/mL and 46.9 µg/mL, respectively, according to their analysis of the MIC of all the compounds against each of the antibacterial species. With MICs of 93.8 µg/mL and 23.4 µg/mL, respectively, the indium curcumin MIC was found to be marginally lower than that of the other two species mentioned above. According to their investigation, indium curcumin exhibits a greater antibacterial impact than curcumin. [25]
Antimicrobial activity of Garlic
Fig 4: Therapeutic properties of Allium sativum(garlic)
Escherichia coli that is eropathogenic. In UTIs, it is highly contagious. A uropathogenic condition is an infection that can be either simple or complex. One of the most frequent tract infections caused by bacteria is a UTI. Neonatals, preschool-aged girls, sexually active women, and older women and men can all have UTIs. Nowadays, several children repeatedly acquire urinary tract infections (UTIs), which are defined by recurrent infections. The issue that arises after taking antibiotics may be caused by improper medicine use. [26]
Anti-bacterial activity:-
In many parts of the world, garlic has been used for centuries to combat infectious diseases. Garlic has been shown in various studies to be beneficial against both gram-positive and gram-negative bacteria. Bacillus subtulis, Salmonella, E. Coli, Staphylococcus aureus, Escherichia coli, Micrococcus, Clostridium, and Mycobacterium are a few of them. Compared to its gram-negative counterpart, the gram-positive Staphylococcus aureus was more susceptible to the harmful effects of garlic. Garlic extract in liquid form has been demonstrated to be effective against healthcare-associated infection agents in hospitals, much like traditional antibiotics. Garlic extract was found to be effective against Streptococcus mutans, the main causative agent of dental caries, in both in vitro and in vivo studies.[27]
Anti – inflammatory activity :-
Extracts from garlic have anti-inflammatory properties. According to one study, taking garlic reduced the amount of inflammation and liver damage brought on by Eimeria papillata infections. Garlic oil primarily exhibits its anti-inflammatory properties by preventing the cytoskeleton's construction and disassembly processes. In inflammatory bowel disease (IBD), cytokines regulate a T-helper-1 (Th1) immune response that is primarily cell-mediated. Leukocyte cell proliferation and cytokine production are modulated by a number of chemicals that have been identified from A. sativum. When treating patients with IBD, whole blood and peripheral blood mononuclear cells (PBMCs) should be evaluated to determine any potential therapeutic benefits of garlic. Using multiparameter flow cytometry, the impact of garlic extract on leukocyte cytokine production was assessed in vitro at different doses.[28]
Anti-viral activity:-
UTI is a frequent tract infection caused by bacteria, and Uropathogenic Escherichia coli is very contagious in this condition. Uropathogenic conditions can be either difficult or simple. Among those infected are newborns, young children, women who are sexually active, and older women and men. Nowadays, several children repeatedly acquire urinary tract infections (UTIs), which are defined by recurrent infections. The issue that arises after taking antibiotics may be caused by improper medicine use.[29]
Anti -fungal activity:-
The garlic enzyme alliance produces allicin daily dithiosulfinate, which has been demonstrated to have broad range antifungal specificity. Garlic extract demonstrated a broad spectrum fungicidal effect against a wide range of fungi, including candida, torulopsis, trichophyton, cryptococous, aspergillus, trichosporon, and rhodotourula species. When combined with allicin, polymyxin B effectively combats a variety of yeast and filamentous fungus. Saccharo cerevisiae's plasma memberane permeability is increased by Hensel combination. It has been demonstrated that garlic inhibits the growth of fungal infections.[30]
Concept of herbal suspension for UTI
The idea behind a turmeric and garlic herbal suspension for a UTI is to combine the two herbs' antibacterial and anti-inflammatory qualities in a liquid form. According theory, the suspension helps fight the infection-causing bacteria and reduce inflammation by delivering these active ingredients to the urinary system. Despite its promise, this method is still being studied and should not be used in place of antibiotics in medical therapy.[31]
Table 2: Evaluation Parameter [31]
|
Parameter |
Purpose |
|
Appearance and color |
Visual inspection |
|
Sedimentation volume |
Physical stability |
|
Ph |
Chemical stability |
|
viscosity |
Flow behaviour |
|
Redispersibility |
Shake test |
|
Antimicrobial assay |
Agar diffusion against E. coli |
|
Stability study |
25oC and 40oC condition for 30-60 days |
The herbal suspension's concept Synergistic action:-
Turmeric and garlic are said to work in concert to produce a stronger antibacterial and anti-inflammatory effect than they would if taken alone. Alternative to antibiotics: Herbal alternatives are being investigated as a novel approach to infection management in light of the growing issue of antibiotic resistance. Garlic and turmeric have both demonstrated efficacy against germs resistant to antibiotics. Delivery target: In the form of a liquid suspension, the The bloodstream can absorb herbal extract.
Additionally, it may be able to transport active substances to the urinary system. The precise concentrations that can be administered to the urinary system and their therapeutic efficacy, however, require further investigation.Turmeric's function in the suspension Curcumin, the primary active ingredient in turmeric, has antibacterial and anti-inflammatory characteristics and is largely responsible for its therapeutic benefits.[32]
Anti-inflammatory: One of the main advantages of Because of its anti-inflammatory properties, curcumin may help lessen the discomfort and swelling brought on by UTIs. Antimicrobial: Curcumin has demonstrated effectiveness against a variety of bacteria in laboratory experiments, including E. coli, the most frequent cause of urinary tract infections. It functions by: damaging the membranes of microorganisms. preventing the development of biofilms, which shield bacteria from immune cells and medications.[33]Garlic's function in the suspension The active sulfur-containing chemicals in garlic, especially allicin, which is released when garlic is diced or crushed, are thought to be responsible for its therapeutic benefits. antibacterial: E. coli and other Gram-positive and Gram-negative bacteria have been shown to be susceptible to the broad-spectrum antibacterial action of garlic extract. It works by interacting with the thiol groups of enzymes that are necessary for the metabolism of bacteria. [34]
Synergy between antibiotics: Allicin's multi-target pathway hinders the development of bacterial resistance. Additionally, it can intensify the effects of traditional antibiotics. Immune system strengthener: Garlic is proven to increase the immune system, which improves the body's ability to fend against infections.[35]
Advantages of herbal suspension:-
Therapeutic benefits:-
Safe for long-term use with minimal side effects [37].
Evidence from preclinical and clinical studies:-
Direct clinical trials for treating UTIs:
I was unable to locate any sizable randomized controlled trials evaluating curcumin or garlic as the main courses of treatment for acute bacterial UTIs in people. The majority of clinical research on garlic and turmeric/curcumin focuses on cardiovascular or general antimicrobial/immune conditions, while the majority of research on garlic focuses on other indications (inflammatory illnesses, metabolic diseases).[37] Case series and brief/observational reports: Although tolerability and necessary dosages vary, case reports and a few clinical observations indicate that garlic extracts may exhibit antimicrobial activity in serum or urine following ingestion. For example, an earlier volunteer study discovered antifungal activity in serum or urine following high doses of garlic extract (with GI side effects at high doses). There is little and poor quality clinical data particularly demonstrating that standardized garlic or turmeric therapy resolves culture-positive UTIs.[38]In model systems, curcumin prevents the production of biofilms and exhibits synergy with some antibiotics (a helpful notion for supplementary therapy). According to some investigations, garlic components also interfere with biofilms and quorum sensing. The organism and antibiotic determine synergy.[39]
curcumin (turmeric): can enhance some antibiotics; has anti-inflammatory (NF-κB regulation), antioxidant, membrane-disrupting, and anti-biofilm properties. [40]
Garlic (allicin and related thiols) has antimicrobial properties that are broad and include immune-modulatory, antioxidant, and quorum-sensing inhibition.[41,42]
Future Direction :
Instead of substituting antibiotics for acute pyelonephritis or complex UTI, concentrate first on complementary therapy for uncomplicated cystitis and preventing recurring UTI. Symptomatic alleviation, anti-biofilm action, and recurrence risk reduction have the best clinical plausibility.[43]There is currently a dearth of high-quality translational work specifically focused on UTIs and on stable, bioavailable suspension formulations of the two agents, despite preclinical data supporting the antimicrobial, anti-biofilm, and anti-inflammatory actions of turmeric (curcuminoids) and garlic (allicin/organosulfur compounds) and some small clinical studies suggesting benefits of herbal combinations for genitourinary and metabolic outcomes. Priority areas to speed up development and clinical translation are listed below.[44]
Broad antimicrobial screenings should give way to models relevant to UTIs, such as polymicrobial infections, biofilm formation on uroepithelium and catheters, and uropathogenic E. coli.[45] Ascertain whether the combination decreases virulence factors crucial for persistence and recurrence, demonstrates anti-biofilm disruption at concentrations attainable in urine, and demonstrates synergy (fractional inhibitory concentration indices). Testing spice-derived phytochemicals specifically against antibiotic-resistant and biofilm-forming uropathogens is encouraged by recent antimicrobial reviews.[46,47]
Pharmacokinetic and urinary exposure:
To measure the quantities of active molecules and key metabolites in plasma and, more importantly, urine over a period of 0–24 hours, conduct PK experiments in healthy volunteers using the precise candidate suspension or suspensions. Report free versus conjugated forms using sensitive LC-MS/MS. Systemic oral dosing by itself is unlikely to be efficacious if urine concentrations fall below MICs observed in vitro. Examine dose-exposure relationships and whether adding micelles, nanoparticles, or phospholipid complexes to the formulation increases the amount of active ingredients excreted in the urine.[47]
Improve curcumin bioavailability within a combined suspension.
It is generally known that curcumin has poor oral bioavailability; nevertheless, formulation techniques (nanoparticles, micellar dispersions, lipid-based systems, solid dispersions, or colloidal suspensions like Theracurmin-like systems) significantly increase systemic exposure and may improve urine levels. Because interactions between excipients and garlic ingredients may change absorption, future formulations should investigate the bioavailability and urine excretion of curcuminoids and garlic organosulfur metabolites when co-formulated.[48]
CONCLUSION:
The possible molecular mechanisms of curcumin's antibacterial properties have been thoroughly investigated in recent decades. These mechanisms include bacterial membrane disruption, inhibition of virulence factor production and biofilm formation, induction of oxidative stress that results in programmed cell death, bacterial metabolic disruption, and phototoxicity. These properties also help to explain curcumin's broad-spectrum antibacterial adjuvant action, as demonstrated by its notable additive or synergistic effects with a variety of conventional antibiotics or non-antibiotic substances, including metals, natural products, and antibacterial agents. Clinical investigations on humans and animals demonstrate curcumin's great safety. However, curcumin as a possible antibacterial treatment still faces numerous obstacles, in contrast to its use as a chemotherapeutic agent in cancer treatment.
his study supports garlic's (Allium sativum) antibacterial ability against UTIs brought on by the uropathogens examined. Therefore, the active ingredient in the extracts that may be turned into an antibacterial medication needs to be isolated and purified.
REFERENCES
Ashwini Mankar*, Manasi Choudhari, Dr. Swati Deshmukh, Dual Herbal Defense: Mechanistic Insights into the Anti-Uti Efficacy of Curcuma Longa Allium Sativum Suspension, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 58-70 https://doi.org/10.5281/zenodo.17499975
10.5281/zenodo.17499975
