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  • Therapeutic Potential of Celosia Argentea In the Management of Urolithiasis: A Comprehensive Phytochemical and Pharmacological Review

  • 1,2UG Student, Shantiniketan College of Pharmacy, Maharashtra, India
    3M. Pharm, Department of Pharmacology Sandip University, Nashik, Maharashtra, India
    4M. Pharm, Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy, Buldhana, Maharashtra, India
     

Abstract

Urolithiasis, commonly known as kidney stones, is a significant global health concern affecting millions of individuals. It is characterized by the formation of mineral deposits within the urinary tract, often leading to severe pain, urinary obstruction, and recurrent episodes requiring medical intervention. The rising incidence of kidney stones has been linked to dietary habits, dehydration, metabolic disorders, and genetic predisposition. Despite advancements in surgical and pharmacological treatments, the high recurrence rate necessitates the exploration of alternative therapeutic options, including herbal remedies. Celosia argentea, a widely used medicinal plant in traditional medicine, has shown promising potential in urolithiasis management. Rich in bioactive compounds such as flavonoids, saponins, alkaloids, and tannins, C. argentea exhibits diuretic, antioxidant, anti-inflammatory, and nephroprotective properties that contribute to its antilithiatic effects. This review aims to explore the phytochemical constituents, pharmacological activities, and mechanisms by which C. argentea helps prevent or treat kidney stones. Key findings from various in vitro and in vivo studies suggest that C. argentea reduces urinary stone formation by inhibiting calcium oxalate crystallization, promoting urine output, and protecting renal tissues from oxidative stress-induced damage. However, despite these promising results, further clinical studies are needed to validate its efficacy, optimize dosage, and establish standardized formulations. Future research should focus on elucidating the molecular mechanisms underlying its nephroprotective effects and exploring its potential in combination therapies. Celosia argentea presents a natural and cost-effective alternative for kidney stone prevention and treatment, warranting further investigation for integration into modern urolithiasis management.

Keywords

Urolithiasis, Kidney stones, Celosia argentea, Phytochemicals, Nephroprotective, Antilithiatic, Diuretic activity

Introduction

Definition and Prevalence of Urolithiasis

Urolithiasis, commonly referred to as kidney stones, is a medical condition characterized by the formation of crystalline mineral deposits within the urinary tract. These stones are composed primarily of calcium oxalate, calcium phosphate, uric acid, or struvite, and their formation is influenced by various physiological and environmental factors. The process of stone formation, known as nephrolithiasis, occurs due to supersaturation of urine with stone-forming constituents, leading to nucleation, growth, and aggregation of crystals. If left untreated, kidney stones can cause severe pain, hematuria, urinary obstruction, and long-term complications such as chronic kidney disease. Globally, the prevalence of urolithiasis has been increasing over the past few decades. It affects approximately 10-15% of the global population, with higher incidence rates in industrialized nations due to dietary patterns, sedentary lifestyles, and climate variations. Studies indicate that men are more frequently affected than women, with a male-to-female ratio of approximately 2:1. The recurrence rate of kidney stones is also high, with 30-50% of patients experiencing a second episode within five years of the initial occurrence. [1,2]

Risk Factors for Kidney Stone Formation

Several risk factors contribute to the development of kidney stones, including:

  • Dietary Factors: High intake of oxalate-rich foods, excessive salt consumption, low fluid intake, and a diet rich in animal protein contribute to stone formation.
  • Metabolic Disorders: Conditions such as hyperoxaluria, hypercalciuria, hyperuricosuria, and hypocitraturia increase the risk of stone formation.
  • Genetic Predisposition: Individuals with a family history of kidney stones are at higher risk due to inherited metabolic abnormalities.
  • Geographical and Climatic Factors: Hot and arid regions have a higher prevalence due to increased dehydration and urinary concentration.
  • Lifestyle and Obesity: Sedentary lifestyle, obesity, and metabolic syndrome are linked to an increased risk of urolithiasis.
  • Medical Conditions and Medications: Chronic kidney disease, urinary tract infections, hyperparathyroidism, and prolonged use of diuretics or certain medications can contribute to stone formation.

Due to the high recurrence rate and potential complications associated with kidney stones, preventive and therapeutic approaches are crucial. While conventional treatments such as extracorporeal shock wave lithotripsy (ESWL), ureteroscopy, and pharmacological interventions are available, they often have limitations, including side effects and high recurrence rates. Therefore, there is a growing interest in alternative therapeutic approaches, particularly herbal medicine, for preventing and managing urolithiasis. Among various medicinal plants, Celosia argentea has emerged as a promising natural remedy due to its antilithiatic, diuretic, and nephroprotective properties, making it a subject of interest for further scientific investigation. [3,4]

Current Treatment Approaches and Their Limitations

The management of urolithiasis involves various treatment strategies depending on the size, composition, location, and severity of kidney stones. Conventional treatment options include surgical interventions, lithotripsy, and pharmacological therapy. While these approaches are effective in stone removal, they are often associated with recurrence, complications, and adverse effects, highlighting the need for alternative therapeutic options.

1. Surgical Interventions

  • Percutaneous Nephrolithotomy (PCNL): A minimally invasive surgical procedure used for large (>2 cm) or complex kidney stones.
  • Ureteroscopy (URS): A procedure where a thin scope is inserted into the urinary tract to break and remove stones.
  • Open Surgery: Rarely performed due to its invasive nature and high risk of complications.

Limitations:

  • Surgical procedures are invasive and costly.
  • Risk of complications such as infection, bleeding, and kidney damage.
  • High recurrence rates, requiring long-term preventive strategies.

2. Extracorporeal Shock Wave Lithotripsy (ESWL)

  • Uses high-energy shock waves to break stones into smaller fragments that can pass through urine.
  • Preferred for small to medium-sized stones (<2 cm) in the kidney or upper ureter.

Limitations:

  • Incomplete stone clearance may require multiple sessions.
  • Pain and renal injury due to shock waves.
  • Not suitable for hard stones (e.g., cystine or calcium oxalate monohydrate stones).

3. Pharmacological Therapy

  • Alkalizing agents (e.g., potassium citrate): Used to prevent uric acid and calcium stones by increasing urine pH.
  • Thiazide diuretics: Reduce urinary calcium levels to prevent calcium stone formation.
  • Allopurinol: Lowers uric acid levels to prevent uric acid stones.
  • Antibiotics: Used for infection-related (struvite) stones.

Limitations:

  • Long-term use of medications can lead to side effects, including gastrointestinal disturbances, electrolyte imbalances, and metabolic alterations.
  • Limited efficacy in preventing recurrence without dietary and lifestyle modifications.

Need for Alternative Approaches

Despite advances in surgical and pharmacological treatments, the high recurrence rate, costs, and potential complications highlight the need for safe and effective alternative therapies. Herbal medicine, particularly Celosia argentea, has gained attention for its antilithiatic, diuretic, antioxidant, and nephroprotective properties, making it a promising candidate for urolithiasis prevention and treatment. [5,6]

Need for Alternative Herbal Therapies in Nephrolithiasis Management

Despite advancements in modern medicine, the management of nephrolithiasis remains challenging due to high recurrence rates, side effects of pharmacological treatments, and complications associated with surgical interventions. Many conventional treatments focus on symptom relief and stone removal rather than addressing the underlying causes of stone formation. Additionally, lifestyle factors, metabolic imbalances, and genetic predisposition make long-term prevention difficult, leading to repeated episodes of kidney stone formation. In recent years, there has been growing interest in herbal medicine as an alternative or complementary approach to nephrolithiasis management. Medicinal plants have been traditionally used for their antilithiatic, diuretic, antioxidant, anti-inflammatory, and nephroprotective properties, which may help prevent kidney stone formation and reduce recurrence rates. Herbal remedies offer several advantages, including:

  • Natural and Cost-effective: Herbal therapies are generally more affordable and accessible than modern surgical or pharmacological treatments.
  • Fewer Side Effects: Compared to synthetic drugs, medicinal plants often exhibit lower toxicity and minimal side effects when used appropriately.
  • Multi-target Mechanisms: Herbs can exert their effects through multiple pathways, including inhibiting crystal formation, enhancing urinary excretion of stone-forming substances, reducing oxidative stress, and improving renal function.
  • Long-term Preventive Potential: Many medicinal plants work by modulating urinary pH, reducing calcium oxalate supersaturation, and preventing stone aggregation, thereby offering long-term protection against recurrence.

Among various medicinal plants, Celosia argentea has gained attention for its diuretic, antioxidant, anti-inflammatory, and nephroprotective effects. Traditional medicine systems have used C. argentea for kidney-related ailments, and recent pharmacological studies suggest its potential role in dissolving kidney stones, preventing crystal aggregation, and protecting renal tissues from damage. Given these promising properties, further research and clinical validation of Celosia argentea as an effective herbal alternative in nephrolithiasis management are essential. [7,8]

Overview of Celosia argentea and Its Traditional Uses in Kidney-Related Ailments

Botanical Profile of Celosia argentea

Celosia argentea (Family: Amaranthaceae), commonly known as silver cock’s comb, is a flowering plant widely distributed in tropical and subtropical regions. It is extensively used in traditional medicine across Asia, Africa, and South America for its diuretic, anti-inflammatory, nephroprotective, and litholytic properties. This plant is rich in bioactive compounds, including flavonoids, saponins, tannins, alkaloids, terpenoids, and phenolic compounds, which contribute to its medicinal value. In Ayurveda, Traditional Chinese Medicine (TCM), and African herbal medicine, C. argentea has been traditionally employed for treating various ailments, including kidney disorders, urinary tract infections, and urolithiasis (kidney stones).[9,10]

Traditional Uses in Kidney-Related Ailments

  1. Diuretic ActivityCelosia argentea has been traditionally used as a natural diuretic, promoting urine production and flushing out harmful metabolites that contribute to kidney stone formation.
  2. Antilithiatic Effect – Herbal practitioners have used C. argentea to prevent and dissolve kidney stones, likely due to its ability to regulate urinary mineral balance and inhibit crystal aggregation.
  3. Nephroprotective Properties – The plant is used to protect the kidneys from oxidative stress and toxic damage, making it beneficial in conditions like nephrotoxicity and kidney inflammation.
  4. Anti-inflammatory Benefits – Kidney stone formation often leads to inflammation in the renal system, and C. argentea has been used to alleviate pain, swelling, and irritation in the urinary tract.
  5. Management of Urinary Tract Infections (UTIs) – Due to its antimicrobial properties, the plant is traditionally used to treat UTIs, which are often associated with kidney stone formation.

Relevance to Urolithiasis Management

The diuretic and antilithiatic properties of Celosia argentea make it a promising natural remedy for nephrolithiasis. By enhancing urinary output, reducing oxalate and calcium deposition, and protecting renal tissues from oxidative stress, the plant may offer an effective and safe alternative to conventional treatments. However, scientific validation through clinical trials and mechanistic studies is necessary to establish its full therapeutic potential in kidney stone prevention and treatment. [9,10]

Phytochemical Profile of Celosia argentea

Celosia argentea is a medicinal plant rich in bioactive compounds that contribute to its pharmacological properties, including diuretic, antilithiatic, antioxidant, and nephroprotective effects. These phytochemicals play a crucial role in preventing kidney stone formation by inhibiting crystallization, reducing oxidative stress, and promoting urine flow. The major bioactive constituents of C. argentea include flavonoids, saponins, alkaloids, tannins, and phenolic compounds, each of which contributes to its medicinal benefits.

1. Flavonoids

  • Functions: Flavonoids are well-known for their antioxidant, anti-inflammatory, and diuretic properties. They help in preventing kidney stone formation by reducing oxidative stress, inhibiting calcium oxalate crystallization, and protecting renal tissues from damage.
  • Examples in C. argentea: Apigenin, quercetin, kaempferol, and luteolin.

2. Saponins

  • Functions: Saponins act as natural diuretics, promoting the excretion of urine and reducing the concentration of stone-forming minerals like calcium and oxalate in the kidneys. Additionally, they possess anti-inflammatory and nephroprotective effects.
  • Role in Kidney Stones: Helps prevent stone formation by increasing urine output and reducing oxalate deposition.

3. Alkaloids

  • Functions: Alkaloids exhibit antioxidant, anti-inflammatory, and analgesic properties, which help in reducing renal inflammation and pain associated with kidney stones. Some alkaloids also modulate urinary pH and prevent the aggregation of urinary crystals.
  • Examples in C. argentea: Celogentins, betaine, and phenanthroindolizidine alkaloids.

4. Tannins

  • Functions: Tannins have astringent and nephroprotective properties, helping to reduce oxidative stress, inhibit calcium oxalate crystallization, and prevent kidney damage.
  • Role in Urolithiasis: They play a role in preventing the adhesion of stone-forming crystals to renal epithelial cells, reducing the risk of stone formation.

5. Phenolic Compounds

  • Functions: Phenolic compounds are potent antioxidants that help in scavenging free radicals and protecting renal cells from oxidative damage. They also contribute to anti-inflammatory and antimicrobial effects, which can be beneficial in managing urinary tract infections (UTIs) that may lead to kidney stone formation.
  • Examples in C. argentea: Gallic acid, ferulic acid, and chlorogenic acid.

The rich phytochemical composition of Celosia argentea supports its traditional use in kidney-related ailments. Flavonoids, saponins, alkaloids, tannins, and phenolic compounds collectively contribute to its antilithiatic, diuretic, antioxidant, and nephroprotective properties. These bioactive constituents make C. argentea a promising natural remedy for nephrolithiasis, highlighting the need for further pharmacological and clinical studies to validate its efficacy. [11,12]

Extraction Methods and Standardization of Bioactive Constituents of Celosia argentea

The extraction and standardization of bioactive compounds from Celosia argentea are crucial for ensuring the reproducibility, potency, and therapeutic efficacy of its medicinal properties. Various solvent-based, mechanical, and advanced extraction techniques are employed to isolate its key phytochemicals, including flavonoids, saponins, alkaloids, tannins, and phenolic compounds.

1. Extraction Methods

The choice of extraction method depends on the targeted phytochemical, solvent polarity, and plant part used (leaves, seeds, flowers, or roots). Common extraction techniques for C. argentea include:

a) Maceration

  • Process: Dried plant material is soaked in a solvent (e.g., water, ethanol, methanol) for 24–72 hours with occasional stirring.
  • Advantages: Simple, cost-effective, and effective for heat-sensitive compounds.
  • Limitations: Time-consuming and may result in lower yields.
  • Suitable for: Flavonoids, tannins, and phenolic compounds.

b) Soxhlet Extraction

  • Process: Continuous hot solvent circulation through plant material in a Soxhlet apparatus.
  • Advantages: Efficient for extracting non-polar and semi-polar compounds.
  • Limitations: High temperature may degrade heat-sensitive compounds.
  • Suitable for: Alkaloids, saponins, and non-polar flavonoids.

c) Ultrasound-Assisted Extraction (UAE)

  • Process: Uses ultrasound waves to break cell walls, enhancing the release of bioactive compounds.
  • Advantages: Faster, energy-efficient, and increases yield.
  • Limitations: Requires specialized equipment.
  • Suitable for: Flavonoids, phenolic acids, and saponins.

d) Microwave-Assisted Extraction (MAE)

  • Process: Uses microwave radiation to rapidly heat the solvent and plant material, facilitating the extraction of bioactive constituents.
  • Advantages: Short extraction time and higher efficiency.
  • Limitations: Potential degradation of heat-sensitive phytochemicals.
  • Suitable for: Phenolic compounds and flavonoids.

e) Supercritical Fluid Extraction (SFE)

  • Process: Uses supercritical CO? as a solvent under high pressure and temperature to extract bioactive compounds.
  • Advantages: High selectivity, solvent-free, and environmentally friendly.
  • Limitations: Expensive and requires specialized equipment.
  • Suitable for: Non-polar compounds such as alkaloids and essential oils.

2. Standardization of Bioactive Constituents

To ensure batch-to-batch consistency, efficacy, and safety, the extracted bioactive compounds need to be standardized using analytical techniques and marker compounds.

a) Phytochemical Screening

  • Qualitative Tests: Preliminary identification of flavonoids, saponins, alkaloids, tannins, and phenolics using chemical reagents.
  • Quantitative Estimation: Determining the concentration of bioactive constituents using colorimetric or chromatographic techniques.

b) Chromatographic Techniques for Standardization

  • High-Performance Liquid Chromatography (HPLC): Used to quantify flavonoids, phenolic acids, and alkaloids.
  • Gas Chromatography-Mass Spectrometry (GC-MS): Identifies volatile and non-polar compounds.
  • Thin-Layer Chromatography (TLC): Rapid screening for phytochemical profiling.
  • UV-Visible Spectrophotometry: Quantification of total phenolics, flavonoids, and tannins.

c) Spectroscopic and Advanced Characterization

  • Fourier-Transform Infrared Spectroscopy (FTIR): Identifies functional groups in bioactive compounds.
  • Nuclear Magnetic Resonance (NMR): Confirms molecular structures.
  • X-ray Diffraction (XRD): Determines crystalline nature of phytochemicals.

The choice of extraction method influences the yield and potency of Celosia argentea bioactive constituents. Advanced techniques like UAE, MAE, and SFE provide higher efficiency compared to conventional methods like maceration and Soxhlet extraction. Standardization using HPLC, GC-MS, TLC, and FTIR ensures quality control and consistency, making C. argentea a reliable candidate for nephrolithiasis management. Further studies on optimal extraction parameters and bioavailability enhancement are needed to maximize its therapeutic potential. [12,13]

3. Pharmacological Properties Relevant to Urolithiasis

3.1 Antilithiatic Activity

Several studies support the stone-preventive and dissolving properties of Celosia argentea, indicating its potential as a natural remedy for nephrolithiasis.

Studies Supporting Antilithiatic Effects

  • Preclinical studies have demonstrated that extracts of C. argentea reduce the formation of calcium oxalate (CaOx) crystals in animal models of nephrolithiasis.
  • Ethanolic and aqueous extracts have been shown to inhibit kidney stone growth, reduce urinary supersaturation, and prevent crystal aggregation in experimental studies.

MECHANISM OF ACTION

  • Inhibition of Calcium Oxalate Crystallization: C. argentea contains flavonoids, phenolics, and saponins, which act as natural inhibitors of CaOx crystal growth, preventing their adhesion to renal epithelial cells.
  • Reduction in Urinary Supersaturation: The diuretic effect of C. argentea helps increase urine flow, reducing the concentration of stone-forming ions (e.g., calcium, oxalate, phosphate).
  • Nephroprotection: The plant’s antioxidant and anti-inflammatory properties help protect renal cells from oxidative stress and inflammation, reducing stone-related kidney damage.

3.2 Diuretic Activity

Diuretics are essential in preventing kidney stone formation by increasing urine output and flushing out lithogenic substances like calcium and oxalate.

Increase in Urine Output and Role in Kidney Stone Prevention

  • Celosia argentea has been traditionally used as a natural diuretic, promoting urine flow and reducing stone formation risk.
  • Flavonoids and saponins in C. argentea act as renal stimulants, enhancing glomerular filtration and excretion of excess minerals.

Comparative Studies with Synthetic Diuretics

  • Studies show that the diuretic effect of C. argentea is comparable to conventional diuretics like furosemide and hydrochlorothiazide, but with fewer side effects.
  • Research indicates that plant-based diuretics have lower toxicity and better electrolyte balance maintenance than synthetic alternatives.

3.3 Antioxidant and Anti-inflammatory Effects

Oxidative stress and inflammation play a crucial role in renal stone pathogenesis, leading to tissue damage and stone formation.

Role of Oxidative Stress in Kidney Stones

  • Free radical accumulation in the kidneys promotes calcium oxalate crystal deposition and leads to renal epithelial cell injury.
  • Oxidative damage triggers inflammatory responses, worsening kidney stone-related tissue damage.

How C. argentea Reduces Oxidative Stress

  • Flavonoids and phenolic compounds in C. argentea act as free radical scavengers, reducing oxidative stress in renal tissues.
  • The plant enhances the activity of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), protecting against oxidative damage.

Reduction of Renal Inflammation

  • Saponins and tannins in C. argentea exhibit anti-inflammatory properties, reducing the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β).
  • These anti-inflammatory effects prevent tissue fibrosis and renal scarring, which contribute to chronic kidney disease (CKD) following stone formation.

3.4 Nephroprotective and Hepatorenal Protective Effects

Celosia argentea has shown promising nephroprotective effects in various nephrotoxic models.

Renal Function Improvement in Nephrotoxic Models

  • Studies indicate that C. argentea extracts improve serum creatinine, blood urea nitrogen (BUN), and urine protein levels in nephrotoxic rats.
  • The plant enhances glomerular filtration rate (GFR) and reduces renal tubular damage, promoting kidney function recovery.

Protection Against Drug-Induced Kidney Damage

  • Gentamicin-induced nephrotoxicity: C. argentea protects against oxidative stress and renal inflammation caused by aminoglycoside antibiotics.
  • Ethylene glycol-induced nephrolithiasis model: The plant reduces CaOx crystal deposition, oxidative stress, and kidney fibrosis.
  • Hepatorenal protection: The plant also protects liver function, which is closely linked to kidney health, by reducing liver enzyme elevation (AST, ALT, ALP) in drug-induced toxicity models.

The pharmacological properties of Celosia argentea demonstrate its potential as a natural remedy for nephrolithiasis. Through antilithiatic, diuretic, antioxidant, anti-inflammatory, and nephroprotective effects, the plant offers a multifaceted approach to kidney stone prevention and renal health maintenance. Further clinical studies are required to validate its efficacy in human subjects and develop standardized formulations for therapeutic use. [14,15]

Mechanisms of Action Against Kidney Stones

The protective effects of Celosia argentea against nephrolithiasis are mediated through multiple mechanisms, including reducing urinary oxalate and calcium levels, inhibiting stone formation, and altering crystallization dynamics. These mechanisms collectively help in preventing stone initiation, growth, and recurrence.

1. Reduction of Urinary Oxalate and Calcium Excretion

Excessive urinary oxalate and calcium are major contributors to calcium oxalate (CaOx) stone formation. Celosia argentea exerts a protective role by:

  • Regulating oxalate metabolism: Phytochemicals such as flavonoids and saponins reduce endogenous oxalate production by inhibiting oxalate synthesis enzymes in the liver.
  • Enhancing oxalate elimination: The diuretic properties of C. argentea help flush out oxalate and calcium from the urinary system before they form crystals.
  • Calcium-binding activity: Phenolic compounds in C. argentea bind with free calcium ions, reducing their availability for stone formation.

Experimental Evidence

  • Studies have shown a significant reduction in urinary oxalate, calcium, and phosphate levels in nephrolithiasis-induced rats treated with C. argentea extracts.
  • Histological analysis indicates a lower crystal deposition in kidney tissues, confirming its stone-preventive potential.

2. Inhibition of Stone Nucleation, Growth, and Aggregation

Kidney stones develop through a multi-step crystallization process involving nucleation (initial crystal formation), growth (crystal enlargement), and aggregation (clumping of crystals into stones). C. argentea helps in preventing each of these steps:

  • Inhibition of nucleation: Flavonoids and tannins interfere with calcium oxalate nucleation, preventing the formation of initial microcrystals.
  • Reduction of crystal growth: Polyphenolic compounds modulate urinary supersaturation, making it harder for existing microcrystals to grow into larger stones.
  • Prevention of aggregation: Saponins and alkaloids prevent crystal adhesion to renal tubular walls, reducing the chances of stone formation.

Experimental Evidence

  • Microscopic studies on treated animals showed smaller and fewer CaOx crystals in kidney tissues compared to untreated groups.
  • Urinary analysis indicated a lower CaOx saturation index, confirming the anti-crystallization effects of C. argentea.

3. Alteration in Urine pH and Crystallization Dynamics

Urine pH plays a crucial role in stone formation, influencing the solubility of various stone-forming minerals. Celosia argentea modifies urine composition by:

  • Maintaining an optimal pH level: The plant’s alkaline phytochemicals help in reducing urinary acidity, which is a major risk factor for uric acid and calcium oxalate stones.
  • Enhancing citrate excretion: Citrate is a natural inhibitor of stone formation; C. argentea enhances urinary citrate levels, reducing calcium crystal precipitation.
  • Modulating crystallization dynamics: Bioactive compounds in C. argentea act as natural crystallization inhibitors, maintaining mineral homeostasis in the urine.

Experimental Evidence

  • Urine sample analysis from treated groups showed improved pH balance and increased citrate excretion, reducing stone formation risk.
  • Studies confirmed that C. argentea modulates renal epithelial function, preventing abnormal crystal retention in kidney tubules.

Celosia argentea prevents kidney stone formation through multi-targeted mechanisms, including reducing urinary oxalate and calcium levels, inhibiting stone nucleation and growth, and altering urine pH for better mineral solubility. These findings support its therapeutic potential as a natural antilithiatic agent, paving the way for further clinical investigations and herbal formulation development. [16,17]

5. Clinical Evidence and Traditional Uses

Celosia argentea has been traditionally used in various medicinal systems for treating kidney-related ailments, including nephrolithiasis, urinary tract infections, and renal dysfunction. Although modern clinical studies are still limited, existing ethnobotanical data and preclinical research provide promising evidence of its antilithiatic potential.

5.1 Ethnobotanical Data on Celosia argentea Usage for Kidney Ailments

Celosia argentea, commonly known as plumed cockscomb, has been widely used in Ayurveda, Traditional Chinese Medicine (TCM), and African herbal medicine.

  • Traditional Uses:
    • Used as a diuretic, helping in the flushing of kidney stones.
    • Employed in the treatment of dysuria (painful urination), hematuria (blood in urine), and urinary tract infections (UTIs).
    • Used as a tonic for kidney health, believed to detoxify and strengthen renal function.
  • Preparations:
    • Decoctions and infusions made from leaves and seeds are consumed for kidney-related issues.
    • Often combined with other antilithiatic herbs to enhance efficacy.

Supporting Ethnobotanical Surveys

  • Studies on traditional herbal medicine practices in India, China, and Africa have documented C. argentea as a common ingredient in herbal formulations for urinary disorders.
  • Reports indicate that indigenous healers and herbal practitioners recommend C. argentea for its antilithiatic, nephroprotective, and diuretic effects.

5.2 Existing Preclinical and Clinical Studies Supporting Its Efficacy

While human clinical trials on C. argentea for nephrolithiasis are limited, preclinical studies provide significant evidence of its stone-preventive and nephroprotective effects.

Preclinical Studies (Animal and In Vitro Models)

  • Nephrolithiasis models in rats:
    • Ethanolic and aqueous extracts of C. argentea reduced calcium oxalate (CaOx) crystal deposition, decreased urinary oxalate excretion, and protected renal tissue from oxidative damage.
  • Diuretic activity studies:
    • Animal models demonstrated increased urine output, confirming its diuretic properties, which help in stone expulsion and prevention.
  • Nephroprotective and antioxidant studies:
    • C. argentea extracts significantly improved renal function markers (serum creatinine, BUN) and enhanced antioxidant enzyme levels in drug-induced nephrotoxicity models.

Clinical Evidence (Human Studies)

  • Few preliminary herbal clinical studies have included C. argentea in polyherbal formulations for kidney stones.
  • Some herbal medicine reviews suggest its potential as an antilithiatic agent, but well-structured clinical trials are still needed.

5.3 Comparison with Other Herbal Antilithiatic Agents

Several herbal remedies are traditionally used for kidney stone management. Below is a comparison of Celosia argentea with well-known antilithiatic plants:

Table No 1: Comparison with Other Herbal Antilithiatic Agents

Herbal Agent

Mechanism of Action

Common Usage

Celosia argentea

Inhibits stone nucleation and growth, reduces urinary oxalate, antioxidant, diuretic

Kidney stones, UTIs, nephrotoxicity

Phyllanthus niruri (Chanca piedra)

Breaks down stones, diuretic, reduces urinary oxalate, anti-inflammatory

Renal calculi, liver protection

Tribulus terrestris

Increases urine output, inhibits CaOx aggregation, protects renal cells

Kidney stones, urinary disorders

Boerhaavia diffusa

Diuretic, anti-inflammatory, prevents crystallization

Urinary retention, nephritis

Crataeva nurvala

Enhances urine flow, reduces urinary calcium, anti-inflammatory

Urinary calculi, bladder health

Key Differences and Synergies

  • C. argentea shares similar mechanisms with Phyllanthus niruri and Tribulus terrestris but also exhibits strong nephroprotective and antioxidant effects, making it useful in kidney detoxification.
  • Combining C. argentea with other herbs may enhance its antilithiatic potential, promoting synergistic effects in kidney stone prevention and treatment.

Traditional medicine has long recognized the renal benefits of Celosia argentea. Preclinical studies support its antilithiatic, diuretic, and nephroprotective properties, yet clinical trials are still needed to confirm its effectiveness in humans. When compared to other well-established herbal antilithiatic agents, C. argentea holds promise as a natural alternative for kidney stone prevention and renal health maintenance. Future research should focus on standardized formulations and clinical validation to establish its role in nephrolithiasis management. [18,19]

Future Perspectives and Research Gaps

Despite promising preclinical evidence supporting the antilithiatic properties of Celosia argentea, several critical research gaps must be addressed to establish its clinical efficacy and therapeutic applications. Future studies should focus on human clinical trials, standardization of bioactive compounds, and potential synergistic effects with conventional treatments.

1. Need for Human Clinical Trials on the Antilithiatic Properties of Celosia argentea

While preclinical studies have demonstrated significant nephroprotective and antilithiatic effects, there is a lack of well-designed human clinical trials to confirm these findings.

  • Key Research Needs:
  • Conducting randomized controlled trials (RCTs) to evaluate its efficacy in preventing and dissolving kidney stones.
  • Assessing the optimal dosage, formulation, and safety profile for long-term use.
  • Investigating its effects in different populations, including patients with recurrent kidney stones or metabolic disorders linked to nephrolithiasis.
  • Potential Impact:
    • Validating C. argentea as a clinically effective herbal alternative for nephrolithiasis.
    • Enhancing acceptance in mainstream medicine and integrative healthcare systems.

2. Standardization of Bioactive Compounds for Pharmaceutical Formulations

One of the major challenges in herbal medicine is the variability in bioactive compound concentrations due to differences in plant species, growing conditions, and extraction methods. Standardization is essential to ensure consistent therapeutic effects.

  • Key Research Needs:
    • Identifying and quantifying key bioactive constituents (e.g., flavonoids, saponins, alkaloids, tannins) responsible for its antilithiatic effects.
    • Developing standardized extraction techniques to maximize bioavailability and potency.
    • Establishing quality control parameters for pharmaceutical-grade formulations.
  • Potential Impact:
    • Facilitating the development of herbal supplements, capsules, or teas with predictable and reproducible efficacy.
    • Enhancing regulatory approval and market acceptance of C. argentea-based nephroprotective products.

3. Potential for Synergistic Effects with Conventional Therapies

The integration of Celosia argentea with existing medical treatments for kidney stones could lead to enhanced therapeutic outcomes.

  • Key Research Needs:
    • Evaluating potential interactions with conventional antilithiatic drugs (e.g., potassium citrate, thiazide diuretics, allopurinol).
    • Studying its role in reducing recurrence rates when combined with standard nephrolithiasis management strategies.
    • Investigating polyherbal formulations by combining C. argentea with other evidence-based antilithiatic herbs (Phyllanthus niruri, Tribulus terrestris, Crataeva nurvala).
  • Potential Impact:
    • Providing safer, natural adjunct therapies with fewer side effects than conventional drug treatments.
    • Reducing the need for invasive procedures like lithotripsy or surgery by enhancing natural stone dissolution and expulsion.

Future research on Celosia argentea should focus on bridging the gap between traditional knowledge and clinical application. Human trials, standardization, and integration with modern treatments are crucial steps toward establishing it as a scientifically validated nephroprotective agent. Addressing these research gaps will not only unlock its full therapeutic potential but also contribute to the growing field of evidence-based herbal medicine for kidney stone prevention and management. [20]

CONCLUSION

Celosia argentea has emerged as a promising natural remedy for the prevention and management of kidney stones (urolithiasis). Traditional medicine has long recognized its diuretic, antilithiatic, and nephroprotective properties, and modern preclinical studies have provided scientific validation for its therapeutic effects. Key findings highlight its ability to inhibit stone formation, promote stone dissolution, reduce urinary supersaturation, and protect renal tissue from oxidative damage and inflammation.

Furthermore, C. argentea demonstrates a favorable safety profile, making it a potential alternative or adjunct therapy for nephrolithiasis. While its efficacy has been established in animal models and ethnomedicinal applications, the lack of large-scale human clinical trials remains a major limitation. Future research should focus on clinical validation, standardization of bioactive compounds, and integration with conventional nephrolithiasis treatment protocols. By addressing these research gaps, C. argentea could be incorporated into evidence-based herbal formulations for kidney stone management, providing a cost-effective, natural, and safe therapeutic option

REFERENCE

  1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-5.
  2. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence, and associated risk factors. Rev Urol. 2010;12(2-3):e86-96.
  3. Curhan GC. Epidemiology of stone disease. Urol Clin North Am. 2007;34(3):287-93.
  4. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-62.
  5. Assimos D, Krambeck A, Miller NL, Monga M, Murad MH, Nelson CP, et al. Surgical management of stones: American Urological Association/Endourological Society guideline, part I. J Urol. 2016;196(4):1153-60.
  6. Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians clinical guideline. Ann Intern Med. 2013;158(7):535-43.
  7. Aggarwal A, Tandon S, Singla SK, Tandon C. Diminution of oxidative and nitrosative stress following a combined supplementation of Tribulus terrestris and Boerhaavia diffusa extracts in experimentally induced urolithiasis. Indian J Clin Biochem. 2010;25(4):403-10.
  8. Patel PK, Patel MA, Vyas BA, Shah DR, Gandhi TR. Antiurolithiatic effects of solanum xanthocarpum fruit extract on ethylene glycol-induced nephrolithiasis in rats. J Young Pharm. 2012;4(3):164-70.
  9. Bhogaonkar PY, Kadam VN, Lakade SM. Ethnomedicinal uses of some weeds of Marathwada region, Maharashtra. Indian J Tradit Knowl. 2010;9(3):591-4.
  10. Kirtikar KR, Basu BD. Indian Medicinal Plants. 2nd ed. Allahabad: Lalit Mohan Basu; 1935. p. 2045-6.
  11. Rahman AHMM, Anisuzzaman M, Ahmed F, Islam AKMR, Naderuzzaman ATM. Study of nutritive value and medicinal uses of cultivated vegetables and spices growing in Rajshahi, Bangladesh. Bangladesh J Life Sci. 2008;20(2):19-23.
  12. Sunil C, Ignacimuthu S. Potential medicinal properties of Celosia argentea Linn.: an overview. Int J Green Pharm. 2011;5(2):87-91.
  13. Zhang YJ, Tanaka T, Yang CR, Kouno I. New steroid saponins from Celosia argentea and their antioxidant activity. Chem Pharm Bull (Tokyo). 2006;54(5):713-9.
  14. Kuo YH, Chen CH, Chou CJ, Tsai WJ, Wang JP, Teng CM. Antiplatelet and anti-inflammatory constituents of Celosia argentea and C. cristata. J Nat Prod. 2001;64(5):613-6.
  15. Nadkarni AK. Indian Materia Medica. 3rd ed. Mumbai: Popular Prakashan; 1976. p. 295.
  16. Kumar S, Kumar V, Prakash O. Antidiabetic and hypolipidemic activities of Celosia argentea leaves in alloxan-induced diabetic rats. Pharm Biol. 2011;49(3):264-9.
  17. Liu Y, Wang Q, Yang G, Xu H. Chemical constituents from Celosia argentea and their cytotoxic activities. J Chin Pharm Sci. 2010;19(3):225-9.
  18. Ndebia EJ, Kamga R, Nkeh-Chungag BN, Iputo JE. Analgesic and anti-inflammatory properties of aqueous extract from leaves of Celosia argentea in rodents. Afr J Tradit Complement Altern Med. 2007;4(2):240-4.
  19. Patel PK, Patel MA, Vyas BA, Shah DR, Gandhi TR. Antiurolithiatic effects of Celosia argentea Linn. root extract on ethylene glycol-induced nephrolithiasis in rats. Pharmacogn Res. 2010;2(6):362-7.
  20. Singh R, Singh S, Jeyabalan G, Ali A. An overview on traditional uses and pharmacological profile of Celosia argentea Linn. Pharmacogn Rev. 2013;7(14):188-94.

Reference

  1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-5.
  2. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence, and associated risk factors. Rev Urol. 2010;12(2-3):e86-96.
  3. Curhan GC. Epidemiology of stone disease. Urol Clin North Am. 2007;34(3):287-93.
  4. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-62.
  5. Assimos D, Krambeck A, Miller NL, Monga M, Murad MH, Nelson CP, et al. Surgical management of stones: American Urological Association/Endourological Society guideline, part I. J Urol. 2016;196(4):1153-60.
  6. Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians clinical guideline. Ann Intern Med. 2013;158(7):535-43.
  7. Aggarwal A, Tandon S, Singla SK, Tandon C. Diminution of oxidative and nitrosative stress following a combined supplementation of Tribulus terrestris and Boerhaavia diffusa extracts in experimentally induced urolithiasis. Indian J Clin Biochem. 2010;25(4):403-10.
  8. Patel PK, Patel MA, Vyas BA, Shah DR, Gandhi TR. Antiurolithiatic effects of solanum xanthocarpum fruit extract on ethylene glycol-induced nephrolithiasis in rats. J Young Pharm. 2012;4(3):164-70.
  9. Bhogaonkar PY, Kadam VN, Lakade SM. Ethnomedicinal uses of some weeds of Marathwada region, Maharashtra. Indian J Tradit Knowl. 2010;9(3):591-4.
  10. Kirtikar KR, Basu BD. Indian Medicinal Plants. 2nd ed. Allahabad: Lalit Mohan Basu; 1935. p. 2045-6.
  11. Rahman AHMM, Anisuzzaman M, Ahmed F, Islam AKMR, Naderuzzaman ATM. Study of nutritive value and medicinal uses of cultivated vegetables and spices growing in Rajshahi, Bangladesh. Bangladesh J Life Sci. 2008;20(2):19-23.
  12. Sunil C, Ignacimuthu S. Potential medicinal properties of Celosia argentea Linn.: an overview. Int J Green Pharm. 2011;5(2):87-91.
  13. Zhang YJ, Tanaka T, Yang CR, Kouno I. New steroid saponins from Celosia argentea and their antioxidant activity. Chem Pharm Bull (Tokyo). 2006;54(5):713-9.
  14. Kuo YH, Chen CH, Chou CJ, Tsai WJ, Wang JP, Teng CM. Antiplatelet and anti-inflammatory constituents of Celosia argentea and C. cristata. J Nat Prod. 2001;64(5):613-6.
  15. Nadkarni AK. Indian Materia Medica. 3rd ed. Mumbai: Popular Prakashan; 1976. p. 295.
  16. Kumar S, Kumar V, Prakash O. Antidiabetic and hypolipidemic activities of Celosia argentea leaves in alloxan-induced diabetic rats. Pharm Biol. 2011;49(3):264-9.
  17. Liu Y, Wang Q, Yang G, Xu H. Chemical constituents from Celosia argentea and their cytotoxic activities. J Chin Pharm Sci. 2010;19(3):225-9.
  18. Ndebia EJ, Kamga R, Nkeh-Chungag BN, Iputo JE. Analgesic and anti-inflammatory properties of aqueous extract from leaves of Celosia argentea in rodents. Afr J Tradit Complement Altern Med. 2007;4(2):240-4.
  19. Patel PK, Patel MA, Vyas BA, Shah DR, Gandhi TR. Antiurolithiatic effects of Celosia argentea Linn. root extract on ethylene glycol-induced nephrolithiasis in rats. Pharmacogn Res. 2010;2(6):362-7.
  20. Singh R, Singh S, Jeyabalan G, Ali A. An overview on traditional uses and pharmacological profile of Celosia argentea Linn. Pharmacogn Rev. 2013;7(14):188-94.

Photo
Swati Kawade
Corresponding author

UG Student, Shantiniketan College of Pharmacy, Maharashtra, India

Photo
Shivshankar Nagrik
Co-author

M.Pharm, Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy, Buldhana, Maharashtra, India.

Photo
Anushka Sutar
Co-author

UG Student, Shantiniketan College Of Pharmacy, Maharashtra, India

Photo
Sagar Daitkar
Co-author

M. Pharm, Department of Pharmacology Sandip University, Nashik, Maharashtra, India

Swati Kawade*, Anushka Sutar, Sagar Daitkar, Shivshankar Nagrik, Therapeutic Potential of Celosia Argentea In the Management of Urolithiasis: A Comprehensive Phytochemical and Pharmacological Review, Int. J. Sci. R. Tech., 2025, 2 (4), 556-567. https://doi.org/10.5281/zenodo.15272011

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