Varuna

Varuna (Crataeva nurvala Buch.-Ham.): A Comprehensive Reference

1. Identity and Botanical Classification

Varuna is the Ayurvedic name for the tree Crataeva nurvala Buch.-Ham. (also spelled Crateva nurvala). The species officially accepted as Varuna is Crataeva nurvala Buch.-Ham., belonging to the family Capparidaceae (also rendered Capparaceae). The genus name Crataeva honors a botanist who lived during the time of Crates, while the specific epithet nurvala is derived from the Malayalam word "Nir," meaning water.

The Crataeva nurvala tree is a medium-sized, deciduous tree that can reach a height of 50 feet. Leaves are trifoliate, about 8–12 cm long, with oval or ovoid leaflets. The bark is smooth and brown in color while the branches are white, tinged with purple and yellow patches. The flowers are greenish-white, light yellowish, or creamy colored and are fragrant. The bark also contains horizontal wrinkles and is smooth and gray in color. The diameter of the fruits is 2.5 cm; they are ovoid berries resembling lemon and turn red after ripening. Seeds contain multiple seeds engulfed in fresh yellow pulp. The flowering season is the month of March, and fruits appear in the month of June.

Common Names and Synonyms

• Common names: Varuna, Three-Leaf Caper, Barun, and Barna, among others.
• English names: Three-leaved caper, holy garlic pear, lengam tree, triune leaf tree, sacred lingam tree.
• Sanskrit etymology: Varuna (the God of water) attains its name in Sanskrit because of its effect on the bodily fluids and urinary system.

Geographic Distribution and Habitat

Varuna is predominantly found in the Indian subcontinent, including regions such as India, Nepal, Sri Lanka, and Bangladesh. It is also distributed in certain parts of Southeast Asia, particularly in countries like Thailand, Myanmar, and Cambodia. The plant is commonly seen in South Asia, especially in the Indo-Malaysian zone where there are dry deciduous forests. It is also planted commonly in gardens and along avenues in Central and Northern parts of India. The plant thrives in a variety of habitats, including riverbanks, marshes, and low-lying areas with moist soils.

Plant Parts Used

Bark, root bark, and leaves are the main usable parts of this plant, and roots are quite abundantly used. The bark of the tree is most prominently used in Ayurveda. The bark is most prized in classical preparations, though contemporary practitioners sometimes use leaf extracts or fruit decoctions for milder actions.

2. Traditional and Historical Use

Ayurveda

This herb has been in use since the time of the Vedas. The use of Varun chhal (bark) dates back to classical Ayurvedic texts such as the Charaka Samhita and Sushruta Samhita, where it is referred to as "Varuna" and praised for its diuretic and lithotriptic (stone-dissolving) properties. In the Charaka Samhita, Varuna is included in the Tikta Skandha (bitter-tasting group of herbs); in the Sushruta Samhita, it is included in the Varunadi Gana (herbs for urinary disorders), Vata Samshamana (pacifying Vata dosha), and Kapha Samshamana (pacifying Kapha dosha).

References of Crataeva nurvala in the Charaka Samhita include: wood from the Varuna tree was used in building Sootikagara (delivery ward); the wood is also used as fuel to perform nadisweda (a type of sweating treatment); and Varuna is mentioned in the treatment of Jwara (fever), Gulma (abdominal tumor), and Arsha (piles). In the Sushruta Samhita, Varuna is used for kaphajarsha (piles due to Kapha increase), Shira shoola (headache), gulma (abdominal tumor), and to treat Vidradhi (abscess).

Usage of Varuna in internal abscesses has been carried out since several centuries, and classical literatures — especially the Sushruta Samhita and Ashtanga Sangraha texts — explain the role of formulations containing Varuna in such conditions.

Other Traditional Medicine Systems

In traditional medicine systems like Ayurveda, Siddha, and Unani, Varuna has been used for centuries due to its medicinal properties. Medicinal usage has been reported in traditional systems of medicine such as Ayurveda and Unani, wherein the plant is frequently preferred in the treatment of urinary disorders that recur owing to the development of antibiotic resistance by the infecting organism. It has been reported for its folkloric use in various disorders such as blood purifier, breathing problems, fever, metabolic disorders, wound healing, memory loss, and weak immune system.

Traditional Preparations

Several classical preparation forms are documented in traditional sources:

• For urinary calculi (Asmari): A decoction is prepared from the root bark of Varuna, to which the paste of root bark is added, and taken internally.
• For diabetes (Prameha): Decoction of Varuna is taken at a dose of 60 ml per day.
• For goitre (Gandamala): Decoction prepared from root bark of Varuna is taken internally.
• For digestive disorders (Agnimandhya): Root bark is crushed and a decoction is made.
• Topical use: An infusion of Varuna bark is used in the management of lymphadenopathy, gout, and internal abscesses. Bark paste is also administered topically to treat a variety of skin conditions.

Taken internally, Varuna has been used to reduce fever, and a decoction made from Varuna leaves has been used as a natural remedy for fever and associated delirium.

3. Phytochemistry: Key Constituents and Active Compounds

The plant is rich in alkaloids, saponins, triterpenes, tannins, flavanoid glycosides, glucosinolates, and phytosterols. Research has identified the following major and minor chemical constituents:

Primary / Major Constituents

• Lupeol: The major chemical constituent isolated from Varuna. The crude drug contains an active principle lupeol, a triterpenoid, which is mainly involved in the pharmacological activities of this plant.
• Betulinic acid, β-sitosterol, and stigmasterol: The chloroform fraction of the crude rectified spirit extract of the stem bark yielded betulinic acid (1), lupeol (2), β-sitosterol (3), and stigmasterol (4).
• Additional stem bark constituents: Friedelin, diosgenin, and volatile components including p-cymene, limonene, linalool, and α- and β-ionones.

Additional Phytochemicals

Minor chemical constituents include cadabicine, cadabicine diacetate, catechin, (−)-epicatechin-5-glucoside, (−)-epiafzelechin, glucocapparin, lupeol acetate, spinasterol acetate, and taraxasterol.

LC-MS and HPTLC analyses have revealed high contents of L-anserine nitrate, resveratrol, flavanone, chlorogenic acid hemihydrate, quercetin, kaempferide, isorhamnetin, rhamnetin, gallic acid, and lupeol in the ethanolic bark extract.

The leaf has been reported to contain dodecanoic anhydride, kaempferol-O-α-D-glucoside, methyl pentacosanoate, isoquercetin, quercetin, quercitin-3-O-α-D-glucoside, rutin, and L-stachydrine.

4. Mechanisms of Action

Anti-urolithiatic (Kidney Stone) Mechanism

The effect of oral administration of Crataeva nurvala bark decoction on calcium oxalate lithiasis has been studied in rats. The elevation of the oxalate-synthesizing liver enzyme glycolate oxidase, produced by feeding glycollic acid, was remarkably reduced with the decoction, showing a regulatory action on endogenous oxalate synthesis. This is considered the primary documented biochemical mechanism of Varuna's anti-stone action: a constituent of Varuna, lupeol, deactivates the enzyme glycolate oxidase, reducing the body's production of oxalates, which combine with calcium to form kidney stones.

Animals treated with lupeol showed a reduced tendency to form stones, and very small stones were dissolved or flushed out. Lupeol (25 mg/kg body weight) has been shown to reduce renal excretion of calcium oxalate and also to reduce renal tubular damage, as seen by lowered levels of several urinary marker enzymes that indicate renal tissue damage. In addition, lupeol has antioxidant activity, which contributes to its protective action against calculosis.

Anti-inflammatory Mechanism

A study aimed to explore the anti-inflammatory effects of Crataeva nurvala extract concluded that it significantly reduced the production of NO and IL-6, and that Crataeva nurvala extract inhibits inflammatory responses via negative regulation of ERK.

Lupeol in doses of 200, 400, and 800 mg/kg produced dose-dependent inhibition (24%, 40%, and 72%) in an acute model of inflammation. In the chronic granuloma pouch model in rats, lupeol exhibited 33% reduction in granuloma weight. In an arthritis model, lupeol exhibited 29% inhibition after 21 days.

Antioxidant and Nephroprotective Mechanism

In a study using two-kidney, one-clip (2K1C) rats, Crataeva nurvala treatment prevented kidney dysfunction. Uric acid and creatinine concentration and CK-MB activities increased in 2K1C rats and were normalized by Crataeva nurvala. The rats also showed increased oxidative stress, depicted by elevated levels of MDA, NO, and APOP in plasma and tissues, which declined upon treatment. These results were attributed to the restoration of antioxidant enzyme activities such as catalase and SOD.

Diuretic Activity

Anti-urolithiatic activity studies have shown that lupeol reduces oxalate levels and promotes super-saturation in renal tissues through diuretic activity. In one experimental study, Varuna (Crataeva nurvala) caused hypercalciuria and hyperphosphoruria, while the total volume of urine increased in 24 hours in the treated group.

Lupeol's Broader Pharmacological Profile

Lupeol has been reported to reduce the deposition of calcium oxalate — the most common stone-forming constituent — in animals. It also possesses antifertility, anticancer, antitumor, anti-arthritic, anti-inflammatory, hepatoprotective, and cardioprotective activities.

5. Scientific Evidence by Area of Use

5.1 Urolithiasis (Kidney and Urinary Stones)

This is the most studied application of Varuna, with a progression from in vitro, through animal models, to limited human data.

Animal studies: The effect of oral administration of Crataeva nurvala bark decoction on calcium oxalate lithiasis has been studied in rats. The elevation of the oxalate-synthesizing liver enzyme glycolate oxidase, produced by feeding glycollic acid, was remarkably reduced with the decoction, showing a regulatory action on endogenous oxalate synthesis. Protein-bound carbohydrates were increased in the renal tissues during calculosis, but these changes were not reversed with the herbal treatment. The increased deposition of stone-forming constituents in the kidneys of calculogenic rats was lowered with decoction administration.

Researchers used a normal human dose of Crataeva nurvala (adjusted for albino rats), and found that the incidence of stone formation and stone weight were greatly reduced. Stones were formed in 56% of the control group, but only 22% in the treated group.

Human/clinical evidence: In an open trial, 46 patients with urinary stone were treated with 50 ml of stem-bark decoction of Crataeva nurvala, administered twice a day for varying periods. It was found that 28 patients were spontaneously able to pass the stone in 1–47 weeks, whereas 18 patients had considerable relief in symptoms. This open-label trial lacked a control group, which significantly limits interpretation.

The Ayurvedic formula "Herbmed" — made up of Crataeva nurvala (Varuna bark) and banana stem (Musa paradisiaca) — was investigated in the management of urinary stones in a randomized, double-blind, placebo-controlled trial that included 77 patients with calculi more than 5 mm in diameter. Treatment group patients were prescribed one capsule comprised of 250 mg Crataeva nurvala and 250 mg Musa paradisiaca in the morning.

In a prospective, randomized, double-blind, placebo-controlled study, Crataeva nurvala showed prospects for kidney stone treatment because it dissolved oxalate concretions and anesthetized their passage. Daily intake of Crataeva nurvala bark reduced urinary calcium excretion and kidney stone formation.

Evidence strength: Data from in vitro, in vivo, and clinical trials reveal that phytotherapeutic agents including Crataeva would be useful as either an alternative or an adjunctive therapy in the management of urolithiasis. However, large-scale, independently conducted, well-controlled human trials remain limited, and the evidence base is primarily preclinical.

5.2 Overactive Bladder (OAB) and Urinary Incontinence

The most methodologically rigorous human clinical data for Varuna relates to its inclusion in a polyherbal combination product for lower urinary tract symptoms.

A proprietary combination called Urox® — which includes Cratevox™ (Crataeva nurvala) stem bark, Equisetum arvense stem, and Lindera aggregata root — was assessed for efficacy on bladder symptoms compared to an identical placebo in a randomised, double-blind, placebo-controlled trial conducted at two primary care centres. Data were collected at baseline, 2, 4, and 8 weeks, with the primary outcome being self-reported urinary frequency.

One hundred and fifty participants (59% female, aged mean ± SD 63.5 ± 13.1 years) took part in the study. At week 8, urinary day frequency was significantly lower (OR 0.01; 95% CI 0.01 to 0.02; p < 0.001) in response to treatment.

Crataeva demonstrated beneficial effects on neurogenic bladder and significantly decreased residual urine volume, normalizing the tone of the urinary bladder. Crataeva has also been shown to be effective in the treatment of urinary calculi and infection.

Limitation: Because Crataeva nurvala was one of three herbal components in the Urox® formula, the contribution of Varuna specifically to the observed outcomes cannot be isolated from the available published data. There is little evidence to suggest how much Crataeva nurvala to take on its own for OAB, as many studies around the herb are animal studies or investigate Crataeva nurvala as a combined supplement with other herbs.

5.3 Benign Prostatic Hyperplasia (BPH) and Prostate Health

Crataeva nurvala, commonly known as Varuna, is a well-known Ayurvedic herb especially effective in urinary disorders, urolithiasis (kidney stones), and enlarged prostate. C. nurvala has also been used in the treatment of prostate enlargement and bladder sensitivity.

The antioxidative potential of Crataeva nurvala bark extract against androgen-mediated oxidative stress in male Wistar rats has been studied. Oxidative damage in prostate was induced in rats by the injection of testosterone (100 mg/kg body weight) for 3 days, followed by injection of the chemical carcinogen N-Methyl N-Nitroso Urea (50 mg/kg body weight) for 1 week. Components from Crataeva nurvala bark have been accounted to play an important role in scavenging free radicals generated by mutagens and carcinogens. These are preclinical (animal) findings; controlled human trials specifically evaluating Varuna for BPH have not been identified in the available peer-reviewed literature.

5.4 Anti-inflammatory and Anti-arthritic Activity

Investigations have indicated the plant has anti-arthritic, hepatoprotective, and cardio-protective actions. These findings are predominantly from animal and in vitro studies. Anti-complement activity of triterpenes from Crataeva nurvala stem bark in adjuvant arthritis in rats has been documented. Human clinical data in this area are lacking.

5.5 Antioxidant Activity

The ethanolic extracts of Crataeva nurvala bark have demonstrated significant antioxidant and antimicrobial activities. LC-MS and HPTLC analyses revealed high contents of resveratrol, quercetin, gallic acid, and lupeol, which likely contribute to these biological effects.

5.6 Antidiabetic Activity

The plant has been reported for use in diseases including diabetes. Research experts have found that the stem bark of Varuna has antidiabetic activities. The bark has also exhibited antidiabetic, antidiarrhoeal, antifertility, and analgesic properties in experimental settings. All findings in this area are currently limited to animal or in vitro models.

5.7 Hepatoprotective Activity

Research in the Indian Journal of Pharmacology demonstrated the hepatoprotective effects of Crataeva nurvala in patients with liver disorders. Animal studies have shown its ability to reduce serum creatinine and urea levels, confirming its potential in renal function improvement. The evidence from human studies in this area is limited, and the existing data require further replication.

5.8 Antimicrobial Activity

The plant has been demonstrated to possess multiple pharmacological activities such as anti-inflammatory, urolithiatic, antidiabetic, antibacterial, analgesic, antifertility, antidiarrhoeal, antinociceptive, and cardioprotective activity. The antimicrobial claims are supported primarily by in vitro and in vivo preclinical research, not human clinical trials.

6. Body Systems and Health Areas Associated With Varuna

Crataeva nurvala (CN), commonly known as Varuna, is reported to possess various pharmacological activities such as analgesic, anthelmintic, anti-arthritic, antibacterial, anticancer, antidiabetic, antidiarrhoeal, antifertility, anti-hemolytic, anti-snake venom, anti-inflammatory, antimycotic, antioxidant, antiurolithiatic, cardioprotective, hepatoprotective, nephroprotective, neuroprotective, and antimalarial activities.

The health areas most consistently associated with Varuna in both traditional and scientific contexts are:

• Urinary system: Crataeva nurvala is used for genitourinary conditions such as atonic bladder, benign prostatic hyperplasia, chronic urinary tract infections, hypotonic bladder, incontinence, and the prevention and treatment of kidney stones.
• Renal system: Nephroprotective effects documented in animal models of renal injury.
• Musculoskeletal system: Anti-arthritic and anti-inflammatory effects in preclinical models.
• Hepatic system: Hepatoprotective effects reported in animal and limited human studies.
• Cardiovascular system: Varuna is often used topically to dilate superficial capillaries and stimulate circulation, and scientific research has demonstrated that Varuna may support the cardiovascular system by maintaining the suppleness and openness of the arteries.

7. Dosage Forms and Reported Dosages

Several plant parts are used in traditional preparations, with the stem bark being the most widely employed in research.

Traditional Preparations

• Bark decoction (Kwatha/Kashaya): In an open clinical trial, 46 patients with urinary stones were treated with 50 ml of stem-bark decoction administered twice a day for varying periods.
• Bark powder (Churna): Varun chhal powder is a traditional Ayurvedic formulation made from the dried bark of the Crataeva nurvala tree, prized for centuries for its targeted action on urinary tract health and kidney stones.
• Proprietary tablet (Varunadi Vati): Varunadi Vati is a herbal medicine made with extracts from the Varun herb and is used for urinary tract health and kidney stone management.

Dosages Reported in Research Studies

• In the 2018 Urox® human study, participants took 2 capsules of the Urox supplement once a day with food for 8 weeks. Researchers based the dosage on prior research of the herbal ingredients and traditional herbal recommendations.
• In a 2023 animal study examining renal-protective activity, the ethanol extract of Crataeva nurvala bark was used at a dose of 100 mg/kg orally to treat 2K1C rats for four weeks.
• In an anti-urolithiatic animal study from Nepal, test groups were fed 150 mg/kg and 300 mg/kg of both bark and root extract, while the standard group was supplied with Cystone at a dose of 750 mg/kg.
• Varalakshmi et al. (1990) reported oral administration of C. nurvala bark decoction at 2 ml/rat/day in a rat study; anti-crystallization properties were also attributed to a bark decoction at 9 ml/kg body weight in an experimental animal model.
• Lupeol at 25 mg/kg body weight has been shown in animal studies to reduce renal excretion of calcium oxalate and reduce renal tubular damage.
• In traditional Ayurvedic practice for diabetes (Prameha), a decoction of Varuna is taken at a dose of 60 ml per day.

8. Safety Considerations and Notable Interactions

Antifertility Effects

This is the most significant source-documented safety concern. The ethanol and aqueous extracts of the dried stem bark of Crataeva nurvala have been found to possess significant anti-fertility effects in rats. Both ethanol and aqueous extracts exhibited partial and complete resorption of implants at 300 and 600 mg/kg body weight dose levels, respectively. In estrogenic activity studies, both extracts increased uterine weight and caused opening and cornification of the vagina in immature rats. These findings are from animal studies, but they have clear implications for use in pregnancy and in individuals attempting to conceive.

Cytochrome P450 Interactions

According to a 2023 study, previous research around Crataeva nurvala suggests it has no severe side effects and does not interfere with certain enzymes known as P450 cytochromes, suggesting it is safe to use with other medicines. However, this finding appears in the context of a specific study and has not been confirmed by comprehensive drug-interaction studies.

General Tolerability

A 2023 animal study on the Urox supplement showed that the herbal supplement — which contains Crataeva nurvala as a key ingredient — was effective in reversing induced changes causing OAB, with no adverse side effects reported. Based on the 2018 Urox clinical study, Crataeva nurvala is described as a well-established traditional medicine that is safe for humans to consume in the studied context.

Toxicological Notes

Ethanolic extracts of the title plant were found to be toxic to mice in one study; acid hydrolysis of the toxic extracts permitted the isolation of six crystalline compounds, which were identified as known triterpenes and a common plant sterol. The toxicological profile at therapeutic doses in humans has not been fully characterized in well-controlled clinical studies.

Diuretic Caution

Given its documented diuretic activity, caution is warranted in patients who are already taking pharmaceutical diuretics, as additive effects on fluid and electrolyte balance are plausible, though specific interaction studies are not available in the peer-reviewed literature identified here.

Conservation Status

Crataeva nurvala has been categorized as rare and vulnerable in the natural environment. This has implications for the sourcing of standardized raw material and for preparations derived from wild-harvested plant material.

References

• Varalakshmi et al. (1990). Effect of Crataeva nurvala in experimental urolithiasis. Journal of Ethnopharmacology. PubMed.
• Agarwal et al. (2010). Urolithic property of Varuna (Crataeva nurvala): An experimental study. Ayu. PMC/PubMed.
• Schoendorfer N et al. (2018). Urox containing concentrated extracts of Crataeva nurvala stem bark, Equisetum arvense stem and Lindera aggregata root, in the treatment of symptoms of overactive bladder and urinary incontinence: a phase 2, randomised, double-blind placebo controlled trial. BMC Complementary and Alternative Medicine.
• Jahan I et al. (2023). Crataeva nurvala Bark (Capparidaceae) Extract Modulates Oxidative Stress-Related Gene Expression, Restores Antioxidant Enzymes, and Prevents Oxidative Stress in the Kidney and Heart of 2K1C Rats. PMC.
• Gopalakrishnan VK (2013). Modulatory effects of Crataeva nurvala bark against testosterone and N-methyl-N-nitrosourea-induced oxidative damage in prostate of male albino rats. PMC.
• Shirwaikar A et al. (2008). Crataeva nurvala: A Valuable Medicinal Plant. Journal of Herbs, Spices & Medicinal Plants, 14(1-2).
• Botanical description, phytochemistry, traditional uses, and pharmacology of Crataeva nurvala Buch. Ham.: an updated review. Future Journal of Pharmaceutical Sciences (2020). ResearchGate/Springer.
• Phytochemical and ethno-pharmacological profile of Crataeva nurvala Buch.-Ham. (Varuna): A review. ResearchGate.
• Utilities of Crataeva nurvala. ResearchGate (2017).
• New cytotoxic quinolone alkaloid and a pentacyclic steroidal glycoside from the stem bark of Crataeva nurvala. European Journal of Medicinal Chemistry (2013). ScienceDirect.
• Kidney stone risk reduction and size reduction using Crataeva nurvala. GSC Biological and Pharmaceutical Sciences (2022).
• Evaluation of phytochemical, antioxidant, anthelmintic and antimicrobial properties of Crataeva nurvala leaves. ResearchGate (2015).
• Evaluation of the anti-fertility activity of stem bark of Crataeva nurvala Buch.-Ham. Academia.edu.
• Plants for Urinary Tract Disorders: Crataeva nurvala. 1library.net.
• Varuna — Benefits, Usage, Dose, Ayurvedic Details. EasyAyurveda.com.
• Crataeva nurvala for OAB: Efficacy, safety, and more. Medical News Today (2024).