Understanding Crateva Religiosa: Medicinal Uses and Benefits

Botanical illustration of Crateva Religiosa with labeled leaves, flowers, fruit, and bark

General features: Crateva religiosa (CR), commonly known as the temple plant or sacred garlic pear, is a perennial tropical species of the family Capparaceae and genus Crateva. Native to Southeast Asia and the South Pacific, it is widely recognized for its medicinal value. Its showy, long-stamened flowers attract birds, flies, and nectar-feeding insects, especially pierid butterflies such as Hebomoia glaucippe [1]. In India, CR grows mainly in subtropical evergreen and deciduous forests of the central and northeastern regions, particularly along watercourses and riverbanks and at elevations above 3,000 feet, including Arunachal Pradesh, Nagaland, Mizoram, and Manipur. It is also found in the Gangetic Plains and the Andaman and Nicobar Islands. Highly valued in Ayurveda, the plant is often grown near temples. It is distinguished by trifoliolate leaves, long-stalked flowers, and pear-shaped fruits. Mature plants usually reach 30–50 feet in height and have smooth brown or gray bark with yellow lenticels. The bright green leaves occur in clusters of three, with ovate to lanceolate leaflets measuring about 4–15 inches long. The flowers are highly ornamental, 8–19 inches long, and borne in dense terminal clusters. They have four clawed petals that are initially white and later turn yellow, pale red, or pink. Both the flowers and fruits emit a garlic-like odor. The fruits are berries, globose to ovoid, borne on long stalks, and contain kidney-shaped seeds embedded in yellow, garlic-scented pulp [2].

History of CR uses and religious significance: Crateva religiosa, commonly known as the sacred garlic pear, is called Varuna in Sanskrit, a name closely tied to Hindu mythology and ancient Indian ritual traditions. The plant has been known since the Vedic Era (1500–500 BC), when it was identified as Varuna. Since then, it has been used in traditional Indian medicine and has become closely integrated into Hindu religious practice. It is associated with Lord Varuna, the Vedic deity of oceans, rivers, and other water bodies. Because it often grows near riverbanks and lakes, it is believed to share a spiritual connection with Varuna’s realm and the natural order of water on earth [3]. Its trifoliolate leaves are said to symbolize the Trishul, the sacred trident of Lord Shiva. As a result, the leaves are commonly offered to Lord Shiva during Puja and other rituals, much like the leaves of the Bel tree (Aegle marmelos). Vedic texts also regard the wood, bark, and flowers of the Varuna tree as highly auspicious. Garlands made from its wooden beads have traditionally been worn as protective amulets, especially by sages and Indian kings. The ancient Ayurvedic text Charaka Samhita also recommends its wood for ritual objects believed to ward off negative energies and protect newborns and village communities [4]. Sushruta Samhita further records the use of Varuna plant parts to treat kaphajarsha (piles), Shira shola (headache), Gulma (abdominal tumor), and Vidradhi (abscess). In Siddha medicine, the plant is known as “Maralingam.” Its root and stem bark are used to stimulate the liver, improve appetite, and act as laxatives. It is also used to treat urinary infections and to help prevent or remove kidney stones. The flowers are astringent and act as cholagogues, promoting bile secretion. The leaves, roots, and bark are used to treat fever, urticaria, skin eruptions, ulcers, and insect bites, and the leaves also show strong diuretic activity [4]. Historically, the genus Crateva was named after Crateuas, an ancient Greek botanist and physician who served King Mithridates in the first century BC. The plant later became widely known as the “spider tree” because of its spidery stamens. During Captain Cook’s first voyage (1768–1771 AD), botanist Sydney Parkinson sketched the plant in the Pacific Islands. It was later formally named Crateva religiosa by the German botanist Johann Adam Forster, who chose the term “religiosa” to reflect its sacred status and frequent presence near temple grounds [5]. In other parts of the world, rural and tribal communities adopted the plant in traditional practices at different times because of the pungent nature of its leaves, buds, and fruits, as well as the medicinal value of its stem bark [2].

Medicinal uses: Traditionally, CR has been valued for a wide range of health benefits. It is a litholytic herb commonly used to treat urolithiasis and crystalluria. Inhibiting glycolate oxidase, it may reduce oxalate formation and help prevent kidney stones and related renal disorders. It is also used in the management of benign prostatic hyperplasia, where it may ease painful urination caused by an enlarged prostate and help strengthen bladder muscles. In addition, CR, or Varuna, has notable anti-inflammatory properties and is used to help relieve inflammation associated with rheumatism and gout, as well as infections of the lymph nodes. The plant is also used as an anthelmintic to expel intestinal worms in both children and adults. It supports liver function by improving metabolism and restoring bilirubin balance, which may help protect the liver from disease. CR is further used to stimulate appetite in cases of anorexia, support bowel movements, and exhibit strong antidiabetic activity [6].

Phytochemicals and their possible biochemical actions: CR is rich in bioactive phytochemicals, with their type and concentration varying among the leaves, bark, and fruits. The main classes include phenolics, flavonoids, tannins, alkaloids, saponins, and terpenoids, many of which are linked to the plant’s medicinal properties [7]. The triterpenoids lupeol and betulinic acid have anti-inflammatory, hepatoprotective, anti-lithic, and antiarthritic effects, while betulinic acid also shows antimicrobial and anticancer potential. Friedelin, another triterpenoid, has strong antioxidant activity. Lupenone, a related pentacyclic triterpene, is associated with anti-inflammatory, antidiabetic, anticancer, and cytoprotective effects through the reduction of inflammatory cytokines and enzymes such as iNOS and COX-2, as well as inhibition of the NF-κB signaling pathway [8]. Sterols such as β- and γ-sitosterol show antioxidant and immunomodulatory effects, and flavonoids such as catechin, epiafzelechin, quercetin, and rutin further contribute to antioxidant activity. Epiafzelechin may support bone formation by stimulating osteoblast activity and inhibiting bone-resorbing osteoclasts, helping protect against estrogen-deficiency-related bone loss and improve bone mineral density [9]. Steroidal saponins, including giganteumagenin/oleanolic acid and derbyssogenin, show strong anti-inflammatory and cytotoxic activities [10]. These compounds may also help regulate hyperthyroidism; molecular docking studies suggest that derbyssogenin binds strongly to the thyroid hormone receptor HTR-α and may modulate thyroid activity [11]. The cardiac glycoside β-κ-strophanthin, a cardenolide aglycone related to ouabain and digitoxin, may increase cardiac contractility by inhibiting membrane-associated Na+/K+-ATPase, which increases intracellular Na+ and Ca2+ levels [12]. This action may benefit arrhythmias and heart failure victims by reducing peripheral vascular resistance, lowering systemic blood pressure, and slowing cardiac conduction [13,14]. However, because it can cause intracellular Ca2+ overload and trigger ventricular tachycardia or fibrillation, it should be used with great caution. It has also been used by Amazonian tribes as an arrow poison [15]. The main alkaloids reported in CR are glucocapparin and L-stachydrine, both of which are associated with the glucosinolate class. Glucocapparin grows mainly in the bark and fruit, whereas L-stachydrine is found primarily in the leaves [16]. Glucocapparin is a methyl-glucosinolate that is also classified as an alkaloid. When the plant material is chewed, endogenous myrosinase converts it into glucose and isothiocyanate, producing a sharp, pungent, slightly bitter taste similar to that of cruciferous vegetables. Glucocapparin-enriched extracts may exert cytotoxic and anti-hyperglycemic effects, supporting their potential role in managing type 2 diabetes and cancer [17]. This compound may also support antioxidant and hepatoprotective activity by reducing oxidative stress.

L-stachydrine, a pyrrolidone alkaloid, has cardioprotective effects by helping prevent vascular endothelial cell hypertrophy, cardiac muscle thickening, and fibrosis [18]. Similar to glucocapparin, it also exhibits anti-inflammatory and antioxidant activities. In addition, L-stachydrine helps regulate uterine smooth muscle contraction and supports immune homeostasis [19].

Pharmacological effects: As a vastly revered Ayurvedic plant, CR extracts of bark, leaf, and flowers have shown a few common pharmacological effects, acting as potent diuretics, antioxidants, anti-inflammatory, and antimicrobial agents. Additionally, it has a significant litholytic role in breaking and preventing kidney stones while regulating metabolic irregularities [16].

Diuretic and litholytic activity – CR extracts have been reported to help eliminate urinary stones and reduce urinary tract infections by promoting the clearance of calcium oxalate and uric acid deposits in the kidneys [10]. Bark extract has been shown to reduce renal calcium oxalate crystal accumulation by nearly 45% [20]. Oral administration of the bark extract may suppress glycolate oxidase, an enzyme involved in oxalate production [21]. In vitro studies using isolated human kidney stones further suggest that methanolic bark extract can dissolve stones in a dose-dependent manner within 24–72 hours [22]. Human pilot studies also indicate that CR may increase urinary output by about 15% compared with placebo, helping flush out small stones and prevent urinary supersaturation [20]. In addition, the extract appears to exert a cholinergic effect on smooth muscle in the bladder and urinary tract, especially relaxing and widening the passage to reduce renal colic pain, facilitating the stone passage [10]. Lupeol has been identified as a key compound responsible for anticrystallization and antilithogenic effects, while saponins and flavonoids may support this action through antioxidant activity, thereby reducing renal inflammation created by stone-induced oxidative stress [23].

Anti-inflammatory and analgesic effect – CR bark and leaf extracts exhibit significant anti-inflammatory and analgesic effects. Experimental studies show that ethanolic extracts markedly reduce carrageenan-induced paw edema, with activity comparable to the standard anti-inflammatory drug indomethacin. They also lessen pain responses in acetic acid-induced writhing tests and in tail-immersion or hot-plate models [24]. These effects are likely associated with bioactive compounds such as flavonoids, terpenoids, alkaloids, saponins, and tannins [25], with giganteumagenin and derbyssogenin appearing to be especially important. These constituents reduce pro-inflammatory cytokines, particularly TNF-α, IL-1β, and IL-6, and downregulate inflammatory markers such as myeloperoxidase (MPO) and mitogen-activated protein kinase (MAPK) [26]. The extracts may relieve pain by inhibiting nociceptive signaling through both central and peripheral pathways [25].

Antidiabetic effect and role in diabetic neuropathy – CR bark extract has long been used in traditional medicine to manage diabetes and help prevent diabetic neuropathy. It may lower blood glucose, reduce diabetes-related nerve pain, and protect tissues from oxidative damage. These effects are mainly attributed to its antioxidant, anti-inflammatory, and enzyme-inhibitory activities. Key active constituents include lupeol, phytosterols, and flavonoids, which may improve glycemic control and limit oxidative stress [23]. Tannins and flavonoids inhibit α-amylase, slowing complex carbohydrate digestion and helping reduce post-meal blood glucose spikes [27]. In alloxan-induced diabetic rats, the extract stimulated insulin secretion from pancreatic β-cells, with effects comparable to glibenclamide, a standard antidiabetic drug [28]. CR extract has also been reported to increase liver glycogen and reduce LDL, VLDL, and triglyceride levels in diabetic subjects [28]. By scavenging reactive oxygen species, CR may help protect nerves from diabetes-induced damage, easing neuropathic pain, burning sensations in the feet, and symptoms associated with restless leg syndrome. Its anti-inflammatory action may further contribute by downregulating pro-inflammatory mediators such as TNF-α and COX-2. Protection against renal inflammation may also support the prevention of diabetic complications. Linalool oxide and selected terpenoids are among the possible contributors to these antidiabetic effects [23].

Antimicrobial effect – CR exhibits notable antimicrobial activity, especially in its methanolic and ethyl acetate fractions, which are rich in flavonoids, steroidal terpenoids, and saponins. These compounds help inhibit the growth of several pathogenic bacteria and fungi [29]. Studies show that CR extracts are active against both Gram-positive and Gram-negative bacteria, including Escherichia coli, Staphylococcus aureus, Shigella sonnei, and Yersinia enterocolitica [30]. Reported minimum inhibitory concentrations range from 0.31 to 0.62 mg/ml. Bark and leaf extracts also demonstrate antifungal activity, with phenolics, steroidal terpenoids, and alkaloids identified as key active constituents [25].

Anti-hyperlipidemic effect – Ethanolic bark extract of CR shows strong anti-hyperlipidemic activity by inhibiting adipocyte differentiation, reducing fat accumulation, and lowering blood lipid levels [31]. In vivo studies indicate that a 400 mg/kg dose significantly reduces LDL, total cholesterol, and triglycerides while increasing HDL levels [7]. In vitro studies using 3T3-L1 cells further show that the extract suppresses adipogenic regulators, including PPARγ and CCAAT/EBP, leading to reduced lipid accumulation. Stigmasterol, γ-sitosterol, and lupeol are considered key active constituents because of their cholesterol-regulating properties [31].

Antioxidant effect – CR exhibits strong antioxidant activity due to its rich content of bioactive phytochemicals, particularly flavonoids, phenolics, and tannins. These compounds help neutralize free radicals and reduce oxidative stress, which is a key contributor to many chronic diseases [32]. Aqueous bark extract shows significant free radical–scavenging activity in the DPPH assay, with an IC50 value of 42.32 µg/ml, as well as strong reducing power in the ferric chloride antioxidant assay, with an IC50 value of 45 µg/ml. Methanolic bark extract has been reported to achieve approximately 95.4% H2O2 scavenging activity, while leaf extracts demonstrate similar antioxidant potential [33,34].

Anticancer activities: Bark, leaf, and flower extracts of CR have demonstrated notable anticancer and antiproliferative activity against several tumor cell lines in vitro. These extracts can inhibit cell proliferation and induce apoptosis in different human cancer cells. Commonly tested cell lines include ovarian PA-1 cells (IC50 = 33.27 µg/ml), lung A549 cells (IC50 = 24.7 µg/ml), cervical HeLa cells (IC50 = 57.11 µg/ml), liver HepG2 cells (IC50 = 29.2 µg/ml), and prostate cancer cells. Their anticancer effects appear to involve apoptosis induction, suppression of cell proliferation, and antioxidant defense, which may help limit DNA damage associated with tumor initiation. Although flavonoids, terpenoids, and phenolics contribute to these effects, lupeol, a pentacyclic triterpene, is considered a major active anticancer constituent [35,36,37].

Effect on CNS – Studies indicate that CR bark and leaf extracts may directly influence neurons in the central nervous system (CNS) [38]. Reported activities include sedative, anxiolytic, analgesic, and neuroprotective effects. The sedative action is thought to involve modulation of the GABAergic pathway, which suppresses nerve transmission, promotes relaxation, reduces locomotor activity, and extends sleep duration [38]. CR phytochemicals may also alleviate neuropathic pain by modulating the opioid system [23]. In addition, antioxidant constituents may support neuroprotection by inhibiting acetylcholinesterase, increasing acetylcholine levels, protecting neurons from injury, and helping reduce the risk of neurodegenerative disorders such as Alzheimer’s disease [35].

Cardiovascular effect – CR extracts may promote cardiovascular health through antioxidant, anti-inflammatory, and lipid-lowering effects [7]. Phytosterols, including stigmasterol and β-sitosterol, may lower LDL cholesterol and triglycerides while increasing HDL levels. Flavonoid- and phenolic-rich extracts may also neutralize endogenous free radicals, which contribute to cardiac tissue damage and cardiovascular dysfunction. Lupeol, a pentacyclic triterpenoid and major active constituent, may help protect cardiac muscle from oxidative stress [7,10]. In addition, the cardiac glycoside β-κ-strophanthin may act as a positive inotrope by enhancing cardiac contraction and as a negative chronotrope by lowering heart rate. It does so by inhibiting Na+/K+-ATPase in cardiac cell membranes, increasing intracellular Na+. This activates the Na+/Ca2+ exchanger and promotes Ca2+ influx. The resulting increase in intracellular Ca2+ enhances troponin binding, strengthens myocardial contraction, improves the pumping capacity of a failing heart, and increases the cardiac index. It may also stimulate vagal activity, slow the heart rate, and allow more time for ventricular filling [10,38,39,40].

Antimicrobial effect – CR exhibits notable antimicrobial activity, especially in its methanolic and ethyl acetate fractions, which are rich in flavonoids, steroidal terpenoids, and saponins. These compounds help inhibit the growth of several pathogenic bacteria and fungi [29]. Studies show that CR extracts are active against both Gram-positive and Gram-negative bacteria, including Escherichia coli, Staphylococcus aureus, Shigella sonnei, and Yersinia enterocolitica [30]. Reported minimum inhibitory concentrations range from 0.31 to 0.62 mg/ml. Bark and leaf extracts also demonstrate antifungal activity, with phenolics, steroidal terpenoids, and alkaloids identified as key active constituents [25].

Anti-hyperlipidemic effect – Ethanolic bark extract of CR shows strong anti-hyperlipidemic activity by inhibiting adipocyte differentiation, reducing fat accumulation, and lowering blood lipid levels [31]. In vivo studies indicate that a 400 mg/kg dose significantly reduces LDL, total cholesterol, and triglycerides while increasing HDL levels [7]. In vitro studies using 3T3-L1 cells further show that the extract suppresses adipogenic regulators, including PPARγ and CCAAT/EBP, leading to reduced lipid accumulation. Stigmasterol, γ-sitosterol, and lupeol are considered key active constituents because of their cholesterol-regulating properties [31].

Antioxidant effect – CR exhibits strong antioxidant activity due to its rich content of bioactive phytochemicals, particularly flavonoids, phenolics, and tannins. These compounds help neutralize free radicals and reduce oxidative stress, which is a key contributor to many chronic diseases [32]. Aqueous bark extract shows significant free radical–scavenging activity in the DPPH assay, with an IC50 value of 42.32 µg/ml, as well as strong reducing power in the ferric chloride antioxidant assay, with an IC50 value of 45 µg/ml. Methanolic bark extract has been reported to achieve approximately 95.4% H2O2 scavenging activity, while leaf extracts demonstrate similar antioxidant potential [33,34].

Anticancer activities: Bark, leaf, and flower extracts of CR have demonstrated notable anticancer and antiproliferative activity against several tumor cell lines in vitro. These extracts can inhibit cell proliferation and induce apoptosis in different human cancer cells. Commonly tested cell lines include ovarian PA-1 cells (IC50 = 33.27 µg/ml), lung A549 cells (IC50 = 24.7 µg/ml), cervical HeLa cells (IC50 = 57.11 µg/ml), liver HepG2 cells (IC50 = 29.2 µg/ml), and prostate cancer cells. Their anticancer effects appear to involve apoptosis induction, suppression of cell proliferation, and antioxidant defense, which may help limit DNA damage associated with tumor initiation. Although flavonoids, terpenoids, and phenolics contribute to these effects, lupeol, a pentacyclic triterpene, is considered a major active anticancer constituent [35,36,37].

Effect on CNS – Studies indicate that CR bark and leaf extracts may directly influence neurons in the central nervous system (CNS) [38]. Reported activities include sedative, anxiolytic, analgesic, and neuroprotective effects. The sedative action is thought to involve modulation of the GABAergic pathway, which suppresses nerve transmission, promotes relaxation, reduces locomotor activity, and extends sleep duration [38]. CR phytochemicals may also alleviate neuropathic pain by modulating the opioid system [23]. In addition, antioxidant constituents may support neuroprotection by inhibiting acetylcholinesterase, increasing acetylcholine levels, protecting neurons from injury, and helping reduce the risk of neurodegenerative disorders such as Alzheimer’s disease [35].

Cardiovascular effect – CR extracts may promote cardiovascular health through antioxidant, anti-inflammatory, and lipid-lowering effects [7]. Phytosterols, including stigmasterol and β-sitosterol, may lower LDL cholesterol and triglycerides while increasing HDL levels. Flavonoid- and phenolic-rich extracts may also neutralize endogenous free radicals, which contribute to cardiac tissue damage and cardiovascular dysfunction. Lupeol, a pentacyclic triterpenoid and major active constituent, may help protect cardiac muscle from oxidative stress [7,10]. In addition, the cardiac glycoside β-κ-strophanthin may act as a positive inotrope by enhancing cardiac contraction and as a negative chronotrope by lowering heart rate. It does so by inhibiting Na+/K+-ATPase in cardiac cell membranes, increasing intracellular Na+. This activates the Na+/Ca2+ exchanger and promotes Ca2+ influx. The resulting increase in intracellular Ca2+ enhances troponin binding, strengthens myocardial contraction, improves the pumping capacity of a failing heart, and increases the cardiac index. It may also stimulate vagal activity, slow the heart rate, and allow more time for ventricular filling [10,38,39,40].

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