Caesalpinia crista

Caesalpinia crista: A Comprehensive Reference

1. Identity and Botanical Description

1.1 Nomenclature and Taxonomy

Caesalpinia crista Linn. is synonymous with Caesalpinia bonducella (L.) Fleming and Caesalpinia bonduc (L.) Roxb., belonging to the family Caesalpiniaceae, and is a prickly shrub widely distributed all over the world, especially found in tropical regions. The genus Caesalpinia belongs to the subfamily Caesalpinioideae of the family Caesalpiniaceae and consists of more than 500 species, which are mostly woody species occurring in tropical and subtropical zones.

Caesalpinia crista is commonly known as Fever Nut or Latakaranja. Additional vernacular names recorded in the literature include Sagargoti in Marathi, Kantakikaranja and Latakaranja in Sanskrit/Ayurveda, and Akitmakit in Urdu. The plant is recognized across Ayurveda, folk medicine, Sowa-Rigpa, Siddha, and Traditional Chinese Medicine.

1.2 Geographic Distribution and Habit

Caesalpinia crista L. belongs to the family Caesalpiniaceae, commonly found along the riverbanks and in the tidal forests that are located close to the Eastern seacoast beginning in Orissa and continuing southward along the Western seacoast beginning in Konkan. It is found in the hotter parts of India, is common in West Bengal and South India, and often grows as a hedge plant. The plant is also widely distributed in Sri Lanka and the Andaman and Nicobar Islands.

1.3 Morphology

Caesalpinia crista (Fabaceae) is a prickly shrub or woody vine that may grow up to 10 metres in length. The rachis is loaded with thick, sharp, recurved spines, and the leaves are bi-pinnate, typically almost 1 m long. The leaflets are arranged in ten pairs, are rectangular, 2 to 5 cm long, and hairy. Flowers are yellow, 1 cm long, and borne in axillary, simple, or panicled racemes. The fruits are rectangular, 5 to 7 cm long pods with one or two seeds that are swollen and coated with thin spines. The seeds are big, ovoid or spherical, hairy, greyish, and gleaming.

1.4 Plant Parts Used and Common Preparations

Various parts of the plant — seeds, leaves, bark, flowers, root, and oils — are used in traditional systems of medicine. All parts of the plant, including the root, leaves, stem, seed, and seed kernel, have medicinal properties. C. crista has been used in traditional and folk medicine for various skin and respiratory ailments since ages. The seed kernel is the most widely used part all over the world in various systems of medicine.

Common preparations documented in the literature include aqueous decoctions, ethanolic extracts, dichloromethane extracts, petroleum ether extracts of the seed kernels, seed powder, and fixed oils. Extraction is carried out by breaking the seed coat; the kernels are then crushed to a coarse powder, which is defatted with petroleum ether (60/80). The petroleum ether is distilled off on a rotary flash evaporator to leave a yellow, oily extract (22% w/w). The defatted marc is then dried and further extracted with 95% ethanol, which yields a sticky ethanolic reddish-brown extract (16% w/w).

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2. Traditional and Historical Use

2.1 Ayurveda

Caesalpinia crista is well known for its medicinal and therapeutic values in Indian Ayurveda, and the Indian traditional scriptures as well as the Ayurvedic texts have various references to the use of this plant. In Ayurvedic classification, it is described as tikta (bitter), ushna (heating), and deepana (digestive stimulant). In Ayurveda, various plant parts such as leaves, stem, root, seed, and oil are used as febrifugal, periodic, tonic, and vesicant for the treatment of gynaecological disorders, skin diseases, constipation, piles, and ulcers.

The plant has been recommended for the treatment of various diseases and disorders such as antispasmodic conditions, malarial fever, leucorrhea, abdominal pain, rheumatoid arthritis, diabetes, cystic fibrosis, and amenorrhoea. The herb is used both internally and externally.

2.2 Siddha and Unani Systems

In Indian traditional plant medicine, it has been considered an important remedy for the treatment of several diseases. It is popular in indigenous systems of medicine like Ayurveda, Siddha, Unani, and Homoeopathy. In Siddha medicine the plant was employed in external applications for joint pain and wounds.

2.3 Traditional Chinese Medicine

The seeds of C. bonduc have been used as a traditional Chinese medicine (TCM) for the treatment of a variety of diseases, including common cold, fever, dysentery, epigastric pain, abdominal pain, eye swelling and pain, and sores.

2.4 African and Other Tropical Traditions

In Benin, Caesalpinia bonduc is used as an aphrodisiac and for the treatment of various ailments including prostatic hyperplasia. It has been traditionally utilized and reported to be effective in the treatment of antimicrobial and anthelmintic complaints, anti-tumor conditions, ethnoveterinary uses, removal of the placenta, and respiratory and liver disorders.

2.5 Ethnobotanical Summary

Across all traditional systems, the consistent cluster of uses relates to fever (particularly malarial fever), helminthic infestations, liver and digestive conditions, gynaecological disorders, skin diseases, and as a general tonic. The plant has thus historically occupied a multi-system medicinal role across South Asia, Southeast Asia, East Asia, and tropical Africa.

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3. Key Constituents and Active Compounds

3.1 Major Chemical Classes

Caesalpinia crista contains flavonoids, tannins, proteins, alkaloids, carbohydrates, reducing sugars, phytosterols, saponins, coumarins, triterpenoids, furano-cassane diterpenes, nor-cassane diterpenes, neo-cassane diterpenes, and many other bioactive compounds.

3.2 Cassane-Type Diterpenoids

Among the chemical constituents, cassane-type diterpenoids are considered to be the most important components and the active constituents of C. bonduc. Plants belonging to the genus Caesalpinia are rich in cassane- and norcassane-type diterpenoids, flavonoids, and peltogynoids.

From the CH₂Cl₂ extract of seed kernels of Caesalpinia crista from Myanmar, five new cassane-type diterpenes — caesalpinins MA–ME (1–5) — and three new norcassane-type diterpenes — norcaesalpinins MA–MC (6–8) — have been isolated, together with 12 known cassane-type diterpenes. Nine new cassane-type diterpenes named taepeenin A–I, and two new norcassane-type diterpenes named nortaepeenin A–B, were also isolated from the stems and roots of Caesalpinia crista, along with three known diterpenes: vinhaticoic acid, methyl vinhaticoate, and ent-11b-hydroxy-rosa-5.

Cassane diterpenoids (CAs) are predominant and characteristic chemical components in various genera of the Fabaceae family, especially the Caesalpinia genus, and have a wide range of biological activities, including anti-inflammatory, antitumor, antimalarial, antiviral, antioxidant, and antimicrobial properties.

3.3 Bitter Principles: Bonducin and Natin

The bitter principles bonducin and natin are the primary constituents of Caesalpinia crista, apart from linolic acid, fatty acid, sitosterol, and different diterpenes, which are mainly believed to be responsible for its wide therapeutic action.

3.4 Constituents by Plant Part

The fruits contain D(+) pinitol, and the leaves contain the glycosidal compounds brazilin and bonducin. The roots contain cassane furan diterpene caesalpinin; cassane diterpenes caesaldekarins C, F, and G; bonducellpins A, B, C, D; and the steroidal saponin diosgenin.

The seeds contain various chemical constituents including furanoditerpenes — α-caesalpin, β-caesalpin, γ-caesalpin, δ-caesalpin, ε-caesalpin, and caesalpin-F — fatty acids such as palmitic, stearic, octadeca-4-enoic, and octadeco-2-4-dienoic, lignocenic, oleic, and linoleic acids, phytosterinin, and β-sitosterol. Also present are homoisoflavone, bonducellin, amino acids including aspartic acid, arginine, and citrulline, and carbohydrates including starch, sucrose, β-carotene, glycoside-bonducin, gums, and resins.

Phenolic acids such as caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, and gallic acid have been identified in the leaves.

Seeds have also been reported to contain proteins, saponin, two phytosterols namely sitosterol and heptasane, and additional fatty acids including palmitic acid, stearic acid, lognoceric, oleic, and linolenic acid, as well as furanoditerpenes.

3.5 Homoisoflavonoids

Phytochemical studies on the ethanolic extracts of Caesalpinia bonduc yielded two new homoisoflavonoids, caesalpinianone and 6-O-methylcaesalpinianone, along with five known natural products: hematoxylol, stereochenol A, 6′-O-acetylloganic acid, 4′-O-acetylloganic acid, and 2-O-β-d-glucosyloxy-4-methoxybenzenepropanoic acid. All of these compounds exhibited different levels of glutathione S-transferase (GST) inhibitory and antifungal activities.

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4. Pharmacology and Mechanisms of Action

This plant has profound medicinal use and has been reported to have adaptogenic, anthelmintic, anti-inflammatory, antipyretic and analgesic, antimalarial, antiamyloidogenic, antibacterial, antifilarial, antitumor, anticonvulsant, nootropic, immunomodulatory, hepatoprotective, anxiolytic, antidiabetic, and hypoglycemic activity.

4.1 Antimalarial Activity

Dichloromethane extract of C. crista seeds from Indonesia showed significant in vivo antimalarial activity against the growth of Plasmodium bergei in mice. Separately, 44 cassane- and norcassane-type diterpenes from C. crista were isolated and evaluated for their antimalarial activity against the malarial parasite Plasmodium falciparum (FCR-3/A2 clone) in vitro. Most of the tested diterpenes showed antimalarial activity, and norcaesalpinin E showed the most potent activity with an IC₅₀ value of 0.090 μM. These findings are from in vitro and rodent model studies; no human clinical antimalarial trials involving C. crista have been documented in the peer-reviewed literature.

4.2 Antidiabetic and Hypoglycemic Activity

The seed extracts of Caesalpinia bonducella were used for determining antidiabetic activity in Wistar rats in the case of alloxan-induced hyperglycemia. After oral administration of the extracts at 300 mg/kg, a significant antihyperglycemic action was observed, along with significantly lowered blood urea nitrogen (BUN) levels. The aqueous and ethanolic extracts of its seeds have been reported to possess in vivo hypoglycemic effect in alloxan- and streptozotocin-induced type 2 diabetes in a rat model at a dose of 25 mg/kg body weight. All published antidiabetic data derive from animal models; no controlled human trials have been conducted.

4.3 Hepatoprotective Activity

A key study was carried out to evaluate the ameliorating effect of Caesalpinia crista methanol extract (CCME) on iron-overload-induced liver injury in mice. Iron overload was induced by intraperitoneal administration of iron dextran. CCME attenuated the percentage increase in liver iron and serum ferritin levels when compared to the control group. CCME also showed dose-dependent inhibition of lipid peroxidation, protein oxidation, and liver fibrosis. Serum enzyme markers were found to be lower, whereas enhanced levels of liver antioxidant enzymes were detected in the CCME-treated group. The study confirmed the hepatoprotective effect of CCME against the model hepatotoxicant iron overload, with the activity likely related to its potent antioxidant and iron-chelating properties. This is a preclinical murine study; no human hepatoprotective clinical trials are available.

4.4 Antioxidant Activity

A 70% methanol extract of Caesalpinia crista (CCME) leaf has shown in vitro antioxidant and iron-chelating properties, and was found to be a rich source of phenolic and flavonoid compounds. CCME also exhibited DPPH radical scavenging and protection against Fe²⁺-mediated oxidative DNA damage. Evidence is confined to in vitro assays and animal models.

4.5 Anti-Inflammatory and Analgesic Activity

Cassabonducin A, a newly characterised cassane diterpenoid from seeds of Caesalpinia bonduc, possessed noteworthy inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, with an IC₅₀ value of 6.12 μM. Anti-inflammatory evidence is primarily in vitro and from animal models; no human studies have been performed.

4.6 Adaptogenic Activity

The adaptogenic potential of seed extracts of C. bonducella has been studied in rats, measuring physiological stress responses. This represents preclinical, animal-model research only.

4.7 Anticonvulsant and Nootropic Activity

The extracts of C. crista have been reported to have nootropic/memory-enhancer and anticonvulsant effects. Published studies on both activities are restricted to rodent models, using standard seizure induction tests and learning/memory paradigms. No human clinical trials have been conducted for these neurological outcomes.

4.8 Antimicrobial and Antifungal Activity

The methanolic, ethyl acetate, and water fractions of crude extracts of C. bonduc exhibit in vitro activity against the growth of an array of pathogenic bacteria and fungi. Evidence is limited to in vitro antimicrobial testing; no clinical evidence in infected human subjects has been reported.

4.9 Anti-amyloidogenic / Neuroprotective Activity

Scientific studies have shed light on the effective usage of C. crista leaves in exploring their potential properties towards treating Alzheimer's disease (AD). This relates to the cholinesterase inhibitory and β-amyloid aggregation inhibitory properties of leaf extracts. Evidence remains at the in vitro and phytochemical screening stage.

4.10 Anthelmintic Activity

Multiple experimental studies in animal models have documented anthelmintic activity of C. crista/bonducella extracts against parasitic nematodes. The extracts of C. crista have been reported to have anthelmintic effects. No controlled human clinical trials for anthelmintic efficacy have been published.

4.11 Reproductive and Hormonal Effects

A study aimed to evaluate the effects of Caesalpinia crista on reproductive abnormalities, reproductive hormones, and glycemic changes in a letrozole-induced model of PCOS in rats. Letrozole was given to the disease control group and four treatment groups for 21 days, followed by a treatment period of 15 days with either clomiphene citrate (1.8 mg/kg) orally or low-dose (100 mg/kg), medium-dose (300 mg/kg), or high-dose (500 mg/kg) Caesalpinia crista. The number of ova was significantly high in the high-dose Caesalpinia crista group compared to the disease control group (p<0.05). A decreased number of atretic follicles was seen in the high-dose and medium-dose Caesalpinia crista group on histopathology, with an increased number of corpus lutea (p<0.05). Treatment with Caesalpinia crista at the high dose of 500 mg/kg significantly improved the reproductive abnormalities (ovulation and menstrual irregularities) and histopathological changes associated with PCOS. It also restored reproductive hormone levels (testosterone, FSH, and LH), which are elevated in PCOS, and normalized the LH/FSH ratio, which is deranged in PCOS. This is an animal model study only.

Antiestrogenic effects of the alcohol seed extract of Caesalpinia crista have been proposed to result from an inhibition of estrogen secretion. However, there are no experiments done in PCOS animal models to claim direct application of C. bonducella in PCOS treatment. Hence, further dose-dependent toxicity studies are warranted in animal PCOS models and in PCOS patients to support the traditional evidence of the plant's potential to treat PCOS.

4.12 Anticancer and Antiproliferative Activity

Chemical investigation of Caesalpinia crista afforded two new diterpenoids, 6β-cinnamoyloxy-7β-acetoxyvouacapen-5α-ol and 6β,7β-dibenzoyloxyvouacapen-5α-ol. The cytotoxicity of these compounds was measured on two different cancer cell lines. Anticancer data for C. crista is confined to cell-line cytotoxicity studies; no clinical trials exist.

4.13 Cystic Fibrosis-Related Activity

The seed extract of C. bonduc has been reported to inhibit human trypsin and chymotrypsin in intestinal secretion, and has promising activity for treating chronic lung infections in cystic fibrosis. This is a preliminary laboratory finding.

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5. Body Systems and Health Areas Associated with Caesalpinia crista

• Parasitic and Infectious Disease: Antimalarial (against Plasmodium spp.), anthelmintic, antibacterial, antifungal, antiviral, antiprotozoal, and antifilarial uses are documented — all at the preclinical stage.
• Metabolic / Endocrine: Antidiabetic (glucose-lowering in alloxan- and streptozotocin-induced animal models); hypolipidemic effects reported in animal research.
• Liver / Hepatic: Hepatoprotective effects demonstrated in mice with iron-overload-induced liver toxicity.
• Nervous System: Nootropic (memory-enhancing), anticonvulsant, anxiolytic, and adaptogenic activities, all demonstrated in rodent models.
• Reproductive System: Anti-estrogenic, antifertility (both male and female), and ovulation-promoting effects studied in animal models of PCOS.
• Gastrointestinal: Antidiarrhoeal, antispasmodic, antiulcer, and anthelmintic activities described in traditional use and animal studies.
• Musculoskeletal / Pain: Analgesic and anti-inflammatory activities demonstrated in rodent pain models.
• Cardiovascular: Cardioprotective and hypotensive effects, studied in animal models.
• Skin: Traditional use for skin diseases; in vitro antimicrobial data relevant to dermatological infections.
• Respiratory: Traditional use for respiratory ailments; preliminary data on protease inhibition relevant to cystic fibrosis.
• Oncology (Preclinical): Cytotoxic and antiproliferative activities against cancer cell lines in vitro.

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6. Scientific Evidence: Strength Assessment by Area

The totality of the scientific evidence for Caesalpinia crista as of the available literature is overwhelmingly preclinical. Further studies on preclinical and clinical trials and toxicological studies on the bioactive molecules of C. bonduc to validate its traditional uses are warranted.

• Antimalarial: Strongest body of preclinical evidence; in vitro data against P. falciparum and in vivo data in P. bergei-infected mice. No human clinical trials. Evidence rated: Preliminary/In vitro–Animal only.
• Antidiabetic: Multiple independent rodent studies using alloxan and streptozotocin models report significant glucose lowering at doses of 25–300 mg/kg. No human trials. Evidence rated: Preliminary/Animal only.
• Hepatoprotective: One published PMC study in mice demonstrating dose-dependent protection against iron overload-induced hepatotoxicity through antioxidant and iron-chelating mechanisms. Evidence rated: Preliminary/Animal only.
• Antioxidant: Reproducible in vitro DPPH assays and phenolic content quantification. Evidence rated: In vitro only.
• Reproductive / PCOS: One animal study (letrozole-induced PCOS rat model) showing significant improvement at 500 mg/kg. There are no experiments done in PCOS animal models to claim the direct application of C. bonducella in PCOS treatment at the human level. Evidence rated: Preliminary/Animal only.
• Anticonvulsant, Nootropic, Anxiolytic, Adaptogenic: Demonstrated in rodent seizure and cognitive models. Evidence rated: Preliminary/Animal only.
• Antimicrobial / Antifungal: In vitro activity against several pathogens; no clinical infection data. Evidence rated: In vitro only.
• Anticancer / Antiproliferative: Cell-line cytotoxicity data only; no animal tumour models or clinical trials. Evidence rated: In vitro only.
• Anthelmintic: Some animal and ex vivo data. Evidence rated: Preliminary/Animal only.

In summary, no controlled human clinical trials for any indication have been published for Caesalpinia crista. The scientific literature is rich at the phytochemical, in vitro, and animal model levels, but the translation to clinical evidence in humans remains entirely to be established.

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7. Dosage Forms and Doses Reported in Research

The following dosages appear in the cited scientific studies and are reported here exactly as stated; they relate exclusively to animal/preclinical research and do not constitute clinical dosage recommendations.

• Seed extracts of Caesalpinia bonducella at 300 mg/kg orally in Wistar rats demonstrated significant antihyperglycemic action in alloxan-induced diabetes.
• The aqueous and ethanolic seed extracts have been reported to possess in vivo hypoglycemic effect in alloxan- and streptozotocin-induced type 2 diabetes in a rat model at a dose of 25 mg/kg body weight.
• In a letrozole-induced PCOS rat study, doses of 100 mg/kg (low), 300 mg/kg (medium), and 500 mg/kg (high) were administered orally for 15 days.
• A 90-day oral toxicity study administered Caesalpinia bonduc root extract by oral gavage at doses of 31.25, 125, and 500 mg/kg/day to male Wistar rats.
• The crude ethanolic seed extract of Caesalpinia bonducella was fed to Swiss mice at a dose of 500 mg/kg body weight at every alternate day such that every mouse received 10 doses in an antispermatogenic study.
• Acute toxicity studies were conducted as per the OECD guidelines 420, using a limit test dose of 2000 mg/kg.

No standardised human dosage range has been established in any published clinical study.

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8. Safety Considerations

8.1 Acute and Subacute Toxicity

Toxicity studies demonstrated the LD₅₀ dose of C. bonduc to be 3000 mg/kg, indicating the use of this plant to be quite safe. In a 90-day oral study, there were no deaths or abnormal clinical signs, no significant changes in body weight gain or urinary parameters, and no changes in necropsy and histopathology findings of vital organs associated with extract treatment. However, some indices such as erythrocytes, total cholesterol, and aspartate aminotransferase increased in rats treated with high doses of the extract, as well as relative weight of testes, followed by a decrease in food intake and prostate relative weight. The results indicate that an ethanolic root extract of Caesalpinia bonduc does not cause significant adverse effects and suggest its tolerability up to 500 mg/kg for daily administration of 90 days.

8.2 Antifertility Effects: A Significant Concern

When Caesalpinia crista meal was fed to mice and rats, it caused antifertility effects. This effect could be attributed to its contents of gossypol and cyclopropane fatty acids, which have been implicated as antifertility compounds. Electron microscopic examination showed that graded doses of an alcoholic extract of Caesalpinia crista caused morphological changes in the sperm of albino rats, including disturbance in the plasma membrane and acrosomal membrane.

Sperm count in experimental groups of mice declined significantly (p≤0.0001) compared to controls. However, there was no increase in abnormal sperm count profile, testicular oxidative stress, or body weight, indicating that the seed extract does not have an adverse effect on testicular physiology per se.

An ethanolic extract of Caesalpinia bonducella at 300 mg/kg/day showed a significant increase in resorption index, reduction in implantation index, and reduced progesterone levels in experimental albino rats.

8.3 Anti-estrogenic Activity

The documented anti-estrogenic and anti-androgenic properties of C. crista extracts, while potentially therapeutically relevant in conditions such as PCOS, also imply the potential for hormonal disruption. Further dose-dependent toxicity studies are warranted in animal PCOS models and in PCOS patients to support the traditional evidence of the plant's potential to treat PCOS.

8.4 Limitations of Safety Data

Despite its numerous ethnomedicinal benefits, toxicological information associated with chronic use of Caesalpinia bonduc is currently limited. The absence of controlled human safety studies means that the long-term risk profile in humans — including interactions with pharmaceutical agents, hepatotoxicity risk at high doses, and reproductive hazard to pregnant or lactating individuals — has not been adequately characterized in the peer-reviewed clinical literature.

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References

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• Bhattacharya S et al. "A Review on Phytopharmacological Properties of Caesalpinia crista." Indian Journal of Pharmaceutical Sciences (IJPS Online), 2020.
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• "Antispermatogenic effects of seed extract of Caesalpinia bonducella in Swiss mice." International Journal of Biosciences 12(4), 2018.
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• Chan et al. "Caesalpinia crista: A coastal woody climber with promising therapeutic values." Journal of Applied Pharmaceutical Science 8(03), 2018.
• "Phytochemical composition of Caesalpinia crista extract as potential source for inhibiting cholinesterase and β-amyloid aggregation." Asian Pacific Journal of Tropical Biomedicine, 2018.
• Brijay H et al. "Morphology, Phytochemistry, Traditional Uses of Plant Caesalpinia crista." IJPPR Human, 23(4), 2022.
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