Cyclanthera pedata

Cyclanthera pedata (Caigua): A Comprehensive Reference

1. Identity: Botanical Classification, Names, and Forms

1.1 Taxonomic Identity

Cyclanthera pedata (L.) Schrad. is an annual herbaceous vine belonging to the family Cucurbitaceae, native to montane regions. Its full accepted binomial authority is Cyclanthera pedata (L.) Schrad., 1831. The basionym, originally described by Linnaeus, was Momordica pedata L. (1753), as recorded in NCBI taxonomy. The plant is classified within the order Cucurbitales, family Cucurbitaceae, tribe Sicyoeae, genus Cyclanthera, and its NCBI taxonomy ID is 198836.

A number of historical synonyms exist in the botanical literature. These include Cucumis pedata L. ex Crantz, Cucumis pedatus L., Cucumis trilobatus L., and Momordica pedata L., as well as Momordica pedisecta Ser. Among the Anguria synonyms recorded are Anguria pedata (L.) Jacq. and several varietal forms. A cultivated variety with edible fruits has been distinguished as Cyclanthera pedata var. edulis (Naudin ex C. Huber) Cogn.

1.2 Common Names

The plant is commonly known as caigua, achocha, or stuffing cucumber. Additional regional names include achojcha (in Andean communities), archucha, caihua, and maxixe do reino (in Brazil). In parts of West Bengal and Sikkim, India, it is locally known as chuche karela.

1.3 Botanical Description and Geographic Origin

Cyclanthera pedata is a herbaceous vine grown for its edible fruit. It is known from cultivation only, and its use goes back many centuries as evidenced by ancient phytomorphic ceramics from Peru depicting the fruits. The plant was presumably first domesticated in the mountainous regions of Peru. It subsequently spread to Southeast Asia and Africa, where it is cultivated only in the highlands of East Africa.

C. pedata is an annual climbing plant with vines that can reach up to 4.5 meters in height. It has a thin stem and palmate leaves that are 10–12 cm wide. The small, unisexual flowers range from white to light green and are located at the leaf axils. As a cultivated plant of the tropics, it can be found at elevations up to 3,000 metres.

The fruit is elongated, between 6 and 20 cm long, slightly flattened, and has bumps or small soft spines on the surface. Its interior is hollow, suitable for filling, and contains large black seeds. When unripe, the flesh is tender and its flavor is reminiscent of cucumber.

1.4 Commercial and Supplement Forms

Most available supplement products in the United States are tablets or capsules of the dried or freeze-dried fruit juice. Products derived from the whole fruit are also found in powder (flour) form, while traditional preparations use the fresh fruit in whole or juiced form. Common dosage forms include teas and infusions from seeds or leaves for internal consumption, decoctions from roots and fruits, and poultices for external applications.

2. Traditional and Historical Use

2.1 Pre-Columbian and Andean Traditions

The use of caigua goes back many centuries as evidenced by ancient phytomorphic ceramics from Peru depicting the fruits. The fruit is a native food of the Andean region used by Inca communities, where it was called achojcha. Also known as achogcha, archucha, caihua, crab, or stuffed cucumber, it is native to tropical America and has been domesticated since pre-Hispanic times; although it was a staple food for civilizations such as the Incas, Mayans, and Aztecs, its cultivation has now spread from Mexico to Argentina and, occasionally, to other regions of the world. The caigua has traditionally been prized not only for its edible fruits, but also for its medicinal properties and its role in Andean agricultural culture.

2.2 Traditional Medicinal Uses

Caigua has been traditionally used in South American folk medicine for its alleged anti-inflammatory, hypoglycemic, and hypocholesterolemic effects, particularly in the management of blood pressure and cholesterol levels. It has been used for its alleged anti-inflammatory, hypoglycemic, and hypocholesterolemic effects, and is believed to be effective against atherosclerosis and circulation problems, and is used as an analgesic.

The fruit juice is recommended in traditional practice as a treatment for conditions such as high blood cholesterol levels, hypertension, tonsillitis, arteriosclerosis, circulatory problems, and diabetes.

In Mexico, boiled fruits and leaves are applied as poultices or ointments—often mixed with olive oil—for topical relief from inflammation and pain, such as in joint or skin conditions.

Caigua is also used to manage hyperglycemia, hypertension, and other circulatory ailments. It is widely used in traditional medicine across Central and South America for its antioxidant, anti-inflammatory, antihyperglycemic, and antihypertensive properties.

2.3 Geographic Spread of Traditional Use

Traditionally, its fruit has been consumed as both a vegetable and a medicinal food, particularly in Peru, Bolivia, and Ecuador. In Brazil, caigua is known as "maxixe do reino" and is traditionally distributed from Colombia to Bolivia, generally consumed either cooked or raw as a salad. The plant's cultivation has also established a foothold in the Italian Alps, where a landrace traditionally cultivated in Camonica Valley (Italian Alps), called "Ciuenlai" (or "Milione/Milioncino"), has been maintained for generations.

3. Key Constituents and Active Compounds

3.1 Flavonoid Glycosides (Fruits and Leaves)

Earlier phytochemical investigations reported the isolation and structure determination of cucurbitacin glycosides from the seeds, triterpenoid saponins and flavone glycosides from the fruits. Flavone glycosides have been identified as the major constituents of the fruits and were isolated for the first time in this plant; for this reason, they have been selected as "marker compounds" for the chemical evaluation and standardization of C. pedata and its products.

Six flavone glycosides (numbered 1–6), among them four new natural compounds, were isolated from the CHCl₃/MeOH extract of the fruits of Cyclanthera pedata. All structures were elucidated by spectroscopic methods, including one- and two-dimensional NMR techniques.

Other components that have been identified include 6-C-glucosyl-luteolin, 6-C-glucosyl-apigenin, 8-C-glucosyl-chrysin, 6-C-(2-acetyl)glucosyl-apigenin, 6-C-(6-malonyl)-glucosyl-apigenin, 8-C-fucosyl-chrysin, 6-C-glucosyl-chrysin, rhamno(1→6)glucosyl-chrysin, 6-C-fucosyl-apigenin, 8-C-(2-acetyl)glucosyl-chrysin, 6-C-(6-malonyl)glucosyl-chrysin, 6-C-(2-acetyl)fucosyl-chrysin, and additional acylated glycoside variants.

The leaves also contain unique flavonoid constituents. Research published in Phytochemical Analysis identified two new malonyl derivatives of flavonoids from the leaves of Cyclanthera pedata.

3.2 Cucurbitacin Glycosides (Seeds)

Six new cucurbitacin glycosides were isolated from the seeds of Cyclanthera pedata. Their structures were elucidated based on spectral and chemical data, including novel norcucurbitane and cucurbitane skeleton glycosides with multiple hydroxyl substitutions and acetoxy groups. The seeds have been reported to contain these six cucurbitacin glycosides.

3.3 Triterpenoid Saponins (Fruits)

Research has also reported the isolation of nine triterpenoid saponins (numbered 1–9), among them six new natural compounds, from the methanol extract of the fruits of caigua. Other ingredients in the extracts include phytosterols, saponins, tannins, and anthocyanins.

3.4 Serine Protease Inhibitors (Seeds)

Seven new trypsin inhibitors, designated CyPTI I–VII, were purified from ripe seeds of Cyclanthera pedata by affinity chromatography. The CyPTIs belong to a well-known squash inhibitor family, contain 28–30 amino acids, and have molecular weights from 3,031 to 3,367 Da. All isolated inhibitors strongly inhibit bovine β-trypsin (Ka > 10¹¹ M⁻¹) and, more weakly, bovine α-chymotrypsin.

3.5 Mineral Composition

The mineral composition of caigua was determined from twenty-nine samples from five farms in Brazil, analyzed using inductively coupled plasma optical emission spectrometry. Elements identified included calcium, magnesium, sodium, potassium, phosphorus, manganese, iron, zinc, copper, and vanadium. Average concentrations (mg/100 g) were: sodium 0.91, potassium 152, phosphorus 19.4, calcium 11.9, magnesium 8.4, manganese 0.074, iron 0.21, copper 0.013, zinc 0.13, and vanadium 0.015.

On the basis of these findings, caigua can be strongly recommended as a nutritional supplement considering its high content of potassium, calcium, phosphorus, and magnesium. Caigua has mineral composition similar to watermelon, cucumber, chayote, pumpkin, and melon, all of which are also cucurbits.

The flour of caigua fruits has additionally been found to be high in potassium (7,400 mg·K/100 g) and low in sodium (77 mg Na/100 g).

3.6 Other Nutritional Components

In fresh fruits, soluble protein (SP), total sugar (TS), free phenolic compounds (FPC), ascorbic acid (AA), total monomeric anthocyanin (TMA), condensed and hydrolyzable tannins (CT, HT) have been characterized by spectrophotometric methods. In the flour of caigua fruits, the total sugar content is 4.74 g/100 g and reducing sugar 3.12 g/100 g, with total protein content of 0.4%.

4. Established Mechanisms of Action

4.1 Lipid-Lowering Mechanisms

The fruits contain flavonoid glycosides, of which four show antioxidant effects. Caigua fruits generally exhibit high antioxidant activity but a low total phenolic content, indicating that non-phenolic water-soluble compounds may be involved. Flavonoids present in this species have antioxidant properties and, with a high intake, are correlated with a decrease in heart disease.

Dried samples of caigua showed α-amylase inhibition and relevant ACE inhibitory activities. The anticholesterolemic activity of caigua was confirmed, promoting cholesterol metabolism and bile acids synthesis in a hepatic cell model, with the extract showing novel choleretic activity.

In an in vitro hepatic cell study, the determination of anticholesterolemic activity using an in vitro hepatic model based on HepG2 cells was performed on C. pedata extract as well as formulations combining it with artichoke and fenugreek extracts.

4.2 Angiotensin-Converting Enzyme (ACE) Inhibition

Caigua (Cyclanthera pedata) significantly inhibited the hypertension-relevant angiotensin I-converting enzyme (ACE) in vitro. Fruit extracts showed notable activity against angiotensin I-converting enzyme, which is relevant to blood pressure regulation in metabolic syndrome. Researchers in Chile reported in 2010 that caigua significantly inhibited the hypertension-relevant angiotensin I-converting enzyme (ACE).

4.3 PPARγ Agonism (Anti-Diabetic Mechanism)

A 2025 in vitro study identified chrysin-6-C-fucopyranoside from leaves as a selective PPARγ agonist (EC50 2.3 µM), potentially offering benefits for diabetes management with fewer side effects than synthetic agonists. These findings indicate that the caigua plant could offer a safer alternative to conventional PPARγ agonists, whose use as antidiabetic drugs is limited by severe side effects that currently restrict the clinical use of conventional PPARγ agonists.

Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors that play a central role in regulating various physiological processes, especially those related to metabolism, inflammation, and cell differentiation. Given their involvement in lipid and glucose metabolism, PPARs have emerged as promising therapeutic targets for treating diseases such as diabetes, obesity, and cardiovascular disorders.

4.4 Anti-Inflammatory Mechanisms

Antioxidant activity and the inhibitory capacity of lipoxygenase (LOX), a pro-inflammatory enzyme, have been analyzed in fruit preparations. Inhibitory capacity on LOX was demonstrated, with IC50 values of 40 µg GAE/mL.

Anti-inflammatory effects are mediated by flavonoids such as chrysin and apigenin glycosides.

4.5 Antioxidant Activity

Aqueous extracts showed strong antioxidant activity (SC50 of 2 µg GAE/mL by the ABTS method). The extract enriched with hydrolyzable tannins (SC50 = 1.7 µg GAE/mL) was more active than the polyphenolic extract (SC50 = 4 µg GAE/mL). All preparations from fresh fruit and flour showed higher antioxidant capacity than the natural and synthetic antioxidants quercetin, ascorbic acid, and BHT in the same assay.

For all isolated flavone glycoside compounds, antioxidant activity was determined by measuring the free radical scavenging activity, using the Trolox equivalent antioxidant capacity (TEAC) method and the coupled oxidation of β-carotene and linoleic acid.

4.6 Trypsin Inhibition in Seeds

A notable aspect of caigua is that the seeds contain a group of trypsin inhibitors, which negatively affect protein absorption. These CyPTI inhibitors, as characterized biochemically, belong to the squash inhibitor family and were purified by affinity chromatography from ripe seeds.

5. Scientific Evidence by Area of Use

5.1 Cholesterol and Lipid Management

This is the area with the most concentrated clinical research on caigua, though the body of evidence remains limited in scale and methodological rigor.

Postmenopausal women study (Gonzales et al., 1995): When postmenopausal women (n=24) were compared to premenopausal women (n=18), dehydrated and encapsulated caigua at a dose of 6 capsules per day (300 mg/capsule) was able to lower levels of total cholesterol and LDL cholesterol, and increase HDL-cholesterol levels. At the end of 12 weeks of treatment, a 33% reduction in LDL-cholesterol levels was observed in postmenopausal women receiving six capsules of caigua.

Randomized double-blind Phase II study: A single-center, randomized, double-blind Phase II study was conducted in 60 subjects (men and women aged 27–63) administered dehydrated and encapsulated caigua in different doses of 2 (600 mg), 3 (900 mg), 4 (1,200 mg), and 6 (2,400 mg) capsules daily compared to placebo, for 12 weeks. Oral administration of 6 capsules of dehydrated caigua taken together while fasting was effective in reducing total cholesterol, LDL cholesterol, and triglycerides, and also raised HDL cholesterol. In this study group, 60% of subjects at baseline had higher values of total cholesterol, and at the end of treatment only 11% had high levels of total cholesterol.

Single-blind trial in hypercholesterolemic men: In a single-blind trial, 25 male subjects aged 40–65 years with hypercholesterolemia were administered daily for 45 days either 800, 1,200, or 1,600 mg of encapsulated caigua extract (each capsule containing 400 mg of extract equivalent to 100 g of fresh caigua), or four capsules of placebo. Treatment with four capsules prior to eating indicated a significantly reduced total cholesterol by an average of 93 mg/dL (33.8% of initial value). The reduction in LDL cholesterol was 88 mg/dL (44.5% of initial value). HDL cholesterol and triglycerides were not modified in this study.

Daily micro-pulverized caigua study: A separate study showed a reduction in cholesterol levels with a daily dosage of 1,800 mg of micro-pulverized caigua. Hypercholesterolemia prevalence was reduced from 75% to 12.5%. The levels of LDL cholesterol decreased while the levels of HDL cholesterol increased.

Lowerchol combination product trial: In a clinical trial of 100 patients with dyslipidemia and hypertension, participants were asked to take a capsule containing 888 mg of phytosterols and 500 mg of Cyclanthera pedata fruit extract after their meals, twice daily for 2 months. In patients who had a prior history of atorvastatin, cholesterol (P<0.0001) and LDL (P≤0.0008) levels increased with the combination product. In contrast, in patients with no prior lipid-lowering drug history, there was a significant decrease in cholesterol (P≤0.0018) and triglycerides (P=0.0014), though no significant changes in LDL or HDL were seen. The overall results indicated that the Lowerchol combination product is not a suitable replacement for statins, especially in elderly patients over 50 years. This study is further limited because the product combined C. pedata extract with phytosterols, making it impossible to attribute effects to either ingredient alone.

Animal evidence: Experiments carried out on hypercholesterolemic rats indicated that supplementation with Cyclanthera pedata extract resulted in statistically significant reductions in serum levels of total cholesterol, LDL cholesterol, and triglycerides compared to hypercholesterolemic rats fed normal food without supplementation and compared to those fed food supplemented with niacin. Unexpectedly, hypercholesterolemic rats fed C. pedata extract also experienced an elevation in serum HDL cholesterol levels.

Evidence strength assessment: While preliminary human evidence is encouraging, all human trials on lipid outcomes are small-scale, some lack placebo controls or blinding, and none have been validated by independent replication in large-scale randomized controlled trials. The evidence is preliminary to moderately suggestive, not conclusive.

5.2 Antihypertensive Effects

The antihypertensive potential of caigua has been documented primarily through in vitro enzyme inhibition assays. Caigua (Cyclanthera pedata) significantly inhibited the hypertension-relevant angiotensin I-converting enzyme (ACE) in vitro. Dried samples of caigua showed relevant ACE inhibitory activities. Direct evidence from controlled human trials investigating blood pressure as a primary outcome is currently absent from the published peer-reviewed literature. The ACE inhibitory effects observed in vitro suggest a plausible mechanism, but the translation to meaningful blood pressure reduction in humans remains unconfirmed in controlled studies.

5.3 Anti-Diabetic and Antihyperglycemic Effects

Dried samples of caigua showed α-amylase inhibition, which is a recognized mechanism of action for mitigating post-meal blood glucose surges. In a broader in vitro study of Latin American medicinal plants, traditionally used medicinal plants, herbs, and spices in Latin America were investigated to determine their phenolic profiles, antioxidant activity, and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension.

The 2025 PPARγ study represents a notable advance: a 2025 in vitro study identified chrysin-6-C-fucopyranoside from leaves as a selective PPARγ agonist (EC50 2.3 µM), potentially offering benefits for diabetes management with fewer side effects than synthetic agonists. However, no human clinical trials on anti-inflammatory outcomes or metabolic syndrome had been conducted as of November 2025. Evidence in the antidiabetic area is therefore confined to in vitro assays and mechanistic studies; there are no published human trials with glucose or insulin as primary endpoints.

5.4 Anti-Inflammatory Effects

Anti-inflammatory activity has been demonstrated in vitro through LOX inhibition. All preparations obtained with fresh and dried fruits showed antioxidant activity with SC50 values between 1.8 and 14.5 µg GAE/mL. Inhibitory capacity on LOX was also demonstrated with IC50 values of 40 µg GAE/mL. This evidence is entirely preclinical (in vitro), and no controlled human trials addressing inflammatory biomarkers as primary endpoints have been published.

5.5 Antioxidant Activity

Antioxidant capacity has been extensively characterized in vitro across multiple preparations. All extracts from both fresh fruit and flour showed higher antioxidant capacity than the natural and synthetic antioxidants quercetin, ascorbic acid (AA), and BHT in comparative assays. The contribution of this antioxidant activity to in vivo health outcomes in humans has not been directly tested in clinical trials.

5.6 Lipoxygenase Inhibition and Potential Oncological Relevance

Extracts of Cyclanthera pedata have been shown to inhibit lipoxygenase activity, which is associated with tumor development and the progression of cancerous diseases. This represents a preliminary in vitro observation with no human trial data. Its significance for cancer prevention or treatment in humans is entirely speculative at the current level of evidence.

6. Body Systems and Health Areas Associated with Caigua

• Cardiovascular system: Traditionally used for its hypocholesterolemic effects, particularly in the management of blood pressure and cholesterol levels. Human pilot studies support lipid-lowering activity; in vitro evidence supports ACE inhibition.
• Metabolic system: Used in traditional medicine across Central and South America for antihyperglycemic properties. Supported by in vitro α-amylase inhibition and a 2025 PPARγ activation study.
• Liver and bile metabolism: The anticholesterolemic activity of caigua was confirmed by promoting cholesterol metabolism and bile acids synthesis in a hepatic cell model, with the extract showing novel choleretic activity.
• Inflammatory pathways: In vitro inhibition of lipoxygenase (LOX) and antioxidant activity demonstrated across multiple preparations.
• Digestive system: The seeds contain trypsin inhibitors that negatively affect protein absorption, which is relevant to digestive physiology, and the plant is used traditionally as a digestive aid.

7. Dosage Forms and Reported Dosages

Dosages reported in the scientific literature vary considerably between studies and preparations:

• In a randomized double-blind Phase II clinical study, caigua was administered in doses of 2 (600 mg), 3 (900 mg), 4 (1,200 mg), and 6 (2,400 mg) capsules of dehydrated encapsulated caigua daily, with the highest dose group showing the most pronounced lipid effects, over 12 weeks.
• In a study of postmenopausal and premenopausal women, dehydrated and encapsulated caigua was given at a dose of 6 capsules per day at 300 mg per capsule (total 1,800 mg/day) over 12 weeks.
• In a single-blind trial of hypercholesterolemic men, 800, 1,200, or 1,600 mg daily of encapsulated extract were tested over 45 days, with each capsule containing 400 mg of extract equivalent to 100 g of fresh caigua.
• A daily dosage of 1,800 mg of micro-pulverized caigua was reported in a separate study showing cholesterol reduction.
• In the Lowerchol combination trial, patients took capsules containing 500 mg of Cyclanthera pedata fruit extract (plus 888 mg phytosterols) after meals twice daily for 2 months.
• Human pilot studies reported LDL reductions after 1 year using 300 mg capsules daily; safety profiles indicated low toxicity with no adverse effects reported at up to 1,800 mg daily for up to 1 year.

No universally standardized dosage has been established in the peer-reviewed literature or by any regulatory pharmacopeia at the time of writing.

8. Safety Considerations

8.1 General Toxicity Profile

Safety profiles from human pilot studies indicate low toxicity, with no adverse effects reported at up to 1,800 mg daily for up to 1 year. Long-term systematic safety data and large-scale controlled safety studies are not available in the peer-reviewed literature.

8.2 Trypsin Inhibitors in Seeds

A notable concern is that the seeds contain a group of trypsin inhibitors, which negatively affect protein absorption. These inhibitors, designated CyPTI I–VII, contain 28–30 amino acids and all strongly inhibit bovine β-trypsin (Ka > 10¹¹ M⁻¹) and, more weakly, bovine α-chymotrypsin. The implications for human digestive protein metabolism upon regular consumption of whole seeds warrant consideration, especially in preparations that include seed material.

8.3 Blood Pressure and Lipid-Lowering Drug Interactions

During the Lowerchol clinical trial, the majority of participants also showed a decline and stabilization in blood pressure, with several patients leaving the study due to a large drop in blood pressure. This observation suggests that caigua preparations may exert additive blood pressure–lowering effects when combined with antihypertensive medications, though this has not been formally characterized in interaction studies.

Similarly, given the evidence for cholesterol-lowering effects, combination with statin drugs may warrant monitoring, as the Lowerchol trial enrolled patients who were transitioning from atorvastatin to the herbal product, and results in that group were not favorable (cholesterol and LDL increased in the atorvastatin-history group).

8.4 Known Drug Interactions

Drug interactions are not currently documented in the available literature. However, the pharmacologically active constituents (ACE-inhibitory flavonoids, saponins, potential PPARγ agonists) suggest theoretical interactions with antihypertensive, hypolipidemic, and antidiabetic drug classes, though these have not been systematically studied.

8.5 Special Populations

Lowerchol (the combination product incorporating caigua) was found not to be a suitable replacement for statins especially in elderly patients (older than 50 years). Data for pregnancy, lactation, pediatric populations, and patients with significant hepatic or renal impairment are absent from the peer-reviewed literature.

8.6 Evidence Gaps

The overall evidence base for Cyclanthera pedata as a dietary supplement is preliminary. All mechanistic studies (ACE inhibition, LOX inhibition, PPARγ agonism, hepatic cholesterol metabolism) are in vitro. Human trials that do exist are small-scale, predominantly pilot studies, and in some cases lack robust placebo controls, blinding, or independent replication. No systematic reviews, Cochrane reviews, or evaluations by major regulatory bodies (NIH ODS, NCCIH, EMA, EFSA, WHO) have been published for this ingredient as of the time of writing. The ingredient is not listed in the German Commission E monographs, ESCOP monographs, or the WHO monograph series.

References

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