colocinto

Otros Nombres

Abu Jahl melonAbu Jahl watermelonAbu Jahl's melonAlhandalAnedribitter applebitter cucumberbitter gourdbitter melonChedu PucchaChitraCinna PaparaCitrullus colocynthisCitrullus colocynthis subsp. insipidusCitrullus colocynthis subsp. stenotomusCitrullus colocynthis var. bipinnatifidusCitrullus colocynthis var. indicusCitrullus colocynthis var. insipidusCitrullus colocynthis var. officinalisCitrullus colocynthis var. stenotomusCitrullus colocynthis var. wenderothiiCitrullus colocynthoidesCitrullus pseudocolocynthisColocynthidis FructusColocynthis citrullusColocynthis officinalisColocynthis officinarumColocynthis vulgarisColoquinteColoquíntidaConcombre AmerCucumis bipinnatifidusCucumis colocynthisCucumis pseudocolocynthisCucurbita colocynthadesert gourddesert squashdesert watermelonegusifox melonGavakshiHadajHandalHandhalHanjalHanzalHendevane abu jahlHindalHindhalIndarvaruniIndravaruniIndrayanKhazaraKoloquinteKoloquintengurkeKoloquintenkürbisKoloquinthenKuturu budamal-hedjaMahaphalaMarara al-SaharimurrahPikkumuttiPita pushpaPomaquintePulpe de ColoquinteRakhalSharangsharyTamate KayiTumbaTurkish colocynthVarunivine of SodomVishaghniVishalawild gourd

Sinopsis

Colocynth (Citrullus colocynthis (L.) Schrad.)

1. Identity and Botanical Description

1.1 Taxonomy and Nomenclature

Citrullus colocynthis, with many common names including colocynth, bitter apple, bitter cucumber, vine of Sodom, or wild gourd, is a poisonous desert viny plant native to the Mediterranean Basin and West Asia, especially the Levant, Turkey, and Nubia. It originally bore the scientific name Colocynthis citrullus. Its accepted current binomial is Citrullus colocynthis (L.) Schrad., belonging to the family Cucurbitaceae, first formally published in Linnaea 12: 414 (1838).

Also known as Bitter Apple or Colocynth, the plant is called Handal in Arabic, Hendevaneh-ye Aboujahl in Farsi, Acı kavun in Turkish, and Cocomero amaro in Italian. In South Asian languages it is known as Hanjal (Urdu), Indrayan (Hindi), and Anedri (Sanskrit). The genus Citrullus comprises annual or perennial herbaceous plants in the family Cucurbitaceae, including four species — C. rehmii, C. lanatus, C. ecirrhosus, and C. colocynthis — distributed throughout tropical and South Africa, Southwest Asia, and the East Mediterranean region.

1.2 Morphology

Citrullus colocynthis is a perennial herbaceous vine in the Cucurbitaceae family, characterized by its trailing growth habit and adaptation to arid environments, featuring angular, rough stems up to 3 m long, supported by a tuberous rootstock that stores water, enabling survival in desert conditions. The leaves are stiff, palmately 3–5-lobed, and measure 2.5–11 cm in length, while the monoecious flowers are solitary, axillary, and greenish-yellow with petals 6–15 mm long.

The plant produces subglobose fruits, 5–12 cm in diameter, that are mottled green when immature and yellow when ripe, enclosing bitter, toxic pulp rich in cucurbitacins and numerous ovate, dark brown seeds 6–10 mm long. Each plant produces 15–30 fruits; the fruit bodies measure 7.0–10.0 cm in diameter and are green with undulating yellow stripes that turn yellow when dried. The fruit is globular and bitter with a smooth texture and contains approximately 250 seeds per gourd.

1.3 Geographic Distribution

The plant is native to the arid sandy areas of West Asia, Arabia, tropical Africa, and the Mediterranean. It is also widely distributed in the desert areas of Pakistan. C. colocynthis originated in Asia and the Mediterranean Basin, particularly Turkey and Nubia, to the western coastal regions of Africa, the Sahara, and Egypt, and is also found in India and the northern coastal regions of the Caspian and Mediterranean seas. Distributed in the desert areas of the world including Sudan, Morocco, Jordan, Tunisia, and Pakistan, it has recognized nutraceutical and medicinal values. The fruits were introduced to Spain and Cyprus by Arabs in the Middle Ages.

1.4 Synonyms and Former Names

Taxonomic synonyms include Colocynthis vulgaris Schrad. The species is accepted by Kew's Plants of the World Online database and is the only widely used member of the Citrullus genus in traditional medicine apart from C. lanatus (common watermelon).

1.5 Commercial and Dosage Forms

Colocynth is encountered in several prepared forms in traditional and modern contexts:

Dried fruit pulp (powder): The most historically prevalent form, obtained by peeling and drying the fruit. Historical remedies included decoctions or powders derived from the dried pulp, which were administered to address digestive complaints, edema, and as a vermifuge.
Oral capsules: Used in modern clinical studies, typically standardized from dried fruit. Clinical trial participants received 100 mg C. colocynthis fruit capsules three times a day. A separate trial used 125 mg of C. colocynthis once per day for 2 months.
Topical extract cream: A cream preparation of C. colocynthis fruit extract (2–8%) has been evaluated for topical anti-inflammatory and antinociceptive activity in animal studies.
Seed oil: Cold-pressed or solvent-extracted oil from seeds, with an oil content of approximately 23.16% from seeds, dominated by linoleic acid (66.73%), oleic acid (14.78%), palmitic acid (9.74%), and stearic acid (7.37%).
Lozenges (troches): Lozenges or pastilles made of colocynth were historically called "troches of alhandal" and used as a laxative; they were usually composed of colocynth, bdellium, and gum tragacanth.
Aqueous and ethanolic extracts: Used in both traditional preparations and modern laboratory/preclinical research, obtained from roots, fruits, seeds, and leaves.
Homeopathic preparations: Colocynth is used in homeopathic practice to treat constipation and liver and gallbladder ailments, sometimes in highly diluted forms.

2. Traditional and Historical Use

2.1 Ancient Egypt and the Ebers Papyrus

Colocynth has been used for medicinal purposes for centuries, dating back to ancient Egyptian and Greek civilizations. Castor oil, senna, and colocynth were consumed in ancient Egypt as part of regular purging practices. Ancient Egyptians believed a toxin (wekhedu) originated in the bowels and could spread to the rest of the body, causing aging and disease. They practiced purging themselves regularly to maintain bodily health. The Ebers Papyrus (c. 1550 BCE) — written in hieratic Egyptian script and representing the most extensive preserved record of ancient Egyptian medicine — contains over 842 magical formulas and folk remedies. Colocynth was among the plants listed therein for its purgative and anti-rheumatic applications.

2.2 Classical Greek and Roman Medicine

The five-volume pharmacopoeia De Materia Medica was written between 50 and 70 CE by Pedanius Dioscorides, a Greek physician in the Roman army, and was widely read for more than 1,500 years. The work describes many drugs known to be effective, specifically listing colocynth alongside aconite, aloes, henbane, opium, and squill. Dioscorides lists colocynth as a palliative for toothache and for intestinal pains.

2.3 Arab and Islamic Medicine

The word Alhandal is derived from Arabic (al-Ḥanẓal), a traditional name for colocynth. Lozenges called "Troches of Alhandal" (Trochisci Alhandalæ), composed of colocynth, bdellium, and gum tragacanth, were used as a laxative in Arabian medicine. The term Alhandal was used in Arabia for the extract of colocynth; in traditional Arab veterinary medicine, colocynth sap was applied to treat skin eruptions in camels. In traditional Persian medicine, C. colocynthis has been used to treat diabetes.

2.4 Ayurveda, Siddha, and South Asian Traditions

In Hinduism and Ayurveda, colocynth is interpreted as a significant plant valued for its medicinal properties and contributions to traditional healing practices. In many Asian countries and the Thar Desert in India it has been used as a laxative to relieve constipation. In Morocco it serves as a laxative, while in Ayurveda and Siddha medicine it has been used to treat ascites and dropsy.

2.5 North African and Berber Traditions

Many pharmacological properties (anti-inflammatory, anti-diabetic, analgesic, anti-epileptic) are ascribed to different organs of this plant; extracts and derivatives of C. colocynthis are used in folk Berber medicine for the treatment of numerous diseases such as rheumatism arthritis, hypertension, bronchitis, mastitis, and even cancer.

2.6 Summary of Traditional Indications

The plant has been reported across cultures to possess a wide range of traditional medicinal uses including in diabetes, leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer, toothache, wound healing, mastitis, and in gastrointestinal disorders such as indigestion, constipation, dysentery, gastroenteritis, colic pain, and different microbial infections.

Colocynth was frequently incorporated into herbal combinations to enhance its effectiveness and moderate its intense action. It was commonly blended with soothing herbs such as licorice root or fennel to protect the stomach and balance its strong purgative effects.

Historical accounts of trade go back to 1895, tracing the harvest and export of colocynth from Palestine's Jaffa to England under the commerce name of "Turkish colocynth."

3. Key Constituents and Active Compounds

3.1 Overview of the Phytochemical Profile

Phytochemical studies of the species have resulted in the identification of 75 components; of these, cucurbitacins have previously been reported as the main constituent. Numerous bioactive compounds have been identified in C. colocynthis fruit and classified into different categories such as glycosides, flavonoids, alkaloids, carbohydrates, fatty acids, and essential oils.

3.2 Cucurbitacins

Cucurbitacins are tetracyclic triterpenoid secondary metabolites, widely distributed in the Cucurbitaceae family. These bitter-tasting compounds act primarily as defense mechanisms against external injuries and against herbivores, and have also found use in folk medicine in the treatment of various diseases.

The chemical constituents of Citrullus colocynthis consist mainly of glycosides which upon enzymatic hydrolysis yield elaterin (cucurbitacin E), elatericin B (cucurbitacin I), and dihydroelatericin B (cucurbitacin L). The chloroform extract of C. colocynthis has been shown to yield four cucurbitacin glycosides: 2-O-β-D-glucopyranosyl-cucurbitacin I, 2-O-β-D-glucopyranosyl-cucurbitacin E, 2-O-β-D-glucopyranosyl-cucurbitacin L, and the novel glycoside 2-O-β-D-glucopyranosyl-(22–27)-hexanorcucurbitacin I. Additional cucurbitacins identified from the fruit include cucurbitacins A, B, C, D, E, I, J, K, and L, along with colocynthosides A and B.

Three flavone glucosides — isovitexin, isosaponarin, isoorientin — and the two cucurbitacin glucosides 2-glucopyranosyl-cucurbitacin L and glucopyranosyl cucurbitacin have been extracted from the fruits of locally grown C. colocynthis and identified.

The primary active ingredient in the fruits of C. colocynthis, colocynthin (cucurbitacin E-2-O-glucoside), has cathartic, antihistaminic, anticholinergic, negative chronotropic, and negative inotropic properties.

3.3 Flavonoids and Phenolic Acids

Phytochemical studies reveal a rich repertoire of bioactive secondary metabolites, most notably cucurbitacins, triterpene glycosides, flavonoids, phenolic acids, and essential fatty acids. The flavonoids were shown to have considerable antioxidant effects, which is a key characteristic for treating various disorders because reactive oxygen species play an important role in inflammation, cancer, tissue damage, and a variety of diseases.

3.4 Seed Oil and Fatty Acids

The fatty acid composition of Citrullus colocynthis seed oil chiefly contains linoleic acid (C18:2n6) at approximately 75%, followed by palmitic acid C16:0 (8%), stearic acid C18:0 (5%), and oleic acid C18:1n9 (9%). The oil contains 17–23% fatty acids consisting of linoleic, palmitic, oleic, and stearic acids, and is also rich in tocopherols, primarily beta-tocopherol. The seed contains approximately 7.0% oil, 11.7% protein, 29.5% carbohydrates, and 5.51% dietary fiber.

3.5 Alkaloids, Saponins, and Other Constituents

Chemically, C. colocynthis contains carbohydrate, protein, separated amino acids, tannins, saponins, phenolics, flavonoids, flavone glucosides, terpenoids, alkaloids, anthranol, steroids, cucurbitacins, saponarin, cardiac glycosides, and terpenes. Among the identified compounds, flavonoids or caffeic acid derivatives are the constituents associated with the inhibition of fungal or bacterial growth, whereas eudesmane sesquiterpenes or sesquiterpene lactones are most active against insects, mites, and nematodes.

4. Mechanisms of Action

4.1 Purgative / Laxative Mechanism

The membranolytic activity of some C. colocynthis ingredients is responsible for the intestinal damage associated with excessive use. Cucurbitacins, particularly cucurbitacin E and I, directly irritate the intestinal mucosa, stimulating peristalsis and secretion. Colocynth acts as a stimulant laxative; stimulant laxatives can decrease potassium levels in the body.

4.2 Anti-Inflammatory Mechanisms

The most cited mechanisms of anti-inflammatory action include inhibition of COX-2 and NOS, reduction of oxidative stress, suppression of proinflammatory cytokines, and modulation of acquired immunity proteins. Several molecular targets for cucurbitacins that have been discovered include fibrous-actin, signal transducer and activator of transcription 3 (STAT3), and cyclooxygenase-2.

In a cell-based investigation, ethanolic fruit extracts and isolated cucurbitacins B, E, and E-glucopyranoside inhibited human T-lymphocyte activation (markers CD69, CD25), reduced production of IL-2, TNFα, and IFNγ, and suppressed NFκB, NFAT, and AP-1 signalling in lymphocytes and lung epithelial cells, suggesting promise for airway inflammatory disorders.

4.3 Antidiabetic Mechanisms

Different Citrullus colocynthis seed extracts have demonstrated an insulinotropic effect, which could at least partially account for the antidiabetic activities of these fruits. Additional proposed mechanisms include inhibition of α-amylase and α-glucosidase enzymes. In vitro, the ethyl acetate fraction showed the highest antioxidant scavenging (76%) and anti-inflammatory (40%) activities at 3 mg/mL; antidiabetic effect was measured by inhibition of α-amylase, where the ethyl acetate fraction (77%) exhibited the highest antidiabetic activity.

4.4 Anticancer Mechanisms

The anticancerous effects of C. colocynthis operate via a variety of pathways including apoptotic pathways (increase in caspase-3 and inhibiting STAT3 function), antioxidant and anti-inflammatory actions (reducing TNF-α, nitric oxide, and pro-inflammatory cytokines such as IL-6, IL-8, and IL-1α), inhibition of Wnt/β-catenin signaling pathway, and antiangiogenesis and antimetastatic effects.

Cucurbitacin I and Q have been shown to specifically inhibit STAT3 phosphorylation, which contributes to the proliferation of many cancerous cells. Another study reported that cucurbitacin E inhibits the proliferation of prostate cancer cells and causes disruption of the cytoskeleton structure of actin and vimentin. Cucurbitacin B, D, E, and I inhibited the growth of several cancer cell lines and inhibited COX-2 enzyme rather than COX-1.

Cucurbitacin-I inhibits cancer cell growth in vitro and in vivo tumor models by disrupting the Janus kinase (JAK)/STAT3 signaling pathway. Cucurbitacins exhibit a striking ability to modulate key signalling pathways within cancer cells, affecting processes such as cell cycle regulation, apoptosis, and angiogenesis.

5. Scientific Evidence by Area of Use

5.1 Diabetes and Blood Glucose Regulation

Human / Clinical Evidence:

Citrullus colocynthis fruit is an herbal medicine used by traditional herbalists for the treatment of diabetes in Iran. To determine its efficacy and toxicity, a 2-month clinical trial was conducted in 50 type II diabetic patients. Two groups of 25 patients each, under standard antidiabetic therapy, received 100 mg C. colocynthis fruit capsules or placebos three times a day. The results showed a significant decrease in HbA1c and fasting blood glucose levels in C. colocynthis-treated patients. Other serological parameters in both groups did not change significantly. No notable gastrointestinal side effect was observed in either group. The authors concluded that C. colocynthis fruit treatment had a beneficial effect on improving the glycemic profile without severe adverse effects in type II diabetic patients.

A second randomized controlled trial studied the plant in Sabzevar, Iran. Seventy patients with type II diabetes were investigated; they were divided into intervention and placebo groups randomly and studied for 2 months. A significant difference was revealed between before and after intervention for HbA1c and FBS levels in the intervention group (p = 0.01 and p = 0.04, respectively). The difference between before and after intervention for FBS and HbA1c levels in the placebo group was not significant. Application of 125 mg C. colocynthis once per day for 2 months led to a considerable decrease in mean levels of HbA1c and FBS among patients with type II diabetes without any reported side effects.

A more recent open-label trial explored topical application. A clinical trial involving 36 T2DM patients revealed a significant reduction in blood glucose levels following topical application of the extract to the feet; blood glucose decreased by 46–65 mg/dL per application, with average values dropping from 157 mg/dL to 99.67 mg/dL at minimum. However, the authors themselves acknowledged a critical limitation: this was an open-label single-arm exploratory clinical trial that did not include a placebo control group, meaning that placebo-related effects cannot be definitively excluded. Well-designed, randomized, double-blind, placebo-controlled trials are still needed to elucidate the extract's unique efficacy.

A separate study investigated the lipid-lowering effects of C. colocynthis capsules in type 2 diabetic patients with dyslipidemia. Researchers demonstrated that the addition of C. colocynthis capsules (125 mg) to lipid-lowering therapy was able to significantly reduce the LDL-C level in type 2 diabetic patients with dyslipidemia when compared to placebo.

Evidence Strength: Multiple small randomized double-blind controlled trials in humans provide preliminary-to-moderate evidence that oral C. colocynthis fruit capsules can improve glycemic markers (HbA1c, fasting blood glucose) in type 2 diabetes. Sample sizes are small (25–70 patients), trial durations are short (2 months), and long-term safety data are lacking. Further clinical studies are recommended to evaluate the long-term efficacy and toxicity of C. colocynthis in diabetic patients.

5.2 Anti-Inflammatory and Analgesic Effects

Preclinical (Animal/In Vitro) Evidence:

A study from Tunisia assessed the in vivo analgesic and anti-inflammatory activities of Citrullus colocynthis immature fruit and seed organic extracts (petroleum ether, chloroform, ethyl acetate, acetone, and methanol) using the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats. All extracts displayed important analgesic and anti-inflammatory activities at different doses without inducing any side effects.

A study evaluated topical anti-inflammatory effects of C. colocynthis fruit extract cream (2–8%) using the carrageenan-induced paw edema model in rats; results showed that the cream dose-dependently reduced carrageenan-induced paw edema and reversed changes in the levels of TNF-α and IL-6 (p < 0.01).

In silico analysis showed that bioactive compounds (α-spinasterol, ascorbic acid, and chlorogenic acid) found in fruit extract have outstanding inhibition properties involving proteins PTGS2, TLR2, and TRPV4. Fruit extract showed results that are statistically significant (p < 0.005) and comparable to a reference drug in animal models.

Evidence Strength: All evidence for anti-inflammatory and analgesic effects currently derives from animal models and in vitro / in silico experiments. No controlled human clinical trials have specifically investigated anti-inflammatory endpoints for colocynth. Evidence is preliminary and cannot yet be extrapolated to clinical settings.

5.3 Antimicrobial Activity

In Vitro Evidence:

Several studies have confirmed antibacterial and antifungal efficacy of C. colocynthis on oral microorganisms including Streptococcus mutans, Streptococcus salivarius, Lactobacillus acidophilus, and Candida. Aqueous extracts from the plant were the most effective on Candida albicans and Escherichia coli. The premature fruit of C. colocynthis demonstrated the lowest amount of minimal inhibitory concentration (MIC) against various species of bacteria and fungi. Ethanolic extract has been shown to inhibit the growth of Staphylococcus aureus, Proteus mirabilis, Escherichia coli, and Streptococcus agalactia.

Among all organic fractions studied, ethyl acetate exhibited strong antimicrobial potential followed by n-hexane and chloroform fractions against selected pathogenic bacteria.

Evidence Strength: All antimicrobial evidence is derived from in vitro laboratory assays. No clinical trials in humans have evaluated C. colocynthis for treating infectious diseases. Evidence is entirely preclinical.

5.4 Anticancer Activity

In Vitro and In Vivo (Animal) Evidence:

Studies have examined the effects of cucurbitacin glucosides (B and E) extracted from C. colocynthis on human breast cancer cells, including the effects on cellular growth, cell-cycle distribution, apoptosis, and the expression of proteins involved in cell-cycle regulation, utilizing both estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cell lines. Cucurbitacin D has been shown to be significantly cytotoxic to a variety of human cancer cell lines, including lung, pancreatic, human colon, human oral epidermoid, hormone-dependent human prostate, retinal pigment epithelial cells, human umbilical vein endothelial cells, breast (MCF-7), and central nervous system (SF-268) cancer cell lines.

Studies of cucurbitacin E isolated from Citrullus colocynthis have been conducted against drug-resistant tumor cell lines. Overall, cucurbitacins have the demonstrated ability to inhibit cell proliferation and induce apoptosis in various cancer cell lines.

There are several studies, both in vitro and in vivo, reporting anticancer / chemopreventive potential; however, a comprehensive review on this topic and future clinical research are recommended.

Evidence Strength: Anticancer evidence for colocynth and its cucurbitacin constituents is exclusively from in vitro and in vivo (animal) studies. No controlled clinical trials in human cancer patients have been published. Evidence is early-stage and hypothesis-generating only.

5.5 Antioxidant Activity

Bitter apple extracts contain organic substances that can act as effective antioxidants, as well as polyphenolic chemicals. The aqueous leaf extract of C. colocynthis has been found to have a DPPH free radical scavenging effect, with an IC50 value of 0.021 mg/mL. Cucurbitacin glycoside derived from bitter apple also demonstrated ABTS radical scavenging capabilities (IC50, 145 µM).

Evidence Strength: Antioxidant evidence is entirely in vitro. Clinical significance in humans is unestablished.

5.6 Gastrointestinal Effects

The dried fruit pulp of C. colocynthis has been used to treat gastrointestinal disorders like indigestion, gastroenteritis, and intestinal parasites. C. colocynthis also has pharmacological properties as a laxative and purgative. However, as discussed under safety, purgative effects occur at doses that may be close to or within the toxic range. No rigorous clinical trials have specifically evaluated controlled laxative applications in humans.

6. Body Systems and Health Areas

C. colocynthis has many documented or investigated biological properties, including antioxidative, hypoglycemic, antibacterial, anti-cancerous, anti-inflammatory, analgesic, gastrointestinal, reproductive, antimicrobial, antidiabetic, hypolipidemic, antineoplastic, profibrinolytic, anti-allergic, pesticidal, and immune-stimulatory effects. The principal body systems and health areas associated with its study include:

Endocrine / Metabolic system: Blood glucose regulation, insulin secretion stimulation, lipid profile modulation in type 2 diabetes.
Gastrointestinal system: Stimulant laxative action, purgative properties, anthelmintic (anti-parasitic) uses.
Immune / Inflammatory system: COX-2 inhibition, pro-inflammatory cytokine suppression (TNF-α, IL-6, IL-2), NFκB and STAT3 pathway modulation.
Oncology (preclinical): Apoptosis induction, cell-cycle arrest, JAK/STAT3 inhibition in multiple cancer cell lines.
Microbiology: Broad-spectrum in vitro antibacterial and antifungal activity against clinically relevant organisms.
Skin and topical applications: Traditional use for wound healing, scabies, and postpartum conditions; topical anti-inflammatory cream formulations studied in animals.
Respiratory system: Traditional use for cough, bronchitis, and asthma; in vitro evidence of immune modulation in lung epithelial cells.

7. Dosages Reported in Studies

Dosages used in published human clinical trials and notable preclinical investigations are summarized below. These are reported solely as described in the cited studies and do not represent recommendations.

Oral capsules (clinical trial, type 2 diabetes): 100 mg C. colocynthis fruit capsules three times a day for 2 months, alongside standard antidiabetic therapy, in 50 patients.
Oral capsules (clinical trial, type 2 diabetes): 125 mg C. colocynthis once per day for 2 months, resulting in a considerable decrease in HbA1c and FBS in 70 patients.
Oral capsules (clinical trial, dyslipidemia in T2DM): 125 mg capsules added to lipid-lowering therapy, resulting in significant reduction of LDL-C levels compared to placebo.
Topical cream (animal study, anti-inflammatory): Fruit extract cream at concentrations of 2–8% evaluated on carrageenan-induced paw edema in rats.
Preclinical extracts (reviews of animal studies): In animal-model antidiabetic studies, doses varied from 10 to 500 mg/kg body weight per day; extracts were derived from roots, fruits, seeds, rinds, and leaves in ethanolic, methanolic, or aqueous form.

8. Safety Considerations and Drug Interactions

8.1 Toxicity Profile

The plant contains cytotoxic cucurbitacins and is thus considered unsafe for unsupervised use as an herbal medicine. The effect of a methanolic extract of C. colocynthis fruit was evaluated on male albino Wistar rats to assess toxicity; the acute median lethal dose (LD50) of the extract was calculated to be 1,311.45 mg/kg. Plasma AST, urea, ALT, and creatinine titers were affected to a notable extent, indicating that the extract was hepato-nephrotoxic. These findings confirmed that consumption of ripe C. colocynthis fruit extract has undesirable effects on the bone marrow, liver, and kidneys of rats.

A case report highlights multiorgan toxicity associated with colocynth ingestion, including gastrointestinal hemorrhage, hepatotoxicity, acute kidney injury, and hypotension. Citrullus colocynthis, traditionally used for its purgative properties, is known for its severe toxicity when consumed in excessive amounts. A 64-year-old male ingested colocynth fruit to relieve constipation; within 2 hours, he developed profuse bloody diarrhea, hematemesis, and altered consciousness.

In a reported case series, the main clinical feature of colocynth intoxication was acute rectorrhagia preceded by mucosal diarrhea with tenesmus, which gradually progressed to bloody diarrhea and overt rectorrhagia within 3 to 4 hours. The only colonoscopic observation was mucosal erosion which completely resolved in follow-up colonoscopy after 14 days.

Taking even very small amounts of colocynth can cause severe irritation of the stomach and intestine lining, bloody diarrhea, kidney damage, bloody urine, and inability to urinate. Other side effects include convulsions, paralysis, and death. There have been reports of death following ingestion of just 1½ teaspoons of the powder.

8.2 Organ-Specific Toxicity

Gastrointestinal toxicity: The membranolytic activity of some C. colocynthis ingredients is directly responsible for intestinal mucosal damage. Clinicians should be aware of C. colocynthis as a probable cause of lower GI bleeding in patients with no other suggestive history, especially diabetics who may self-medicate with the plant.

Hepatotoxicity / Nephrotoxicity: Documented cases of colocynth ingestion–associated toxicity include hepatotoxicity and acute kidney injury. Undesired effects include disturbance of gastrointestinal and urinary tracts.

8.3 Drug Interactions

Antidiabetic medications: Caution needs to be taken because of the potential impact on blood glucose levels. Mixing colocynth with diabetes drugs leads to the risk of hypoglycemia.
Digoxin: Colocynth acts as a stimulant laxative; stimulant laxatives can decrease potassium levels in the body, which is clinically relevant in patients taking digoxin (Lanoxin) due to the risk of cardiac arrhythmias from hypokalemia.
NSAIDs: Concurrent usage with non-steroidal anti-inflammatory medicines (NSAIDs) can increase the risk of gastrointestinal side effects.
Hepatotoxic or nephrotoxic substances: Because of its potential hepatotoxic and nephrotoxic effects, colocynth should be used with caution in conjunction with other substances that can cause liver or kidney damage, including certain over-the-counter medications, prescription drugs, and alcohol.

8.4 Use in Pregnancy and Lactation

Colocynth is considered unsafe in pregnancy and lactation. Its powerful stimulant purgative and potential uterotonic effects make it contraindicated in these populations.

8.5 Correctives in Traditional Practice

In traditional practice, if the fruit is administered with its correctives such as Arabic gum, adverse events are reduced and larger doses are allowed. This reflects the longstanding ethnopharmacological recognition of colocynth's narrow therapeutic window.

9. Summary of Evidence Quality

The overall body of scientific evidence for Citrullus colocynthis is characterized by the following:

Antidiabetic effects (human): Preliminary-to-moderate evidence from multiple small randomized controlled trials. Results are consistent in direction (lowering HbA1c and fasting glucose) but studies have small sample sizes, short durations, and limited independent replication.
Anti-inflammatory and analgesic effects: Currently supported only by animal and in vitro data. No controlled human trials exist for these endpoints.
Antimicrobial activity: Demonstrated in vitro across multiple organisms and extract types; not validated in human clinical settings.
Anticancer potential: Supported exclusively by in vitro and in vivo animal studies. Clinical trials in cancer patients are entirely absent from the published record.
Purgative / laxative effects: Well-documented historically and mechanistically; however, the narrow margin between effective and toxic doses makes controlled clinical evaluation problematic. Case reports of serious harm are documented.

It is evident from the literature that Citrullus colocynthis possesses a wide range of documented medicinal uses and has been studied for its antidiabetic, anticancer, antioxidant, antimicrobial, and anti-inflammatory activities, while its therapeutic potential for gut, airway, and cardiovascular disorders remains to be explored. Critical analysis reveals that the plant has significant potential for pharmaceutical and nutraceutical application, with some indications for the presence of synergistic and/or side-effect-neutralizing combinations of activities.

References

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