Bitter-apple
StarCitrullus colocynthis
Synonyms: Colocynthis officinalis, Colocynthis vulgaris, Cucumis colocynthis, Citrullus colocynthis var. bipinnatifidus, Citrullus colocynthis var. officinalis, Citrullus colocynthoides, Citrullus colocynthis var. wenderothii, Citrullus pseudocolocynthis, Citrullus colocynthis var. indicus, Cucumis bipinnatifidus, Cucumis colocynthoides, Citrullus colocynthis subsp. insipidus, Citrullus colocynthis var. insipidus, Cucurbita colocyntha, Citrullus colocynthis subsp. stenotomus, Citrullus colocynthis var. stenotomus
Safety at a glance
No rule in our tables for this herb: pregnancy, breastfeeding, incompatible pairs (十八反 / 十九畏), herb–drug, dose ceiling. This is not a safety clearance.
Not graded — No toxicity grade is recorded. Most herbs in the catalogue carry none.
Traditionally used for
- Bowel health
Cautions & contraindications
- Bleeding disorders
- Kidney conditions
- Diabetes
- Toxic — professional use only
Western Herbalism Properties
Traditional Uses
WARNING: highly toxic (cucurbitacins) - drastic and dangerous in even small doses. Citrullus colocynthis is one of the most ancient and widely used purgative drugs of the Old World. In classical and European herbal medicine the dried fruit pulp was a famous drastic cathartic and was incorporated into compound purgative pills (Grieve, 1931). In the Unani and Ayurvedic traditions the fruit (indrayan) is used, with great caution, for constipation, jaundice, and as a remedy reputed to help "sugar disease" (diabetes), as well as topically for joint pain (Khare, 2007). It is similarly recorded in traditional Chinese materia medica. The seeds and root also have folk applications. Internal use can cause severe gastroenteritis, bloody diarrhoea, kidney damage and death, and the plant is regarded as a dangerous poison.
Gallery
Botanical Description
Citrullus colocynthis (bitter apple, colocynth, bitter cucumber) is a perennial trailing or climbing herb of the gourd family, with rough, angular vines arising from a large fleshy perennial rootstock and bearing branched tendrils. The leaves are deeply three- to seven-lobed, rough-hairy and triangular in outline, pale beneath. The solitary yellow flowers are unisexual. The fruit is a smooth, hard-rinded gourd about the size of an orange (5-10 cm), mottled green ripening to yellow, with extraordinarily bitter, spongy white pulp containing many flat, smooth seeds. It is native to the deserts and dry sandy soils of North Africa, the Mediterranean basin, the Middle East and across to India, and is widely distributed in arid regions.
Active Constituents
Cucurbitacin E and its 2-O-beta-D-glucoside
Highly oxygenated tetracyclic triterpene and its glycosideConcentration: Fruit pulp and rind; the dominant cucurbitacin of the drug and the principal bitter and purgative principle
Cucurbitacin E is the constituent that makes this a drastic, not a gentle, purgative. Cucurbitacins are direct cytotoxins that disrupt the actin cytoskeleton and inhibit STAT3 signalling, and in the gut they injure the colonic epithelium rather than simply stimulating motility. This is why colocynth ingestion produces dysenteric, frequently bloody diarrhoea within hours rather than an ordinary laxative effect, and why colonic biopsies after ingestion show erosions with fibrinopurulent exudate, early lamina propria fibrosis and hyaline thickening of the superficial epithelial basement membrane. Cucurbitacins are also the basis of the drug's uterine stimulant and abortifacient reputation.
Cucurbitacins B, I, J, K and L, with their glucosides
Cucurbitane-type triterpene glycosidesConcentration: Fruit; a mixture rather than a single compound, the historic pharmacy fraction called colocynthin
The full cucurbitacin family isolated from colocynth fruit. Historic pharmacy names for the drug's active fraction, colocynthin for the glycoside mixture and colocynthein for the aglycone, describe this mixture and not a single chemical entity, so extracts standardised on one marker do not control the whole toxic burden. The same compounds account for the cytotoxicity reported in cancer cell line work; that activity is not selective enough to represent a therapeutic window in a patient.
Fixed seed oil, rich in linoleic and oleic acid
Triacylglycerols of polyunsaturated and monounsaturated fatty acidsConcentration: Seed; linoleic acid about 46 percent and oleic acid about 23 percent of the oil in a characterised Ethiopian sample
The seed and its expressed oil are a chemically separate drug from the fruit pulp. The oil is largely fatty acids and carries far less of the cucurbitacin load, which is why washed or processed colocynth seed is eaten as famine food in some desert regions while the pulp is a poison. Topical trials of colocynth in neuropathy have used an extract oil rather than a pulp preparation. Do not import fruit-pulp toxicity data onto seed oil, or seed-oil safety onto the pulp.
Methyl gallate
Phenolic acid esterConcentration: Fruit; isolated alongside cucurbitacin E glycoside
A phenolic constituent isolated from the fruit with antioxidant and antibacterial activity in vitro. It contributes to the measured phenolic content of extracts but has no role in the purgative action.
Flavonoids (flavone C-glycosides and quercetin derivatives)
FlavonoidsConcentration: Fruit and seed extracts; total flavonoid content of a characterised seed oil extract about 127 mg catechin equivalents per gram
The flavonoid fraction accounts for most of the antioxidant capacity measured in colocynth extracts and is the fraction usually credited in in vitro anticancer and antimicrobial work. It is pharmacologically unremarkable compared with the cucurbitacins and is not what makes the drug dangerous.
⚠ Drug Interactions
Insulin, sulfonylureas, metformin and other antidiabetic agents
This is the best-evidenced interaction for the herb because the human trial was deliberately run on top of drug therapy. In a randomised double-blind placebo-controlled trial, 50 type 2 diabetic patients already on standard antidiabetic therapy took 100 mg of colocynth fruit capsules three times daily or placebo for two months; HbA1c and fasting blood glucose fell significantly in the colocynth arm. Separately, hypoglycaemia is a documented feature of acute colocynth poisoning, reported in a patient admitted after drinking a fruit decoction. The glucose-lowering effect is therefore real and can be additive.
Clinical note: If a diabetic patient is using colocynth, expect glucose to fall and arrange more frequent self-monitoring, with anticipatory reduction of insulin or sulfonylurea. Note that the trial dose was a controlled 100 mg capsule three times daily of a standardised fruit preparation, not a home-prepared decoction; decoctions are the preparation implicated in poisoning.
Digoxin and other cardiac glycosides
Colocynth is a drastic hydragogue cathartic that produces profuse and often bloody diarrhoea beginning eight to twelve hours after ingestion, with documented hypotension and shock in severe cases. The resulting potassium and magnesium depletion sensitises the myocardium to digitalis. This is the classic and well-established interaction of drastic purgatives as a class, and colocynth is at the severe end of that class.
Clinical note: Do not use colocynth in any patient on digoxin. If exposure has occurred, check potassium and magnesium urgently and correct before assuming a digoxin level is reassuring.
Anticoagulants and antiplatelet agents
Colocynth causes direct colonic mucosal injury rather than a functional laxative effect. Acute rectorrhagia has been reported as a presenting emergency after colocynth ingestion, and the case series that defined the lesion documented dysenteric diarrhoea with congested, hyperaemic mucosa and abundant exudate on colonoscopy. Superimposing pharmacological anticoagulation on eroded colonic mucosa converts a self-limiting injury into a bleeding emergency.
Clinical note: Colocynth is contraindicated with anticoagulants. Rectal bleeding after a herbal purgative in an anticoagulated patient warrants urgent assessment and should not be attributed to haemorrhoids without endoscopy.
Loop and thiazide diuretics, corticosteroids, other stimulant laxatives
Each of these causes potassium loss or fluid depletion by a different route, and colocynth adds a hydragogue cathartic loss on top. Documented colocynth poisoning presents with hypotension, sinus tachycardia and acute kidney injury from that fluid loss. Combining it with another agent that depletes volume or potassium is directly additive.
Clinical note: Never combine colocynth with another stimulant laxative or with diuretics. In an exposed patient, treat as an acute volume and electrolyte emergency: aggressive fluid resuscitation with potassium replacement is the mainstay, and reported cases recovered on supportive care within days.
Nephrotoxic and hepatotoxic drugs (NSAIDs, aminoglycosides, paracetamol, methotrexate)
Colocynth toxicity is multiorgan, not confined to the gut. A reported case of a man who ate the fruit for constipation developed profuse bloody diarrhoea, haematemesis and altered consciousness within two hours, with hypotension, acute kidney injury and raised liver enzymes; another case in a pregnant woman showed moderate hepatic cytolysis with intestinal inflammation, and a third described rising ALT and AST after a fruit decoction. Rodent acute toxicity work likewise shows the extract to be hepato-nephrotoxic with raised ALT, AST, urea and creatinine.
Clinical note: Withhold nephrotoxic and hepatotoxic drugs where possible during and after an exposure, and check renal and hepatic function even when the presentation looks purely gastrointestinal.
Orally administered medicines, including oral contraceptives
Drastic catharsis with profuse watery and bloody stool for several days will substantially reduce the absorption of anything taken by mouth in that window. This is a general property of hydragogue cathartics and colocynth is among the most violent of them.
Clinical note: Assume oral doses taken during a colocynth-induced catharsis were not absorbed. Advise back-up contraception and use parenteral routes for critical medication.
Dosage Calculator
⚖ Dosage Calculator
A weight-based mathematical estimate for Bitter-apple. Not a prescription.
Evidence Tier
3 RCTs · 7 studies on recordRecorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.
Systematic review / meta-analysis
0
Randomized controlled trial
3
1 verified · 2 unverified
Show 3 studies
- The clinical investigation of citrullus colocynthis (L.) schrad fruit in treatment of Type II diabetic patients: a randomized, double blind, placebo-controlled clinical trial
- Topical Citrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: A double-blind randomized placebo-controlled clinical trial
- Efficacy of topical Citrullus colocynthis (bitter apple) extract oil in chemotherapy-induced peripheral neuropathy: A pilot double-blind randomized placebo-controlled clinical trial
Other clinical trial
0
Observational / case report
4
1 verified · 3 unverified
Show 4 studies
In vitro / animal
0
Other / unclassified
0
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
The clinical investigation of citrullus colocynthis (L.) schrad fruit in treatment of Type II diabetic patients: a randomized, double blind, placebo-controlled clinical trial
50 type 2 diabetic patients on standard antidiabetic therapy were randomised to 100 mg Citrullus colocynthis fruit capsules three times daily or placebo for two months. HbA1c and fasting blood glucose fell significantly in the treated group; lipids, transaminases, alkaline phosphatase, urea and creatinine were unchanged, and no notable gastrointestinal adverse effect was seen at this dose. This is the only substantive human efficacy trial of the fruit and it used a small, controlled capsule dose over a short period, which is a very different exposure from the traditional decoction implicated in poisoning.
Peculiar acute toxic colitis after ingestion of colocynth: a clinicopathological study of three cases.
Three patients developed acute toxic colitis after ingesting colocynth for ritual purposes. The presentation was dysenteric diarrhoea beginning eight to twelve hours after intake; colonoscopy showed congestion, hyperaemia and abundant exudate without ulceration or pseudopolyps. Biopsies at 27, 44 and 72 hours showed erosions with fibrinopurulent exudate, early fibrosis of the lamina propria and hyaline thickening of the superficial epithelial basement membrane, all of which resolved by day 14 alongside clinical recovery in three to six days. This paper defines the characteristic colonic lesion of colocynth and is the reason the drug is described as directly injuring the colon rather than merely purging it.
Colocynth induced multiorgan toxicity: a case report
A 64-year-old man ate colocynth fruit for constipation and within two hours developed profuse bloody diarrhoea, haematemesis and altered consciousness, presenting with hypotension, sinus tachycardia, leukocytosis, acute kidney injury and raised liver enzymes. Infection and other causes of colitis were excluded. He recovered fully within five days on aggressive fluid resuscitation and supportive care. The case documents that colocynth toxicity is gastrointestinal, hepatic, renal and cardiovascular, and that the onset can be within two hours of a single self-treatment dose.
Citrullus colocynthis as the Cause of Acute Rectorrhagia
Emergency presentation with acute rectal bleeding attributed to Citrullus colocynthis ingestion. Documents that colocynth belongs on the differential for haematochezia in populations where it is used as a folk purgative, and reinforces that the injury is mucosal and haemorrhagic rather than a simple osmotic or stimulant laxative effect.
Acute Citrullus colocynthis L. poisoning in a pregnant woman: About a case
A 32-year-old pregnant woman was admitted with bloody diarrhoea after drinking a decoction of Citrullus colocynthis, with moderate hepatic cytolysis and intestinal inflammation. The case is important because colocynth has a long abortifacient reputation and pregnant women are among those most likely to be given it; it establishes maternal hepatic and colonic injury as a documented consequence.
Topical Citrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: A double-blind randomized placebo-controlled clinical trial
Double-blind randomised placebo-controlled trial of a topical colocynth extract oil in painful diabetic neuropathy. This is a topical seed-oil-based preparation, an entirely different exposure from the oral fruit, and it is the route with the more favourable risk profile. Results from this trial cannot be used to justify oral use of the fruit.
Efficacy of topical Citrullus colocynthis (bitter apple) extract oil in chemotherapy-induced peripheral neuropathy: A pilot double-blind randomized placebo-controlled clinical trial
Pilot double-blind randomised placebo-controlled trial of topical colocynth extract oil in chemotherapy-induced peripheral neuropathy. As with the diabetic neuropathy trial, the preparation is a topical oil; the finding does not transfer to the oral fruit preparation, and the trial is explicitly a pilot.
Historical Texts
Dioscorides, De Materia Medica, under kolokynthis agria
Greek, 1st century CEAvicenna, Al-Qanun fi al-Tibb (The Canon of Medicine), under hanzal
Persian and Arabic medicine, completed 1025 CEAyurvedic classical materia medica, under indravaruni
Classical and later Ayurvedic traditionBritish Pharmacopoeia and nineteenth-century Western pharmacy, Pilula Colocynthidis Composita and Pilula Colocynthidis et Hyoscyami
European and North American pharmacy, 19th to mid-20th centuryReferences
- Hatam NAR, Whiting DA, Yousif NJ. Cucurbitacin glycosides from Citrullus colocynthis . Phytochemistry (1989) [DOI]
- Hoffola AA, Robi AG, Tefera ZT, Abera WG. Physicochemical characterization, antioxidant capacity, and antimicrobial activity of Citrullus colocynthis seed oil . Scientific Reports (2026) [DOI]
- Adhikari A, Sapkota A, Shah SMZ, Aryal K, Acharya P. Synthesis of Gold Nanoparticles Using Cucurbitacin E-Glycoside and Methyl Gallate Isolated from Citrullus colocynthis L. Fruit and Evaluation of their Antibacterial and Antibiofilm Activities . Pharmaceutical Nanotechnology (2025) [DOI]
- Fallah Huseini H, Haghighi M, Kianbakht S, Ziaee M. Persian Medicinal Plants as Antidiabetic Agents: Mechanisms and Evidence from Bench to Bedside . Iranian Biomedical Journal (2025) [DOI]
- CABI. Citrullus colocynthis (colocynth) . CABI Compendium (2021) [DOI]
This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.
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