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This sheet was compiled from PubMed (NIH) abstracts using AI assistance. Every factual claim is cited to a real PubMed article (see the source list). It has not yet been human-reviewed — confirm with a healthcare provider before use.
Compiled from 30 PubMed articles · model: gemma4:31b
Summary
Citrullus colocynthis is a desert-dwelling herbaceous plant with diverse biological properties, including antidiabetic, anti-inflammatory, and anticancer activities [PMID:35145403, PMID:37687049].
Background
Citrullus colocynthis, also known as bitter apple, is a member of the Cucurbitaceae family widely distributed in desert areas globally [PMID:24936768, PMID:37687049].
Traditional uses
Traditional medicinal uses include the treatment of diabetes, leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer, toothache, wounds, mastitis, and gastrointestinal disorders such as indigestion, constipation, and dysentery [PMID:24936768, PMID:32237481]. It has also been used in traditional Persian medicine for pain relief, specifically neuralgia [PMID:31373112].
Anticancer effects against colorectal cancer are associated with apoptotic pathways (increasing caspase-3 and inhibiting STAT3), antioxidant and anti-inflammatory traits (affecting TNF-α, nitric oxide, IL-6, IL-8, and IL-1α), inhibition of the Wnt/β-catenin signaling pathway, and antiangiogenesis [PMID:31463888].
Clinical evidence
Evidence BPainful diabetic polyneuropathy (PDPN)
Topical formulation of C. colocynthis significantly decreased mean pain scores compared to placebo over 3 months [PMID:25800045]
A pilot trial found no significant improvement in the total FACT/GOG-Ntx score for breast cancer patients using topical C. colocynthis oil compared to placebo [PMID:31373112]
Evidence AType II Diabetes (Glycemic and Lipid Profile)
Meta-analysis indicated that C. colocynthis does not have a significant effect on fasting blood sugar (FBS), hemoglobin A1c (HBA1c), low-density lipoprotein (LDL), total cholesterol, and triglycerides [PMID:36404820]
Evidence CGouty Arthritis
Identified as a pharmaceutical plant additive in the management of gouty arthritis [PMID:39409183]
Safety & adverse effects
C. colocynthis can be severely toxic if consumed in excessive amounts, potentially causing multiorgan toxicity, hypotension, sinus tachycardia, and leukocytosis [PMID:41088384]. Ingestion has been linked to hemorrhagic colitis, bloody diarrhea, hematemesis, hypoglycemia, and transaminitis [PMID:35821084, PMID:41088384, PMID:2583569]. Undesired effects may also include disturbances of the gastrointestinal and urinary tracts [PMID:25265814]. Roasting the fruit before use is commonly practiced in traditional medicine to reduce toxicity [PMID:35496437].
Evidence summary
Evidence is mixed; while some RCTs suggest efficacy for topical treatment of diabetic neuropathic pain, a meta-analysis found no significant effect on glycemic factors in type II diabetes, and case reports highlight severe systemic toxicity upon ingestion.
PubMed sources
1.PMID: 39409183 (2024) — Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions. · International journal of molecular sciences
2.PMID: 24111621 (2013) — Antidiabetic oils. · Current diabetes reviews
3.PMID: 35145403 (2021) — Citrullus colocynthis (L.) Schrad (Bitter Apple Fruit): Promising Traditional Uses, Pharmacological Effects, Aspects, and Potential Applications. · Frontiers in pharmacology
4.PMID: 24936768 (2014) — Citrullus colocynthis (L.) Schrad (bitter apple fruit): a review of its phytochemistry, pharmacology, traditional uses and nutritional potential. · Journal of ethnopharmacology
No direct government monograph is available for this herb. The content below is AI-generated and has not been verified against an authoritative government source. Use the search links to check official sources before relying on this information.
— Citrullus colocynthis (L.) Schrad.: A Promising Pharmaceutical Resource for Multiple Diseases.
· Molecules (Basel, Switzerland)
6.PMID: 35821084 (2022) — A Bitter Experience-A Bitter Apple (Citrullus colocynthis) Ingestion in a Child. · The American journal of emergency medicine
7.PMID: 31463888 (2020) — The Anticancer Efficiency of Citrullus colocynthis Toward the Colorectal Cancer Therapy. · Journal of gastrointestinal cancer
8.PMID: 30783472 (2019) — Topical treatments for diabetic neuropathic pain. · Experimental and therapeutic medicine
9.PMID: 25800045 (2016) — Topical Citrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: A double-blind randomized placebo-controlled clinical trial. · Journal of diabetes
10.PMID: 36518144 (2022) — Effect of Citrullus colocynth fruit extract on pro and anti apoptotic molecules in human melanoma cell line (A375). · Bioinformation
11.PMID: 32237481 (2020) — [Research progress on chemical constituents of Citrullus colocynthis and their pharmacological effects]. · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
12.PMID: 30768427 (2019) — Plant-derived medicines for neuropathies: a comprehensive review of clinical evidence. · Reviews in the neurosciences
13.PMID: 25265814 (2014) — A review on antidiabetic activity of Citrullus colocynthis Schrad. · Acta poloniae pharmaceutica
14.PMID: 35454193 (2022) — Citrullus colocynthis Seed Ameliorates Layer Performance and Immune Response under Acute Oxidative Stress Induced by Paraquat Injection. · Animals : an open access journal from MDPI
15.PMID: 31373112 (2019) — Efficacy of topical Citrullus colocynthis (bitter apple) extract oil in chemotherapy-induced peripheral neuropathy: A pilot double-blind randomized placebo-controlled clinical trial. · Phytotherapy research : PTR
16.PMID: 41088384 (2025) — Colocynth induced multiorgan toxicity: a case report. · Journal of medical case reports
17.PMID: 32948080 (2020) — Isolation of Cysteine-Rich Peptides from Citrullus colocynthis. · Biomolecules
18.PMID: 36459867 (2023) — Multifunctional bioactive properties of hydrolysates from colocynth (Citrullus colocynthis) seeds derived proteins: Characterization and biological properties. · Plant physiology and biochemistry : PPB
19.PMID: 16644537 (2006) — Cucurbitacin glucosides from Citrullus colocynthis. · Natural product research
20.PMID: 36296358 (2022) — Microbiome of Citrullus colocynthis (L.) Schrad. Reveals a Potential Association with Non-Photosynthetic Cyanobacteria. · Microorganisms
21.PMID: 30703909 (2014) — Natural Infection of Citrullus colocynthis by Papaya ringspot virus-W in Iran. · Plant disease
22.PMID: 35496437 (2021) — Comparative metabolomics reveals the cytotoxic and anti-inflammatory discriminatory chemical markers of raw and roasted colocynth fruit (Citrullus colocynthis L.). · RSC advances
23.PMID: 31874814 (2020) — Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy. · Journal of integrative medicine
24.PMID: 2583569 (1989) — Peculiar acute toxic colitis after ingestion of colocynth: a clinicopathological study of three cases. · Gut
25.PMID: 37973959 (2023) — Anticancer activity, phytochemical investigation and molecular docking insights of Citrullus colocynthis (L.) fruits. · Scientific reports
26.PMID: 25617810 (2015) — Protective effect of olive oil and colocynth oil against cadmium-induced oxidative stress in the liver of Wistar rats. · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
27.PMID: 29796216 (2018) — Medicinal herbs in the treatment of neuropathic pain: a review. · Iranian journal of basic medical sciences
28.PMID: 36404820 (2022) — Effect of Citrullus colocynthis on glycemic factors and lipid profile in type II diabetic patients: a systematic review and meta-analysis. · Journal of diabetes and metabolic disorders