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Family Cucurbitaceae
Bitter apple
Citrillus colocynthis Schard.

Scientific names Common names
Citrullus colocynthis (L.) Schrad.            Bitter apple (Engl.)
Citrullus colocynthis var. bipinnatifidus Alef.            Bitter cucumber (Engl.)
Citrullus colocynthis var. indicus Alef.            Bitter gourd (Engl.)
Citrullus colocynthis subsp. insipidus (Pangalo) Fursa            Colocynth (Engl.)
Citrullus colocynthis var. insipidus Pangalo            Desert gourd (Eng.)
Citrullus colocynthis var. officinalis Alef.            Vine of Sodom (Engl.)
Citrullus colocynthis subsp. stenotomus (Pangalo) Fursa            Wild gourd (Engl.)
Citrullus colocynthis var. stenotomus Pangalo             
Citrullus colocynthis var. wenderothii Alef.             
Citrullus colocynthoides Pangalo             
Citrullus pseudocolocynthis M.Roem.             
Colocynthis officinalis Schrad.             
Colocynthis vulgaris Schrad.             
Cucumis bipinnatifidus Wight ex Naudin             
Cucumis colocynthis L.             
Cucumis colocynthoides Schult.             
Cucurbita colocyntha Link              
Citrullus colocynthis (L.) Schrad. is an accepted species. KEW: Plants of the World Online

Other vernacular names
ARABIC: Handhal.
BENGALI: Makhal.
FRENCH: Coloquinte.
GERMAN: Koloquinte, Bitterzitrulle.
GREEK: Kolokunthis.
HINDI: Indrayan, Tumba.
ITALIAN: Coloquintide, Cocomero amaro.
MALAYALAM: Paikummatti.
MARATHI: Kadu indravani.
NEPALESE: Indrenii.
PAKISTAN: Indryan, Tumba.
PERSIAN: Hinduwana (?).
PORTUGUESE:  Colocintida.
PUNJABI: Ghurunba, Kortuma.
SANSKRIT: Indravaruni.
SPANISH: Coloquintida, Coloquinta.
SWEDISH: Kolokvint.
TAMIL: Kommatti, Palam, Paedikari attutummatti.

Gen info
- Citrullus colocynthis is an entry in The Project Gutenberg eBook of The Medicinal Plants of the Philippines by T H Pardo de Tavera (1901).
- Citrullus colocynthis
originally bore the scientific name Colocynthis citrillus.

- It resembles a common watermelon vine but bears small, hard fruits with a bitter pulp.
- The characteristic small seed has been found in early archaeological sites in northern Africa and Near East, specifically at Neolithic Armant, Nagada in Egypt, at sites dating 3800 BC to Roman times in Libya; also in pre-pottery Neolithic levels at the Nahal Hemar Caves in Israel. The information suggests the wild colocynth was probably used by humans prior to domestication. (4)

Citrillus colocynthis is an herb with long, prostrate stems covered with stiff hairs. Leaves alternate, triangular, deeply cleft in 3 lobules that subdivide. Petioles long. The color of the leaves is pale green above, whitish or gray and covered with white hairs underneath. Flowers yellow, monœcious, solitary, axillary, with long peduncles. Staminate: receptacle cup-formed, 5 sepals and 5 free, yellow petals; 5 stamens in pairs, one free. Pistillate: the receptacle globose, covering the lower part of the ovary; 3 staminodes take the place of the stamens. Ovary unilocular, uniovulate, with a short style bearing 3 lobules at its apex. Fruit globose, 6–8 centimeters in diameter, smooth, greenish, later yellow with white spots; it is full of a whitish pulp that becomes dry and pithy and that contains the obovate seeds, smooth, flattened, brown, lacking albumen. (2) Each of the three carpels bears six seeds. Each plant produces 15 to 30 fruits. (4)

Perennial trailing herbs with somewhat woody tuberous root. Stems shortly hairy when young becoming scabrid. Tendrils simple, rarely bifid, slender, glabrous. Leaf blade ± elongate-ovate in outline, 10-60 (-110) mm long, 8-55 (-66) mm broad, distinctly scabrid-hairy beneath, smooth except on the nerves above, palmately deeply 3-5-lobed, ultimate lobes pinnately lobulate with central lobe longest, long-ovate in outline; petiolate, petiole rather densely rough-hairy; probracts lanceolate-elliptic, 4-5 mm long and c. l. 5 mm broad, caducous. Male flowers on long pedicels; calyx campanulate, c. 9 (4-8) mm long, lobes c. 5 mm broad; corolla pale yellow, ovate-acute, c. 8 mm long and c. 5 mm broad; female flowers on longer pedicels than male, receptacle-tube short, lobes lanceolate, c. 5 mm long. Ovary hairy, subglobose or obovate. Fruit on long stalk, c. 5 cm in diameter, globose, smooth, longitudinally green striped, 5-7 cm in diameter, eipcarp thin, filled with a dry spongy very bitter pulp. Seeds numerous, ovate-oblong, yellowish brown, not margined, c. 6 mm long and c. 3 mm broad. (Flora of Pakistan)

- Introduced.
- The native range of the species is Macronesia, Medit. to Myanmar, NE Tropical Africa to N. Kenya. (1)

- Pulp contains a yellow, intensely bitter substance, quite soluble in water and alcohol, discovered by Hubschmmann and named coloquintina. The seeds contain 17% insipid oil. (2)
- Proximate analysis revealed 24.37% protein, 1.91% fiber, 10.88% carbohydrate, 56.61% fat, 3.15% ash, and 3.08% moisture (Ogundele et al, 2012). (5)
- Phytochemical screening of C. colocynthis revealed carbohydrates, alkaloids, proteins, glucosides, tannins, saponins, cardiac glycolipids, flavone and terpenoids, cucurbitacins, anthranol, saponarin, steroids, and trace elements. (5)
- Seeds contain 567.32 kcal per 100g dry weight or lower, 17-23% fatty acids (dry weight), proteins at 11.67% of total weight, non-fibrous carbohydrate at 29.47% total weight, dietary fiber 5.51% total weight, 7.51% moisture, 2.94-3.22% ash content (dry weight), vitamin E 121.85mg/100g.
- Fruit pulp contains colocynthin (bitter component), colocynthein and colocynthetin (resin), cucurbitacin E glucose (0.05% DW), and I glucoside (0.01% DW).
- GC-MS and HPLC study yielded 70 chemically diverse metabolites from different plant parts, including colocynthin (242.00 mg/g dw) and substantial concentration of 2,4-di-tert butyl phenol (3.2%), squalene (4.2%), and δ-tocopherol (2.5%). (see study below) (18)
- Study of chemical constituents of seed yielded protein (8.25%), rich in lysine, leucine, and sufo-amino acids viz., methionine. Kernels yielded oil (52%), protein (28.4%), fiber (2.7%), ash (3.6%), and carbohydrate (8.2%). (21)
- Fruits and aerial parts yielded flavone c-glucosides. Fruit contains iso-vitexin, iso-orientin 3'-methylether, while aerial parts contain C-p-hydroxyl benzene derivatives viz., 8-C- p-hyddroxybenzyl-isovitexin, 6-C-p-hydroxybenzylvitexin and 8-C-p hydroxybenzylisovitexin 4'-O-glucosde. (21)

- Considered purgative, emmenagogue.
- Studies have suggested antioxidant, anticancer, anti-prostatic hyperplasia, hair growth-promoting, antidiabetic, hypolipidemic, wound healing, antibacterial, anthelmintic, antifungal properties.

Toxicity concerns
- The fruit pulp is known as a potent cathartic.
- Excessive consumption of fruits have been reported to cause vomiting and bloody diarrhea.
- Toxicity seems more related to fruit pulp consumption.
- See toxicity related studies below: (6) (15) (26) (27) (37)

Parts used
Fruit pulp, seeds.


- The fruits are edible, extremely bitter in taste. (see toxicity concerns)
- Seeds of colocynth must be separated from the pulp and heated to make edible. Used since antiquity as a food source in the Sahara and Sahel where regular farming is impossible. The flowers are ediible. (13)
- Seed powder used as soup thickener and flavoring agent.
- The fruit pulp, official in old pharmacopaeias, is known as a very energetic hydrogogue cathartic. It is seldom given alone, but in combination with other drugs to modify it energy and action, (2)
- In large doses, it causes vomiting, bloody diarrhea, and nervous phenomenon that may cause death. It operates with great force on the large intestines and sympathetically upon the uterus. Six to ten grams constitute a toxic dose. (2)
- In ancient folk medicine, Johann Weyer in De praestigiis daemonuum (1563), mentions it as a cure for lycantrophy (lycanthrope: werewolf). (4)
- In pre-modern medicine, used as laxative or purgative. Boiled in water or beer, used as emmenagogue, for obstruction of menses. Women were reported to use it early in pregnancy as abortifacient. (4)
- Powder of colocynth used for parasitic worms; pulp used as enema. Troches, or lozenges, made of colocynth were called "troches of alhandal". (4)
- Dried fruit pulp used for indigestion, gastroenteritis, and intestinal parasites.
- Fruit used for colds, fever, diarrhea, deworming, ulcers, asthma, leukoplakia, bronchitis, diabetes, constipation, anemia, joint pains, rheumatism, jaundice, ascites. (5)
- Used for toothaches, leprosy, bronchitis, mastitis, skin infections.
- In India, used for treatment of boils, pimples, constipation, inflammation of the joints. Fruits used for cancer, constipation, biliousness, deafness, dental caries, dropsy, diabetes, dyspepsia. Seeds used for epilepsy, hair growth, malaria, syphilis.
- In Tunisian folk medicine, used for treatment of hypertension and inflammatory diseases, including rheumatism and rheumatoid arthritis. (14)
- Fruit used for treatment of diabetes, at low doses to avoid gastrointestinal side effects.
- In India, fruit juice mixed with sugar used for dropsy. Poultice of roots used for breast inflammation. Root powder mixed with ginger and jaggery used for joint inflammation. Seed oil used for epilepsy, hair growth and hair tinting. Fruit and root paste used for boils and pimples.  Fruits and roots used as snake poison antidote. Dried and powdered fruit pulp used as abortifacient. Root base mixed with cow milk applied to hypogastrium to facilitate delivery. (25)
- In Persian medicine, bitter apple has been used for effective pain relief, especially for neuralgia.
- Oil: Oil from seed (47%) can be used for medicinal and soap production.
- Livestock: In Pakistan where the poultry industry is a key sub-sector of the livestock industry, phytobiotics are added to poultry feed as growth and nutrient promoter and as antimicrobial substitute. Ten bioactive components were isolated from C. colocynthis seeds (CCS). CCS contains 13.5% protein, rich in methionine and cysteine, and seed protein with 75% invitro digestibility. (5)
- Veterinary: In traditional Arab veterinary medicine, colocynth sap is used to treat skin eruptions in camels. (13)
- Hair tinting: Seed oil used for blackening of hair.

Toxicity Study:
Study evaluated the toxic effect of C. colocynthis. Thirty male rabbits were treated with 100 or 200 mg/kg/day for a month of either pulp or seed extract. No animals treated with 200 mg/kg/day of pulp extract survived. Animals treated with 100 mg/kg/day of pulp extract displayed severe lesions in the small intestine, kidney, and liver.  Animals treated with either doses of seed extract displayed only minor intestinal insult. Results suggest the pulp extract can be fatal to rabbits. The seed extract may be the preferred mode of therapeutic application. (6)
Effect on Hair Growth: Study evaluated the effect of petroleum ether and ethanol extracts of C. colocynthis for effect on hair growth in albino rats. Extracts incorporated into oleagenous ointment base were applied topically on shaved denuded skin of albino rats. Minoxidil 2% solution was applied topically and served as standard. Hair growth initiation time was significantly reduced. Time required for complete hair growth was also considerable reduced. Treatment was successful in bringing greater number of hair follicles (>70%) to anagenic phase than standard minoxidil (67%). The results of treatment  with 2% and 5% petroleum ether extracts were comparable with standard minoxidil. (7)
Effect on Testosterone-Induced Alopecia / Fruits: Study evaluated C. colocynthis fruit for hair growth activity in androgen-induced alopecia in albino mice. Alopecia was induced by intramuscular administration of testosterone for 21 days. The petroleum ether extract was applied topically. Finasteride (5α-reductase inhibitory) solution was applied topically as positive control. The extract showed promising growth-promoting activity, as reflected from follicular density, A/T ration and skin sections. There was a greater number of hair follicles in the anagenic phase than standard finasteride. The 2 and 5% extracts were comparable to positive control finasteride. Results suggest potential for the treatment of androgen-induced alopecia. (8)
Effect on Testosterone-Induced Benign Prostatic Hyperplasia / Fruits: Study evaluated the effect of petroleum ether extract of fruits and a steroidal compound on prostatic hyperplasia induced by testosterone in Wistar rats. Treatment significantly reduced prostatic weights of treated animals. The steroidal fraction also dose-dependently decrease prostatic weight. Histological architecture showed less involution of epithelial cells and reduction in connective tissue. In vitro study showed inhibition of 5-alpha reductase activity. Results suggest potential use in management of androgen dependent BPH. (9)
Cytotoxicity / Anticancer / Radical Scavenging / Seeds: Study evaluated the phytochemical composition, cytotoxic and antioxidant activities of C. colocynthis seed extract. Cytotoxicity testing showed IC50s of seed extract in inhibiting MDA-MB-231 (breast cancer cell line) and HT-29 (colon cancer cell line) were 170.34 and 132.31 µg/mL, respectively. The seed extract exhibited strong antioxidant power with IC50 of 1.37 mg/mL. Results suggest potential against cancer and free radicals damage. (10)
Antiulcer / Antioxidant / Seed: Study evaluated the antioxidant and antiulcerogenic activity of C. colocynthis methanolic seed extract. The extract showed good antioxidant potential with maximum percentage inhibition of 79.4 and 72.4% by DPPH and Hydrogen Peroxide assays respectively at 300 µg/mL. On anti-ulcerogenic activity by pyloric ligation induced ulcer method in Wistar albino rats, the extract at 200 mg/kg showed maximum inhibition of gastric volume, free acid and total acidity at 1.68, 39.86 and 61.23, respectively. Results suggest significant antiulcerogenic activity attributed to its free radical scavenging property. (11)
Protective Effect on High Glucose-Induced Neurotoxicity in PC-12 Cells / Fruits: Diabetic neuropathy is a consequence of chronic hyperglycemia that leads to neural damage. Study evaluated the protective effects of C. colocynthis against high glucose-induced neurotoxicity in PC-12 cells in vitro model for neuronal functions. Results showed significantly reduced PC-12 cell viability in well containing high glucose. Extract treatment significantly enhanced cell viability under toxic high glucose condition in a dose- and time-dependent manner. Results suggest neuroprotective properties against high glucose condition in vitro. (12)
Anti-Inflammatory / Analgesic / Fruit and Seed: Study evaluated the invivo analgesic and anti-inflammatory activities of immature fruit and seed organic extracts using acetic acid writhing test in mice and carrageenan-induced paw edema assay in rats. All extracts (petroleum ether, chloroform, ethyl acetate, acetone, and methanol) exhibited analgesic and anti-inflammatory activities without inducing side effects. (14)
Human Toxicology: Use of 100 mg of dried fruits three times daily (total dose of 300mg) for two months caused mild diarrhea at the start of the study in only 13% of participants, which dissipated near the end of the study. There were no other alterations in biochemical or clinical parameters to suggest toxicity. In hyperlipidemics, 100mg of seed extract three times daily showed no toxicity. In two other studies, other than minor diarrhea that faded resolved with time, no toxicity was observed when oral dose was kept below 300 mg daily of either seed or fruit daily. Consumption of high levels of Citrullus colocynthis--single dose of 1,500-1,600 mg of dried fruits or tea made from plant have resulted in intestinal problems viz., pseudomembranous colitis, acute colitis, and anal bleeding. (15)
Antibacterial / Antifungal: Study evaluated the inhibitory effects of alcoholic extract of C. colocynthis on bacteria and fungi common in oral bacterial diseases. Microbial tests were conducted on S. mutans, E. coli, S. salivarius, L. acidophilus, C. albicans, and S. aureus and cytotoxicity by MTT assay. MIC and MBC values for  S. mutans, S. salivarius, and L. acidophilus were 1.56 mg/ml and 3.12 mg/ml respectively. (16)
Antibacterial against Staphylococcus aureus: Study evaluated the antibacterial activity of CC water and ethanolic extracts of leaves and fruits against standard ATCC 25923 and hospital isolated strains of S. aureus from novobiocin treated patients by disc diffusion method. Results showed dose dependent inhibitory activity against S. aureus, the ethanol extract more than the water extract. Activity was greater than novobiocin. Phytochemical screen yielded alkaloids, flavonoids, and glucosides, which may be responsible for the powerful antibacterial effect. (17)
Wound Healing / Antioxidant: Study evaluated fractions of various plant parts of CC for antioxidant and wound healing activities in an excision wound model. GC-MS and HPLC analysis yielded 70 chemically diverse metabolites. Concentration of colocynthin, principal active secondary metabolite, ranged from 3.15 to 242.00 mg/g dry weight, lowest in leaves and highest in pulp. Fruit pulp showed DPPH radical scavenging activity of 196.44 µg/mL in fruit pulp to 413.33 µg/mL in leaves. Significant wound contraction and increase in hydroxyproline content of granulation tissue were observed with an ointment formulation of methanolic fruit pulp extract. (18)
Anticandidal / Antibacterial: Study evaluated aqueous and diluted acetone extracts of various plant parts (roots, stems, leaves, and three maturation stages of fruits and seeds) for activity against Gram negative and Gram positive bacteria and various Candida spp. All extracts showed activity against all strains. Highest MICs and MBCs/MFCs were seen with fruit aqueous extracts (MIC 0.10 mg/mg against C. albicans and C. glabrata, 0.20 mg/mg against E. coli and P. aeruginosa), and lowest activity with root extracts. (19)
Antidiabetic / Fruit / Clinical Trial: A 2-month randomized, double-blind, placebo-controlled clinical trial was conducted in 50 type II diabetic patients to determine efficacy and toxicity of C. colocynthis fruit. Results showed significant decrease in HbA1c and fasting glucose levels in Cc treated patients. Results showed significant improvement in glycemic profile without severe adverse effects. (20)
Hypoglycemic / Roots: Study evaluated the effect of aqueous extract of root of Cc on biochemical parameters of normal and alloxan-induced diabetic rats. Results showed significant reduction in blood sugar level (58.70%) with aqueous extract of roots compared to chloroform (34.72%) and ethanol (36.60%) extracts (p<0.001). Aqueous extracts showed improvement in various parameters viz. body weight, creatinine, urea and serum protein as well as lipid profile, and restored levels of bilirubin, SGOT,  SGPT, and ALP. (22)
Hypolipidemic / Roots: Study evaluated the hypolipidemic effect of powdered seeds of Citrullus colocynthis in 100 dyslipidemic patients in measures of serums TG, TC. LDL-C, HDL-C, SGOT and SGPT. Results showed significant differences within treated and placebo groups (p<0.05). A daily intake of 300 mg/day of powdered seeds of Cc can significantly lower triglyceride and cholesterol levels in nondiabetic hyperlipidemic patients. (23)
Effect in Diabetic Peripheral Neuropathy / Fruit Pulp: Study evaluated the effect of topically oil-based or ointment formulation of fruit pulp powder of C. colocynthis on peripheral neuropathy in male Sprague-Dawley rats with STZ-induced diabetes. Results showed improved metabolic outcomes in Cc treated groups as compared to placebo. Tail-flick and hot-plate tests showed lower latency. Measurements of oxidative stress markers (malondialdehyde, SOD, and catalase) showed antioxidant effects. Histological evaluation of sciatic nerve showed decreased number of demyelinated and degenerated nerve fibers. The dose of 100 mg/kg powder per day showed best treatment outcome. Effect was attributed to antioxidant and hypoglycemmic effects. (24)
Acute Rectorrhagia / Colocynth Intoxication / Case Report: Study reports on four cases of patients with colocynth intoxication presenting with acute rectorrhagic preceded by mucosal diarrhea with tenesmus, gradually progressing to bloody diarrhea and overt rectorhhagia within 3 to 4 hours. Colonoscopy only showed mucosal erosions. All four patients ingested considerably larger amounts of C. colocynthis than the permitted dose.  Whole fruits were ingested. The intestinal damage was attributed to membranolytic activity of some C. colocynthis ingredients. Study suggests herbalists should acquaint themselves with side effects,  toxic dosages of different parts of the fruit, encouraging use of seeds (containing no saponin) instead of whole fruit of pulps.  According to TIM (Traditional Iranian Medicine), the acceptable dosage of the fruit ranges from 0.6 to 1.75 g/day and 0.1-0.4 g/day; the seed at 120-300 mg (max: 600 mg) per day, and root powder from 0.2-0.4g/day. Administering the fruit with correctives such as Arabic gum reduced adverse events and allows larger doses. (26)
Toxic Effect on Rat Liver: Study evaluated the effect of alcoholic extract of C. colocynthis on rat liver using single doses of alcoholic extract (50, 100, 200, 400 g/kg) administered intraperitoneally. Results showed morphological change in liver cells including karyrrhexis, chromatolysis, and granulation of cytoplasm. Also, collagen and reticular fibers were evident in liver parenchyma in high doses. Results suggest the C. colocynthis may cause toxic effects on the liver cells in the form of hepatocyte necrosis and liver fibrosis. Effects are dose dependent. (27)
Anthelmintic Effect on Rat Liver: Study evaluated the anthelmintic efficacy of aqueous-methanol and ethyl acetate fruit extracts C. colocynthis against Haemonchus contortus through egg hatch and adult motility assays. Both extracts paralyzed all adult worms at 4 to 8 hours post-exposure at dose of 25 mg/mL. In egg hatch assay, 83.67% and 80.67% of eggs failed to hatch. The anthelmintic effect was attributed to presence of phenolic acids. (28)
Gold Nanoparticles / Seeds: Study reports on the synthesis of gold nanoparticles using seed extract of Citrullus colocynthis as capping and reducing agent. (29)
Anti-Inflammatory / Osteoarthritis / Seeds: Study evaluated the effects of ethanol extract of Colocynth root on pro-inflammatory cytokine COX-2, iNOS, IL-1ß, TNF-α, and NO, PGE2 on inflammatory cells, similar osteoarthritis in chondrocyte cells and manocytes/macrophages. Results showed the plant can reduce the amount of IL-1ß, and affect very high levels of expression of TNF-α, PGE2, NO, iNOS, COX-2 and reduced the expression of inflammatory cytokines and reduce inflammation and joint pain and swelling caused by expression of these cytokines in people with osteoarthritis. (30)
Anticonvulsant / Fruit: Study evaluated the anticonvulsant activity of C. colocynthis fruit extract in albino mice. Mice were pretreated with extract in different doses (10, 25, 50 and 100 mg/kg) prior to injection of pentylenetetrazole. Pretreatment with flumazenil could inhibit the effect of C. colocynthis on latency of seizure to some extent and naloxone significantly inhibited changes in latency and duration of seizure produced by C. colocynthis. Results showed significant anticonvulsant effect in pentylenetetrazole-induced seizures in mice. Effects may be related to its effect on γ-aminobutyric acid-ergic and opioid systems. (31)
Cytotoxicity / Gastric Adenocarcinoma and Breast Cancer Cell Lines / Fruit: Study evaluated the antiproliferative and cytotoxic activity of hydroalcoholic extracts of C. colocynthis on AGS and MCF-7 cell lines. Results showed significant antiproliferative effect pm MCF7 and AGS cell lines. There were significant differences in cell viability after 24, 48, and 72 h. Cytotoxicity was dose-dependent and probably induced by apoptosis. Results suggest a potential chemotherapeutic agent. (32)
Effect on Hepatocytes Glycogen Stores / Pulp and Seed: Study evaluated the effects of pulp and seed extract of Cc on hepatocyte's glycogen stores in diabetic rabbits. Results showed large amounts of glycogen stores in hepatocytes of diabetic animals treated with pulp and seed extracts. In seed-treated diabetic animals, deposited glycogen was significantly more in centrilobular than periportal hepatocytes.
Dose escalation of seed showed no effect on distribution patter of accumulated glycogen. (33)
Genoprotective / Mitigating Effect Against Genotoxicity Induced by Cyclophosphamide / Fruit: Study evaluated the possible genoprotective effect of C. colocynthis fruit extract against cyclophosphamide (CP-)induced DNA damage in mice bone marrow cells. Pretreatment with fruit extract significantly reduced the number of MnPCEs induced by CP in bone marrow cells (p<0.001).  The extract showed antigenotoxic effect against cyclophosphamide-induced oxidative DNA damage in mice. Results suggest potential use as supplement during chemotherapy. (34)
Anti-Colorectal Cancer / Review: Review discusses the anticancer traits of C. colocynthis against colorectal cancer (CRC), active compounds, mechanisms, combination therapies, and clinical trials. The anticancerous effects are via a variety of pathways including apoptotic pathways (increase in caspase-3 and inhibiting STAT3 function), antioxidant and anti-inflammatory (TNF-α, nitric oxide, and pro-inflammatory cytokines such as IL-6, IL-8, and IL-1α) traits, inhibition of Wnt/ß-catenin signaling pathway, and antiangiogenesis and antimetastatic effects.  (35)
Effect on Strep mutans, C. albicans, and Breast Cancer Cells: Study evaluated the inhibitory effects of C. colocynthis aqueous and alcoholic fruit extracts on growth of Streptococcus mutans and Candida albicans and their cytotoxic effect on normal gingival fibroblast cells and breast cancer cells. The growth of S. mutans and C. albicans were effectively inhibited by CC extracts. LC50s on MCF-7 cells were 4589.19 µg/mL and 3933.84 µg/mL by aqueous and ethanolic extracts, respectively. Results showed significantly decreased growth of breast cancer and normal gingival fibroblast cells. Results suggest potential for treatment of oral mucosal disease and prevention of dental caries. (36)
Acute Toxicity Study / Fruit: Study evaluated the toxic effects of extract at single daily oral dose  (131 mg/kg) in albino rats. Acute median lethal dose of extract was found to be 1311.45 mg/kg. Plasma ALT, AST, urea, and creatinine levels were significantly effected, indicating hepato-nephrotoxicity. Hematological parameters were not affected quantitatively but bone marrow functions were disrupted qualitatively. Study showed intake of extract of ripe C. colocynthis fruit presented some adverse effects on the function of the liver, kidney, and bone marrow in rats. (37)
No Effect of Topical Oil on Chemotherapy-Induced Peripheral Neuropathy / Clinical Trial: A randomized, double-blind, placebo-controlled clinical trial evaluated the safety and efficacy of topical C. colocynthis oil in the management of chemotherapy induced peripheral neuropathy (CIPN) in breast cancer patients. Results showed no improvement in the symptoms of CIPN compared to placebo. (38)
Insulinotropic Effect on Rat Pancreatic Islets / Seeds: Study evaluated the direct invitro effects of seed extracts on glucose-stimulated insulin release from pancreatic islets isolated from rats. Six extracts were tested viz., crude aqueous, defatted aqueous, ethyl acetate, H2O-methanol and n-butanol extract and an extract containing a major component (fraction A). The majority of extracts exhibited a positive insulinotropic action. Concentration-response correlation showed participation of distinct chemical compounds, including compounds with inhibitory insulinotropic potential, in the modulation of insulin secretory response to D-glucose. Further studies should seek to identify compounds exhibiting positive insulinotropic actions, which may be suitable for treatment of human diabetic subjects. (39)

Seeds in the cybermarket.

July 2023

                                                 PHOTOS / ILLUSTRATIONS
IMAGE SOURCE: Photo: Citrillus colocynthis / H Zell / CC BY-SA 3.0 Unported / click on image or link to go to source page / Wikimedia Commons
IMAGE SOURCE: Photo: Citrillus colocynthis / Leaves and flower / H Zell / CC BY-SA 3.0 Unported / click on image or link to go to source page / Wikimedia Commons
IMAGE SOURCE: Photo: Citrillus colocynthis fruit / © Flowers in Israel / image modified / Non-commercial use / click on image or link to go to source page / Flowers In Israel
IMAGE SOURCE: Photo: Citrillus colocynthis / Flower / H Zell / CC BY-SA 3.0 / image modified / click on image or link to go to source page / Wikimedia Commons

Additional Sources and Suggested Readings
Citrullus colocynthis / KEW: Plants of the World Online
Citrullus colocynthis (L.) Schrad. / T H Pardo de Tavera / The Project Gutenberg eBook of The Medicinal Plants of the Philippines

Sorting Citrullus names / Maintained by: Michel H. Porcher / MULTILINGUAL MULTISCRIPT PLANT NAME DATABASE / Copyright © 1995 - 2020 / The University of Melbourne. Australia.

Citrullus colocynthis / FichesPlantes
Citrullus colocynthis (L.) Schrad (Bitter Apple Fruit): Promising Traditional Uses, Pharmacological Effects, Aspects, and Potential Applications / Qin-Yuan Li, Mahzaib Munawar, Muhammad Saeed, Ji-Qiang Shen, Muhammad Sajjad Khan, Chang-Xing Li et al /  Front Pharmacol, 2021; 12: 791049 / PMID: 35145403 /
DOI: 10.3389/fphar.2021.791049
Citrullus colocynthis as a medicinal or poisonous plant: A revised fact / Hajar Shafaei, Abolghasem Esmaeili, Jafar Soleimani Rad, Abbas Delazar, Mohaddeseh Behjati / Journal of Medicinal Plants Research, 2012; 6(35): pp 4922-4927 / DOI: 10.5897/JMPR11.264 / ISSN: 1996-0875
Effect of Citrullus colocynthis. on Hair Growth in Albino Rats / R K Roy, M Thakur, V K Dixit / Pharmaceutical Biology / DOI: 10.1080/13880200701585709 / Corpus ID: 84358372
Effect of Citrullus colocynthis Schrad fruits on testosterone-induced alopecia / R Dhanotia, Nagendra Singh Chauhan, V Dixit et al /  Natural Product Research / DOI: 10.1080/14786410802632820 / Corpus ID: 22117508
Effect of Citrullus colocynthis Schard on Testosterone-Induced Benign Prostatic Hyperplasia / R Dhanotiya, Nagendra Sing Chauhan, V Dixit / Journal of Complementary and Integrative Medicine, 2009 /
DOI: 10.2202/1553-3840.1266 / Corpus ID: 72288097
Citrullus colocynthis (L.) Schrad: Chemical characterization, scavenging and cytotoxic activities / Moohammed Bourhia, Mouhcine Messaoudi, Hanane Bakrim, Laila Benbacer et al / Open Chemistry, 2020 / DOI: 10.1015/chem-2020-0124
Screening of Antioxidant and Antiulcer Potential of Citrullus colocynthis Methanolic Seed Extract / N S Gill, Supreet Kaur, R Arora, Dr M Bali / Research Journal of Phytochemistry, 2011; 5(2): pp 98-106
Protective effect of Citrullus colocynthis (L.) Schard. fruit extract on high glucose-induced neurotoxicity in PC-12 cells / Hasan Fallah Huseini, Sina Andalib, Eghbal Jasemi, Mojtaba Ziaee et al / J Med Plants, 2021; 20(80): pp 60-68
Citrullus colocynthis / Wikipedia
Anti-inflammatory and analgesic activities of Tunisian Citrullus colocynthis Schrad. immature fruit and seed organic extracts / B Marzouk, Z Marzouk, N Fenina, A Bouraoui, M Aouni / European Review for Medical and Pharmacological Sciences, 2011; 15: pp 665-672
Bitter cucumber: Human Toxicology / Kamal Patel, MPH, MBA / Examine
The Antifungal and Antibacterial Effect of Citrullus Colocynthis: In Vitro Study / Elahe Tahmasebi, Mohsen Yazdanian, Hamid Tebyaniyan, Mohammad Taghi Vatandoust et al / Open Access Macedonian Journal of Medical Sciences, 2022; 10(A): pp 1585-1591 / DOI: 10.3889/oamjms.2022.10871
Phytochemical screening and antibacterial activity of Citrullus colocynthis (Linn.) Schrad against Staphylococcus aureus / Shahla Najafi, Nima Sanadgol, Batool Sadeghi Nejad, Maryam Ashofteh Beiragi and Ehsan Sanadgol /  Journal of Medicinal Plants Research, 2010; 4(22): pp 2321-2325 / ISSN: 1996-0875
Phytochemical investigation, antioxidant and wound healing activities of Citrullus colocynthis (bitter apple) / Sateesh Chandra Gupta, Tusha Tripathi, Shravan Kumar Paswan, Annie G Agarwal, Chandana V
Rao, Om P Sidhu / Asian Pacific Journal of Tropical Biomedicine, 2018; 8(8): pp 418-424 /
DOI: 10.4103/2221-1691.239430
Anticandidal screening and antibacterial of Citrullus colocynthis in South East of Iran / Rasool khatibi and Jahanbakhsh Teymorri / Journal of Horticulture and Forestry, 2011; 3(13): pp 392-398 / ISSN: 2006-9782 / DOI: 10.5897/JHF11.030
The clinical investigation of citrullus colocynthis (L.) schrad fruit in treatment of Type II diabetic patients: a randomized, double blind, placebo-controlled clinical trial / H Fallah Huseini, F Darvishzadeh, R Heshmat, Z Jafariazar, Mohsin Rza, B Larijani / Phytotherapy Research, 2009; 23(9): pp 1186-1189 /
DOI: 10.1002/ptr.2754
Bitter Apple (Citrullus colocynthis): An Overview of Chemical Composition and Biomedical Potentials / S Gurudeeban, K Satyavani, T Ramanathan / Asian Journal of Plant Sciences, 2010 / ISSN: 1682-3974
The hypolipidemic effect of Citrullus colocynthis on patients with hyperlipidemia. / A R Rahbar, Nabipour / PJBS: Pakistan Journal of Biological Sciences, 2010; 13(24): pp 1202-1207 / PMID: 21313901 /
DOI: 10.3923/pjbs.2010.1202.1207
Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy / Mohadesh Ostovar, Abolfazl Akbari, Mohammad Hossein Anbardar, Mesbah Shams et al /  Journal of Integrative Medicine, 2020; 18(1): pp 59-67 / DOI: 10.1016/j.joim.2019.12.002
Ethnobotanical studies of Citrullus colocynthis (Linn.) Schrad. An important threatened medicinal herb  / Mahesh Chand Meena, Rishi Kesh Meena, Vidya Patni / Journal of Medicinal Plants Studies, 2014; 2(2): pp 15-22 / ISSN: 2320-3862
Citrullus colocynthis as the Cause of Acute Rectorrhagia
/ Hamid Reza Javadzadeh, Amir Davoudi, Farnoush Davoudi, Mehrdad Faraji et al / Case Reports in Emergency Medicine, Volume 2013; Article ID 652192 / DOI: 10.1155/2013/652192
The Toxic Effect of Alcoholic Extract of Citrullus colocynthis on Rat Liver  / FARZANEH DEHGHANI and MOHAMMAD REZA PANJEHSHAHIN / Iranian Journal of Pharmacology & Therapeutics, 2006; 5: pp 117-119
In vitro anthelmintic efficacy of Citrullus colocynthis (L.) Schrad on Haemonchus contortus
/ Tauseef Rehman, Khalid J Iqbal, Azra Anwer, Rao Z Abbas /  Veterinarski arhiv, 2021; 91(3) /
DOI: 10.24099/vet.arhiv.1024
Phytochemicals Mediated Synthesis of AuNPs from Citrullus colocynthis and Their Characterization  / Bismillah Mubeen, Mahvish Ghulam Rasool, Inam Ullah et al / Molecules, 27(4) /
DOI: 10.3390/molecules27041300
The Effect of Citrullus Colocynthis on the Reduction of InflammatoryAgents in Osteoarthritis  / Mohadese Akhzari, Maryam Mirghiasi S, Mahnesa Vassaf, Maryam Sadat Mesbahi Bidgoli, Zahra Shirkhodae Tari / Molecular Biology: Open Access, 2015; 4(4) / DOI: 10.4172/2168-9547.10000147
Anticonvulsant Activity of Hydroalcoholic Extract of Citrullus colocynthisFruit: Involvement of Benzodiazepine and Opioid Receptors / Saeed Mehrzadi PhD, Asie Shojaii PhD, Manijeh Motevalian PhD / Journal of Evidence-Based Integrative Medicine, 2016 / DOI: 10.1177/2156587215615455
Cytotoxic Activity of Citrullus colocynthis (L.) Schrad Fruit Extract on Gastric Adenocarcinoma and Breast Cancer Cell Lines  / Masumeh Rezai, Ali Davoodi, Mohsen Asori, Mohammad Azadbakht /Int J Pharm Sci Rev Res., 2017; 45(1): Article No 34: pp 175-178 / ISSN: 0976-044X
The effect of pulp and seed extract of Citrullus Colocynthis, as an antidiabetic medicinal herb, on hepatocytes glycogen stores in diabetic rabbits / Hajar Shafaei, Jafar Soleimani Rad, Abbas Delazar, Mohaddeseh Behjati / Advanced Biomedical Research, 2014; 3 / DOI: 10.4103/2277-9175.1488230
The Mitigating Effect of Citrullus colocynthis (L.) Fruit Extract against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells /  Mohammad Shokrzadeh, Aroona Chabra, Farshad Naghshvar, Amirhossein Ahmadi /  The Scientific World Journal, Volume 2013; Article ID 980480 /
DOI: 10.1155/2013/980480
The Anticancer Efficiency of Citrullus colocynthis Toward the Colorectal Cancer Therapy
/ Manal Khalid Abdulridha, Ali-H Al-Marzoqi, Abdolmajid Ghasemian / Journal of Gastrointestinal Cancer, 2020; 51: pp 439-444 / DOI: 10.1007/s12029-019-00299-6
The effect of Citrullus colocynthis extracts on Streptococcus mutans, Candida albicans, normal gingival fibroblast and breast cancer cells /  Hossein Seifi Kafshgari, Mohsen Yazdanian, Reza Ranjbar, Elaheh Tahmasebi, Seyed Rahim Ghazi Mirsaeed, Hamid Tebyanian, Mohammad Ali Ebrahimzadeh, Hamid Reza Goli et al /  Journal of Biological Research, 2019; 92(1) / DOI:  10.4081/jbr.2019.8201
Acute Toxicity study on Citrullus colocynthis fruit methanol extract in Albino rats /  Soufane S, A Bedda, N Mahdeb, A Bouzidi / JAPS: Journal of Applied Pharmaceutical Science, 2013; 3(6) /
DOI: 10.7324/JAPS.2013.3614
Efficacy of topical Citrullus colocynthis (bitter apple) extract oil in chemotherapy-induced peripheral neuropathy: A pilot double-blind randomized placebo-controlled clinical trial / Nematollah Rostami, Seyed Hamdollah Mosavat, Ghazaleh Heydarirad, Roya Arbab Tafti, Mojtaba Heydari / Phytotherapy Research, 2019; 33(10): pp 2685-2691   / DOI: 10.1002/ptr.6442
Insulinotropic action of Citrullus colocynthis seed extracts in rat pancreatic islets / Nabila Benariba, Rabeh Djaziri, Emeline Hupkens, Karim Louchami, Willy J Malaisse, Abdullah Sener / Molecular Medicine Reports, 2012 / DOI: 10.3892/mmr.2012.1151

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