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Citrullus colocynthis

Citrullus colocynthis, also known as bitter cucumber, is a fruit-bearing plant. Low doses of its seeds and fruit can reduce blood glucose levels. Higher doses are associated with side-effects like colonic inflammation and rectal bleeding.

Our evidence-based analysis on citrullus colocynthis features 27 unique references to scientific papers.

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Research Breakdown on Citrullus colocynthis


1Sources and Composition

1.1Sources

Citrullus colocynthus (of the family Cucurbitaceae) is a fruit bearing plant known traditionally mainly due to its potency as a hydragogue (causes water accumulation in the colon) and catharsis (induces defecation) producer in humans when consumed at more than two grams dry fruit weight[1] and other traditional usages being for the treatment of rheumatism, stimulating the immune system, tuberculosis, diabetes, and analgesic.[2] Oral ingestion of the fruit at doses lower than this (300-800mg daily) tends to be prescribed in some middle eastern locations for the treatment of diabetes to avoid the intestinal side-effects.[1]

Traditionally, most names for this plant have pertained to its bitterness. It has the names of 'bitter thing' (Algham and Sharang), 'bitter cucumber' (khiar talkh), and 'bitter melon' (kharboze talkhak),[3] but should not be confused with the plant momordica charantia which has the name of bitter melon or bitter gourd. Furthermore, a dry resin of this plant has traditionally been referred to as citrulline,[4] which should not be confused with the amino acid L-Citrulline and may have given rise to a mistaken idea that the amino acid was a laxative (compounded with the potential laxative properties of the related amino acid, L-Arginine, when consumed in high doses).

Citrullus colocynthis is a medicinal herb used mostly for the treatment of diabetes and inflammatory diseases, while it is most well known for its bitter taste and the diarrhea it can cause when consumed as a food product; it is unrelated to the amino acid L-citrulline

1.2Composition

The seeds of citrullus colocynthis are known to possess:

  • 567.32kcal per 100g dry weight[5] or lower, since this study found the highest known lipid content in the seeds and others suggest that it is a lower concentration (which would reduce calories)

  • 17-23% fatty acids by dry weight[6][7] (one study noted 50% lipids[5]) of which a low amount of free fatty acids (1.57% total seed weight and 7% total oil[6]) and both triglycerides and free fatty acids comprise mostly linoleic acid (66-76.4%), palmitic acid (6.3-8.1%), oleic acid (7.8-14.2%), and stearic acid (6.1-7.3%);[7][6] it appears to have high heat tolerance assessed by low lipid peroxidation values[6][5]

  • Proteins at 11.67% of total weight[5]

  • Non-fibrous carbohydrates at 29.47% total weight[5]

  • Dietary fiber at 5.51% total weight[5]

  • 7.51+/-0.53% moisture content[6][5]

  • 2.94-3.22% ash content (dry weight)[6][5]

  • Vitamin E at 121.85mg/100g[6] with a high γ-tocopherol content (116.36+/-0.15mg/100g; 95% total vitamin E) and lower α (0.72+/-0.06mg/100g), β (0.57+/-0.03mg/100g), and δ (4.19+/-0.12mg/100g) content[6]

The seeds of this plant are fairly balanced in the macronutrient profile (like most seeds in the cucurbitaceae family) and the oil derived from these seeds is very high in both omega-6 fatty acids and in the form of vitamin E that is seen as more desirable for supplementation (γ-tocopherol, although there does not appear to be a significant γ-tocotrienol content)

While the fruit pulp contains:

  • Colocynthin (bitter component)[3]

  • Colocynthein and colocynthetin (resin)[3]

  • Cucurbitacin E glucose (0.05% dry weight[8]) and I glucoside (0.01% dry weight[8])

The fruits appear to, on the equivalent of dry mass, contain a 0.74% phenolic content (gallic acid equivalents or GAEs) and a 0.13% flavonoid content (catechin equivalents).[9] The seeds also contain flavonoids and polyphenolics.[10]

It is said that the potency of this plant starts to decay when the fruit is opened, and is lost within two years;[3] suggesting the main bioactive is unstable.

The unique bioactive molecules in the fruit pulp, the main medicinal component of this plant, are not well known

2Cardiovascular Health

2.1Cholesterol

100mg of citrullus colocynthus thrice daily for two months in type II diabetes has failed to significantly modify any measured parameter of cholesterol metabolism (LDL-C, HDL-C, or total cholesterol)[1] although total cholesterol can be reduced if the same dose of the seed extract is given to hyperlipidemics (17.57+/-39.55mg/dL; average 8.6% reduction);[11] the alterations in HDL-C (2.41+/-5.63mg/dL; average 5.4% increase) and LDL-C (7.33+/-30.34mg/dL; average 6.3% reduction) also showed promise, but were statistically insignificant.[11]

May reduce cholesterol in those with high cholesterol, but the one study to find this occurring in humans noted a remarkable degree of variance. More studies would be needed to confirm if this variance is true or not, since the two studies conducted at this moment in time are less than ideal (methodologically speaking)

2.2Triglycerides

100mg of citrullus colocynthus thrice daily for two months in type II diabetes has failed to significantly reduce triglycerides.[1] The seed powder at the same dose (100mg) of the mature seed extract has managed to reduce triglycerides in hyperlipidemic persons after six weeks, but the reductions (31.52+/-73.98mg/dL; average of 16% reduction) was very unreliable in magnitude.[11]

The reduction in triglycerides managed to reach statistical significance, but this was also associated with huge variance in how much triglycerides were reduced

3Interations with Glucose Metabolism

3.1Insulin

Citrullus colocynthis has been traditionally used as a medicinal plant for diabetes[12] thought to be related to being an insulin releasing agent of sorts;[13] this has been noted in vitro[14] and in vivo as acute oral ingestion of 300mg/kg of the pulp (ethanolic extraction) to rats has been noted to increase serum insulin AUC by 59.5% alongside a reduction in glucose (33%)[15] and has elsewhere this extraction has been noted to increase insulin content of pancreatic β-cells.[16]

Higher than normal doses (potentially within the toxic range) appear to have an ability to stimulate insulin secretion from the pancreas. The bioactive that does this is currently not known

When looking at rodent studies, citrullus colocynthis (8% of the seed oil) has been found to preserve β-cell structure in streptozotocin induced diabetic rats relative to control, and outperformed oils from sunflower and olive at preserving insulin sensitivity.[7]

When the oil is isolated, it appears to be more protective of pancreatic β-cells (that secrete insulin) than other dietary oils during diabetes

3.2Type II Diabetes

In type II diabetics given 100mg of the dried fruit extract thrice daily (totalling 300mg) for a period of two months noted significant reductions in blood glucose (8.2%) and HbA1c (13.5%) while insulin was not measured; these two parameters, however, were significantly higher at baseline in the experimental group relative to placebo.[1]

One human study has noted improvements in fasting blood glucose and HbA1c associated with supplementation of the fruit pulp (insulin not measured), but there were differences at baseline which may have influenced the results observed

4Peripheral Organ Damage

4.1Kidney

Oral ingestion of 25mg/kg citrullus colocynthis daily to rats also given the nephrotoxin gentamicin has noted that supplementation failed to protect the rats from nephrotoxicity (assessed by necrosis of tulubes) despite causing an apparently beneficial change in serum biomarkers of creatinine and BUN.[17]

Has once failed to exert kidney protective effects despite having an antioxidant property to it

5Interactions with Cancer

5.1Liver Cancer

In isolated HepG2 carcinoma cells, cucurbitacin glucosides (I and E) have cytotoxic activity with IC50 values of 3.5μM and 2.8μM respectively.[8]

6Interactions with Aesthetics

6.1Hair

A petroleum ether extract (3.23% yield) of the fruits of citrullus colocynthis at 2-5% given to mice alongside testosterone injections (to induce male-pattern baldness) for three weeks appears to induce hair follicle density with a potency nonsignificantly greater than a 2% finasteride solution.[18] this may be related to a 5α-reductase inhibitory effect of this plant.[19]

Possible hair growth stimulating properties, which may be of larger magnitude in men with male pattern baldness due to also possessing a 5α-reductase inhibitory potential

7Safety and Toxicology

7.1General

Citrullus colocynthis is traditionally known as both a medicinal plant and a toxic plant,[20] and in animals high doses of the fruits or leaves of citrullus colocynthis have been noted to possess toxicity towards various animals such as sheep[21] and chicks;[22] these changes are associated mostly with intestinal damage and lesions associated with bleeding,[23] but may be reversible with removal of the food product from the diet.[22]

There are various case studies where consumption of high levels of citrullus colocynthis have resulted in intestinal damage such as pseudomembranous colitis (mistaking a citrullus colocynthis fruit as a zucchini),[24] acute colitis,[25] and anal bleeding (single dose of 1,500-1,600mg of the dried fruits or consumption of a tea made from the plant).[26][27] These symptoms may be reversible in as little as two weeks of cessation.[25][26]

Although it is reversible, there appears to be intestinal and liver toxicity associated with inflammation and rectal bleeding with 'high' doses of the supplement. In regards to 'high', that is relative to the recommended dose (300-800mg) since these negative effects have occurred with less than two grams of the dried fruit weight

7.2Human Toxicology

When using 100mg of the dried fruits thrice daily (total dose of 300mg) for a period of two months, it was noted that only 13% of participants reported mild diarrhea at the start of the study which dissipated near the end of the study; there were no other alterations in biochemical or clinical parameters indicating toxicity;[1] this lack of alterations in toxicity (assessed by liver enzymes SGOT and SGPT) has been replicated with 100mg of the seed extract thrice daily for six weeks in hyperlipidemics.[11]

Two studies have failed to note toxicity with citrullus colocynthis when the oral dose is kept below 300mg of either the seed or fruit dry weight daily, with only minor diarrhea that fades with time

References

  1. ^ a b c d e f Huseini HF, et al. The clinical investigation of Citrullus colocynthis (L.) schrad fruit in treatment of Type II diabetic patients: a randomized, double blind, placebo-controlled clinical trial. Phytother Res. (2009)
  2. ^ Daoudi A, Aarab L, Abdel-Sattar E. Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants. Toxicol Ind Health. (2013)
  3. ^ a b c d Rahimi R, Amin G, Ardekani MR. A review on Citrullus colocynthis Schrad.: from traditional Iranian medicine to modern phytotherapy. J Altern Complement Med. (2012)
  4. ^ Fragkos KC, Forbes A. Was citrulline first a laxative substance? The truth about modern citrulline and its isolation. Nihon Ishigaku Zasshi. (2011)
  5. ^ a b c d e f g h Obasi NA, et al. Proximate composition, extraction, characterization and comparative assessment of coconut (Cocos nucifera) and melon (Colocynthis citrullus) seeds and seed oils. Pak J Biol Sci. (2012)
  6. ^ a b c d e f g h Nehdi IA, et al. Evaluation and characterisation of Citrullus colocynthis (L.) Schrad seed oil: Comparison with Helianthus annuus (sunflower) seed oil. Food Chem. (2013)
  7. ^ a b c Sebbagh N, et al. Comparative effects of Citrullus colocynthis, sunflower and olive oil-enriched diet in streptozotocin-induced diabetes in rats. Diabetes Metab. (2009)
  8. ^ a b c Ayyad SE, et al. In vitro and in vivo study of cucurbitacins-type triterpene glucoside from Citrullus colocynthis growing in Saudi Arabia against hepatocellular carcinoma. Environ Toxicol Pharmacol. (2012)
  9. ^ Kumar S, et al. Antioxidant and free radical scavenging potential of Citrullus colocynthis (L.) Schrad. methanolic fruit extract. Acta Pharm. (2008)
  10. ^ Benariba N, et al. Phytochemical screening and free radical scavenging activity of Citrullus colocynthis seeds extracts. Asian Pac J Trop Biomed. (2013)
  11. ^ a b c d Rahbar AR, Nabipour I. The hypolipidemic effect of Citrullus colocynthis on patients with hyperlipidemia. Pak J Biol Sci. (2010)
  12. ^ Traditional medicinal plants of Manipur as anti-diabetics.
  13. ^ Patel D, et al. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. (2012)
  14. ^ Benariba N, et al. Insulinotropic action of Citrullus colocynthis seed extracts in rat pancreatic islets. Mol Med Rep. (2013)
  15. ^ In vivo, Acute, Normo-hypoglycemic, Antihyperglycemic, Insulinotropic Actions of Orally Administered Ethanol Extract of Citrullus colocynthis (L.) Schrab Pulp.
  16. ^ Concomitant Down Regulation of Glycolytic Enzymes, Upregulation of Gluconeogenic Enzymes and Potential Hepato-Nephro-Protective Effects Following the Chronic Administration of the Hypoglycemic, Insulinotropic Citrullus colocynthis Pulp Extract.
  17. ^ Ullah N, et al. Citrullus colocynthis failed to combat against renal derangements, in spite of its strong antioxidant properties. Acta Pol Pharm. (2013)
  18. ^ Dhanotia R, et al. Effect of Citrullus colocynthis Schrad fruits on testosterone-induced alopecia. Nat Prod Res. (2011)
  19. ^ Nahata A, Dixit VK. Evaluation of 5α-reductase inhibitory activity of certain herbs useful as antiandrogens. Andrologia. (2013)
  20. ^ Jouad H, et al. Ethnobotanical survey of medicinal plants used for the treatment of diabetes, cardiac and renal diseases in the North centre region of Morocco (Fez-Boulemane). J Ethnopharmacol. (2001)
  21. ^ Elawad AA, et al. The effect of Citrullus colocynthis on sheep. Vet Hum Toxicol. (1984)
  22. ^ a b Bakhiet AO, Adam SE. An estimation of Citrullus colocynthis toxicity for chicks. Vet Hum Toxicol. (1995)
  23. ^ Al Faraj S. Haemorrhagic colitis induced by Citrullus colocynthis. Ann Trop Med Parasitol. (1995)
  24. ^ Berrut C, et al. Pseudomembranous colitis caused by the ingestion of colocynth. Schweiz Med Wochenschr. (1987)
  25. ^ a b Goldfain D, et al. Peculiar acute toxic colitis after ingestion of colocynth: a clinicopathological study of three cases. Gut. (1989)
  26. ^ a b Javadzadeh HR, et al. Citrullus colocynthis as the Cause of Acute Rectorrhagia. Case Rep Emerg Med. (2013)
  27. ^ Khan SA, et al. Colocynth toxicity. A possible cause of bloody diarrhea. Saudi Med J. (2003)