A Review on Citrullus colocynthis Schrad.: From Traditional Iranian Medicine to Modern Phytotherapy

Introduction

C itrullus colocynthis Schrad. from the family Cucurbitaceae is an ancient medicine believed to be the wild gourd of the Old Testament. Its extremely bitter tastes and its violent purgative properties were well known to the ancient Greek and Roman physicians. ¹ Its popular common names in English are bitter apple, bitter cucumber, colocynth, and bitter gourd. ² It is also a well-known medicinal plant in traditional Iranian medicine (TIM) and is used alone or in compounds for many medicinal purposes. It is distributed mainly in Asia and Africa. It is found in the southwest (Khouzestan, Fars), southeast (Kerman, Bandarabbas, Balouchestan), central (Yazd), and eastern parts (Lout desert) of Iran. ³ The names mentioned in traditional Iranian manuscripts for C. colocynthis are kabast, ^4,5 Sharang (bitter thing), ⁶ Khiar Talkh (bitter cucumber), Kharboze talkhak (bitter melon), ⁵ Kharboze roubah (fox melon), Hanzal, Hindavane Aboujahl (Aboujahl's melon), Algham (bitter thing), and Kousht. ⁷ Many of these names imply the extremely bitterness of this plant.

Botanical Characteristics

C. colocynthis is an annual plant resembling the common watermelon. The stems are herbaceous and beset with rough hairs; the leaves stand alternately on long petioles. They are triangular, manycleft, variously sinuated, obtuse, hairy, a fine green on the upper surface, and rough and pale underneath. Its flowers are yellow, appearing singly at axils of leaves; its fruit is globular, the size of an orange, yellow and smooth, which when ripe contains within it a hard coriaceous rind, and a white spongy pulp enclosing many ovate compressed white or brownish seeds (Fig. 1). ⁸ The fruit is very bitter. In TIM it is believed that if there is only one fruit on the plant, this fruit is very poisonous and it should not be used because it is extremely toxic. ^4,6

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FIG. 1.

Dried fruit of Citrullus colocynthis.

Constituents

The pulp contains a bitter compound called colocynthin, a resin called colocynthein, colocynthetin, pectin, and gum. The seed contains fixed oil and albuminoids. ⁹

Temperament

The principles of TIM are based on quadratic elements. These four elements are air, fire, water, and soil and each one has their specific quality: air is hot and moist, fire is hot and dry, water is cold and moist, and soil is cold and dry. Followers of this doctrine believe that the entire world is made from quadratic elements and the differences and diversities between objects are attributed to different ratios of these four elements used in their structures. Thus, every object in the world has a specific quality based on dominant element(s) in its structure. This specific quality has been known as temperament (Midzaj). ^10,11 Belief about temperament has existed not only in TIM but also in many other traditional medical theories, including Unani (Greek), Arabic, Roman, Indian, European, and Chinese traditional medicines. ¹² Plants also are not an exception to this rule and have their own temperaments. In a recent study, it has been shown that there is a significant relationship between the temperament of plants and their major chemical constituents. ¹³ Based on this theory, C. colocynthis is called to have a hot and dry nature. ^4,14

Medicinal Parts

The main medicinal part of the plant is the fruit pulp, and it is better to remove this pulp from the fruit when it is administered, because after the pulp is taken out of the fruit its potency is decreased over time ⁴ and lost after 2 years. ^7,15 When it remains in the fruit, the pulp keeps its potency for about 4 years. ^4,7,15 Other medicinal parts of plant are the seed, leaf, and root. ¹⁵

Pharmacologic Activities

Dosage

The acceptable dosage of C. colocynthis fruit in TIM is from 0.6 to 1.75 g per day. ¹⁵ In modern phytotherapy, 0.1–0.4 g/day is allowed to be administered. The acceptable dosage for other parts of the plant is 120–300 mg up to 600 mg/day of seed and 0.2 to 0.4 g/day of root powder. ³⁰ The difference between TIM and modern phytotherapy in acceptable dosage may be due to administering fruit with its correctives such as Arabic gum, gum tragacanth, and myrrh gum in TIM. These correctives reduce adverse events of fruit and allow the administration of larger doses. Its substitutes, if it is not available, are equal weight of Ricinus communis L. seed and a third of its weight in Peganum harmala L. seed. ⁷

Adverse Events, Precautions, and Contraindications

C. colocynthis is harmful for patients with a hot nature. The most important characteristics of people with a hot nature are feeling hot more than normal in a hot condition, getting warm easily in a cold condition, warm fingertips in a normal condition, preferring cold drinks, not easily standing hunger, having enough energy, suffering from eye aches and headaches, having a sudden hot feeling in a normal condition, and having blood hypertension. ¹² C. colocynthis causes headache, abdominal cramps, and nausea in very cold weather and dysentery and inflammation in very hot weather. ¹⁵ Therefore, it should not be administered during summer and winter. ⁷ Toxic dosage of C. colocynthis reported in modern phytotherapy is 600–1000 mg and may cause colic, diarrhea, hematochezia, nephrosis, and vomiting. Lethal doses (≥2 g) may cause convulsions, paralysis, and possibly death caused by circulatory collapse. ³⁰ In 1989, three examples of toxic acute colitis were reported, which occurred after ingestion of C. colocynthis. The prominent clinical features were dysenteric diarrhea, colonoscopic changes including congestion and hyperemia of the mucosa with abundant exudates, but no ulceration or pseudopolyp formation. These pathologic features disappeared within 14 days in all three cases. ³¹ Herbal medicine sellers also are aware of adverse events of C. colocynthis and do not prescribe this medication for more than 2 months. The most reported adverse events by these sellers are diarrhea, inaction of intestine, and liver impairment. In a recent study, C. colocynthis extract was found to be free of hepatotoxic effects in concentrations up to 100 μg/mL incubation mixture from liver slices. ²⁷ However, another study on rat liver showed that alcoholic extract of C. colocynthis in concentration above 100 mg/kg can have toxic effects on liver cells, which may induce hepatocyte necrosis and liver fibrosis. ³² The daily use of 0.25 g of C. colocynthis fruit/kg for 42 days was not fatal to sheep and caused slight diarrhea, catarrhal enteritis, centrilobular hepatocellular fatty change, and degeneration of the renal tubular cells. ³³ In case of poisoning, stomach evacuation is recommended followed by administration of tincture of opium, followed by stimulating and mucilaginous beverages. ³⁰

For preventing adverse events, it is recommended in TIM to administer equal weights of starch, Arabic gum, myrrh gum, or gum tragacanth. ^4,7 In addition, it should be ground carefully until it is completely powdered, because if there is any unground particle present, it can cause inflammation of the gastrointestinal tract. ⁶ It is also harmful for slender people, and it should be administered with fruit juice for these people. ¹⁵

C. colocynthis is abortifacient; thus, it is contraindicated during pregnancy. ¹⁵ A recent study has indicated that 12 weeks exposure of female rats to C. colocynthis causes adverse effects on the reproductive system and fertility. ³⁴ Reversible antifertility effects of ethanolic extract of C. Colocynthis fruit was demonstrated in male albino rats. ³⁵

Conclusions

C. colocynthis has different pharmacologic activities. Some of pharmacologic properties declared for this plant in TIM are confirmed by different studies done in modern phytotherapy. Among these properties, antidiabetic activity of the fruit and seed of this plant is very popular in TIM, and although some in vivo and clinical trials in modern phytotherapy confirm this activity, there are not any approved products from this herb in Iran. Moreover, some herbal sellers administer it illegally especially for diabetes. Considering the points recommended in TIM such as using C. colocynthis with correctives and grinding well, it may be possible to produce a more safe and tolerable product from this plant. The other pharmacologic properties of C. colocynthis mentioned in TIM and confirmed by modern research include analgesic, anti-inflammatory, abortifacient, purgative, and hair growth–promoting activities. Two (2) clinical trials were found for this plant; one confirmed antidiabetic properties of 100 mg fruit 3 times a day for 2 months in patients with type 2 diabetes, ²¹ and another confirmed hypolipidemic activity of 300 mg per day of seed for 6 weeks in patients with hyperlipidemia. ²³ No serious adverse events were reported from these two studies.

The toxic range in modern phytotherapy (600–1000 mg) has overlap with therapeutic dosage in TIM (600–1750 mg). This overlap as discussed above may be due to using the fruit of C. colocynthis with its correctives in TIM. Moreover, TIM is a holistic therapeutic system, and the nature of the patient is considered before treatment. With regard to TIM, the most adverse events of this plant are seen in people with a hot nature, and it is preferred not to administer this plant in them, whereas in modern medicine the nature of patients is not considered for treatment. It is emphasized again that it is contraindicated during pregnancy because it is abortifacient.

Diseases that have been mentioned for treatment with C. colocynthis in TIM but that have not evaluated in modern phytotherapy until now include sciatica, paralysis, asthma, chronic cough, tinnitus, epilepsy, elephantiasis, and scorpion and snail bites. Since serious adverse events have been reported from this plant, it is not recommended that it be used before doing further studies on its possible adverse events, in order to assess more precisely the risk–benefit ratio of this plant and to judge conclusively about its clinical use. Considering points in TIM such as use with correctives and taking into account the nature of patients may be useful in reducing adverse events of C. colocynthis.