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Ethnopharmacological relevance: Citrullus colocynthis (L.) Schrad is a valuable cucurbit plant, widely distributed in the desert areas of the world. Citrullus colocynthis fruits are usually recognized for its wide range of medicinal uses as well as pharmaceutical and nutraceutical potential. This review aims to appraise the published information on the ethnobotanical knowledge, phytochemistry, ethnopharmacology, nutraceutical potential and safety studies of Citrullus colocynthis (bitter apple) fruit, with critical analysis on the gaps and potential for future studies.

Material and methods: A literature survey was performed by searching the scientific databases including PubMed, Scopus, SciFinder, Google Scholar, Web of Science, ACS as well as published books.

Results: The plant has been reported to possess a wide range of traditional medicinal uses including in diabetes, leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer, toothache, wound, mastitis, and in gastrointestinal disorders such as indigestion, constipation, dysentery, gastroenteritis, colic pain and different microbial infections. Several bioactive chemical constituents from fruits were recorded, such as, glycosides, flavonoids, alkaloids, fatty acids and essential oils. The isolation and identification of curcurbitacins A, B, C, D, E, I, J, K, and L and Colocynthosides A, and B were also reported. The fruit of Citrullus colocynthis has been studied extensively for its wide range of biological activities, which include antioxidant cytotoxic, antidiabetic, antilipidemic, insecticide, antimicrobial and anti-inflammatory. The plant was also shown to be rich in nutritional value with high protein contents and important minerals as well as edible quality of seed oil.

Conclusion: It is evident from the literature that Citrullus colocynthis possesses a wide range of medicinal uses and has been well studied for its antidiabetic, anticancer, antioxidant antimicrobial and anti-inflammatory activities, while its therapeutic potential for gut, airways and cardiovascular disorders remains to be explored. Critical analysis revealed that the plant has the huge potential for pharmaceutical and nutraceutical application, with some indications for the presence of synergistic and/or side effects neutralizing combinations of activities. (C) 2014 Elsevier Ireland Ltd. All rights reserved.