title: Citrullus colocynthis (L.) Schrad (bitter apple fruit): a review of its phytochemistry, pharmacology, traditional uses and nutritional potential.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Applied Chemistry & Biochemistry, Government College University, Faisalabad, Pakistan; School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia. Electronic address: abdullahijaz@gcuf.edu.pk.
authors.forename: Abdullah I
authors.initials: AI
authors.lastname: Hussain
authors.affiliation: School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia.
authors.forename: Hassaan A
authors.initials: HA
authors.lastname: Rathore
authors.affiliation: School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia.
authors.forename: Munavvar Z A
authors.initials: MZ
authors.lastname: Sattar
authors.affiliation: Department of Applied Chemistry & Biochemistry, Government College University, Faisalabad, Pakistan.
authors.forename: Shahzad A S
authors.initials: SA
authors.lastname: Chatha
authors.affiliation: Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, England, UK.
authors.forename: Satyajit D
authors.initials: SD
authors.lastname: Sarker
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi 74800, Pakistan; Department of Pharmacy, College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia.. Electronic address: anwar.gilani@aku.edu.
authors.forename: Anwar H
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D065986:Citrullus colocynthis / Q000737:chemistry*; D020834:Ethnopharmacology; D005638:Fruit; D006801:Humans; D008519:Medicine, Traditional / Q000379:methods*; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts
keywords: Anticancer; Antidiabetics; Antioxidants; Bitter apple; Cucurbitacins; Medicinal uses