{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T10:00:37Z","timestamp":1789293637470,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,6,29]],"date-time":"2015-06-29T00:00:00Z","timestamp":1435536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2016,3]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>The aim of the present study was to examine the safety and efficacy of a topical formulation of C<\/jats:styled-content>itrullus colocynthis<\/jats:italic> in patients with painful diabetic polyneuropathy (PDPN<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>The study was designed as a two\u2010arm double\u2010blind randomized placebo\u2010controlled clinical trial using a parallel design. Sixty patients with PDPN<\/jats:styled-content> were randomly allocated to receive either a topical formulation of C<\/jats:styled-content>. colocynthis<\/jats:italic> or placebo (1:1 allocation ratio) for 3 months. Patients were evaluated before and after the intervention using the neuropathic pain scale, electrodiagnostic findings, World Health Organization Biomedical Research and Education Foundation (BREF<\/jats:styled-content>) quality of life (WHOQOL\u2010BREF<\/jats:styled-content>) scores, and reported adverse events.<\/jats:p><\/jats:sec>Results<\/jats:title>There was a significantly greater decrease in mean pain score after 3 months in the C<\/jats:styled-content>. colocynthis<\/jats:italic> (\u22123.89; 95% confidence interval [CI<\/jats:styled-content>] \u22123.19, \u22124.60) than placebo (\u22122.28; 95% CI<\/jats:styled-content> \u22121.66, \u22122.90) group (P<\/jats:italic>\u2009<\u20090.001). Mean changes in nerve conduction velocity of the tibial nerve, distal latency of the superficial peroneal nerve and sural nerve, and sensory amplitude of the sural nerve were significantly higher in the intervention than placebo group (P<\/jats:italic>\u2009<\u20090.001) in favour of the intervention. In the different domains of WHOQOL\u2010BREF<\/jats:styled-content>, there was a significant improvement only for the mean score in the physical domain.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Application of a topical formulation of C<\/jats:styled-content>. colocynthis<\/jats:italic> fruit extract can decrease pain in patients with PDPN<\/jats:styled-content>. It also may have some uncertain effects on nerve function and the physical domain of quality of life, which require further investigation in studies with larger sample sizes and of longer duration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12287","type":"journal-article","created":{"date-parts":[[2015,3,20]],"date-time":"2015-03-20T21:50:00Z","timestamp":1426888200000},"page":"246-252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Topical C<\/scp>itrullus colocynthis<\/i> (bitter apple) extract oil in painful diabetic neuropathy: A double\u2010blind randomized placebo\u2010controlled clinical trial"],"prefix":"10.1111","volume":"8","author":[{"given":"Mojtaba","family":"Heydari","sequence":"first","affiliation":[{"name":"Research Center for Traditional Medicine and History of Medicine Shiraz University of Medical Sciences Shiraz 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