Antidiabetic and antioxidant effects of topically applied Citrullus colocynthis extract in type 2 diabetes: A clinical and phytochemical study

Abstract

The present study investigates the phytochemical composition, antioxidant potential, and hypoglycemic efficacy of topical Citrullus colocynthis (bitter apple) fruit extract in individuals with type 2 diabetes mellitus (T2DM). The fruit extract, obtained through solvent extraction and analyzed via Gas-Liquid Chromatography (GLC), revealed a high concentration of bioactive compounds, notably terpinene (16.58 %), camphor (12.25 %), p-cymene (8.46 %), limonene (7.12 %), and saponins (9.58 %), contributing to a total identified component concentration of 71.41 %. The extract demonstrated strong antioxidant activity, with DPPH and ABTS radical scavenging assays showing up to 77.04 % and 76.97 % inhibition, respectively, and an Oxygen Radical Absorbance Capacity (ORAC) peaking at 574.82 μmol TE/g extract. Interestingly, metal chelating activity followed an inverse trend, with the highest activity observed at the lowest concentration (25 μL), likely driven by low-molecular-weight phenolics and flavonoids with high bioavailability. A clinical trial involving 36 T2DM patients revealed a significant reduction in blood glucose levels following topical application of the extract to the feet. Blood glucose decreased by 46–65 mg/dL per application, with average values dropping from 157 mg/dL to 99.67 mg/dL (minimum) and from 374.67 mg/dL to 321.33 mg/dL (maximum), irrespective of gender. These findings demonstrate that C. colocynthis extract, rich in terpenes, saponins, phenolics, and flavonoids, exhibits potent antioxidant and hypoglycemic properties, supporting its potential as a safe, effective, and complementary therapeutic approach for managing type 2 diabetes. However, due to the open-label, single-arm design of this pilot study, placebo effects cannot be excluded, and the results require confirmation in randomized, double-blind, placebo-controlled trials.