Introduction. In traditional medicine, Citrullus colocynthis is used to treat diabetes, hyperlipidemia, cardiovascular diseases, inflammation, and oxidative stress, all of which can appear when a diet rich in vegetable fats, such as palm oil, is continuously consumed. Such high-fat diets are chronic stressors of the hypothalamic–pituitary–adrenal axis. The objective of our study was to analyze and evaluate the effects of colocynth total alkaloids and glycosides on metabolic, hormonal, and structural disorders of the adrenal medulla in Wistar rats fed a high-fat diet.

Material and methods. Twenty six Wistar rats were distributed as follows: six control animals received a standard laboratory diet; twenty experimental rats received the standard laboratory diet supplemented with palm oil — the high-fat diet (HFD). After seven months of this diet, the HFD group was subdivided into rats treated for the next 2 months with either alkaloid extract (HFD-ALk group) or ethanol extract of glycosides (HFD-GLc) or animals on HFD only. Plasma metabolites and ACTH concentrations were measured by standard methods. Sections of adrenal medulla were stained by Heidenhain-Azan method and Sudan Black.

Results. The adrenal medulla of the HFD rats showed prominent structural changes, such as hypertrophy of chromaffin and ganglion cells, vacuolation, inflammatory foci, and fibrosis. The biochemical and hormonal parameters were significantly improved in the HFD rats treated with alkaloid and glycoside extracts of Citrullus colocynthis. Moreover, the morphological changes of the adrenal medulla were attenuated in HFD-ALk and HFD-Glc rats.

Conclusions. The results of the study indicate that phytotherapy using Citrullus colocynthis alkaloids may correct metabolic and hormonal perturbations as well as adrenal medulla structure of rats maintained on HFD.