Phytosterol-enriched extract from Urtica dioica roots as potential therapeutic agent for neuroinflammation-based diseases

Phytosterols are natural compounds produced by plants and marine organisms, not found in humans. Structurally similar to cholesterol, phytosterols are of great importance in human diet for their cholesterol-lowering activity, together with antioxidant and anti-inflammatory properties [ 1 ]. In order to investigate possible interventions on neurodegenerative disorders, the ability of phytosterols to stimulate de novo neurosteroidogenesis in microglia was selected as a new approach for verifying a possible impact on cholesterol homeostasis. Urtica dioica L. (Urticaceae), commonly known as stinging nettle, was selected as a promising source of phytosterols. Urtica dioica roots has a long history for its use in traditional medicine and several studies suggested its potential in the treatment of several conditions, including prostate cancer and urological diseases [ 2 ], but its potential for the treatment of neurodegenerative disorders remained unexplored. To obtain a phytosterol-enriched phytocomplex, a n -hexane extract was prepared by dynamic maceration of 50 g of dried roots in 500 mL at 25°C renewing the solvent every 24 h for three times. The obtained extract (50.6 mg) was analyzed by UHPLC-HR-Orbitrap/ESI-MS 2 and the content of phytosterols was estimated to be 171.2±7.4 μg/mg of dried extract by using stigmasterol calibration curve. The neurosteroidogenesis stimulation in activated human microglia mediated by phytosterols and cholesterol mechanistic pathways were investigated. The results showed that U. dioica root phytosterol-enriched extract efficiently stimulate the de novo neurosteroidogenesis influencing cholesterol clearance. These findings encourage further investigations for supporting this approach to relieve neuroinflammation in patients suffering from neurodegenerative disorders. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany