Thymelaea hirsuta extract attenuates testosterone-induced benign prostatic hyperplasia in rats: Effect on oxidative stress, inflammation and apoptosis

Abstract

Ethnopharmacological relevanceBenign prostatic hyperplasia (BPH) is one of the most prominent diseases of the aged men urinary system. It is associated with cellular proliferation, hormonal imbalance, oxidative stress, inflammation and apoptosis. Traditionally, Thymelaea hirsuta (L.) (TH) leaves and flowers were used as a decoction or infusion in traditional medicine to treat skin disorders, urinary tract infection and infertility. To date, its potential protective effects for benign prostatic hyperplasia (BPH) have not been investigated. Aim of the studyThis study explored the effects of Thymelaea hirsuta extract (THE) on the development of BPH using a rat model of testosterone induced BPH. Materials and methodsThe THE phenolic composition was identified by liquid chromatography with a diode array detector (LC-DAD). Then, 21 male Wistar rats (Ten-week old) weighting 200–250 g were separated into three groups: the group 1 was considered as a control while the group 2 and 3 received intramuscular injection of testosterone at dose of 3 mg/kg (BPH). Only the group 3 received orally THE at dose of 36 mg/kg. After four-week experimental time, the animals were sacrificed, and reproductive tissue was taken for histological and immunohistochemical analyses. Biochemical tests were also carried out. Additionally, the protein expression levels including in the inflammation pathway were analyzed by western blot. ResultsOur results revealed that THE treatment reduced the prostate weight and index. Orally THE administration improved the prostate biochemical and morphological characteristic in BPH rats and then lead to a normal prostate morphology restoration. As expected, THE supplementation significantly inhibited rat prostate enlargement, improved the pathological feature and reduced the epithelial thickness. Additionally, the anti-hyperplasic effect of THE is related to its possible ability to regulate the apoptotic and inflammatory pathways. Indeed, immunohistochemical and western blot analyses displayed a significant regulation of the apoptotic markers (Bax and Bcl-2) and a decrease in the inflammatory protein expression (NF-κB and TNF-α). Similarly, THE treatment increased the prostate cells' endogenous antioxidant capacity through the improvement of GSH level and the SOD activity. Conversely, it decreased the prostatic lipid peroxidation content. The HPLC-ESI-MSn analysis showed that chlorogenic acid and vicenin-2 were putatively identified as the major compounds of THE. ConclusionThe advanced results revealed the THE efficiency in the prevention of the testosterone-induced BPH in rats indicating that THE can be used as an alternative therapy for BPH management.