Feki Ines, Hadrich Fatma, Mahmoudi Asma, Llorent-Martínez Eulogio J, Bouallagui Zouhaier, Souilem Safa, Louati Mariem, Chamkha Mohamed, Sayadi Sami
Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, P.O. Box 1177, 3018, Sfax, Tunisia.
Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, P.O. Box 1177, 3018, Sfax, Tunisia.
J Ethnopharmacol. 2025 Feb 27;342:119373. doi: 10.1016/j.jep.2025.119373. Epub 2025 Jan 17.
Benign 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.
This study explored the effects of Thymelaea hirsuta extract (THE) on the development of BPH using a rat model of testosterone induced BPH.
The 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.
Our 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-MS analysis showed that chlorogenic acid and vicenin-2 were putatively identified as the major compounds of THE.
The 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.
良性前列腺增生（BPH）是老年男性泌尿系统最常见的疾病之一。它与细胞增殖、激素失衡、氧化应激、炎症和细胞凋亡有关。传统上，多毛瑞香（Thymelaea hirsuta (L.)，TH）的叶和花在传统医学中被用作煎剂或浸剂，用于治疗皮肤疾病、尿路感染和不孕症。迄今为止，其对良性前列腺增生（BPH）的潜在保护作用尚未得到研究。
本研究使用睾酮诱导的BPH大鼠模型，探讨了多毛瑞香叶提取物（THE）对BPH发展的影响。
采用二极管阵列检测器液相色谱法（LC-DAD）鉴定THE的酚类成分。然后，将21只体重200 - 250克的10周龄雄性Wistar大鼠分为三组：第1组为对照组，第2组和第3组肌肉注射剂量为3毫克/千克的睾酮（BPH）。只有第3组口服剂量为36毫克/千克的THE。经过四周的实验时间后，处死动物，取生殖组织进行组织学和免疫组织化学分析。还进行了生化测试。此外，通过蛋白质免疫印迹法分析炎症途径中的蛋白质表达水平。
我们的结果显示，THE治疗降低了前列腺重量和指数。口服THE改善了BPH大鼠的前列腺生化和形态特征，进而使前列腺形态恢复正常。正如预期的那样，补充THE显著抑制了大鼠前列腺增生，改善了病理特征并降低了上皮厚度。此外，THE的抗增生作用与其调节凋亡和炎症途径的可能能力有关。实际上，免疫组织化学和蛋白质免疫印迹分析显示凋亡标志物（Bax和Bcl-2）有显著调节，炎症蛋白表达（NF-κB和TNF-α）降低。同样，THE治疗通过提高GSH水平和SOD活性，增加了前列腺细胞的内源性抗氧化能力。相反，它降低了前列腺脂质过氧化含量。HPLC-ESI-MS分析表明，绿原酸和异荭草苷-2被推测为THE的主要成分。
先进的结果揭示了THE在预防睾酮诱导的大鼠BPH方面的有效性，表明THE可作为BPH治疗的替代疗法。
