Bio-screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt; Department of Medical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria, Egypt.
Bio-screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Int J Pharm. 2024 Dec 25;667(Pt A):124892. doi: 10.1016/j.ijpharm.2024.124892. Epub 2024 Oct 30.
Despite the remarkable biological effects of berberine (BBR), particularly on fertility, its bioavailability is low. This study aims to test the effectiveness of novel nanostructured biloalbuminosomes (BILS) of BBR and its metabolite berberrubine (M1) in treatment of testicular and prostatic lesions. M1 was semi-synthesized from BBR using microwave-assisted reaction. The solvent evaporation method was used to prepare BBR-BILS and M1-BILS by three different concentrations of sodium cholate (SC) or glycocholate (SG), along with the incorporation of bovine serum albumin (BSA). The prepared BILS were fully characterized. Male infertility was induced by cadmium (Cd) at 5 mg/kg and lead (Pb) at 20 mg/kg contaminated water for 90 days, followed by treatment with BBR, M1, and their BILS (BBR-BILS and M1-BILS) for 45 days. Blood male infertility markers, testicular and prostatic oxidative stress status, autophagy, inflammation, along with testicular and prostatic concentrations of Cd and Pb, and histopathology of both tested tissues were determined using standardized protocols. The optimal BBR-BILS and M1-BILS nano-preparations, containing 30 mg SC, were chosen based on the best characterization properties of the preparations. Both nano-preparations improved heavy metals-induced testicular and prostatic deformities, as they reduced Bax and elevated Bcl-2 expressions in both tissues. Moreover, they activated the mTOR/PI3K pathway with a marked reduction in AMPK and activated LC-3II protein levels. Consequently, testicular and prostatic architecture and functions were improved. This study is the first to report the preparation of BBR and M1 BILS nano-preparations and proved their superior efficacy compared to free drugs against testicular and prostatic deformities by attenuating oxidative stress-induced excessive autophagy, offering a new hope to manage male infertility.
尽管小檗碱 (BBR) 具有显著的生物学效应，特别是对生育能力的影响，但它的生物利用度很低。本研究旨在测试新型纳米结构双白蛋白泡囊（BILS）的 BBR 和其代谢产物小檗红碱（M1）在治疗睾丸和前列腺病变中的效果。M1 是通过微波辅助反应从小檗碱半合成得到的。采用溶剂蒸发法，分别用三种不同浓度的胆酸钠（SC）或甘胆酸钠（SG），并加入牛血清白蛋白（BSA），制备 BBR-BILS 和 M1-BILS。对制备的 BILS 进行了全面的表征。雄性不育是通过 5mg/kg 的镉（Cd）和 20mg/kg 的铅（Pb）污染水诱导的，持续 90 天，然后用 BBR、M1 及其 BILS（BBR-BILS 和 M1-BILS）治疗 45 天。采用标准化方案测定血液男性不育标志物、睾丸和前列腺氧化应激状态、自噬、炎症以及睾丸和前列腺中 Cd 和 Pb 的浓度和这两种组织的组织病理学变化。基于制剂的最佳特性，选择了含有 30mg SC 的最佳 BBR-BILS 和 M1-BILS 纳米制剂。两种纳米制剂都改善了重金属诱导的睾丸和前列腺畸形，因为它们降低了两种组织中的 Bax 并升高了 Bcl-2 的表达。此外，它们激活了 mTOR/PI3K 通路，显著降低了 AMPK，并激活了 LC-3II 蛋白水平。因此，改善了睾丸和前列腺的结构和功能。本研究首次报道了 BBR 和 M1 BILS 纳米制剂的制备，并证明与游离药物相比，它们在改善睾丸和前列腺畸形方面具有更好的疗效，通过减轻氧化应激诱导的过度自噬，为治疗男性不育提供了新的希望。
