Qinghai University, Xining 810000, China.
Qinghai Provincial Key Laboratory of Traditional Chinese Medicine Research for Glucolipid Metabolic Diseases, Xining 810000, China.
Int J Mol Sci. 2024 Oct 13;25(20):11004. doi: 10.3390/ijms252011004.
The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.
由于糖尿病相关勃起功能障碍(DMED)的发生率不断上升,新的药物不断被研发出来。原花青素(PROs)是 DMED 的潜在治疗药物。在这项研究中,使用链脲佐菌素(STZ)建立 DMED 大鼠模型,并使用阿扑吗啡(APO)评估大鼠的勃起功能。之后,大鼠接受 PRO 口服治疗。然后,我们评估了 PROs 对 DMED 大鼠的影响。结果表明,PROs 可显著增强 DMED 大鼠的勃起功能。PROs 通过降低血糖和血脂水平,同时增加肝糖原和血清胰岛素水平,调节 DMED 大鼠的糖脂代谢。此外,PROs 通过增加一氧化氮(NO)水平和降低内皮素-1(ET-1)和凝集素样氧化型低密度脂蛋白受体-1(LOX-1)水平来增强 DMED 大鼠的血管内皮功能。此外,PROs 还可以提高睾酮(T)水平,减轻病理性睾丸损伤,提高精子浓度和存活率。最后,使用网络药理学筛选核心靶点,然后通过分子对接、酶联免疫吸附测定(ELISA)和实时 PCR 方法进行验证。我们的研究结果表明,PROs 通过升高 AKT1 水平同时降低 CASP3 水平,可能通过有效调节 PI3K-Akt 信号通路来治疗 DMED。总的来说,这些结果支持使用 PROs 作为治疗 DMED 的潜在候选药物。