Changchun University of Chinese Medicine, Changchun 130117, China.
Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China.
Biomed Pharmacother. 2024 Aug;177:116987. doi: 10.1016/j.biopha.2024.116987. Epub 2024 Jun 18.
Erectile dysfunction is a complex and common complication of diabetes mellitus, which lacks an effective treatment. The repairing role of vascular endothelium is the current research hotspot of diabetic mellitus erectile dysfunction (DMED), and the activation of PI3K/AKT/eNOS pathway positively affects the repair of vascular endothelium. The herbal extract isorhamnetin has significant vasoprotective effects and has great potential in treating DMED. This study aimed to clarify whether isorhamnetin has an ameliorative effect on DMED and to investigate the modulation of the PI3K/AKT/eNOS signaling pathway by isorhamnetin to discover its potential mechanism of action. In vivo experiments were performed using a streptozotocin-induced diabetic rat model, and efficacy was assessed after 4 weeks of isorhamnetin gavage administration at 10 mg/kg or 20 mg/kg. Erectile function in rats was assessed by maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), and changes in corpus cavernosum (CC) fibrosis, inflammation levels, oxidative stress levels, and apoptosis were assessed by molecular biology techniques. In vitro experiments using high glucose-induced corpus cavernosum endothelial cells were performed to further validate the anti-apoptotic effect of isorhamnetin and its regulation of the PI3K/AKT/eNOS pathway. The findings demonstrated that isorhamnetin enhanced erectile function, decreased collagen content, and increased smooth muscle content in the CC of diabetic rats. In addition, isorhamnetin decreased the serum levels of pro-inflammatory factors IL-6, TNF-α, and IL-1β, increased the levels of anti-inflammatory factors IL-10 and IL-4, increased the activities of SOD, GPx, and CAT as well as the levels of NO, and decreased the levels of MDA in corpus cavernosum tissues. Isorhamnetin also increased the content of CD31 in CC tissues of diabetic rats, activated the PI3K/AKT/eNOS signaling pathway, and inhibited apoptosis. In conclusion, isorhamnetin exerts a protective effect on erectile function in diabetic rats by reducing the inflammatory response, attenuating the level of oxidative stress and CC fibrosis, improving the endothelial function and inhibiting apoptosis. The mechanism underlying these effects may be linked to the activation of the PI3K/AKT/eNOS pathway.
勃起功能障碍是糖尿病的一种复杂且常见的并发症，目前缺乏有效的治疗方法。血管内皮的修复作用是糖尿病性勃起功能障碍（DMED）的当前研究热点，PI3K/AKT/eNOS 通路的激活对血管内皮的修复有积极影响。草药异鼠李素具有显著的血管保护作用，在治疗 DMED 方面具有巨大潜力。本研究旨在阐明异鼠李素是否对 DMED 具有改善作用，并探讨异鼠李素对 PI3K/AKT/eNOS 信号通路的调节作用，以发现其潜在的作用机制。通过链脲佐菌素诱导的糖尿病大鼠模型进行体内实验，在异鼠李素灌胃给药 10mg/kg 或 20mg/kg 4 周后评估疗效。通过最大海绵体内压/平均动脉压（ICPmax/MAP）评估大鼠的勃起功能，通过分子生物学技术评估海绵体纤维化、炎症水平、氧化应激水平和细胞凋亡的变化。使用高糖诱导的海绵体内皮细胞进行体外实验，进一步验证异鼠李素的抗凋亡作用及其对 PI3K/AKT/eNOS 通路的调节作用。结果表明，异鼠李素增强了糖尿病大鼠的勃起功能，降低了海绵体胶原含量，增加了平滑肌含量。此外，异鼠李素降低了血清中促炎因子 IL-6、TNF-α 和 IL-1β 的水平，增加了抗炎因子 IL-10 和 IL-4 的水平，提高了 SOD、GPx 和 CAT 的活性以及 NO 的水平，并降低了海绵体组织中 MDA 的水平。异鼠李素还增加了糖尿病大鼠海绵体组织中 CD31 的含量，激活了 PI3K/AKT/eNOS 信号通路，抑制了细胞凋亡。综上所述，异鼠李素通过减轻炎症反应、减弱氧化应激和海绵体纤维化程度、改善内皮功能和抑制细胞凋亡，对糖尿病大鼠的勃起功能发挥保护作用。这些作用的机制可能与激活 PI3K/AKT/eNOS 通路有关。
