First Clinical College of Guizhou University of Traditional Chinese Medicine, Guizhou Province, China.
Department of Urology Surgery, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou Province, China.
J Cell Mol Med. 2024 Sep;28(17):e70075. doi: 10.1111/jcmm.70075.
Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.
高尿酸血症（HUA）的特征是血液尿酸水平升高，这会增加勃起功能障碍（ED）的风险。临床研究表明，QYHT 中药方剂改善 ED 的疗效令人满意。此外，该方剂的主要单体成分亚麻酸乙酯和马钱子苷在治疗 ED 方面显示出潜力。本研究建立了 HUA 诱导的 ED 大鼠模型，并给予亚麻酸乙酯和马钱子苷进行治疗。通过 HE 和 TUNEL 检测组织变化，ELISA 检测血清睾酮（T）、MDA、NO、CRP 和 TNF-α水平，qPCR 和 WB 检测全血中 NLRP3、ASC、Caspase-1、JAK2 和 STAT3 的表达水平。结果表明，亚麻酸乙酯和马钱子苷改善了肾脏组织形态，减少了阴茎组织中的细胞凋亡，显著增加了 T 和 NO 水平，同时显著降低了 MDA、CRP 和 TNF-α水平。同时，NLRP3、ASC 和 Caspase-1 的 mRNA 和蛋白表达明显减少，JAK2 和 STAT3 的磷酸化受到抑制。粪便微生物群移植结果进一步验证了这些发现。综上所述，亚麻酸乙酯和马钱子苷可以抑制 NLRP3 炎性小体的激活，减轻炎症和氧化应激反应，抑制 JAK-STAT 信号通路的活性，为 HUA 诱导的 ED 提供了一种潜在的治疗方法。
