Liu Yuanyuan, Sun Dalin, Xing Dong, Rui Yiqi, Jin Yihan, Wang Peng, Cai Bin, Li Chuyu, Gao Chao, Cui Yugui, Jin Baofang
School of Medicine, Southeast University, Nanjing, Jiangsu, 210003, People's Republic of China.
Department of Integrative Medicine and Andrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People's Republic of China.
Drug Des Devel Ther. 2025 Apr 3;19:2609-2628. doi: 10.2147/DDDT.S495366. eCollection 2025.
Simiao Biejia (SMBJ) granules, a traditional Chinese herbal remedy, have been used to treat erectile dysfunction caused by diabetes mellitus (DMED). However, the molecular mechanisms underlying SMBJ's therapeutic effects remain unclear. This study aimed to investigate the effects and mechanisms of SMBJ in a rat model of DMED using network pharmacology, proteomics, and molecular docking.
A rat model of DMED was established, and SMBJ granules were administered (0, 7.1, 14.2, and 28.4 mg/kg/d, respectively) for 4 weeks. Erectile function was evaluated by measuring intracavernous pressure and mean arterial pressure. The active compounds in SMBJ were analyzed by gas chromatography and identified using network pharmacology and bioinformatics. Potential targets in the penile tissue was identified via proteomics and validated by Western blotting. Molecular docking was used to assess the binding affinity between bioactive compounds and primary targets.
SMBJ significantly improves erectile function and ameliorates DMED in rats by reducing corpus cavernosum fibrosis, decreasing eNOS and nNOS levels, alleviating oxidative stress in penile tissue, and mitigating damage to smooth muscle cells (SMCs) and vascular endothelial cells (VECs). Network pharmacology and proteomics identified 24 potential SMBJ targets in DMED. The 4 drug molecules identified were involved in the therapeutic effects of SMBJ, among which luteolin was predicted to be the core drug component. Luteolin bound directly with AKT1, a key differentially expressed protein in the penile tissue of DMED rats. Further analysis showed that luteolin in SMBJ activates the PI3K/Akt pathway and regulation of nNOS and NF-kB expression in the penile tissue of DMED rats to improve erectile function.
SMBJ improved oxidative stress damage, vascular endothelial repair, and angiogenesis in the penile tissue of DMED rats. Luteolin is one of the core drug components of SMBJ in DMED treatment that regulates PI3K/AKT-related pathways.
四妙鳖甲（SMBJ）颗粒是一种传统中药方剂，已被用于治疗糖尿病性勃起功能障碍（DMED）。然而，SMBJ治疗作用的分子机制仍不清楚。本研究旨在利用网络药理学、蛋白质组学和分子对接技术，研究SMBJ对DMED大鼠模型的影响及其机制。
建立DMED大鼠模型，并分别给予SMBJ颗粒（0、7.1、14.2和28.4mg/kg/d）4周。通过测量海绵体内压和平均动脉压评估勃起功能。采用气相色谱法分析SMBJ中的活性成分，并利用网络药理学和生物信息学进行鉴定。通过蛋白质组学鉴定阴茎组织中的潜在靶点，并通过蛋白质免疫印迹法进行验证。利用分子对接技术评估生物活性化合物与主要靶点之间的结合亲和力。
SMBJ通过减少海绵体纤维化、降低eNOS和nNOS水平、减轻阴茎组织氧化应激以及减轻平滑肌细胞（SMC）和血管内皮细胞（VEC）损伤，显著改善大鼠勃起功能并改善DMED。网络药理学和蛋白质组学鉴定出DMED中24个潜在的SMBJ靶点。鉴定出的4种药物分子参与了SMBJ的治疗作用，其中木犀草素被预测为核心药物成分。木犀草素与DMED大鼠阴茎组织中关键的差异表达蛋白AKT1直接结合。进一步分析表明，SMBJ中的木犀草素激活PI3K/Akt通路并调节DMED大鼠阴茎组织中nNOS和NF-kB的表达，从而改善勃起功能。
SMBJ改善了DMED大鼠阴茎组织的氧化应激损伤、血管内皮修复和血管生成。木犀草素是SMBJ治疗DMED的核心药物成分之一，可调节PI3K/AKT相关通路。
