Mechanism of the Traditional Chinese Medicine Simiao Biejia Decoction Improves the Diabetes Mellitus-Induced Erectile Dysfunction in Rats.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S495366

Yuanyuan Liu, Dalin Sun, Dong Xing, Yiqi Rui, Yihan Jin, Peng Wang, Bin Cai, Chuyu Li, Chao Gao, Yugui Cui, Baofang Jin

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引用次数: 0

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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中药四调别加汤改善糖尿病大鼠勃起功能障碍的机制

目的：采用中药四芍别甲颗粒治疗糖尿病性勃起功能障碍。然而，SMBJ治疗作用的分子机制尚不清楚。本研究旨在通过网络药理学、蛋白质组学和分子对接等手段，探讨SMBJ在DMED大鼠模型中的作用及其机制。方法：建立DMED大鼠模型，分别以0、7.1、14.2、28.4 mg/kg/d给药4周。通过测量海绵内压和平均动脉压来评估勃起功能。采用气相色谱法和网络药理学及生物信息学方法对其活性成分进行鉴定。通过蛋白质组学鉴定了阴茎组织中的潜在靶点，并通过Western blotting进行了验证。分子对接用于评估生物活性化合物与主要靶点之间的结合亲和力。结果：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，减轻平滑肌细胞（SMCs）和血管内皮细胞（VECs）损伤，显著改善大鼠勃起功能，改善DMED。网络药理学和蛋白质组学鉴定了DMED中24个潜在的SMBJ靶点。所鉴定的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。木犀草素直接与AKT1结合，AKT1是DMED大鼠阴茎组织中关键的差异表达蛋白。进一步分析发现，SMBJ中的木犀草素可激活PI3K/Akt通路，调控DMED大鼠阴茎组织中nNOS和NF-kB的表达，从而改善勃起功能。结论：SMBJ可改善DMED大鼠阴茎组织氧化应激损伤、血管内皮修复和血管新生。木草素是DMED治疗中SMBJ的核心药物成分之一，调节PI3K/ akt相关通路。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.