Gao Jing-Xin, Yue Mei-Ying, Huang Jin-Zhu, Guo Ze-Yi, Wang Huan, Deng Lin-Wen, Ding Wei-Jun, Zhou Hang
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, 611137, China.
Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610037, China.
Phytomedicine. 2025 Jun 19;145:157013. doi: 10.1016/j.phymed.2025.157013.
Scutellaria baicalensis Georgi (SBG) is traditionally used to prevent miscarriage through its anti-inflammatory, antioxidant, and antiapoptotic effects. However, its mechanisms in early-stage abortion (ESA) remain unclear.
A novel network pharmacology workflow was developed to identify bioactive compounds in SBG, including the nontargeted detection of SBG components, extraction of compounds from the HERB database, manual screening and filtering. These compounds were confirmed via high-performance liquid chromatography (HPLC). Targets associated with bioactive compounds were enriched via the SWISS database, and disease-related targets were identified via GeneCards. Overlapping targets were analyzed to construct a protein - protein interaction (PPI) network, with interactions predicted via STRING and visualized via Cytoscape. Molecular docking, dynamic simulations, and transcriptomics were used to prioritize key bioactive compounds. Two ESA models were used to evaluate therapeutic effects: one induced by lipopolysaccharide (LPS) and the other by mifepristone (Ru486). Decidual histopathology was observed via transmission electron microscopy (TEM) and hematoxylin - eosin (HE) staining. Key targets and pathways were validated through network pharmacology, immunohistochemistry (IHC), immunofluorescence (IF), Western blotting (WB), and ELISA. Finally, the effects of SBG on pregnancy maintenance were investigated by modulating the HIF-1α pathway, with a focus on its impact on critical biomarkers identified through the screening process.
Compared with RU486, SBG demonstrated greater efficacy in treating LPS-induced ESAs, as evidenced by lower embryo absorption rates, fewer miscarriages, and milder decidual pathological changes. Through multilevel screening, we identified 10 compounds in SBG with the highest drug potential, which were confirmed in the original plant. These compounds are predicted to specifically modulate LPS-ESA through 38 targets, influencing 525 biological processes and 126 signaling pathways. Integrated pharmacological analysis highlighted the HIF-1α signaling pathway as the key mechanism underlying the therapeutic effects of SBG on ESAs. Experiments involving HIF-1α pathway activation and inhibition confirmed that SBG inhibits decidual and embryonic cell apoptosis and hypoxia by blocking HIF-1α signal transmission.
This study established a rigorous framework for screening and analyzing the therapeutic components of SBG and revealed that SBG is specifically effective against ESAs and maternal-fetal interface inflammation through the HIF-1α signaling pathway. These findings highlight SBG as a therapeutic agent for ESA and provide a foundation for future mechanistic studies.
黄芩传统上用于预防流产，通过其抗炎、抗氧化和抗凋亡作用。然而，其在早期流产（ESA）中的机制仍不清楚。
开发了一种新的网络药理学工作流程，以鉴定黄芩中的生物活性化合物，包括黄芩成分的非靶向检测、从中药数据库中提取化合物、人工筛选和过滤。这些化合物通过高效液相色谱（HPLC）进行确认。通过SWISS数据库富集与生物活性化合物相关的靶点，并通过GeneCards鉴定疾病相关靶点。对重叠靶点进行分析以构建蛋白质-蛋白质相互作用（PPI）网络，通过STRING预测相互作用并通过Cytoscape可视化。分子对接、动态模拟和转录组学用于确定关键生物活性化合物的优先级。使用两种ESA模型评估治疗效果：一种由脂多糖（LPS）诱导，另一种由米非司酮（Ru486）诱导。通过透射电子显微镜（TEM）和苏木精-伊红（HE）染色观察蜕膜组织病理学。通过网络药理学、免疫组织化学（IHC）、免疫荧光（IF）、蛋白质印迹（WB）和酶联免疫吸附测定（ELISA）验证关键靶点和途径。最后，通过调节HIF-1α途径研究黄芩对维持妊娠的影响，重点关注其对通过筛选过程确定的关键生物标志物的影响。
与Ru486相比，黄芩在治疗LPS诱导的ESA方面表现出更高的疗效，较低的胚胎吸收率、较少的流产和较轻的蜕膜病理变化证明了这一点。通过多级筛选，我们在黄芩中鉴定出10种具有最高药物潜力的化合物，并在原植物中得到证实。这些化合物预计通过38个靶点特异性调节LPS-ESA，影响525个生物学过程和126条信号通路。综合药理学分析突出了HIF-1α信号通路是黄芩治疗ESA疗效的关键机制。涉及HIF-1α途径激活和抑制的实验证实，黄芩通过阻断HIF-1α信号传递来抑制蜕膜和胚胎细胞凋亡及缺氧。
本研究建立了一个严格的框架，用于筛选和分析黄芩的治疗成分，并揭示黄芩通过HIF-1α信号通路对ESA和母胎界面炎症具有特异性疗效。这些发现突出了黄芩作为ESA治疗药物的作用，并为未来的机制研究提供了基础。
