Gao Kai, Xu Dong, Mu Fei, Zhao Meina, Zhang Wei, Tao Xingru, Guo Chao, Wang Jingwen
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Rejuvenation Res. 2025 Apr;28(2):54-66. doi: 10.1089/rej.2024.0051. Epub 2024 Nov 6.
The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while and were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.
本研究旨在阐明人参治疗心力衰竭（HF）作用的药理机制，为其临床应用提供理论依据。采用系统药理学方法，结合网络药理学、基因表达综合数据库（GEO）分析、分子对接和实验验证，研究人参在HF中的潜在作用机制。利用网络药理学确定药物-疾病靶点。随后，通过将网络药理学与GEO整合，对核心基因靶点进行富集分析。利用分子对接预测已确定靶点与人参化合物之间的结合亲和力。此外，在异丙肾上腺素（ISO）诱导的HF大鼠模型中验证了人参的治疗效果。通过蛋白质免疫印迹分析证实了人参对关键信号通路的调节作用。通过网络药理学分析，共确定了人参治疗HF的154个潜在靶点。对GSE71613的分析表明，PI3K-Akt通路、活性氧、氧化磷酸化、MAPK信号通路和Ras信号通路主要与HF患者相关。通过整合网络药理学和GEO分析的结果，确定人参皂苷Rg1和人参皂苷Rb3为人参的潜在成分，而 和 分别被认为是PI3K-AKT和AMPK通路中的关键靶点。分子对接分析显示潜在成分与已确定的核心靶点之间具有很强的亲和力。实验表明，人参提取物（EPG）通过改善心脏参数，如心脏左心室内径、左心室舒张末期容积、左心室收缩末期容积和左心室射血分数，显著改善了ISO诱导的心脏功能障碍，同时还减少了丙二醛的产生。此外，发现EPG可增强超氧化物歧化酶活性和ATP水平，同时降低白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α的水平。该提取物还降低了心肌耗氧量、炎症细胞浸润和受损心肌纤维的数量。此外，观察到EPG上调p-PI3K、p-Akt、p-AMPK和Bcl-2的表达，同时下调p-NFκB、TGF-β和Bax的表达。人参对HF的治疗作用主要通过PI3K-Akt和AMPK通路介导。人参皂苷Rg1和人参皂苷Rb3已被确定为HF的潜在治疗药物。
