整合网络药理学和转录组学探讨甘草素治疗心肌梗死后心力衰竭的作用机制。
Integration of network pharmacology and transcriptomics to explore the mechanism of isoliquiritigenin in treating heart failure induced by myocardial infarction.
机构信息
Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Institute of Cardiovascular Translational Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
出版信息
Toxicol Appl Pharmacol. 2024 Nov;492:117114. doi: 10.1016/j.taap.2024.117114. Epub 2024 Sep 30.
BACKGROUND
The inflammatory response and myocardial remodeling play critical roles in the progression of heart failure (HF) following myocardial infarction (MI). Isoliquiritigenin (ISL) possesses anti-inflammatory properties and has been investigated in cardiovascular diseases such as atherosclerosis. However, the effects and mechanism of ISL on MI-induced HF remain unclear. This research aimed to explore the effects and mechanism of ISL in the treatment of HF on the basis of network pharmacology, transcriptomics, and experimental verification.
METHODS AND RESULTS
We established an MI-induced HF mouse model in which ISL was administered via gavage for 28 days. Ultrasonic cardiogram data were collected from the mice, and pathological staining was conducted. Then, network pharmacology and molecular docking were performed. Transcriptomic analysis was also conducted on mouse myocardial tissue. Ultimately, we integrated transcriptomic data and network pharmacology to reveal the underlying mechanism, with the results verified through in vivo experiments. Our experiments indicated that ISL improved cardiac function, preserved myocardial structure, inhibited collagen fiber accumulation, reduced inflammatory factor secretion, and mitigated myocardial cell apoptosis in mice with MI-induced HF. A combination of transcriptomics and network pharmacology analysis revealed that core targets of ISL related to HF were significantly enriched in the Tumor Necrosis Factor (TNF) signaling pathway. Molecular docking validation demonstrated that ISL shows strong binding to these core targets. Additionally, in vivo experiments verified that ISL protects against HF post-MI by inhibiting the TNF signaling pathway.
CONCLUSION
We clarified the anti-inflammatory and antimyocardial remodeling mechanisms of ISL in the treatment of HF post-MI, which involves the TNF signaling pathway.
背景
炎症反应和心肌重构在心肌梗死后心力衰竭（HF）的进展中起着关键作用。甘草素（ISL）具有抗炎特性，已在动脉粥样硬化等心血管疾病中进行了研究。然而，ISL 对 MI 诱导的 HF 的影响和机制尚不清楚。本研究旨在基于网络药理学、转录组学和实验验证，探讨 ISL 治疗 HF 的作用和机制。
方法和结果
我们建立了 MI 诱导的 HF 小鼠模型，通过灌胃给予 ISL 治疗 28 天。从小鼠中收集超声心动图数据，并进行病理染色。然后进行网络药理学和分子对接。对小鼠心肌组织进行转录组分析。最终，我们整合转录组数据和网络药理学来揭示潜在的机制，并通过体内实验进行验证。我们的实验表明，ISL 改善了心脏功能，保护了心肌结构，抑制了胶原纤维积累，减少了炎症因子的分泌，减轻了 MI 诱导的 HF 小鼠的心肌细胞凋亡。转录组学和网络药理学分析的组合表明，ISL 与 HF 相关的核心靶点在肿瘤坏死因子（TNF）信号通路中显著富集。分子对接验证表明，ISL 与这些核心靶点具有很强的结合能力。此外，体内实验验证了 ISL 通过抑制 TNF 信号通路来预防 MI 后 HF。
结论
我们阐明了 ISL 治疗 MI 后 HF 的抗炎和抗心肌重构机制，涉及 TNF 信号通路。
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