基于系统药理学的策略研究总黄酮治疗慢性心力衰竭的药理机制。
Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in on Chronic Heart Failure.
机构信息
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
出版信息
Int J Mol Sci. 2022 Jul 29;23(15):8409. doi: 10.3390/ijms23158409.
Heart failure (HF) is a clinical syndrome of cardiac insufficiency caused by abnormalities in cardiac structure and function that arise for various reasons, and it is the final stage of most cardiovascular diseases' progression. Total flavonoid extract from L. (TFDM) has many pharmacological and biological roles, such as cardioprotective, neuroprotective, anti-atherogenic, antihypertensive, anti-diabetic, anti-inflammatory, antioxidant, etc. However, its effect on HF and its molecular mechanism are still unclear. In this study, we used systems pharmacology and an animal model of HF to investigate the cardioprotective effect of TFDM and its molecular mechanism. Eleven compounds in TFDM were obtained from the literature, and 114 overlapping genes related to TFDM and HF were collected from several databases. A PPI network and C-T network were established, and GO enrichment analysis and KEGG pathway analysis were performed. The top targets from the PPI network and C-T network were validated using molecular docking. The pharmacological activity was investigated in an HFpEF (heart failure with preserved ejection fraction) mouse model. This study shows that TFDM has a protective effect on HFpEF, and its protective mechanism may be related to the regulation of proinflammatory cytokines, apoptosis-related genes, fibrosis-related genes, etc. Collectively, this study offers new insights for researchers to understand the protective effect and mechanism of TFDM against HFpEF using a network pharmacology method and a murine model of HFpEF, which suggest that TFDM is a promising therapy for HFpEF in the clinic.
心力衰竭（HF）是一种由各种原因引起的心脏结构和功能异常导致的心脏功能不全的临床综合征，是大多数心血管疾病进展的终末阶段。 从虎杖中提取的总黄酮提取物（TFDM）具有许多药理和生物学作用，如心脏保护、神经保护、抗动脉粥样硬化、降压、抗糖尿病、抗炎、抗氧化等。 然而，其对 HF 的作用及其分子机制尚不清楚。 在这项研究中，我们使用系统药理学和 HF 动物模型来研究 TFDM 的心脏保护作用及其分子机制。 从文献中获得了 TFDM 中的 11 种化合物，并从多个数据库中收集了与 TFDM 和 HF 相关的 114 个重叠基因。 建立了 PPI 网络和 C-T 网络，并进行了 GO 富集分析和 KEGG 通路分析。 使用分子对接验证了 PPI 网络和 C-T 网络中的顶级靶标。 在 HFpEF（射血分数保留性心力衰竭）小鼠模型中研究了药理学活性。 这项研究表明，TFDM 对 HFpEF 具有保护作用，其保护机制可能与调节促炎细胞因子、凋亡相关基因、纤维化相关基因等有关。 总之，这项研究使用网络药理学方法和 HFpEF 小鼠模型为研究人员提供了新的见解，了解 TFDM 对 HFpEF 的保护作用和机制，表明 TFDM 是临床治疗 HFpEF 的一种有前途的疗法。
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