Quercetin, the key constituent of Astragali Radix, modulates ferroptosis in PASMCs and attenuates hypoxia pulmonary hypertension via the MAPK signaling pathway

doi:10.5246/jcps.2024.08.053

Abstract

Abstract:

This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension, employing a combination of network pharmacology and experimental validation techniques. Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database, while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database. The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension. Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software, with core targets and sub-networks identified using the CytoHubba plug-in. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID database. Additionally, the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis. The investigation revealed 18 active constituents selected from Astragali Radix, with quercetin emerging as the key component. A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted. Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway, resulting in reduced Fe²⁺ and lipid peroxide levels, increased GPX4 expression, and the reversal of ferroptosis. In summary, this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension. Specifically, quercetin, a core constituent of Astragali Radix, was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.

Key words: Network pharmacology, Astragali Radix, Quercetin, PASMCs, Ferroptosis, Hypoxia pulmonary hypertension

Supporting:

Xia Li, Beibei Cheng, Junlan Tan, Jiajing Wan, Yuhong Wang, Aiguo Dai. Quercetin, the key constituent of Astragali Radix, modulates ferroptosis in PASMCs and attenuates hypoxia pulmonary hypertension via the MAPK signaling pathway[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(8): 714-729.

Figures/Tables 15

Table 1. Information on the active ingredients of Astragali Radix.

Table 2. Astragali Radix active ingredients-target network topology analysis results.

Table 3. MMC algorithm extracts core targets.

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