[Mechanistic study of Scutellariae Radix against atherosclerosis through inhibition of pyroptosis based on network pharmacology and experimental verification].

Authors

Ying Sun, Jing Li, Jun-Li Gou, Chao-Yuan Ma, Ai-Qin Li, Wei-Wei Ma, Yue Jiang

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 12. Pages 3553-3562.

Abstract

This study systematically investigated the mechanism of Scutellariae Radix against atherosclerosis(AS) through the integrated application of network pharmacology, molecular docking, and animal experiments. A total of 34 active ingredients of Scutellariae Radix were screened from the TCMSP database, and 65 potential therapeutic targets were identified by combining SwissTargetPrediction and GEO data analysis. Protein-protein interaction(PPI) network construction, molecular docking, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses indicated that Scutellariae Radix might exert the anti-AS effect by modulating inflammatory responses, negatively regulating pyroptosis, and influencing the NOD-like receptor(NLRP) signaling pathway. In vivo, AS was induced in ApoE~(-/-) mice by 16-week high-fat diet feeding, followed by intervention with Scutellariae Radix extract. The results showed that Scutellariae Radix significantly attenuated lipid deposition and plaque area in the aortic wall, decreased serum levels of total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and triglycerides(TG), and increased the high-density lipoprotein cholesterol(HDL-C) level, thereby improving lipid metabolism disorders. Meanwhile, it markedly inhibited the expression of proinflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and IL-6. In addition, Scutellariae Radix significantly suppressed nuclear factor-κB(NF-κB) phosphorylation and downregulated the protein expression of NOD-like receptor pyrin domain-containing protein 3(NLRP3), cleaved caspase-1, and the N-terminal fragment of gasdermin D(N-GSDMD), which suggested that Scutellariae Radix effectively inhibited pyroptosis in arterial tissues. Collectively, these findings suggested that Scutellariae Radix ameliorated AS by suppressing pyroptosis in arterial tissues, attenuating inflammation, and improving lipid metabolism via regulating the NLRP3/caspase-1/GSDMD signaling pathway.

PMID:
42543314
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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