Astragalus mongholicus and Scutellaria baicalensis Extracts Mixture Target Pyroptosis in Ischemic Stroke via the NLRP3 Pathway

Int J Mol Sci. 2025 Jan 9;26(2):501. doi: 10.3390/ijms26020501.

Abstract

Ischemic stroke, caused by blocked cerebral blood flow, requires prompt intervention to prevent severe motor and cognitive impairments. Despite extensive drug development efforts, the failure rate of clinical trials remains high, highlighting the need for novel therapeutic approaches. This study investigated the therapeutic potential of a natural herbal extract mixture of Astragalus mongholicus Bunge (AM) and Scutellaria baicalensis Georgi (SB), traditionally used in Eastern Asian herbal medicine (EAHM) for ischemic stroke treatment. Using transient middle cerebral artery occlusion (tMCAO) and photothrombotic (PTB) mouse models, oral administration of the AM-SB mixture was evaluated during both acute and chronic phases. Results showed that AM-SB significantly reduced infarction volume, inflammation (IL-1β, TNF-α), and pyroptosis-related markers (NLRP3, GSDMD, ASC, Caspase-1), while decreasing gliosis and improving cerebral metabolites. Behavioral assessments revealed that early and sustained AM-SB intervention enhanced motor and cognitive functions, as measured by mNSS, Rotarod, Novel Object Recognition, and Passive Avoidance tests. These findings suggest that AM-SB extract is a promising alternative therapy for ischemic stroke management.

Keywords: Astragalus mongholicus; EAHM; Scutellaria baicalensis; inflammation; ischemic stroke; middle cerebral artery occlusion; pyroptosis.

MeSH terms

  • Animals
  • Astragalus Plant* / chemistry
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Ischemic Stroke* / drug therapy
  • Ischemic Stroke* / metabolism
  • Ischemic Stroke* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Pyroptosis* / drug effects
  • Scutellaria baicalensis* / chemistry
  • Signal Transduction / drug effects

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Plant Extracts
  • Scutellaria baicalensis extract
  • Nlrp3 protein, mouse