PUBLICATION
A newly discovered bioactive equivalence of combinatorial components of Angong Niuhuang pills improves ischemic stroke via the PI3K/AKT axis
- Authors
- Zhang, X., Qi, F., Gao, W., Li, Y., Yang, H., Li, P.
- ID
- ZDB-PUB-250209-11
- Date
- 2025
- Source
- Journal of ethnopharmacology : 119453119453 (Journal)
- Registered Authors
- Keywords
- Angong Niuhuang pill, Bioactive equivalence of combinatorial components, Ischemic stroke, PI3K/AKT
- MeSH Terms
-
- Phosphatidylinositol 3-Kinases/metabolism
- Mice, Inbred C57BL
- Autophagy/drug effects
- Infarction, Middle Cerebral Artery*/drug therapy
- Male
- Zebrafish*
- Signal Transduction/drug effects
- Proto-Oncogene Proteins c-akt*/metabolism
- TOR Serine-Threonine Kinases/metabolism
- Disease Models, Animal
- Ischemic Stroke*/drug therapy
- Neuroprotective Agents/pharmacology
- Phosphatidylinositol 3-Kinase/metabolism
- Mice
- Network Pharmacology
- Drugs, Chinese Herbal*/chemistry
- Drugs, Chinese Herbal*/pharmacology
- Animals
- PubMed
- 39922326 Full text @ J. Ethnopharmacol.
Citation
Zhang, X., Qi, F., Gao, W., Li, Y., Yang, H., Li, P. (2025) A newly discovered bioactive equivalence of combinatorial components of Angong Niuhuang pills improves ischemic stroke via the PI3K/AKT axis. Journal of ethnopharmacology. :119453119453.
Abstract
Ethnopharmacological relevance Angong Niuhuang pill (ANP) is effective in preventing and treating ischemic stroke, however, the pharmacodynamic substances and mechanism of ANP have not been scientifically clarified.
Aim of the study This study aims to identify the bioactive equivalence of combinatorial components (BECCs) of ANP for the treatment of ischemic stroke, and discusse the underlying mechanisms.
Materials and methods Network pharmacology was performed to screen key compounds and predict potential pathways. The effect of BECCs on ischemic stroke were screened and verified in ponatinib-induced zebrafish model and mice middle cerebral artery occlusion (MCAO) model. Finally, the mechanism of BECCs was preliminarily investigated.
Results Through network pharmacology, the degree values of each component in ANP were determined, and five candidate BECCs were obtained by combining the content of the components in the original prescription. The BECCs V has the same efficacy as the original formula in reducing the movement disorder and neuronal injury of zebrafish cerebral ischemia models and lowering the neurologic deficits and cerebral infarction volume of mouse MCAO models. Mechanistically, BECCs V blocked neuronal autophagy through the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian aimed of rapamycin (mTOR) axis, inhibited microglial inflammatory activation through the PI3K/AKT/ hypoxia inducible factor-1α (HIF-1α) axis, protected microvascular endothelial function through the PI3K/AKT/ forkhead box O3 (FoxO3a) axis, thereby improving ischemic cerebral injury.
Conclusions The newly discovered BECCs V clarified the composition of ANP for the treatment of ischemic stroke, and its efficacy was verified in zebrafish and mice in vivo. Mechanistically, ANP and BECCs V ameliorate ischemic brain injury through the PI3K/AKT pathway, which was confirmed in cells in vitro.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping