Ischemic stroke accounts for approximately 85% of all strokes and remains a major cause of death and long-term disability. Current treatments can restore blood flow in eligible patients, but therapeutic options remain limited, particularly for protecting threatened brain tissue and supporting recovery. P. notoginseng and P. ginseng have long been used in traditional Chinese medicine and are commonly associated with “activating blood” and “replenishing qi,” respectively. Modern studies have reported anti-inflammatory, antioxidant, and anti-apoptotic effects for their saponins. However, conventional bulk and single-cell analyses cannot fully show where drug-induced molecular changes occur within the spatially heterogeneous brain, leaving the regional differences between these treatments insufficiently understood.
A study (DOI: 10.48130/targetome-0026-0038) published in Targetome on 25 August 2026 by Jie Liao's team, Zhejiang University, reports that the two saponin preparations alleviate ischemic brain injury through shared neuroprotective effects but preferentially regulate vascular-cytoskeletal and mitochondrial-metabolic pathways, respectively.
The researchers established permanent middle cerebral artery occlusion in male C57BL/6 mice and administered low or high doses of P. notoginseng saponins (PNS) or P. ginseng saponins (PGS), with edaravone serving as a positive control. Twenty-four hours later, they assessed neurological deficits, infarct volume, tissue damage, neuronal integrity, and apoptosis; a separate experiment monitored survival for seven days. At 200 mg·kg⁻¹, PNS and PGS lowered neurological scores from 3.67 in untreated model mice to 2.00 and 2.17, respectively. PNS reduced average infarct volume from 30.73% to 11.70%, comparable to edaravone, while PGS reduced it to 13.33%. Seven-day survival increased from 25% in model mice to 75% with PNS and 50% with PGS. Histological analyses further showed that both treatments reduced edema, neuronal damage, Nissl-body loss, and apoptosis, with PNS generally producing stronger acute protection. To map the underlying molecular responses, the team applied Spatial-seq 2.0 to 384 spatial spots collected from brain sections representing sham, model, PNS, and PGS groups, with three biologically independent mice per group. The eight spots showing the greatest disease-related transcriptional changes were spatially aligned with the ischemic penumbra. Gene Ontology and pathway analyses revealed shared regulation of mitochondrial transport, protein localization, and tight-junction organization. PNS, however, preferentially affected actin-filament and cytoskeletal organization, while PGS more strongly influenced the tricarboxylic acid cycle and NADH dehydrogenase-complex assembly. Quantitative real-time PCR confirmed representative expression patterns in ischemic brain tissue and cellular models. Western blotting provided further support: PNS more strongly restored Rac1 and VE-cadherin, associated with cytoskeletal remodeling and endothelial repair, whereas PGS exerted greater effects on the mitochondrial proteins SDHA and ATP5A. Both treatments increased Nrf2, suggesting a shared antioxidant mechanism.
Overall, the study provides a spatially resolved molecular explanation for the different pharmacological profiles of PNS and PGS. The results suggest that PNS may be particularly relevant to early vascular protection, while PGS may contribute more strongly to metabolic support and subsequent neural recovery. Because the experiments used mice and examined primarily the first 24 hours after stroke, clinical effectiveness and stage-specific benefits remain to be established. Future studies incorporating additional time points, chemical profiling, spatial multi-omics, and causal experiments will be needed before these findings can inform human treatment.
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References
DOI
10.48130/targetome-0026-0038
Original Source URL
https://doi.org/10.48130/targetome-0026-0038
Funding information
This work was supported by the Natural Science Foundation of Zhejiang Province LD25H280002
the National Natural Science Foundation of China U23A20513
the National Natural Science Foundation of China 82522092
the Key Project of Zhejiang Provincial Administration of Traditional Chinese Medicine GZY-KJS-ZJ-2025-071
the Starlit South Lake Leading Elite Program 2023A303005
the China Postdoctoral Science Foundation 2025M783944
About Targetome
Targetome refers to the complete collection of molecular targets (e.g., proteins, RNA or DNA) that interact with and mediate the effect of a specific biomolecule, such as a drug, toxin, metabolites, transcription factor or microRNA, within a biological system. Targetome is an open access journal publishing rigorously peer-reviewed original research articles, reviews, break-through methods, and perspectives that advance our understanding, identification and validation of molecular targets for new drug development.