ArticleFrontiers in pharmacology2026
Salidroside derivative SHPL-49 enhances synaptic remodeling in BCCAO rats via the CDK5/p35/p25 signaling pathway.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: In recent years, significant attention has been directed toward the development of therapeutic agents targeting cognitive and motor dysfunction following ischemic stroke. Our research team synthesized SHPL-49, a salidroside derivative, which has demonstrated neuroprotective effects in rat models of ischemic stroke in prior studies. However, the underlying mechanisms remain poorly understood. This study aims to evaluate the therapeutic potential of orally administered SHPL-49 over a 28-day period in rats with bilateral common carotid artery occlusion (BCCAO), specifically focusing on improvements in cognitive and motor deficits, and to further elucidate its mechanism of action. Methods: A BCCAO rat model was employed to investigate the effects of SHPL-49 on cognitive and motor functions following ischemic stroke. Behavioral performance was assessed using the Morris water maze, shuttle box, running wheel, gait analysis, and rotarod tests. Synaptic remodeling in the brain was evaluated through Golgi staining, Western blotting, and immunofluorescence. Results: SHPL-49 significantly ameliorated cognitive and motor impairments in BCCAO rats. SHPL-49 markedly increased dendritic spine density in brain tissue and promoted synaptic remodeling by upregulating the mRNA expression of synapse-related genes, including MAP-2, SYP, and βIII-tubulin, as well as the expression of the key synaptic protein SYN1. Furthermore, transcriptomic analysis of SHPL-49-treated PC-12 cells suggested that SHPL-49 may regulate synaptic remodeling through CDK4 and CDK5 signaling. Subsequent experiments confirmed that SHPL-49 enhanced the expression of CDK5 and its activator p35 in both primary neurons and BCCAO rats, meanwhile inhibited the cleavage of p35 into p25 (a proteolytic event associated with dendritic spine atrophy and synaptic protein degradation). Conclusion: In summary, SHPL-49 significantly improved memory and motor impairments in BCCAO rats, highlighting the role of synaptic remodeling in this therapeutic effect. The underlying mechanism is closely linked to the modulation of CDK5/p35/p25 signaling pathway. These findings provide important theoretical evidence supporting the potential for the long-term clinical oral application of SHPL-49 in treating ischemic stroke.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.