Table 1_Neuroprotective effects and mechanistic insights of sinomenine in ischemic stroke: a systematic review and meta-analysis of preclinical animal studies.docx

Data synthesis and quantitative analyses were performed with RevMan 5.3 and Stata 17.0. Subgroup and sensitivity analyses were conducted for outcomes with high heterogeneity. Additionally, dose-response curves were fitted using restricted cubic spline models.</p>Results<p>This meta-analysis included 15 studies.

In animal models of ischemic stroke, sinomenine significantly reduced cerebral infarct volume, improved neurological function score (NFS), and preserved blood-brain barrier (BBB) integrity. Sinomenine also downregulated neuroinflammation-related biomarkers, enhanced superoxide dismutase (SOD) activity, and modulated apoptosis-related marker levels. RCS analysis suggested nonlinear dose-response relationships between sinomenine dosage and cerebral infarct volume, NFS, and brain water content.

Subgroup analyses revealed that animal strain, comorbidity status, experimental blinding, drug dosage, and timing of administration may influence effect sizes. Trim-and-fill analysis showed that the pooled standardized mean difference (SMD) for cerebral infarct volume attenuated from −3.02 (95% CI [-3.96, −2.08]) to −1.97 (95% CI [-2.93, −1.01]) after adjustment, whereas that for NFS attenuated from −1.57 (95% CI [-2.18, −0.97]) to −1.06 (95% CI [-1.72, −0.40]).</p>Conclusion<p>In animal models, sinomenine may mitigate ischemic stroke injury through multiple pathways, with the efficacy following nonlinear dose-response relationships, suggesting its potential as an adjunctive neuroprotective intervention warranting further investigation.

However, given the methodological limitations of the included studies, these findings should be interpreted cautiously. To facilitate clinical translation, future studies should incorporate more rigorous and standardized experimental designs to strengthen the evidence base and validate its therapeutic potential.</p>Systematic Review Registration<p>crd.york.ac.uk/PROSPERO/view/CRD420261359581, identifier CRD420261359581.</p>