Apigenin as a Possible Treatment Candidate in Stroke: A Systematic Review and Meta-analysis on Preclinical Evidence

Background: Cerebrovascular diseases had been devastatingly crushing health care system, with no efficient treatment for them. The present study aims to systematically review and analyze existing preclinical evidence regarding one of the treatment candidates, apigenin, that could possibly serve the purpose. Methods: Databases of Medline, Scopus, Web of Science and Embase were systematically searched for records relevant to administrating apigenin in animal models of stroke. Meanwhile, studies that used derivatives or compounds of apigenin, review studies, uncontrolled and in vitro studies were excluded. Afterwards, two independent reviewers gathered data, and analyses were performed using STATA 17.0 and its random effects model. Results are presented as pooled standardized mean differences (SMD) with a 95% confidence interval (CI). Risk of bias and level of evidence were assessed using SYRCLE’s tool and GRADE framework, respectively. Results: The systematic search yielded 581 articles, of which 10 articles were included. Analyses depicted a significant effect of apigenin administration as a treatment in decreasing infarct volume (SMD = -2.32; 95%CI: -3.00, -1.65; p<0.001) and neurological deficit (SMD = -1.21; 95%CI: -1.59, -0.84; p<0.001). No publication bias regarding the two outcomes was identified. Conclusion: Moderate level of evidence emphasized on apigenin being a suitable candidate of further stroke treatment research. However, current evidence is scarce, specifically regarding the underlying mechanisms of apigenin protecting brain tissue after ischemic/reperfusion injury. Nonetheless, apigenin seems to modulate blood brain barrier, inflammation, apoptosis and brain edema. More studies are encouraged to further enlighten the effects of apigenin administration in animal stroke models.