Apigenin Protects Against Ischemic Stroke Through Anti- Inflammatory Mechanisms: A Study Combining Comprehensive Network Analysis, Mendelian Randomization and Animal Experiments for Validation.
TL;DR
APG can protect against IS by inhibiting the inflammatory response, providing a theoretical basis for clinical translation and further experimental research of APG.
Abstract
Background
AND
Objective
There is a well-established link between inflammation and Ischemic Stroke (IS) pathology. A natural compound, Apigenin (APG), has a neuroprotective effect. However, the specific mechanisms underlying the anti-inflammatory effects of APG and its protective effects on the blood-brain barrier following IS are unclear. This study aimed to explore the mechanisms behind the anti-inflammatory effect of APG in IS.
Methods
Male Sprague-Dawley rats were used to establish a model of unilateral middle cerebral artery occlusion (MCAO) and were administered APG by oral gavage at doses of 30, 60, or 120 mg/kg for 7 days. On the following day, brain tissues were collected after MCAO. Brain injury was evaluated by measuring brain water content, hematoxylin and eosin (H&E) staining, and Evans blue extravasation. To investigate potential proteins associated with inflammation, methods such as molecular docking, molecular dynamics simulations, Mendelian randomization analysis, immunohistochemistry, and Western blotting were employed.
Results
APG therapy has improved neurological deficiencies, lowered brain edema, and improved blood-brain barrier integrity. It has also resulted in decreased levels of inflammatory proteins TLR4, MyD88, NFκB, IL1β, MMP9, and iNOS after IS. Furthermore, IL1R2 was identified as a potential predictive target for IS.
Discussion
APG can repair nerve damage post-IS, with its protective effects mediated by anti-inflammatory mechanisms. The TLR4/myD88/NF-kB signaling pathway is a protective pathway of the body. APG may exert a protective effect on the blood-brain barrier after IS through the TLR4/MyD88/NF-kB signaling pathway.
Conclusion
APG can protect against IS by inhibiting the inflammatory response, providing a theoretical basis for clinical translation and further experimental research of APG.