Carnosic acid ameliorates ischemic stroke injury by regulating the interleukin-17A/NF-κB signaling pathway

Abstract: BACKGROUND: Ischemic stroke presents significant global challenges due to the lack of effective treatments. Although rosemary has demonstrated potential for brain protection, its mechanisms remain unclear. Therefore, this study aimed to explore the pharmacological effects and underlying mechanisms of carnosic acid (CA), one of the major active components of rosemary extract, in ischemic stroke. METHODS: A mouse model of middle cerebral artery occlusion was employed to assess the effects of rosemary extract on ischemic stroke. Brain tissue RNA sequencing was performed 24 h after the stroke, and ischemia/reperfusion injury improvement was assessed 72 h later, with subsequent validation through biological experiments and molecular docking. RESULTS: Rosemary extract and its active component CA decreased the infarct volume and improved neurological outcomes in ischemic stroke. Quantitative polymerase chain reaction results indicated that CA downregulated the expression of inflammatory markers. In addition, transcriptome analysis suggested that the therapeutic effects of CA involved the interleukin (IL)-17A/nuclear factor kappa B (NF-κB) signaling pathway, which was also confirmed by western blotting analysis. Molecular docking revealed a strong binding affinity with IL-17A. CONCLUSION: CA, the active component of rosemary extract, reduces neuroinflammation after ischemic stroke by suppressing the IL-17A/NF-κB signaling cascade. This discovery offers a potential therapeutic strategy for ischemic stroke.