Anisodine hydrobromide inhibits inflammation and metabolic reprogramming to alleviate the inflammatory response in an acute cerebral infarction model.

Abstract

Acute ischemic stroke (AIS), a primary cause of global mortality and disability, involves the sudden interruption of cerebral blood flow, leading to significant neurological impairment. Inflammation plays a critical role in exacerbating brain damage following stroke, making effective anti-inflammatory treatments essential. This study explored the therapeutic potential of anisodine hydrobromide (Ani), a traditional Chinese medicine, in modulating inflammatory responses and glycolysis in the lymphocytes of AIS patients. We evaluated the impact of Ani on peripheral blood mononuclear cells (PBMCs) and purified Treg cells from these patients. Our findings indicated that Ani significantly increased the proportion of Treg cells and upregulated Foxp3 expression, suggesting enhanced anti-inflammatory effects. Ani also reduced the levels of proinflammatory cytokines and inhibited NLRP3 inflammasome activation in T cells. Additionally, Ani influenced glycolysis by downregulating the expression of key glycolytic enzymes, PKM2 and LDHA, through its effects on DNA methylation. Chromatin immunoprecipitation and molecular docking studies revealed that Ani interacts with DNMT1, modifying DNA methylation patterns and increasing 5hmC levels at the promoters of PKM2 and LDHA. These results indicate that Ani exerts neuroprotective effects by modulating both inflammatory and metabolic pathways, suggesting a promising avenue for AIS therapy. Further clinical validation and exploration of the therapeutic efficacy of Ani are warranted to confirm its potential as a treatment for AIS.