Neuroinflammatory mechanism of Volatile oil from Acori graminei Rhizoma in tourette syndrome: GC-MS, network pharmacology and experimental validation

Abstract

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics that significantly impair childhood development. Volatile oil from Acori graminei Rhizoma (VOA), known for its anti-inflammatory and neuroprotective properties, holds therapeutic potential for TS, though its molecular mechanisms remain undefined. In this study, VOA was extracted via hydrodistillation (yield: 1.03 %), and the TS rat model was established to evaluate behavioral improvements through intragastric administration of varying VOA doses. The high-dose group (most effective in alleviating tics) was selected for subsequent mechanistic investigations. Utilizing GC-MS data from our group, network pharmacology and molecular docking analyses prioritized the cAMP/PKA/CREB signaling pathway as a potential target. Behavioral assessments confirmed that VOA significantly alleviated stereotyped and motor behaviors. In the striatum, VOA reduced pro-inflammatory cytokines, attenuated neuronal damage, and shifted microglial polarization from M1 to M2 phenotypes. From a mechanistic perspective, VOA upregulates key components in the cAMP/PKA/CREB signaling pathway and enhances BDNF levels, while suppressing the expression of NF-κB p65 and phosphorylation levels. These findings demonstrate that VOA mitigates tic behaviors by activating the cAMP/PKA/CREB signaling pathway, thereby curbing neuroinflammation, rectifying MG polarization, and preserving neuronal integrity. This study elucidates the critical link between TS pathogenesis and neuroinflammatory dysregulation, unveiling VOA’s molecular interplay with the cAMP/PKA/CREB signaling pathway and offering novel therapeutic insights for TS.