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BackgroundParkinson's disease (PD) is a neurodegenerative disorder with limited therapeutic options. Shao Di Pa Ning Decoction (SDPND), a traditional Chinese medicine (TCM) compound formula for PD, has demonstrated therapeutic efficacy, but its underlying mechanisms remain unclear.PurposeThis research aims to systematically investigate the mechanisms of SDPND, focusing on its anti-inflammatory effects and related pathways in PD.MethodsThe bioactive components of SDPND were first characterized to establish its material basis. Subsequently, A53T mice were administered SDPND to evaluate therapeutic improvements in motor dysfunction and neuroinflammatory responses, followed by transcriptomic profiling to identify potential pathways. Network pharmacology analysis was employed to validate biological pathways associated with these therapeutic effects. Molecular docking was used to study binding interactions between components and inflammatory, thereby offering mechanistic insights, with western blotting ultimately confirming the modulation of PI3K/AKT pathway activity.ResultsChemical composition analysis revealed 91 compounds. SDPND alleviated motor deficits and mitigated neuroinflammatory responses in A53T mice. Transcriptomic profiling revealed significant downregulation of the PI3K/AKT pathway. Network pharmacology analyses independently reaffirmed the enrichment of PI3K/AKT signaling as a pivotal hub. Molecular docking demonstrated robust binding affinities between bioactive components and core targets within the PI3K/AKT pathway, while western blotting analysis confirmed SDPND mediated suppression of PI3K/AKT phosphorylation, further validating pathway inhibition as a key mechanistic driver.ConclusionOur findings first revealed a novel anti-neuroinflammatory mechanism of SDPND via PI3K/AKT pathway suppression, which underlies its efficacy in mitigating PD symptoms. This discovery provides a robust theoretical foundation and pinpoints a strategic target for refining clinical PD therapeutics.
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