Tan I modulates astrocyte inflammatory responses through enhanced NAD⁺-Sirt1 pathway: Insights from metabolomics...

Over the past decade, research has increasingly demonstrated that oligomeric α-synuclein (O-αS) plays a pivotal role in the pathogenesis of Parkinson's disease (PD), particularly in mediating dopaminergic neuron injury and neuroinflammation. In this study, we investigated the anti-inflammatory effects of tanshinone I (Tan I), an active component of the traditional Chinese medicine Danshen, on O-αS-induced inflammation in primary mouse astrocytes. Using metabolomics analysis, we identified key pathways regulated by Tan I. Our results showed that Tan I significantly suppressed O-αS-induced mRNA expression of pro-inflammatory cytokines, including interleukin-1β, IL-6, tumor necrosis factor-α and cyclooxygenase-2. Metabolomic profiling revealed that Tan I enhanced NAD⁺ metabolism, leading to activation of the NAD⁺-Sirt1 pathway and subsequent inhibition of nuclear factor-κB activity. Together, these findings suggest that Tan I attenuates neuroinflammatory response in astrocytes by modulating NAD⁺-dependent signaling mechanisms.