Mechanism of Taohong Siwu Decoction in Alleviating PD-Related Cellular Damage based on the MAPK Signaling Pathway.

This study aimed to investigate the effects of Taohong Siwu Decoction (THSWD) on apoptosis, viability, and oxidative stress status in a 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cell injury model, and to analyze the potential involvement of stress-related MAPK (p38/JNK) signaling, specifically p38 and JNK, in its cytoprotective effects. A Parkinson's disease (PD)-related neurotoxic cell injury model was established by exposing SH-SY5Y cells with 6-OHDA. After administering different doses of THSWD, the mRNA expression levels of apoptosis-related genes were quantified by quantitative real-time PCR, apoptotic cell proportions were assessed by flow cytometry, and cell viability was evaluated using the CCK-8 assay. In parallel, intracellular oxidative stress indicators, including ROS, MDA, and antioxidant defense indicators, including SOD, CAT, and GSH, were measured. A drug-component-target-disease network was constructed using network pharmacology methods, followed by protein-protein interaction analysis and Gene Ontology and KEGG pathway enrichment analyses to identify potential signaling pathways. Western blot analysis was performed to assess the phosphorylation levels of p38 and JNK proteins, and mechanistic validation was further conducted using the p38 inhibitor BIRB796. Under 6-OHDA-induced SH-SY5Y cell injury conditions, THSWD treatment significantly downregulated the mRNA expression of BAX and CASPASE-3, reduced apoptotic cell proportions, and decreased inflammatory cytokine levels, while markedly improving cell viability. Meanwhile, THSWD alleviated oxidative stress imbalance induced by 6-OHDA, as evidenced by reduced ROS and MDA levels, along with restored SOD and CAT activities, and GSH content. Network pharmacology analysis revealed that THSWD-associated candidate targets were significantly enriched in the MAPK signaling pathway. Western blot results demonstrated that THSWD significantly suppressed 6-OHDA-induced phosphorylation of p38 and JNK proteins. Furthermore, BIRB796 exhibited effects consistent with THSWD in attenuating oxidative stress, inhibiting stress-activated MAPK signaling, reducing apoptosis, and enhancing cell viability, with enhanced protective effects observed upon combined treatment. THSWD attenuates 6-OHDA-induced SH-SY5Y cell injury under PD-related neurotoxic conditions. Its cytoprotective effects may be mediated, at least in part, through regulation of the p38/JNK-related MAPK signaling pathway.