Exploring the anti-depression mechanism of Danshen Baoxin Cha in CUMS mice through tryptophane-kynurenine metabolism pathway

Aim of the study: This study investigated whether DBC alleviates depression in a chronic unpredictable mild stress (CUMS) mouse model and explored its mechanism related to the tryptophan-kynurenine (Trp-Kyn) metabolic pathway. Materials and Methods: CUMS was applied for 4 weeks to establish the model, followed by 2 weeks of DBC treatment. Depression-like behaviors were assessed using open field (OFT), forced swimming (FST), and tail suspension tests (TST). Serum levels of cytokines (IL-6, TNF-α, IFN-γ) and Trp-Kyn pathway metabolites were measured by ELISA. Hippocampal mRNA expression of IL-6, TNF-α, IFN-γ, IDO, 5-HT, and hepatic TDO was analyzed by qRT-PCR. IDO and TDO protein levels were determined by Western blot. Results: Compared with the model group, DBC treatment significantly improved behavioral outcomes in the OFT, FST, and TST. DBC decreased serum pro-inflammatory cytokines and increased serum TRP and KYNA, while reducing KYN, QUIN, 3-HK, and 3-HAA. The KYN/TRP and KYN/KYNA ratios decreased. Furthermore, DBC downregulated hippocampal mRNA expression of IL-6, TNF-α, IFN-γ, and IDO, as well as hepatic TDO mRNA, and increased hippocampal 5-HT mRNA. Protein levels of hippocampal IDO and hepatic TDO were also reduced. Conclusion: This study concludes that DBC effectively alleviates depressed-like behaviors in a CUMS mouse model by inhibiting pro-inflammatory cytokines and neurotoxic metabolic pathways, suggesting that DBC can modulate the Trp-Kyn pathway to exert a therapeutic effect on depression.