Protocatechuic acid and tanshinone IIA improve cyclophosphamide-induced immunosuppression

Protocatechuic acid (PCA) and tanshinone IIA (TanIIA), the major functional constituents of Phellinus baumii (PB) and Salvia miltiorrhiza (SM), respectively, regulate innate and adaptive immune pathways and converge on nuclear factor-κB (NF-κB) signaling, providing a mechanistic basis for cooperative immune enhancement. Based on these characteristics, this study evaluated the immunomodulatory effects of a PB-SM complex and examined whether combined treatment with PCA and TanIIA could cooperatively enhance immune recovery. In a cyclophosphamide (CPA)-induced immunosuppressed mouse model, PB-SM administration significantly alleviated body weight loss and splenic atrophy and restored the reduced proportions of CD3⁺ T cells, CD335⁺/NKR-P1C⁺ NK cells, and F4/80⁺ macrophages. PB-SM also significantly improved the proliferative responses of T and B cells suppressed by CPA. At the cellular level, PB-SM enhanced phagocytic activity of macrophages and NK cell-mediated tumor killing. Consistently, PCA and TanIIA individually activated MAPK and NF-κB p65 signaling and improved macrophage functions, with the combination exhibiting enhanced activity. These findings suggest that PCA and TanIIA may contribute to immune restoration and support their combined application as a promising functional strategy for alleviating chemotherapy-induced immunosuppression.