Introduced paeoniflorin reduces the main toxicity induced by diosbulbin B, the major toxic compound of Dioscorea bulbifera L.: involved inhibiting inflammation and ferroptosis

Rhizoma Dioscoreae Bulbiferae (HYZ) is a widely utilized herb in clinical practice, known for its significant biological activities. However, the associated hepatotoxicity poses limitations to its application. Our previous research indicated that the effective mitigation of HYZ-induced hepatotoxicity through the concoction with Radix Paeoniae Alba medicinal juice involves the incorporation of paeoniflorin (Pae) and a reduction in diosbulbin B (DB), the primary toxic compound in HYZ. This finding suggests that the introduced Pae may exert a direct attenuating effect on DB. In light of this, this study represents the first investigation into Pae’s detoxification effect against DB-induced hepatotoxicity after administration for 2 months in mice vivo while also exploring underlying mechanisms related to inflammation and ferroptosis based on network pharmacology results. Our findings demonstrate that Pae significantly alleviates DB-induced hepatotoxicity in a dose-dependent manner. Western blotting and ELISA analyses revealed that Pae effectively reversed elevated levels of hepatic inflammation-related markers—such as NF-κB, p38 MAPK, NLRP3, TNF-α, and IL-1β—as well as excessively high concentrations of ferroptosis-related MDA and Fe2+. Furthermore, it restored low levels of GSH, SOD, GPX4, and FTH1. In summary, introduced Pae substantially mitigated DB-induced hepatotoxicity by inhibiting both hepatocyte inflammation and ferroptosis.