Toxicological risks of Rhizoma paridis saponins in rats involved NF-κB and Nrf2 signaling

Abstract

The aim of the study is to evaluate the safety of long-term use of Rhizoma paridis saponins (RPS). After 90 day administration of RPS in rats, it induced liver and lung injury through the over-expression of reactive oxygen species (ROS) and pro-inflammatory cytokines, and by down-regulating the levels of antioxidant and detoxification enzymes. Meanwhile, RPS treatment also activated the self-protective transcription of Nrf2 and elevation of GSH and HO-1 expression to inhibit worsening tissue conditions in the rats. After 30 days' recovery, the abnormalities in liver and lungs disappeared, accompanied by the return of phase II enzyme, pro-inflammatory cytokine, and nuclear factor levels to normal. In conclusion, 350 mg kg⁻¹ d⁻¹ of RPS induced toxicity and detoxicity reactions involving NF-κB and Nrf2 signaling. Our work provides useful data for the correct administration of RPS and minimizing the danger of toxic herbal product use.