Paeoniflorin alleviates toxicity and accumulation of 6-PPD quinone by activating ACS-22 in Caenorhabditis elegans.

6-PPD quinone (6-PPDQ) is extensively existed in various environments. In Caenorhabditis elegans, exposure to 6-PPDQ could cause multiple toxic effects. In the current study, we further used C. elegans to investigate the effect of paeoniflorin (PF) treatment on 6-PPDQ toxicity and accumulation and the underlying mechanism. Treatment with PF (25-100 mg/L) inhibited 6-PPDQ toxicity on reproduction capacity and locomotion behavior and in inducing reactive oxygen species (ROS) production. Additionally, PF (25-100 mg/L) alleviated the dysregulation in expression of genes governing oxidative stress caused by 6-PPDQ exposure. Moreover, PF (25-100 mg/L) inhibited the enhancement in intestinal permeability caused by 6-PPDQ exposure and the accumulation of 6-PPDQ in the body of nematodes. In 6-PPDQ exposed nematodes, PF (25-100 mg/L) increased expression of acs-22 encoding a fatty acid transporter. RNAi of acs-22 could inhibit the beneficial effect of PF against 6-PPDQ toxicity in decreasing reproductive capacity and locomotion behavior, in inducing intestinal ROS production, and in enhancing intestinal permeability. RNAi of acs-22 could also suppress the PF beneficial effect against 6-PPDQ accumulation in the body of nematodes. Therefore, our results demonstrate the function of PF treatment against 6-PPDQ toxicity and accumulation in nematodes by activating the ACS-22.