Effect of a new arctigenin derivative against Gyrodactylus kobayashii through inhibition of ATP production

Abstract

Noxious pathogens always lead to high rates of mortality, which results in severe economic losses in aquaculture. Currently, gyrodactylosis treatments mainly rely on unapproved chemicals, which are not always satisfactory. According to the previous study, arctigenin is an efficient natural product for controlling gyrodactylosis. For the sake of seeking high-efficiency compounds, a new arctigenin derivative (CCA) was synthesized. Next, we evaluated the anthelmintic activity of CCA in vitro and in vivo, and studied the mechanism of action. The number of Gyrodactylus kobayashii significantly reduced as compared with the control group, the EC50 value at 24 and 48-h after CCA treatment was 0.616 and 0.451 mg/L, respectively, with EC100 at CCA concentration of 3 mg/L after 1 h bath treatment. In vitro results showed that CCA can rapidly reduce the amount of G. kobayashii and inhibit its mobility that could normally lead to death. The concentration and duration of CCA were positively correlated with the mortality of G. kobayashii. In addition, CCA displayed 100% efficacy against G. kobayashii at 4.0 mg/L after only 20 min exposure. Acute toxicity assay demonstrated that the LC50 of CCA against goldfish was 5.012 mg/L, which was 8.13 times higher than that of the EC50. Furthermore, the results of confocal microscope study revealed that CCA leaded to the epidermal structure and dissolved muscles of worms. Moreover, the ATP level of worms were decreased sharply after both in vitro and in vivo exposures with CCA. The anthelminthic mechanism of CCA against gyrodactylids was related to epidermal structure damages and energy insufficient. From the previous study, the EC50 of CCA against G. kobayashii (0.616 mg/L) was much lower than the EC50 (1.85 mg/L) of arctigenin (Tu et al., 2018). In summary, CCA is more effective than arctigenin and has great potential in control of Gyrodactylus infections.