Changpu Yujin Tang mitigates tourette syndrome by enhancing mitophagy and suppressing NLRP3 inflammasome-mediated pyroptosis

Background: Changpu Yujin Tang (CPYJT) is an effective Chinese herbal compound for treating Tourette syndrome (TS). However, its precise molecular mechanisms remain to be fully elucidated.

Methods: 105 SD rats were randomly divided into the Control (n = 15) and the TS (n = 90) groups. The TS group was induced by intraperitoneal injection of 3,3'-iminodipropionitrile. After successful modeling, the TS group was further divided into 6 subgroups (n = 15 in each group): the Model group, the Tiapride group, the CPYJT group, the Rapamycin (RAPA) group, the 3-methyladenine (3-MA) group, and the CPYJT +3-MA group, and were treated with the corresponding drugs for 4 weeks.

Results: Compared with the Control group, rats in the Model group showed increased stereotyped and motor behaviors, damage to striatal neuronal cells and mitochondrial ultrastructure, decreased PINK1/Parkin-mediated Mitophagy, and activation of NLRP3 inflammasome. CPYJT reduced stereotyped and motor behaviors, attenuated neuronal cell damage, and repaired mitochondrial pathology in the TS rats. Furthermore, both CPYJT and RAPA enhanced PINK1/Parkin-mediated Mitophagy, eliminated ROS accumulation, and inhibited NLRP3 inflammasome activation. Notably, CPYJT counteracted 3-MA's inhibitory effect on PINK1/Parkin-mediated Mitophagy, thereby suppressing NLRP3 inflammasome activation and Pyroptosis.

Conclusion: CPYJT inhibits NLRP3 inflammasome activation and reduces Pyroptosis by enhancing PINK1/Parkin-mediated Mitophagy and attenuating ROS accumulation, which in turn ameliorates TS.

Changpu Yujin Tang; NLRP3 inflammasome; PINK1/Parkin-mediated mitophagy; Pyroptosis; Tourette syndrome.