Rhynchophylline Attenuates Neurotoxicity in Tourette Syndrome Rats.
Tourette syndrome (TS) is a chronic neuropsychiatric disorder with clinical manifestations of involuntary and repeated muscle twitching and vocal twitching. The drugs used to treat TS are relatively limited. The aim of this study was to investigate the effects of rhynchophylline (RH) and the underlying mechanism in 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced neurotoxicity in a TS rat model. A TS model was induced with DOI. The rats were divided into control, TS, TS tiapride (25 mgkg), and TS RH (20 and 40 mgkg) groups. Behavioral tests were performed 24 h after the last administration by nodding and stereotype experiments. Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) levels in striatum and serum were detected with an enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the expression levels of Toll-like receptor (TLR)nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3)nuclear factor kappa B (NF-κB) signal proteins in the striatum. The expression of TLR2 and NF-κB p65 subunit was detected with immunohistochemical analysis. RH may significantly improve behavioral changes in rats with DOI-induced TS and reduce the levels of inflammatory factors in serum and striatum. RH inhibited the activation of TLRNLRP3NF-κB signaling proteins in the striatum of TS rats. In BV2 cells, DOI-induced inflammation mediated through TLRNLRP3NF-κB was significantly inhibited following RH administration. The therapeutic effect of RH in TS was studied and its mechanism of action mediated via the TLRNLRP3NF-κB pathway was clarified in vitro and in vivo.