rhyncophylline and Tourette-Syndrome

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 mg/kg), and TS + RH (20 and 40 mg/kg) 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 TLR/NLRP3/NF-κB signaling proteins in the striatum of TS rats. In BV2 cells, DOI-induced inflammation mediated through TLR/NLRP3/NF-κB was significantly inhibited following RH administration. The therapeutic effect of RH in TS was studied and its mechanism of action mediated via the TLR/NLRP3/NF-κB pathway was clarified in vitro and in vivo.

Topics: Amphetamines; Animals; Behavior, Animal; Cell Line; Cell Survival; Corpus Striatum; Disease Models, Animal; Dopamine; Encephalitis; Male; Oxindoles; Rats, Sprague-Dawley; Signal Transduction; Tourette Syndrome

The aim of this study was designed to investigate the effects of rhynchophyllin (RH) on neuroinflammation in Tourette syndrome (TS) rats. TS model was established in rats by the injection of selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior in DOI-induced rats was tested. Inflammatory cytokines levels such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The expression levels of janus kinase 2 (JAK2)/signal transducer and transcription activator 3 (STAT3) and nuclear factor (NF)-κB pathways in striatum were measured by Western blot. Data indicated that RH can significantly reduce the numbers of nodding experiment of TS rats. RH significantly decreased IL-6, IL-1β, and TNF-α in serum and striatum of TS rats, with altered expression of P-JAK2, P-STAT3, P-NF-κBp65, and P-IκBα in TS rats, as evidenced by Western blot analysis and immunohistochemistry, suggesting that the regulation of JAK2/STAT3 and NF-κB pathways might be involved in the mechanism of RH on TS.

Topics: Animals; Corpus Striatum; Drugs, Chinese Herbal; Humans; Interleukin-1beta; Interleukin-6; Janus Kinase 2; Male; NF-kappa B; Oxindoles; Propane; Rats; Rats, Wistar; Signal Transduction; STAT3 Transcription Factor; Tourette Syndrome; Tumor Necrosis Factor-alpha; Uncaria

Tourette syndrome (TS) is characterized by one of the chronic neuropsychiatric disorders in multiple children, and the pathogenesis of Tourette syndrome (TS) has not been previously elucidated.The aim of this study was designed to investigate the effects of rhynchophylline (RH) on Tourette syndrome (TS) in rats.TS model was established in rats and BV2 cells by the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior evaluations including stereotypy recording and autonomic activity test were performed. Inflammatory cytokine levels such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, striatum, and cell supernatant were detected. The expression levels of BDNF/NF-κB pathway in striatum and BV2 cells were measured by Western blot. Dopamine (DA) and dopamine receptor D 2 (D2) in striatum were also measured.Data indicated that RH significantly decreased IL-6, IL-1β, and TNF-α in serum, striatum, and cell supernatant of TS model, with altered expression of P-NF-κBp65, P-IκBα, and BDNF in TS rats, and DOI-induced BV2 cells, as evidenced by Western blot analysis and immunohistochemistry analysis. RH also significantly reduced the levels of DA and D2 in striatum.Our results shown that the regulation of BDNF/NF-κB pathway might be involved in the effects of RH on TS model.

Topics: Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Cell Line; Cell Survival; Corpus Striatum; Dopamine; Encephalitis; Inflammation Mediators; Male; Neuroprotective Agents; NF-kappa B; Oxindoles; Rats, Wistar; Receptors, Dopamine D2; Signal Transduction; Tourette Syndrome