Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-κB pathways.

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-1ß (IL-1ß), 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-1ß, 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.

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 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-1ß, 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.

Lipopolysaccharide aggravated DOI-induced Tourette syndrome: elaboration for recurrence of Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder characterized by highest familial recurrence rate among neuropsychiatric diseases with complicated inheritance. Recurrence of Tourette syndrome was frequently observed in clinical. Unexpectedly, the mechanism of recurrence of Tourette syndrome was failure to elucidate. Here, we first shown that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome. The TS model in rats was induced by DOI (the selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl) -2- aminopropane). The rats were randomly divided into 4 groups:(1)Control;(2) Control + LPS; (2)TS; (3)TS + LPS. The results demonstrated that the LPS treatment significantly increased stereotypic score and autonomic activity. LPS treatment also significantly increased inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in serum and striatum. Also, highly expressed TLR4, MyD88, P-NF-κBp65, P-IκBα in TS rats were increased respectively by LPS treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome and its mechanism was related to TLR/NF-κB pathway.

WITHDRAWN: Anti-arthritic effect of pilose antler peptide on adjuvant-induced rheumatoid arthritis in rats.

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LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats.

The present study was designed to investigate the effects of LY294002 on Tourette syndrome (TS) in rats. TS model was induced in rats by DOI (the selective 5-HT2A/2C agonist 1- (2, 5- dimethoxy -4 - iodophenyl) -2- aminopropane). Behavior was assessed by stereotypic score and autonomic activity. Inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The protein levels of PI3K/Akt/NF-B in striatum were detected by Western Blot. LY294002 treatment significantly reduced IL-6, IL-1ß and TNF-α in serum and striatum of TS rats, Also, highly expressed P-PI3K, P-Akt, P-NF-κBp65, P-IκBα in TS rats were restored respectively by LY294002 treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that the protective effect of LY294002 against TS in rat might be associated with the regulation of PI3K/Akt/NF-B pathway.

Protective effect of pilose antler peptide on carbon tetrachloride-induced hepatotoxicity in mice.

The present study was designed to investigate the beneficial effects of pilose antler peptide (PAP) against carbon tetrachloride (CCl4) hepatotoxicity in mice, and explore the underlying mechanisms. In our results, animals were treated with either CCl4 and/or PAP for six consecutive weeks. The levels of inflammatory cytokines in serum and liver, hepatotoxicity markers in serum and histopathological evaluation were determined. PAP (50, 100mg/kg) significantly inhibited the CCl4-incuded overproduction of inflammatory cytokines including tumor necrosis factor α (TNF-α), cytokines interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in serum and liver. Animals treated with PAP exhibited lower levels of alanine transaminase (ALT) and aspartate transaminase (AST), PAP administration alleviated CCl4 induced hepatic fibrosis as manifested in histopathological records. In fact, PAP prevented the activation of TLR/NF-κB pathway, by inhibiting the expression of TLR2, TLR4 MyD88, p-NF-κBp65 and p-IκBα. In addition, PAP also significantly reversed CCl4-induced alteration of TGF-ß and p-samd-3 in liver tissue. In conclusion, PAP restored CCl4-induced hepatotoxicity via TLR/NF-κB and TGF-ß/samd-3 pathways.

Dang Gui Bu Xue Tang ameliorates coronary artery ligation-induced myocardial ischemia in rats.

Dang The present study was designed to investigate cardioprotective effects of Dang Gui Bu Xue Tang (DGBUT) on coronary artery ligation-induced myocardial ischemia. Myocardial ischemia (MI) model was induced in SD rats by surgical ligation of the left anterior descending coronary artery. ST segment elevation of Electrocardiograph (ECG) infarct size, levels of lactate dehydrogenase (LDH), creatine kinase (CK), glutathione (GSH) and catalase (CAT), catalase (SOD), malondialdehyde (MDA), and inflammatory cytokines and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun NH2 terminal kinases (JNK), nuclear factor (NF)-κBp65, inhibitory kappa B (IκB) α, IκB kinase (IKK) α and IKKß were evaluated in rats treated with or without DGBUT. DGBUT treatment significantly reduced the elevation of the ST segment of ECG, the myocardial infarct size of MI. The level of LDH, CK and MDA were suppressed, the contents of SOD, GSH and CAT were enhanced with DGBUT. The elevated concentration of inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and IL-6 in MI rats were effectively reversed by the DGBUT administration. Also, highly expressed p-JNK, p-ERK, p-p38, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKß in MI rats were restored respectively by DGBUT treatment. The protective effect of DGBUT against MI injury might be associated with MAPK/NF-кB pathway.

Effects of Jiaotaiwan on depressive-like behavior in mice after lipopolysaccharide administration.

Jiao-Tai-Wan (JTW), has been usually used for insomnia in traditional Chinese medicine (TCM). The previous study shown that JTW was benefit for depression-like behavior, but the possible mechanism is not clear. This study is to determine whether JTW was benefit for the treatment of lipopolysaccharide (LPS)-induced depression-like behavior in mice and explore its possible mechanism. All drugs were intragastrically administered once daily for 7 consecutive days. On the 7th day, LPS was injected into mice 30 min after drug administration. Behavioral tests were performed 24 h after LPS administration. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). The 5-hydroxytryptamine (5-HT) and nor-epinephrine (NE) levels in prefrontal cortex were determined by UPLC-MS. The protein expressions of NF-κB signaling in prefrontal cortex were determined by western blot. Behavioral tests were measured via tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT) and open field test (OFT). In addition, effects of JTW on the TNF-α induced depressive-like behavior were also examined. Pretreatment with JTW (4.2 and 8.4 g/kg) or fluoxetine (20 mg/kg) effectively attenuated LPS-induced upregulations of the serum TNF-α and IL-6 contents and JTW (4.2 and 8.4 g/kg) or fluoxetine (20 mg/kg) effectively increased the contents of 5-HT and NE compared with LPS-treated group. Meanwhile, the western blot analysis results indicated the correlation between the antidepressant activity of JTW and the regulation of NF-κB signaling in brain. Besides, JTW (4.2 and 8.4 g/kg) or fluoxetine (20 mg/kg) significantly shortened LPS-induced increases in immobility time of TST, FST and weakened the reduction of the sucrose preference in SPT without significant alterations of locomotor activity in OFT. Additionally, JTW effectively reversed the depressive-like behavior induced by TNF-α (0.1 fg/site, i.c.v.). Our findings indicated that Jiao-Tai-Wan (JTW) played an important role in monoaminergic response and anti-inflammation in lipopolysaccharide (LPS)-induced mouse model, which may be therapeutically exploited to alleviate depression-like behavior.

Antihyperuricemic effect of liquiritigenin in potassium oxonate-induced hyperuricemic rats.

The aim is to investigate the anti-hyperuricemic and renal protective effects of liquiritigenin in potassium oxonate-induced hyperuricemic rats. Hyperuricemia in rats was induced were induced with potassium oxonate (250mg/kg) intragastrically for 7 days, and liquiritigenin (20, 40mg/kg) and allopurinol (5mg/kg) were daily administrated to the rats orally 1h after the potassium oxonate exposure. Liquiritigenin significantly reversed the elevated productions of uric acid in serum and urine and pro-inflammation cytokines in serum and kidney, which shown that liquiritigenin has renal protective effects. Histological study shows that liquiritigenin inhibited severe necrosis and inflammatory cell infiltration in potassium oxonate-treated rats. Furthermore, liquiritigenin mediated the activities of aquaporins 4 (AQP4), and regulated the activation of NF-κB p65 and the degradation of IκBα. Finally, significant increases of nod-like receptor protein 3 (NLRP3) inflammasome, apoptosis-associated speck-like protein adaptor (ASC) adaptor and cleaved caspased-1 were restored by liquiritigenin. Therefore, liquiritigenin might improve renal inflammation by suppressing renal AQP4/NF-κB/IκBα and NLRP3 inflammasome activation in hyperuricemic rats.

Retracted: Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced mice via RIP140/NF-κB pathway.

The above article from IUBMB Life, published online on October 5th, 2016 in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editors-in-Chief, Dr. Angelo Azzi and Dr. William Whelan, and Wiley Periodicals, Inc. The retraction has been agreed because the article was submitted and approved for publication by Chunhua Ma and Long Hongyan without consent in any form by the named Corresponding Author, Kong Lingdong. REFERENCE: Chunhua, M., Lingdong, K., Hongyan, L. and Zhangqiang, M. (2016), Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced mice via RIP140/NF-κB pathway. IUBMB Life. doi:10.1002/iub.1570 © 2017 IUBMB Life, 69(9):767-767, 2017.

Esculetin Attenuates Th2 and Th17 Responses in an Ovalbumin-Induced Asthmatic Mouse Model.

The purpose of the current study was to investigate the anti-asthmatic effect of esculetin (ES) and explore its potential mechanism with a mouse model of allergic asthma. A total number of 50 mice were randomly assigned to five groups: control, model, dexamethasone (Dex, 2 mg/kg), and ES (20 mg/kg, 40 mg/kg). Mouse asthma model was developed with the sensitization and challenge of ovalbumin (OVA). The levels of IgE in serum, eosinophilia infiltration, Th2/Th17 cytokines, Th17 cell frequency, histological condition, and the protein expressions of RORγt, GATA3 were detected. Our study demonstrated that ES inhibited, OVA-induced eosinophil count, interleukin-4 (IL-4), IL-5, IL-13, and IL-17A levels were recovered in bronchoalveolar lavage fluid. Flow cytometry (FCM) studies revealed that ES substantially inhibited Th17 cells' percentage. Western blot study also indicated that ES downregulated RORγt and GATA3 expressions. Meanwhile, ES had beneficial effects on the histological alteration. These findings suggested that ES might effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.