Gastrodin - A potential drug used for the treatment of Tourette Syndrome.

Gastrodin (Gas) represents the major active component of Gastrodia elata, a Chinese herb. Clinically, Gas is widely used for its sedative, anticonvulsive and neuroprotective properties. This work aimed to assess Gas for its efficacy in Tourette Syndrome (TS) treatment. Twenty-four rats were randomized to the blank control (n = 6) and experimental (n = 18) groups. The experimental group was administered continuous injection of 3, 3'-iminodipropionitrile (IDPN) intraperitoneally for 7 days, and subdivided into the IDPN + NS, IDPN + Hal, and IDPN + Gas groups (n = 6). The control and IDPN + NS groups received saline intragastrically, while the IDPN + Hal and IDPN + Gas groups were administered Gas and Haloperidol, respectively, for 8 weeks. Then, micro-positron emission tomography (PET) was performed for measuring the density and brain distribution of dopamine D2 receptors (D2Rs), dopamine transporters (DATs), 5-HT2A receptors (5-HT2ARs) and 5-HT transporters (SERTs). According to stereotypical behavior experiments, IDPN significantly induced abnormal stereotypical behaviors in rats in comparison with control animals. In addition, micro-PET revealed that by reducing the amounts of D2Rs and increasing those of DATs, Gas could significantly reduce stereotypical TS-like behaviors in this rat model system. Furthermore, Gas treatment reduced the density of SERTs, which could indirectly decrease DA release. The current study demonstrated that Gas could be effective in treating TS.

[Effect of Ningdong Granule on the levels of IL-12 and TNF-alpha in children patients with Tourette's syndrome].

OBJECTIVE: To observe the effect of Ningdong Granule (NG) on serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) of children patients with Tourette's syndrome (TS). METHODS: Totally 90 TS children patients were randomly assigned to the NG group, the NG + Tiapride group (abbreviated as the combined treatment group), and the Tiapride group, 30 in each group. Besides,another 30 healthy children were recruited as the healthy control group. Patients in the NG group were treated with NG (consisting of all gastrodia rhizome, Codonopsis pilosula, Ophiopogon japonicus, white peony root, Rhinocerotidae, oyster, earthworm, licorice root, etc.), one dose daily, administered by dissolving it in boiled water, taken in two portions in the morning and in the evening respectively. Patients in the Tiapride group took Tiapride Tablet, 50 -100 mg each time, twice daily. The dosage was adjusted according to individual difference and changes of pathogenic conditions. The maximal dosage was 300 mg per day. Those in the combined treatment group were treated with equal dose of NG and Tiapride Tablet in combination. The treatment course was 3 months for all. Changes of pathogenic condition before and after treatment were assessed by Yale global tic severity scale (YGTSS). Serum levels of IL-12 and TNF-alpha were detected by enzyme-labeled immunosorbent assay (ELISA) before and after treatment. RESULTS: (1) The total effective rate of the NG group, the combined treatment group, and the Tiapride group was 79.3%, 83.3%, and 67.9%, respectively. It was the lowest in the Tiapride group (P < 0.05). It was significantly higher in the combined treatment group than in the NG group (P < 0.05). (2) The post-treatment YGTSS score was obviously lower in each group after treatment than before treatment (P < 0.05). The posttreatment YGTSS score was obviously lower in the NG group and the combined treatment group than in the Tiapride group (P < 0.05), but with no statistical difference between the fromer two groups (P > 0.05).(3) Compared with the healthy control group before treatment, serum levels of IL-12 and TNF-alpha (pg/mL) were 124.95 +/- 22.78 and 209.52 +/- 21.69 in the NG group, 126.14 +/- 25.65 and 208.97 +/- 22.46 in the combined treatment group, 123.00 +/- 24.26 and 205.10 +/- 26.16 in the Tiapride group, being higher than those in the healthy control group (64.56 +/- 27.59 and 78.13 +/- 33.42; P < 0.05). After treatment, serum levels of of IL-12 and TNF-alpha were 104.67 +/- 16.84 and 183.01 +/- 24.95 in the NG group, 109.04 +/- 16.81 and 179.87 +/- 23.45 in the combined treatment group, significantly lower than before treatment (P < 0.05). But there was no statistical difference in serum levels of IL-12 or TNF-alpha in the Tiapride group between before treatment (123.00 +/- 24.26 and 205.10 +/- 26.16) and after treatment (117.75 +/- 16.79 and 199.76 +/- 33.21; P > 0.05). CONCLUSION: NG could modulate abnormal serum levels of IL-12 and TNF-alpha in TS children patients, which might be one of its pharmacodynamic mechanisms for treating TS.

[Effect of ningdong granule on stereotyped behaviors in Tourette syndrome model rats of different Chinese medical syndromes].

OBJECTIVE: To observe the effect of Ningdong Granule (NDG) on stereotyped behaviors in Tourette's syndrome (TS) model rats of different Chinese medical syndromes. METHODS: Thirty-two Wistar rats were used to establish TS models of different Chinese medical syndromes (n =8) induced by TS children patients' sera of 4 syndromes, i.e., Xin-Gan deficiency syndrome (XGDS), Gan-Shen yin deficiency syndrome (GSYDS), sputum-turbid blocking aperture syndrome (STBAS), and Gan hyperactivity Pi deficiency syndrome (GHPDS). Corresponding sera was micro-infused to them while administering NDG (120 mg/kg each time, thrice daily, for 3 successive weeks). Besides, another normal control group (n =8) was set up by injecting sera from healthy children plus intragastric perfusion of normal saline. Stereotyped behaviors were recorded on the 1st, 7th, 14th, and 21st day after administration of NDG. RESULTS: The anti-neural antibody serum concentration in TS children was significantly higher than that in healthy control [(1.28 +/- 0.36) UL vs. (0.52 +/- 0.24) U/L, P < 0.01 ]. It was (1.34 +/- 0.41) U/L in the XGDS group, (1.19 +/- 0.51) U/L in the GSYDS group, (1.29 +/- 0.61) U/L in the STBAS group, and (1. 17 +/- 0.45) U/L in the GHPDS group, showing no statistical difference (P > 0.05). There was no statistical difference in stereotypic behaviors of rats after treatment among the four different Chinese medical syndromes (P > 0.05). At day 7, 14, and 21 after treatment by NDG, the times of stereotyped behaviors were significantly less in the XGDS group than in the other three groups at the same time points except in the GHPDS group at day 14 (P < 0.05, P < 0.01). Meanwhile, the total numbers of stereotyped behaviors in the XGDS group [(42.8 +/- 12.6)] was obviously superior to that in the GSYDS group [(29.3 +/- 13.7)], the STBAS group [(21.9 +/- 10.4)], and the GHPDS group [(30.6 +/- 9.6)], showing statistical difference (P < 0.01, P < 0.05) after treatment by NDG at day 21. CONCLUSIONS: The anti-neural antibody serum concentration in TS children was significantly higher than that in healthy children. Stereotyped behaviors could be induced in rats after intrastriatal micro-infusion of TS sera rich in anti-neural antibody. TS model rats of XGDS were better improved than rats in the other 3 groups after treatment by NDG.

Effects of ningdong granule on DA, DRD2, and HVA in a rat model of Tourette's syndrome.

OBJECTIVE: Ningdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome. METHODS: Sixty-four rats were randomly assigned to a control group and three experimental groups, respectively. Rat models of Tourette's syndrome were established via intraperitoneal injection of apomorphine (Apo). The rats in the experimental groups were subsequently intragastrically injected with haloperidol at 10 mg/kg (haloperidol group), ningdong granule at 370 mg/kg (NDG group), and normal saline (0.9%) at 10 mL/kg (Apo group), respectively. Rat behaviors were observed and recorded on a daily basis. After 12 w, all rats were sacrificed, and sera and striatal tissues were harvested. Homovanillic acid levels in sera, as well as dopamine and dopamine D2 receptor mRNA expression in the striatum, were measured to determine possible mechanisms of Ningdong granule on the dopamine system in a rat model ofTourette's syndrome. RESULTS: Following intervention, stereotype actions of the Tourette's syndrome rats were significantly inhibited in the haloperidol and NDG groups, respectively (P < 0.01). Homovanillic levels were significantly greater in the haloperidol and NDG groups, respectively (P < 0.05). In addition, dopamine levels were significantly less in the NDG group (P < 0.01), and DRD2 mRNA expression was significantly reduced in the haloperidol and NDG groups, respectively (P < 0.05). CONCLUSION: Results demonstrated that Ning-dong granule effectively inhibited stereotype actions and Tourette's syndrome symptoms by promoting dopamine metabolism, reducing dopamine levels in the striatum, increasing homovanillic acid content in sera, and reducing mRNA expression of DRD2 in the striatum.

Ningdong granule: a complementary and alternative therapy in the treatment of attention deficit/hyperactivity disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common neurobehavioral and neuropsychiatric disorder in school-age children, and recent studies provide evidence implicating the metabolic abnormalities of dopamine (DA) for its pathophysiology. Methylphenidate, a kind of psychostimulant, is widely used in the treatment of ADHD, but some patients do not respond to it or cannot bear its side effects. As a traditional Chinese medicine preparation, Ningdong granule (NDG) has been used in the treatment of ADHD for several years in China. However, a systematical pharmacological study on its safety and mechanism still remains obscure. OBJECTIVE: This paper aims to evaluate the efficiency, safety, and possible mechanism of NDG on ADHD children compared to methylphenidate. METHODS: Seventy-two ADHD children were recruited to perform an 8-week, randomized, methylphenidate-controlled, doubled-blinded trial. The subjects were equally assigned to two groups receiving either NDG 5 mg/kg/day or methylphenidate 1 mg/kg/day for 8 weeks. The efficiency was assessed by the Teacher and Parent ADHD Rating Scales every 2 weeks for a total of 8 weeks. The side effects were recorded during the study. Blood, urine, and stool routine samples, liver and renal function test, and DA and homovanillic acid (HVA) concentration in sera were tested at the beginning and end of the trial. RESULTS: NDG ameliorated ADHD symptoms after an 8-week medication with fewer side effects compared to methylphenidate (P < 0.05). The result also showed NDG to be safe and tolerable for ADHD children as monitored by the blood, urine, and stool analysis and liver and renal function for 8 weeks (P < 0.05). Moreover, the level of HVA in sera increased in NDG-treated group (P < 0.05), while the content of DA had no significant change during the study. An analysis of Pearson correlation coefficients also showed that the increased content of HVA in sera was associated with the improved scores of Teacher and Parent ADHD Rating Scales. CONCLUSIONS: Compared to methylphenidate, NDG is effective and safe for ADHD children in the short term, increases the HVA concentration in sera to regulate DA metabolism, and promises to be an alternative medication, safely and effectively.

[Apoptosis-inducing effect of cinobufacini on human hepatoma cell line HepG2 and its mechanism of action].

To investigate the apoptosis-inducing effect of cinobufacini (Huachansu) on human hepatoma cell line HepG2 and its possible mechanism of action, HepG2 cells were treated with different concentrations of cinobufacini. Cell proliferation was measured by methylthiazolyl tetrazolium (MTT) assay. The morphological changes of apoptosis were observed by Hoechst 33258 staining. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry (FCM). Quantitative real-time RT-PCR and Western blotting analysis were used to detect the mRNA and protein expressions of apoptosis related factors Bcl-2, Bax and p53. The results indicated that cinobufacini could inhibit the proliferation of HepG2 cells in a dose and time dependent manner. Remarkable morphological changes of apoptosis including cytoplasmic and nuclear condensation and partition of cytoplasm were observed by Hoechst 33258 staining. According to FCM analysis, HepG2 cells were arrested in G2/M phase and the apoptotic rate increased with the increase of the concentration of cinobufacini. Both the mRNA and protein expressions of Bax and p53 were up-regulated while Bcl-2 expression down-regulated. Thus, cinobufacini could inhibit the proliferation and induce apoptosis of human hepatoma cell line HepG2. Furthermore, up regulation of Bax and p53 as well as down regulation of Bcl-2 expressions may be one of the important apoptotic inducing mechanisms.

Clinical observation on treatment of Tourette syndrome by integrative medicine.

OBJECTIVE: To explore the clinical efficacy of integrative Chinese and Western medicine in treating Tourette syndrome (TS). METHODS: Ninety children with TS were randomized into two groups by randomizing: digital table method: the 60 patients in the treated group were treated by Ningdong Granule (NDG) plus haloperidol, and the 30 in the control group treated by haloperidol alone. The course for both groups was 6 months. Conditions of the patients were estimated before and after treatment with Yale Global Tic Severity Scale (YGTSS), the short-term efficacy, adverse reaction of treatment were assessed at the end of treatment, and the long-term efficacy as well as the recurrent rate were evaluated half a year after the treatment was ended. RESULTS: Of the 60 patients in the treated group, the treatment on 36 was evaluated as remarkably effective, 21 as effective, and 3 as ineffective, the total effective rate being 95.0% (57/60), while of the 30 patients in the control group, the corresponding data were 9, 13, 8 and 73.3% (22/30), respectively, differences between groups in markedly effective rate and total effective rate were statistically significant (chi(2)=7.20, and chi(2)=6.85, P<0.01). The improvement on the condition of illness, motor tic and vocal tic, as well as the long-term efficacy of treatment were all better in the treated group than in the control group (P<0.05 or P<0.01). The incidence of adverse reaction and the recurrent rate in the treated group were 13.3% (8/60) and 8.3% (5/60) respectively, all were lower than those in the control group, 36.7% (11/30) and 43.3 (13/30), showing statistical significances (P<0.05 and P<0.01). CONCLUSION: Integrative medical treatment on TS was markedly effective in clinical practice with less adverse reaction and lower recurrent rate.

[Value of multi-slice computed tomography in diagnosis of coronary plaque characterization].

OBJECTIVE: To investigate the value of multi-slice computed tomography in diagnosis of different types of coronary atherosclerotic plaques. METHODS: Twenty-eight patients undergoing CT angiography (CTA) with normal coronary arteries were randomly selected to measure the CT values of different sections of the 4 main branches of coronary artery. Twenty-five specimens of human heart from the bodies of the patients who died of non-cardiogenic diseases were scanned by 16-slice CT scanner and 64-slice CT scanner: a mixture of CT contrast media and normal saline was injected into the coronary arteries to achieve in-vivo-like contrast enhancement within the coronary artery lumen to detect atherosclerotic plaques. The CT values of plaques were measured in several regions of interest (ROI) selected in each plaque. The CT images thus obtained were evaluated by 2 experienced radiologists. There are nine specimens with coronary atherosclerotic plaques among them. Then the atherosclerotic lesions in the coronary were made into tissue specimens to undergo pathological examination. RESULTS: 7560 CT values were obtained from the 28 patients. Thirty-eight atherosclerotic plaques were found by CAT in 9 heart specimens and confirmed by pathology. When the CT value of coronary lumen was 370 HU, the predominant lipid-rich plaque showed a mean CT value of 53 +/- 12 HU; the fibrous-rich plaque showed a mean CT value of 106 +/- 17 HU; and the calcified plaque showed a mean CT value of 429 +/- 94 HU measured by 16-slice CT; and the predominant lipid-rich plaque showed a mean CT value of 51 +/- 13 HU; the fibrous-rich plaque showed a mean CT value of 110 +/- 19 HU; and the calcified plaque showed a mean CT value of 435 +/- 87 HU measured by 64-slice CT. The CT value of the fibrous-rich plaque was significantly higher than that of the lipid-rich plaque (P = 0.008), and lower than that of the calcified plaque (P < 0.01). There was no significant difference between the results obtained by the two kinds of CT scanners. CONCLUSION: CTA can non-invasively assess the atherosclerotic plaques.

Multi-slice CT angiography by triple-phase enhancement in preoperative evaluation of hepatocellular carcinoma.

BACKGROUND: Triple-phase enhancement of multi-slice computed tomography (MSCT) has markedly improved the diagnostic accuracy of hepatocellular carcinoma (HCC), and MSCT angiography (MSCTA) has been proved useful in detecting vascular anatomy noninvasively. This study aimed to explore the value of MSCTA by triple-phase enhancement in preoperative evaluation of HCC. METHODS: Fifty-six consecutive cases of primary HCC scheduled for resection were studied with MSCTA by triple-phase enhancement. The raw data images were processed on a workstation for multiplanar reconstruction (MPR) and three-dimensional (3D) reconstruction. The findings after processing of the data were compared with those after surgery or intraoperative sonography. RESULTS: The false positive rate of MSCTA by triple-phase enhancement was 10.1% and its false negative rate was 4.3% in detecting HCC. No significant difference was observed in MSCTA and surgery or intraoperative sonography in detecting vascular anatomy anomalies and pathologic variations, whereas significant difference was found in detecting bile duct invasion with MSCT compared to intraoperative sonography. CONCLUSIONS: MSCTA by triple-phase enhancement not only improves the detection of HCC, but also provides valuable preoperative information about hepatic vascular architecture and parenchyma. MSCTA by triple-phase enhancement is worthy of application as a non-invasive method in preoperative evaluation of HCC.