[Effect of baicalin on growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKâ ¡ and ERK1/2].

The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study,a total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride group,and low,medium,and high dose baicalin groups,with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group(0.07 g·L~(-1))and the low(3.33 g·L~(-1)),medium(6.67 g·L~(-1)),and high dose(10 g·L~(-1))baicalin groups received corresponding drugs by gavage administration according to the body weight(0.015 m L·g~(-1)),while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks,twice a day.The body weight of the rats and the amount of remaining feed were weighed daily,and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods,respectively.RESULTS: showed that baicalin did not affect the normal eating and weight gain of rats,and the weight gain of rats was even more significant than that in the normal group(P<0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes,the expression of both proteins in each drug-administered group was higher than that in the model group(P<0.05);besides,the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group(P<0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats(P<0.05).In conclusion,baicalin does not affect the normal growth and development of SHR rats,so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein,and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.

[Regulatory effect of Shudihuang on expressions of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of ADHD model rats].

To observe the effect of Shudihuang on behaviors and expression of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of attention deficit hyperactivity disorder (ADHD) model rats. Thirty 4-week-old spontaneous hypertension rats (SHR) were randomly divided into model group, methylphenidate hydrochloride (MPH, 2 mg·kg⁻¹·d⁻¹) and Shudihuang group (2.4 g·kg⁻¹·d⁻¹). Another 10 Wistar-Kyoto (WKY) rats were selected as normal control group. The 0.5% CMC-Na solution was administered to model group and WKY rats (2 mL·kg⁻¹·d⁻¹). All of the rats were treated for 4 weeks. The open field test was performed at the 14th and 28th days after gavage, in order to evaluate the spontaneous and impulsive behaviors. Subsequently, gene and protein expressions of BDNF/TrkB and NRG-3 were tested by RT-qPCR and Western blot. Compared with model group, MPH and Shudihuang groups showed significant reduction in total distance, mean velocity and central distance in the open field test (P<0.05), and Shudihuang group displayed a shorter central distance than MPH group (P<0.05). RT-qPCR and Western blot analysis indicated that expressions of BDNF/TrkB and NRG-3 were lower in prefrontal cortex and striatum of SHR compared with WKY rats. Four weeks later after administration, both Shudihuang and MPH significantly elevated mRNA and protein expressions of BDNF/TrkB and NRG-3 (P<0.05).In conclusion, neurodevelopmental disorder mediated by BDNF/TrkB and NRG-3 was closely related with SHR rats' behaviors. Shudihuang may ameliorate the spontaneous and impulsive behaviors by up-regulating the expressions of BDNF/TrkB and NRG-3 and improving growth and maturation of neurons in SHR.

A Randomized Controlled Trial of Chinese Patent Medicine Xiao'er Biantong Granules in the Treatment of Functional Constipation in Children.

OBJECTIVE: To confirm the effect and safety of Xiao'er Biantong (XEBT) granules for treating chronic constipation in children. METHODS: This randomized, double-blind, multicenter study enrolled 480 children with age of 1-14 years who had FC. All of them were randomly assigned to receive either XEBT granules or its placebo in the ratio of 3 : 1. The primary efficacy outcome was the frequency of spontaneous bowel movements (SBM) for 14 days, and secondary outcomes were effectual time, score of main symptoms, effect of constipation, disappearance rate of accompanying symptoms, and recurrence rate. We also observed the adverse event (AE) and adverse drug reaction (ADR) to evaluate safety. RESULTS: The sociodemographic characteristics and efficiency data were comparable in the two groups at baseline. The mean values of SBM for 14 days were 8.89 and 5.63 in the XEBT group and the placebo group, respectively, and there were 86.87% and 30.91% subjects in two groups up to SBM ≥ 3/week, respectively. There were significant differences between the two groups. The effects in the XEBT group on median effectual time of defecation, main symptom score, disappearance rate of symptoms, and the differences were significant. The conclusions based on full analysis set (FAS) and per protocol set (PPS) were consistent. Nine AEs were reported, of which 7 were in the XEBT group (2.02%) while 2 were in the placebo group (1.77%). There were no significant differences in the occurrence rate of AE and ADR between the two groups. CONCLUSIONS: Xiao'er Biantong granules have superior efficacy compared to the placebo for the treatment of functional constipation in children and are well tolerated.

Corrigendum to "A Randomized Controlled Trial of Chinese Patent Medicine Xiao'er Biantong Granules in the Treatment of Functional Constipation in Children".

[This corrects the article DOI: 10.1155/2018/4941505.].

[Effect of baicalin on behavioral characteristics of rats with attention deficit hyperactivity disorder].

OBJECTIVE: To investigate the effect of baicalin on the behavioral characteristics of rats with attention deficit hyperactivity disorder (ADHD), and to provide a basis for further research on baicalin in the treatment of ADHD. METHODS: A total of 40 SHR rats were randomly divided into model group, methylphenidate hydrochloride (MPH) group, and low-, medium-, and high-dose baicalin groups, with 8 rats in each group. Eight WKY rats were selected as normal control group. The rats in the MPH group (0.07 mg/mL) and the low- (3.33 mg/mL), medium- (6.67 mg/mL), and high-dose (10 mg/mL) baicalin groups were given the corresponding drugs (1.5 mL/100 g) by gavage twice a day, and those in the normal control group and the model group were given an equal volume of normal saline by gavage twice a day. The course of treatment was 4 weeks for all groups. The open field test was performed to observe total moving distance and average moving speed on day 0 of experiment and at 7, 14, 21, and 28 days after gavage and to evaluate the control effects of drugs on hyperactivity and impulsive behavior. The Morris water maze test was used to observe the latency, time spent in the target quadrant, and number of platform crossings and to evaluate the effects of drugs on attention. RESULTS: The open field test showed that the model group and the drug treatment groups had a significantly longer total moving distance and a significantly higher average moving speed than the normal control group on day 0 (P<0.05). On day 7, the MPH group had significant reductions in total moving distance and average moving speed compared with the model group (P<0.05). On day 14, the MPH group and the high-dose baicalin group had significant reductions in total moving distance and average moving speed compared with the model group (P<0.05). The data on days 21 and 28 showed that compared with the model group, the low-, medium-, and high-dose baicalin groups had gradual reductions in total moving distance and average moving speed (P<0.05). The water maze test showed that compared with the model group, the MPH group and the medium- and high-dose baicalin groups had a significantly longer time spent in the target quadrant (P<0.05), and the MPH group and the high-dose baicalin group had a significantly higher proportion of the moving distance in the target quadrant in total moving distance (P<0.05). The high-dose baicalin group had the highest number of platform crossings among all groups (P<0.05). CONCLUSIONS: Both baicalin and MPH can regulate the motor ability and learning and memory abilities of SHR rats with ADHD and thus control the core symptoms of ADHD, i.e., hyperactivity, impulsive behavior, and inattention. Baicalin exerts its effect in a dose-dependent manner, and high-dose baicalin has the most significant effect, but compared with MPH, it needs a longer time to play its therapeutic effect.

Attention deficit hyperactivity disorder may be a highly inflammation and immune-associated disease (Review).

Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder. Previous research has indicated that genetic factors, family education, environment and dietary habits are associated with ADHD. It has been determined that in China many children with ADHD also have allergic rhinitis or asthma. These children are more susceptible to the common cold or upper respiratory infections compared with normal healthy children. Additionally, the common cold or an upper respiratory infection may lead to disease recurrence or worsen the symptoms in these children. Previous studies have determined that ADHD may have a close association with allergic disease. Based on the clinically observed phenomenon and previous studies, it was hypothesized that ADHD is a high inflammation and immune­associated disease. Therefore, the authors designed clinical and animal experiments to test this hypothesis in the future. Immune system disorders may be a novel part of the etiology of ADHD. The current report may have implications for future clinical practice.

[Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder].

OBJECTIVE: To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). METHODS: A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. RESULTS: Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05). CONCLUSIONS: Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial.

BACKGROUND: Tourette syndrome (TS) is a common tic disorder in children and adolescents. There is preliminary evidence that herbal medicine may possess the potential to treat tics. The purpose of this study was to formally evaluate the efficacy and safety of 5-Ling Granule (5-LGr), a proprietary polyherbal product, for the treatment of patients with TS in comparison with tiapride and placebo. METHODS: In this multisite, double-blind, double-dummy, randomized, placebo-controlled trial, 603 patients with TS aged 5-18 years were randomly assigned to treatment with placebo (n = 117), tiapride (n = 123, 200-400 mg/day) or 5-LGr (n = 363, 15-22.5 g/day) for 8 weeks. The primary outcome was measured using the Yale Global Tic Severity Scale (YGTSS) and its subscales, total tic Score (TTS) and tic-related impairment. Incidence of adverse events was compared among the three groups. RESULTS: While tics of all patients were reduced over time, 5-LGr and tiapride treatment produced significantly greater improvement on the YGTSS overall scale and subscale for TTS and impairment at endpoint than the placebo. Seventy-four percentage of patients in the 5-LGr arm and 68.3% in the tiapride arm had clinical response and these rates of response were significantly higher than those on placebo (44.0%, p < .001). The incidence of overall adverse events was significantly fewer for patients on placebo and 5-LGr compared to tiapride (11.2% and 13.8% vs. 26.0%, p = .002); in particular physical tiredness, dizziness and sleep disturbance. CONCLUSIONS: The clinical efficacy of 5-LGr is comparable to tiapride in reducing tics. Its safety profile is better than tiapride. 5-LGr can be considered a safe and effective therapy for TS (Trial registration: www.clinicaltrials.gov: NCT01501695).

[A Meta-analysis on Acupuncture Treatment of Attention Deficit/Hyperactivity Disorder].

OBJECTIVE: To assess the efficacy and safety of acupuncture in treating attention-deficit/hyperactivity disorder (ADHD) children. METHODS: A literature search was conducted to retrieve randomized cotrolled clinical trials of acupuncture in treating ADHD covering the period of the years of establishment of the databases to January 2014 from database of CBM, CNKI, PubMed, Cochrane Library by using key words "attention deficit hyperactivity disorder" "hyperactivity""minimal brain dysfunction" "acupuncture". Two independent researchers extracted data from located articles in a pre-defined structured way, and consulted the third researcher if necessary. RESULTS: Thirteen original trials including 1 304 cases of children with ADHD were obtained in this study according to our included criteria and excluded criteria. In these trials, acupuncture intervention alone, or acupuncture plus pharmacotherapy (methylphenidate, haloperidol) or acupuncture plus behavioral therapy were compared with simple pharmacotherapy or behavioral therapy alone. Results of Meta-analysis indicated that the total effective rate and Conners' index of hyperactivity (CIH) score-reduction rate in the acupuncture group were significantly superior to those of the other treatment groups [OR = 2.22, 95% CI (1.65, 3.00), Z = 5.22, P < 0.00001] [SMD = -0.94, 95% CI (-1.41, -0.47), Z = 3.89, P < 0.0001]. Acupuncture treatment is more effective than haloperidol in reducing the score of Conners' Rating Scale for ADHD [SMD = -7.28, 95% CI (-8.32, -6.23), Z = 13.62, P < 0.00001]. Acupuncture is similarly effective as Methylphenidate (Ritalin) in improving the Chinese medicine syndrome (liver-kidney yin hypoactivity) of children with ADHD [SMD = -1.14, 95% CI (-2.53, 0.25), Z = 1.60, P = 0.11]. Less severe adverse effects were reported with acupuncture therapy than the pharmacotherapy (poor appetite, dry mouth, nausea and constipation). These effects were not likely due to publication bias (approximately symmetry funnel plot, Egger's test P > 0.1). CONCLUSION: Acupuncture is an effective and safe therapy in treating ADHD, combined administration of acupuncture and pharmacotherapy or behavioral therapy is more effective than the pharmacotherapy or behavioral therapy alone. However, more rigorously designed and high-quality RCTs are needed to confirm the above conclusion.

[Study on medication regularity of traditional Chinese medicines in treating attention deficit hyperactivity disorder based on data mining].

In this study, efforts were made to collect 88 traditional Chinese medicine (TCM) prescriptions for treating ADHD from public literatures, establish a medication database and conduct data mining on the efficacy, properties, tastes, meridian entries and compatibility regularity of TCMs by using frequency analysis, association rules analysis and cluster analysis. The results showed 33 herbs with a high frequency (≥ 10%). The top 12 frequently applied ADHD herbs were respectively Acori Tatarinowii Rhizome, Polygalae Radix, Prepared Rehmanniae Radix, Os Draconis, Glycyrrhizae Radix et Rhizome, Poria, Concha Ostreae, Testudinis Carapacis et Plastri, Paeoniae Alba Radix, Schisandrae Fructus Chinensis, Fructus Corni, Dioscoreae Rhizoma. The top seven types of frequently applied ADHD herbs by effect were respectively tonic herb, sedative herbs, livei-wind calming herbs, heat clearing herbs, astringent herbs, awaking herbs and damp clearing and diuresis promoting herbs. The top three properties were warm, cold and neutral, with warm as the dominance. The top three tastes were sweetness, bitterness and acridity, with sweetness as the dominance. The top three meridian entries were liver meridian, heart meridian and kidney meridian. The association rules analysis showed commonly used herbal pairs. Polygalae Radix-Acori Tatarinowii Rhizome, Concha Ostreae-Os Draconis, Prepared Rehmanniae Radix-Fructus Corni-Os Draconis. Eight highly frequent cluster prescriptions were summarized based on the cluster analysis. This study indicates that basic TCM prescriptions for treating ADHD were principally composed of tonics (nourishing liver and kidney, invigorating heart and spleen) and tranquilization, which were supplemented with herbs for calming liver, clearing heat, promoting qi-circulation, promoting blood-circulation, reducing phlegm and calming endogenous wind. The combination of multiple data mining techniques can reflect the clinical medication regularity of herbs for treating ADHD in an overall and objective manner.

[Analysis of Applying Chinese Medical Clinical Pathway for Treating Attention-deficit Hyperactivity Disorder].

OBJECTIVE: To evaluate the application effect of Chinese medical clinical pathway for treating attention-deficit hyperactivity disorder (ADHD), and to provide evidence for further improving clinical pathways. METHODS: Totally 270 ADHD children patients were recruited and treated at pediatrics clinics of 9 cooperative hospitals from December 2011 to December 2012. The treatment course for all was 3 months. Scores of attention deficit and hyperactivity rating scale, scores of behavior, Conners index of hyperactivity (CIH), and Chinese medical syndrome scores were compared between before and after treatment. The efficacy difference in various sexes, ages, and disease courses were evaluated by judging standards for Chinese medical syndrome and ADHD. RESULTS: Fifteen children patients who entered clinical pathway dropped out, and the rest 255 completed this trial. Compared with before treatment, total scores of attention deficit and hyperactivity rating scale, scores of attention deficit and hyperactivity rating scale, CIH, and Chinese medical syndrome scores obviously decreased (all P < 0.01). The total effective rate in disease efficacy was 87.8% (224/255 cases), and the total effective rate in Chinese medical syndrome curative effect was 87.5% (223/255 cases). The clinical curative effect was not influenced by age, gender, or course of disease when statistically analyzed from judging standards for Chinese medical syndrome or for disease efficacy. CONCLUSION: Intervention by Chinese medical clinical pathway could improve ADHD patients' symptoms, and its efficacy was not influenced by sex, age, or course of disease.

[Considerations regarding animal research of traditional Chinese medicine on attention deficit hyperactivity disorder].

Attention-deficit/hyperactivity disorder (ADHD) is a common developmental neuropsychiatric disorder. Although ADHD can often be treated with stimulant class medications to alleviate symptoms, such treatments may cause undesirable side effects. Recently, Traditional Chinese medicine (TCM) has been gaining interest with treatment potential for ADHD and the lack of the stimulant-associated undesirable side effects. Animal models are useful for study the efficacy and mechanisms of TCM treatment for ADHD, however, previous studies of TCM on ADHD animal models, in general, have not considered appropriate experiemental designs. There were many concerns regarding the choice and source of the model and control animals, drug administration methods, behavioral and biochemical testing criteria, humane use of animals, and statistical power, etc. In this review, we discuss these issues present in the previous literature of animal research, and propose guidelines for future studies in particular consideration with the unique characteristic of Chinese medicine itself.