New Model of Traditional Chinese Medicine with Effect of Invigorating Kidney and Filling Sea of Marrow in Regulating Delay in Cortical Maturation of ADHD Based on Theory of Steady Yin and Vexed Yang / 中国实验方剂学杂志

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder among children. The theory of traditional Chinese medicine (TCM) does not have a special term of this disease, and classifies ADHD to the category of " forgetfulness" " dysphoria" " injudiciousness" according to its clinical manifestations. TCM theoretic and clinical systems for treating ADHD have been developed, but current pharmacodynamics studies of TCM on ADHD have mostly focused on neurotransmitter metabolic system and its receptor signaling pathway to reflect the advantages of multi-component and multi-target effect of TCM, but failed to demonstrate the scientific connotations of TCM theory, such as " coordination between kidney and brain" and " steady Yin and vexed Yang" , and ignored the delay in cortical maturation as the core neuropathology of ADHD. The symptoms relating to " restlessness of Yang" due to Yin deficiency that cannot inhibit hyperactivity of Yang, kidney-Yin deficiency and liver-Yang excess syndrome is the most common syndrome of ADHD, and TCMs with effect of invigorating kidney and filling sea of marrow are mostly used by TCM practitioners. According to anatomy basis of neuronal development disorder, the new theory of " energy metabolism dysfunction" , the pathogenesis hypothesis of sea of marrow development disorder and its relevant clinical practices and experimental studies, substantial basis studies of the therapy for " invigorating kidney and filling sea of marrow" , as well as pharmacodynamics study of <italic>Rehmannia glutinosa</italic> (Shudihuang) for treating ADHD, we put forward ADHD pathogenesis that " restlessness of Yang due to Yin deficiency" is related to the disorder of executive function due to the delay in cortical maturation, energy metabolism dysfunction and neurodevelopmental disorder, and regarded that TCMs with effect of invigorating kidney and filling sea of marrow are the most commonly used to treat ADHD, and improve delay in cortical maturation corresponding to sea of marrow insufficiency by regulating dysfunction of neurodevelopment and energy metabolism, so as to relieve the core symptoms of ADHD. The new treatment model of TCM with effect of invigorating kidney and filling sea of marrow for treating ADHD will provide a theoretical basis for improving the clinical efficacy of ADHD.

Effect of baicalin on growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡ and ERK1/2 / 中国中药杂志

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.

Research progress and application prospect of bain microdialysis in neuropsychiatric diseases / 医学研究生学报

Brain microdialysis (BMD) is a technique for continuous, on-line and real-time quantitative analysis for collected samples and it has been widely used in the quantitative detection of neurotransmitters in the brain in recent years. BMD has broad prospects in the research of neuropsychiatric diseases, but it is limited in studies because of its complicated operation, high cost, long time consuming, individual difference and poor reproducibility of the probe. Optimizing experimental design and developing multilocus microdialysis are main directions of research. Monitoring the changes of the metabolic state of the brain microenvironment in the neuropsychiatric diseases is another prospect of BMD. This article reviews the principle, characteristics and key points of brain microdialysis, along with the relationship between neurotransmitters and neuropsychiatric diseases, and the progress of microdialysis in neuropsychiatric diseases.

Regulatory effect of Shudihuang on expressions of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of ADHD model rats / 中国中药杂志

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 (<0.05), and Shudihuang group displayed a shorter central distance than MPH group (<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 (<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.

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 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Effect of baicalin on behavioral characteristics of rats with attention deficit hyperactivity disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Study on medication regularity of traditional Chinese medicines in treating attention deficit hyperactivity disorder based on data mining / 中国中药杂志

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 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Intervention by Chinese medical clinical pathway could improve ADHD patients' symptoms, and its efficacy was not influenced by sex, age, or course of disease.</p>

Considerations regarding animal research of traditional Chinese medicine on attention deficit hyperactivity disorder / 中国中药杂志

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.