[Effect of Rehmanniae Radix Praeparata on energy metabolism in prefrontal cortex of rats with attention deficit hyperactivity disorder based on "static Yin and dynamic Yang" theory].

The present study investigated the effect of Rehmanniae Radix Praeparata(RRP) on the energy metabolism of prefrontal cortex(PFC) of spontaneously hypertensive rats with attention deficit hyperactivity disorder(ADHD) based on the "static Yin and dynamic Yang" theory.Thirty spontaneously hypertensive male rats aged 3 weeks were randomly divided into a model group, a methylphenidate(MPH) group(2 mg·kg~(-1)), and an RRP group(2.4 g·kg~(-1)).Wistar-Kyoto(WKY) male rats of the same age were assigned to the normal group.Rats were treated with corresponding drugs twice per day, and those in the model group and the normal group received the same volume of 0.9% sodium carboxymethyl cellulose(CMC-Na) solution by gavage.The open-field test was performed to evaluate the spontaneous and impulsive behaviors of rats before treatment and on the 4~(th) week after treatment.Four weeks after treatment, PFC was isolated and mitochondria were prepared.The content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in the PFC was determined by high-performance liquid chromatography(HPLC), and energy charge(EC) was calculated.The parameters related to mitochondrial respiratory function were measured by the Clark oxygen electrode, specifically, state 3 respiration(ST3), state 4 respiration(ST4), and respiratory control rate(RCR).Enzymatic activities of succinate dehydrogenase(SDH), cytochrome C oxidase(COX), Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase were measured by chemical colorimetry.Mitochondrial permeability transition pore(mPTP) opening was measured by spectrophotometry.Protein expression of glucose transporter 1(GLUT1) and GLUT3 in PFC was tested by Western blot.Compared with the results in the model group, RRP could significantly reduce the total distance of movement, vertical times, and distance in the central area in the open field test(P<0.05 or P<0.01), increase the content of ATP and EC, decrease the content of AMP(P<0.05), elevate ST3 and RCR(P<0.05), potentiate activities of SDH, COX, Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase(P<0.05 or P<0.01), inhibit the opening of mPTP, and increase the expression levels of GLUT1 and GLUT3 proteins(P<0.05).It was inferred that RRP could inhibit hyperacti-vity and impulsivity by improving the energy metabolism disorder in PFC of ADHD rats, and its mechanism may be related to the improvement of mitochondrial respiratory function, potentiation of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, and mitochondrial respiratory enzymes, inhibition of the opening of mPTP, and up-regulation of the expression of glucose transporter proteins.This study initially reveals the biological connotation of the "static Yin and dynamic Yang" theory in ADHD.

[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.

[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.

[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.

[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.